Adrenocortical Carcinoma—Health Professional Version

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Adrenocortical carcinoma is also called cancer of the adrenal cortex. A tumor of the adrenal cortex may be functioning or nonfunctioning. Most adrenocortical tumors are functioning. Find evidence-based information on adrenocortical carcinoma including treatment and research.

Adrenocortical carcinoma, an unusual cause of secondary hypertension.

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Veron Esquivel, Daniel; Batiz, Fernando; Farias Vega, Alfonso; Carrillo Gonzalez, Perla A

2016-12-07

We present the case of a female patient aged 39 years who was admitted to our hospital due to hypertension, severe hypokalaemia and metabolic alkalosis; physical examination was remarkable for plethoric moon face, centripetal obesity and bilateral lower extremity oedema. She was admitted for intravenous potassium replacement and further assessment of hypertension and associated clinical findings. Laboratory testing showed increased levels of aldosterone, renin, cortisol, testosterone and androstenedione. An abdominal CT revealed a large mass in the right adrenal gland with hepatic involvement. The patient was started on antihypertensive medications and underwent laparoscopic surgery for mass and liver biopsy. The pathological diagnosis was adrenocortical carcinoma with liver metastasis. Hyperaldosteronism is a cause of secondary hypertension and its diagnosis is usually benign. Adrenocortical carcinoma is a rare condition and aldosterone secreting tumours are even rarer; associated hypertension usually improves after tumour resection, but with the presence of metastasis, blood pressure control is difficult. 2016 BMJ Publishing Group Ltd.

Expression of StAR and Key Genes Regulating Cortisol Biosynthesis in Near Term Ovine Fetal Adrenocortical Cells: Effects of Long-Term Hypoxia.

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Vargas, Vladimir E; Myers, Dean A; Kaushal, Kanchan M; Ducsay, Charles A

2018-02-01

We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs. Ewes were maintained at high altitude (3820 m) from ∼40 days of gestation (dG). At 138 to 141 dG, fetal adrenal glands were collected from LTH (n = 5) and age-matched normoxic controls (n = 6). Fetal adrenocortical cells were challenged with ACTH (10 -8 M) with or without UO126 (10 µM) for 18 hours. Media samples were collected for cortisol analysis and messenger RNA (mRNA) for CYP11A1, CYP17, and StAR was quantified by quantitative real-time polymerase chain reaction. Cortisol was higher in the LTH versus control ( P StAR mRNA was decreased in LTH versus control ( P StAR expression.

Marital Conflict Predicts Mother-to-Infant Adrenocortical Transmission.

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Hibel, Leah C; Mercado, Evelyn

2017-12-21

Employing an experimental design, mother-to-infant transmission of stress was examined. Mothers (N = 117) were randomized to either have a positive or conflictual discussion with their marital partners, after which infants (age = 6 months) participated in a fear and frustration task. Saliva samples were collected to assess maternal cortisol responses to the discussion and infant cortisol responses to the challenge task. Results indicate maternal cortisol reactivity and recovery to the conflict (but not positive) discussion predicted infant cortisol reactivity to the infant challenge. Mothers' positive affect during the discussion buffered, and intrusion during the free-play potentiated, mother-to-infant adrenocortical transmission. These findings advance our understanding of the social and contextual regulation of adrenocortical activity in early childhood. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

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MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

1981-01-01

To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

Testosterone-secreting adrenal adenoma in a peripubertal girl

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Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-01-01

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-β-[ 75 Se] selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor

Testosterone-secreting adrenal adenoma in a peripubertal girl

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Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

Salivary cortisol as an indicator of adrenocortical function in healthy infants, using massage therapy

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Monalisa de Cássia Fogaça

Full Text Available CONTEXT AND OBJECTIVE: The evaluation of adrenocortical function with the use of therapeutic massage has been little studied in Brazil. The purpose of this study was to evaluate the salivary cortisol levels before and after Shantala massage therapy on healthy infants. DESIGN AND SETTING: Prospective case series, in a public nursery, in São Paulo. METHODS: Saliva was obtained from 11 infants at the times of 8:00-9:00 a.m. and 4:00-5:00 p.m. in a nursery and 9:00-10:00 p.m. at home. They received a 15-minute therapeutic massage on two consecutive days, and saliva was collected before and after the massage. The procedure was repeated after a one-week interval. Cortisol values (intra-assay < 5%; inter-assay < 10% at different times of the day were compared by ANOVA. RESULTS: The mean cortisol values (nmol/l ± SD on the first day were: morning (M = 14.1 ± 5.7, afternoon (A = 8.3 ± 2.7, night (N = 3.3 ± 1.1; after two consecutive days of therapeutic massage: M = 22.3 ± 13.5, A = 13.4 ± 6.0, N = 5.8 ± 3.5; after a one-week interval: M = 15.8 ± 7.7, A = 14.3 ± 7.7, N = 3.4 ± 2.0. CONCLUSION: There was a modification in the salivary cortisol values following massage, thus reflecting possible adaptation of the hypothalamic-pituitary-adrenal axis.

Adrenocortical tumors in children

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R.C. Ribeiro

2000-10-01

Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Laparoscopic Partial Adrenalectomy for Bilateral Cortisol-secreting Adenomas

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Jeffrey P. Domino

2007-04-01

Full Text Available Bilateral cortisol-secreting adenomas are a rare cause of Cushing's syndrome. We report a case of a 35-year-old woman who presented with ACTH-independent Cushing's syndrome and bilateral adrenal adenomas. Adrenal venous sampling confirmed both adenomas to be hyper-secreting cortisol. She underwent bilateral laparoscopic adrenalectomy; total right and partial left adrenalectomies. At 2-year follow-up, she is maintained on low-dose fludrocortisone and hydrocortisone, and without recurrence of hypercorticolism. Laparoscopic partial adrenalectomy is a feasible option for this rare condition; however, long-term follow-up is needed to determine her total independence from steroid usage.

The Role of gsp Mutations on the Development of Adrenal Cortical Tumors and Adrenal Hyperplasias

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Maria Candida Barisson Villares Fragoso

2016-07-01

Full Text Available Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune Albright syndrome and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors and primary macronodular adrenocortical hyperplasia (PMAH. [1-3]The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. in 1990. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear. [3] PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. in 2003 identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of McCune Albright syndrome. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production. [2, 4] With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion.In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia.

Does somatostatin have a role in the regulation of cortisol secretion in primary pigmented nodular adrenocortical disease (PPNAD)? A clinical and in vitro investigation

NARCIS (Netherlands)

Z. Bram (Zakariae); P. Xekouki (Paraskevi); E. Louiset (Estelle); M. Keil (Mark); D. Avgeropoulos (Dimitrios); C. Giatzakis (Christoforos); M. Nesterova (Maria); N. Sinaii (Ninet); L.J. Hofland (Leo); R. Cherqaoui (Rabia); H. Lefebvre (Hervé); C.A. Stratakis (Constantine)

2014-01-01

textabstractContext: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex

No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone before Surgery

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Rachel M. Saroka

2016-01-01

Full Text Available Background Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA axis, eliminating the need for postoperative glucocorticoid replacement. Case Presentation A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours. Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL, suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2–63.3 pg/mL, and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9–295.6 µg/dL. Because of his poor medical condition and uncontrolled diabetes, his Cushing's syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL and cortisol levels (44.8 µg/dL were significantly elevated, reflecting an appropriate HPA axis

No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone Before Surgery

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Saroka, Rachel M.; Kane, Michael P.; Robinson, Lawrence; Busch, Robert S.

2016-01-01

BACKGROUND Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement. CASE PRESENTATION A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier’s gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2–63.3 pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9–295.6 µg/dL). Because of his poor medical condition and uncontrolled diabetes, his Cushing’s syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL) and cortisol levels (44.8 µg/dL) were significantly elevated, reflecting an appropriate HPA axis response to

Adrenocortical Secreting Mass in a Patient with Gardner's Syndrome: A Case Report

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Nabila Mejdoub Rekik

2010-01-01

Full Text Available Gardner's syndrome (GS is a dysplasia characterized by neoformations of the intestine, soft tissue, and osseous tissue. Endocrine neoplasms have occasionally been reported in association with GS. Adrenal masses in GS are rare, and few have displayed clinical manifestations. In the current paper, The authors report a 37-year-old male patient with GS including familial adenomatous polyposis (FAP and mandible osteoma who presented with an incidental adrenal mass. Computerized tomography adrenal scan identified bilateral masses. Functional analyses showed a hormonal secretion pattern consistent with pre-Cushing's syndrome. Other extraintestinal manifestations were hypertrophy of the pigmented layer of the retina and histiocytofibroma in the right leg. This paper describes a rare association of adrenocortical secreting mass in an old male patient with Gardner syndrome.

Environmental influence of problematic social relationships on adolescents' daily cortisol secretion: a monozygotic twin-difference study.

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Brendgen, M; Ouellet-Morin, I; Lupien, S J; Vitaro, F; Dionne, G; Boivin, M

2017-02-01

This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence. This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8. The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother-child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope). Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence.

Relationship between cyberbullying roles, cortisol secretion and psychological stress

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González-Cabrera, Joaquín (UNIR); Calvete, Esther; León-Mejía, Ana (UNIR); Pérez-Sancho, Carlota; Peinado, José M.

2017-01-01

Although cyberbullying is associated with different psychological problems, the role of biological markers of stress in cyberbullying has been relatively neglected. The aims of this study were: 1) to analyze the profile of cortisol secretion along the day in subjects involved in cyberbullying and 2) to investigate whether the predictive relationship between cyberbullying victimization and subjective symptoms of stress and anxiety are accounted for by cortisol reactivity. A longitudinal study ...

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

NARCIS (Netherlands)

Rasmussen, L.S.; O'Brien, J.T.; Silverstein, J.H.; Johnson, T.; Siersma, V.D.; Canet, J.; Jolles, J.; Hanning, C.D.; Kuipers, H.M.; Abildstrom, H.; Papaioannou, A.; Raeder, J.; Yli-Hankala, A.; Sneyd, J.R.; Munoz, L.; Moller, J.T.

2005-01-01

Background: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in

Long-term stability of diurnal salivary cortisol and alpha-amylase secretion patterns.

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Skoluda, Nadine; La Marca, Roberto; Gollwitzer, Mario; Müller, Andreas; Limm, Heribert; Marten-Mittag, Birgitt; Gündel, Harald; Angerer, Peter; Nater, Urs M

2017-06-01

This study aimed to investigate long-term stability and variability of diurnal cortisol and alpha-amylase patterns. Diurnal cortisol and alpha-amylase secretion patterns were assessed on a single workday with three waves of measurement across a total time period of 24months in 189 participants. Separate hierarchical linear models were analyzed, with and without a number of potential predictor variables (age, BMI, smoking, chronic stress, stress reactivity). While low long-term stability was found in diurnal cortisol, the stability of diurnal alpha-amylase was moderate across the time period of 24months. Several predictor variables had a positive impact on diurnal cortisol and alpha-amylase secretion patterns averaged across waves. Our findings underpin the notion that long-term stability is not necessarily warranted in longitudinal studies. It is important to choose an appropriate study design when attempting to disentangle clinically and biologically relevant changes from naturally occurring variations in diurnal cortisol and alpha-amylase. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.

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Heck, Dorothee; Wortmann, Sebastian; Kraus, Luitgard; Ronchi, Cristina L; Sinnott, Richard O; Fassnacht, Martin; Sbiera, Silviu

2015-12-01

Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

Magnetic resonance imaging of adrenocortical adenomas in childhood: correlation with computed tomography and ultrasound

International Nuclear Information System (INIS)

Hanson, J.A.; Weber, A.; Reznek, R.H.; Cotterill, A.M.; Ross, R.J.M.; Harris, R.J.; Armstrong, P.; Savage, M.O.

1996-01-01

There are few descriptions of the magnetic resonance (MR) appearance of hyperfunctioning adrenocortical tumours, particularly those occurring in childhood. We studied five patients, two girls and three boys, aged 6-14.3 years, presenting with clinical syndromes of adrenocortical hyperfunction. The diagnoses were Cushing's syndrome (n = 2), virilisation (n = 2), and Conn's syndrome (n = 1). Biochemical features suggested an adrenal lesion in each case. MR and ultrasound were performed in all five cases, with CT in four. Each patient had a functional adrenal tumour secreting either cortisol, androgens or aldosterone alone, or a combination of cortisol, androgens and oestradiol. The histological diagnosis was adenoma in four cases and tumour of indeterminate nature in one case. MR clearly showed the tumours (diameter 1.0-7.5 cm), all the lesions being of high signal intensity relative to liver on T2-weighted sequences. CT revealed an adrenal mass in each of the four patients scanned, three of which enhanced after intravenous contrast medium injection. The multiplanar imaging of MR allowed better distinction from adjacent structures and also demonstrated an unenlarged contralateral adrenal gland. In the patient with a 1-cm Conn's adenoma the lesion was more easily seen on MR than CT. Ultrasound showed the four larger tumours but was unable to visualise the contralateral adrenal or the Conn's adenoma. In conclusion, the MR appearances of four adrenocortical adenomas and one indeterminate tumour in children are described. MR has been found to be at least equal to CT in the detection of these tumours, with some possible advantages. Both techniques are superior to ultrasound. (orig.). With 4 figs

Clinical results of the use of mitotane for adrenocortical carcinoma

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Kasperlik-Zaluska A.A.

2000-01-01

Full Text Available Mitotane (o,p'-DDD acts mainly as an inhibitor of intramitochondrial pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for 40 years in the treatment of adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of adrenocortical carcinoma. In our experience, mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with adrenocortical carcinoma, 59 patients have been treated with mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with mitotane soon after the operation and only 6 survivors in the group receiving mitotane with a delay. All patients were simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane with good results in Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.

Cross-country differences in basal and stress-induced cortisol secretion in older adults.

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Juliana N Souza-Talarico

Full Text Available Several studies have emphasized the association between socioeconomic status (SES and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries.Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST in both populations.Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants.These findings suggest that country context may modulate cortisol secretion and could impact the population health.

Cross-country differences in basal and stress-induced cortisol secretion in older adults.

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Souza-Talarico, Juliana N; Plusquellec, Pierrich; Lupien, Sonia J; Fiocco, Alexandra; Suchecki, Deborah

2014-01-01

Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. These findings suggest that country context may modulate cortisol secretion and could impact the population health.

24-hour secretory pattern of dehydroisoandrosterone and dehydroisoandrosterone sulfate

International Nuclear Information System (INIS)

Rosenfeld, R.S.; Rosenberg, B.J.; Fukushima, D.K.; Hellman, L.

1975-01-01

Dehydroisoandrosterone (DHA) and cortisol were measured by radioimmunoassay and protein binding techniques respectively in plasma from blood taken at 20-min intervals over 24-h periods in 3 normal men, 2 women with Stein-Leventhal syndrome, and a man with a benign adrenocortical adenoma. In all subjects but the latter, DHA and cortisol were episodic and synchronous throughout the entire day; in this patient, continuous secretion of cortisol by the tumor apparently abolished stimulation of the contralateral adrenal, and DHA production was negligible. Dehydroisoandrosterone sulfate analyses in plasma displayed a pattern which, probably because of its origin both by secretion and sulfation and its long half-life, showed less synchronicity with DHA and cortisol and less fluctuation than did the free hormones. (U.S.)

Multiple Salivary Cortisol Measurements Are a Useful Tool to Optimize Metyrapone Treatment in Patients with Cushing's Syndromes Treatment: Case Presentations.

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Yoshida, Kenichi; Fukuoka, Hidenori; Odake, Yukiko; Nakajima, Shinsuke; Tachibana, Mariko; Ito, Jun; Hosokawa, Yusei; Yamada, Tomoko; Miura, Hiroshi; Suematsu, Natsu; Matsumoto, Ryusaku; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Iguchi, Genzo; Ogawa, Wataru; Takahashi, Yutaka

2017-01-01

Measuring salivary cortisol is both convenient and non-invasive for patients; however, its usefulness as a marker for monitoring medical therapy has not yet been established. The aim of this study was to assess the utility of multiple salivary cortisol measurements in patients with Cushing's syndrome (CS) during medical therapy. Six patients with CS (three with cortisol-secreting adrenocortical adenoma and three with ACTH-secreting pituitary adenoma) were recruited. Samples for morning serum cortisol, urinary free cortisol (UFC), and multiple salivary cortisol levels were collected before and during metyrapone treatment. The area under the curve (AUC) and mean value (MV) of daily salivary cortisol levels were calculated. In five out of six patients, UFC were normalized; however, multiple salivary cortisol measurements revealed an impaired diurnal cortisol rhythm in these patients. To verify the usefulness of multiple salivary cortisol measurements, we performed a prospective case study of a patient in whom the excess secretion of cortisol was not controlled (UFC 211 μg/day) with 2,250 mg/day in four divided doses of metyrapone. Multiple measurements of salivary cortisol revealed that cortisol levels elevated before the next administration. Accordingly, we shortened the interval by increasing the number of administration from four to five times per day, with a slight increment of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement of diurnal pattern as well as UFC level (101 μg/day). Changes in both the MV and AUC of salivary cortisol levels were more correlated with those in UFC levels (Correlation coefficient 0.75, p  = 0.007, and 0.70, p  = 0.017) than those in the morning serum cortisol levels (0.42, p  = 0.200), indicating that multiple salivary cortisol measurements reflect more precisely the excess secretion of cortisol. Our preliminary data suggest that multiple salivary cortisol measurements can be a useful

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

Science.gov (United States)

Mete, Ozgur; Duan, Kai

2018-01-01

Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Diurnal salivary cortisol concentrations in Parkinson’s disease: increased total secretion and morning cortisol concentrations

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Skogar Ö

2011-08-01

Full Text Available Ö Skogar1,4, P-A Fall2, G Hallgren3, J Lökk4, B Bringer2, M Carlsson1, U Lennartsson3, H Sandbjork3, C-J Törnhage51Department of Geriatrics, Ryhov Hospital, Jonkoping, 2Department of Geriatrics, University Hospital, Linkoping, 3Department of Neurology, Skaraborg Hospital, Skovde, 4Institute of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 5Department of Pediatrics, Skaraborg Hospital, Skövde, SwedenBackground: Parkinson’s disease (PD is a chronic neurodegenerative disorder. There is limited knowledge about the function of the hypothalamic-pituitary-adrenal axis in PD. The primary aim of this prospective study was to analyze diurnal salivary cortisol concentrations in patients with PD and correlate these with age, gender, body mass index (BMI, duration of PD, and pain. The secondary aim was to compare the results with a healthy reference group.Methods: Fifty-nine PD patients, 35 women and 24 men, aged 50–79 years, were recruited. The reference group comprised healthy individuals matched for age, gender, BMI, and time point for sampling. Salivary cortisol was collected at 8 am, 1 pm, and 8 pm, and 8 am the next day using cotton-based Salivette® tubes and analyzed using Spectria® Cortisol I125. A visual analog scale was used for estimation of pain.Results: The median cortisol concentration was 16.0 (5.8–30.2 nmol/L at 8 am, 5.8 (3.0–16.4 at 1 pm, 2.8 (1.6–8.0 at 8 pm, and 14.0 (7.5–28.7 at 8 am the next day. Total secretion and rate of cortisol secretion during the day (8 am–8 pm and the concentration of cortisol on the next morning were lower (12.5 nmol/L in the reference group. No significant correlations with age, gender, BMI, duration of PD, Hoehn and Yahr score, Unified Parkinson’s Disease Rating Scale III score, gait, pain, or cortisol concentrations were found.Conclusion: The neurodegenerative changes in PD does not seem to interfere with the

Night work, long working hours, psychosocial work stress and cortisol secretion in mid-life: evidence from a British birth cohort.

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Thomas, C; Hertzman, C; Power, C

2009-12-01

To examine the relationships between exposure to workplace factors (night work, extended working hours, psychosocial work stress) and cortisol secretion, and to test whether workplace factors interact, resulting in combined effects. Multiple linear and logistic regression was used to test relationships between workplace factors and cortisol secretion in the 1958 British birth cohort at 45 years. Salivary cortisol was measured twice on the same day to capture the post-waking decline, facilitating the analysis of different cortisol patterns: (1) time 1 (T1, 45 minutes post-waking); (2) time 2 (T2, 3 h after T1); (3) average 3 h exposure from T1 to T2 cortisol; and (4) T1 to T2 change. To identify altered diurnal cortisol patterns we calculated: (1) flat T1-T2 change in cortisol; (2) top 5% T1; (3) bottom 5% T1; and (4) T1 hypo-secretion or hyper-secretion. Models were adjusted for socioeconomic position at birth and in adulthood, qualifications, marital status, dependent children, and smoking status. 25% of men and 8% of women were exposed to >1 workplace factor (night work, extended work hours, job strain). Night work was associated with a 4.28% (95% CI 1.21 to 7.45) increase in average 3 h cortisol secretion independently of job strain or work hours. Night workers not exposed to job strain had elevated T1 cortisol (5.81%, 95% CI 1.61 to 10.19), although for T2 cortisol it was night workers exposed to low job control who had elevated levels (11.72%, 95% CI 4.40 to 19.55). Men (but not women) working >48 h/week had lower average 3 h cortisol secretion (4.55%, 95% CI -8.43 to -0.50). There were no main effects for psychosocial work stress. All associations for T2 and average 3 h cortisol secretion weakened slightly after adjustment for confounding factors, but associations for T1 cortisol were unaffected by adjustment. Our study suggests that night work in particular is associated with elevated cortisol secretion and that cortisol dysregulation may exist in subgroups

A comparative assessment of the adrenotoxic effects of cadmium in two teleost species, rainbow trout, Oncorhynchus mykiss, and yellow perch, Perca flavescens

Energy Technology Data Exchange (ETDEWEB)

Lacroix, Alexandra; Hontela, Alice

2004-03-30

Rainbow trout (Oncorhynchus mykiss) and yellow perch (Perca flavescens) have a different sensitivity to cadmium (Cd) in vivo (troutcortisol secretion by adrenocortical cells in both species. The purpose of the present study was to assess in vitro the effect of Cd on cortisol secretion by adrenocortical cells of trout and perch, to compare the sensitivity of adrenal steroidogenesis in these two teleosts. Adrenocortical cells were exposed to Cd for 60 min, then stimulated with ACTH, dbcAMP or with pregnenolone, a cortisol precursor. Cd inhibited ACTH-stimulated cortisol secretion in a dose-dependent manner in both fish species, however, the EC50s (concentration resulting in 50% inhibition of cortisol secretion) was significantly lower in trout (EC50=0.09 mM) than perch (EC50=0.26 mM). To test the specificity of Cd to act as an endocrine disrupter, the LC50 (concentration that kills 50% of the cells) was also evaluated to determine the LC50/EC50 ratio (LC50/EC50{sub O.mykiss}=175.6>LC50/EC50{sub P.flavescens}=37.7). Adrenocortical cells of trout were more sensitive than those of perch and Cd had a higher endocrine-disrupting potential and specificity in trout than in perch. However, in both species, Cd had the same effect on ACTH, dbcAMP and pregnenolone-stimulated cortisol secretion, with pregnenolone maintaining cortisol secretion until cell viability was impaired. These results confirm that for both species, Cd interferes in the signalling pathway of cortisol synthesis in a step prior to the pregnenolone formation. Data provided by the present study revealed important differences in vulnerability of adrenal steroidogenesis between rainbow trout and yellow perch.

Non-invasive measurement of adrenocortical activity in a ...

African Journals Online (AJOL)

Measuring physiological stress reactions through the quantification of plasma cortisol often involves physical restraint, which acts as a stressor itself. Here, we present the validation of a non-invasive method for assessing adrenocortical activity as an indicator of stress in the bat-eared fox (Otocyon megalotis). By conducting ...

Multiple Salivary Cortisol Measurements Are a Useful Tool to Optimize Metyrapone Treatment in Patients with Cushing’s Syndromes Treatment: Case Presentations

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Kenichi Yoshida

2018-01-01

Full Text Available Measuring salivary cortisol is both convenient and non-invasive for patients; however, its usefulness as a marker for monitoring medical therapy has not yet been established. The aim of this study was to assess the utility of multiple salivary cortisol measurements in patients with Cushing’s syndrome (CS during medical therapy. Six patients with CS (three with cortisol-secreting adrenocortical adenoma and three with ACTH-secreting pituitary adenoma were recruited. Samples for morning serum cortisol, urinary free cortisol (UFC, and multiple salivary cortisol levels were collected before and during metyrapone treatment. The area under the curve (AUC and mean value (MV of daily salivary cortisol levels were calculated. In five out of six patients, UFC were normalized; however, multiple salivary cortisol measurements revealed an impaired diurnal cortisol rhythm in these patients. To verify the usefulness of multiple salivary cortisol measurements, we performed a prospective case study of a patient in whom the excess secretion of cortisol was not controlled (UFC 211 μg/day with 2,250 mg/day in four divided doses of metyrapone. Multiple measurements of salivary cortisol revealed that cortisol levels elevated before the next administration. Accordingly, we shortened the interval by increasing the number of administration from four to five times per day, with a slight increment of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement of diurnal pattern as well as UFC level (101 μg/day. Changes in both the MV and AUC of salivary cortisol levels were more correlated with those in UFC levels (Correlation coefficient 0.75, p = 0.007, and 0.70, p = 0.017 than those in the morning serum cortisol levels (0.42, p = 0.200, indicating that multiple salivary cortisol measurements reflect more precisely the excess secretion of cortisol. Our preliminary data suggest that multiple salivary cortisol measurements can be a

Assessment of survey radiography and comparison with x-ray computed tomography for detection of hyperfunctioning adrenocortical tumors in dogs

International Nuclear Information System (INIS)

Voorhout, G.; Stolp, R.; Rijnberk, A.; Waes, P.F.G.M. van

1990-01-01

Results of abdominal survey radiography and x-ray computed tomography (CT) were compared in 13 dogs with hyperadrenocorticism histologically attributed to adrenocortical tumors. X-ray computed tomography enabled accurate localization of the tumor in all 13 dogs. Apart from 2 poorly demarcated irregular-shaped and mineralized carcinomas, there were no differences between adenoma (n = 3) and carcinoma (n = 10) on CT images. In 1 dog, invasion of the caudal vena cava by the tumor was suggested on CT images and was confirmed during surgery. Suspicion of adhesions between tumors of the right adrenal gland and the caudal vena cava on the basis of CT images was confirmed during surgery in only 2 of 6 dogs. Survey radiography allowed accurate localization of the tumor in 7 dogs (4 on the right side and 3 on the left). In 6 of these dogs, the tumor was visible as a well-demarcated soft tissue mass and, in the other dog, as a poorly demarcated mineralized mass. The smallest tumor visualized on survey radiographs had a diameter of 20 mm on CT images. Six tumors with diameter less than or equal to 20 mm were not visualized on survey radiographs. In 1 of these dogs, a mineralized nodule was found in the left adrenal region, without evidence of a mass. In a considerable number of cases, survey radiography can provide presurgical localization of adrenocortical tumors in dogs with hyperadrenocorticism; CT is redundant in these instances. In the absence of positive radiographic findings, CT is valuable for localization of adrenocortical tumors

Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD).

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Scheidegger, M D; Gerber, V; Bruckmaier, R M; van der Kolk, J H; Burger, D; Ramseyer, A

2017-10-01

This study tested the hypothesis that adrenocortical function would be altered in horses with equine gastric ulcer syndrome (EGUS). Twenty-six sport horses competing at national or international levels in eventing (n=15) or endurance (n=11) were subjected to a gastroscopic examination and an adrenocorticotropic hormone (ACTH) stimulation test. Salivary cortisol concentrations were measured before (baseline) and after (30, 60, 90, 120 and 150min) IV ACTH injection (1μg/kg bodyweight). Within EGUS, two distinct diseases, equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), can be distinguished. ESGD was diagnosed in 8/11 (73%; 95% confidence intervals [95%CI], 43-92%) endurance horses and 5/15 (33%; 95% CI, 14-58%) eventing horses. EGGD was observed in 9/11 (82%; 95% CI, 53-96%) endurance horses and 9/15 (60%; 95% CI, 35-81%) eventing horses. The presence or severity of ESGD was unrelated to the presence or severity of EGGD. ACTH stimulation induced a larger increase in cortisol concentration in horses with moderate EGGD than in horses with mild EGGD. Cortisol concentration during the entire sampling period (total increase in cortisol concentration during the entire sampling period [dAUC], 31.1±6.4ng/mL) and the highest measured concentration at a single time point (maximal increase in cortisol concentration [dMAX], 10.3±2.3ng/mL) were increased (P=0.005 and P=0.038, respectively), indicating that horses with glandular gastric disease exhibited increased adrenocortical responses to ACTH stimulation. These results suggest that EGGD might be associated with an enhanced adrenocortical sensitivity. Further investigations are warranted to confirm the association between adrenocortical sensitivity and EGGD and to elucidate the pathophysiological mechanisms involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

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Ozgur Mete

2018-03-01

Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

A nonlinear relationship of generalized and central obesity with diurnal cortisol secretion in the Whitehall II study.

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Kumari, Meena; Chandola, Tarani; Brunner, Eric; Kivimaki, Mika

2010-09-01

Evidence for an association of measures of generalized and central obesity with salivary cortisol secretion is equivocal. The objective of this study was to assess the relationship between body mass index (BMI), waist circumference, and salivary cortisol. The design was a cross-sectional study of BMI, waist circumference, and salivary cortisol from phase 7 (2002-2004) of the Whitehall II study. The occupational cohort was originally recruited in 1985-1988. Participants included 2915 men and 1041 women aged 50-74 yr with complete information on height, weight and waist circumference, and cortisol secretion. Saliva samples were taken on waking, waking plus 0.5, 2.5, 8, and 12 h, and bedtime for the assessment of cortisol. The cortisol awakening response and slope in diurnal secretion were calculated. After adjustment for age, sex, social position, waking time, and time since waking of sample collection, increasing central and generalized obesity was associated with lower waking cortisol (P = 0.001). U-shaped associations were apparent between diurnal slope in salivary cortisol and both BMI and waist circumference (P cortisol were associated with highest (>31 kg/m(2)) and lowest (levels of BMI, and the steepest slopes were apparent for those with BMI of 26 kg/m(2), independently of the 12 covariates examined. No associations were apparent for the cortisol awakening response (P > 0.05). The associations of measures of generalized and central obesity with diurnal slope in salivary cortisol are not linear in older adults. These nonlinear associations may explain previously described mixed findings.

Impact of age, sex and body mass index on cortisol secretion in 143 healthy adults

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Ferdinand Roelfsema

2017-09-01

Full Text Available Context: Studies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting. Objective: To investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI range with different analytic tools. Setting: Clinical Research Unit. Design: Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic and 24-h rhythms. Results: Total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02, but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001, but not in subjects older than 50 years. ApEn peaked during the daytime. Conclusion: Sex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.

Adrenocortical function and reserve in children treated for acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Pawlaczyk, B.; Malecka, E.H.; Krause, W.

1993-01-01

Serum cortisol and 17 OHS, 17 KS and DHA levels in 24-hour urine were determined in 30 children (22 girls and boys) 0.5 to 4 years after completion of therapy (radio- and chemotherapy) for acute lymphoblastic leukemia (ALL). Serum cortisol after Syncthen (adrenocortical reserve) was determined in 15 girls and 4 boys. The results show that therapy for ALL depresses glucocorticosteroid synthesis; however, it does not disturb the adrenal reserve or androgenesis. (author)

Imaging Findings of Pelvic Tumor Thrombosis Extending from Sacral Bone Metastasis of Adrenocortical Carcinoma

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Kenichiro Ishida

2012-01-01

Full Text Available We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with 18F-fluorodeoxyglucose and single-photon emission computed tomography with 131I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.

Diurnal Cortisol Secretion at Home and in Child Care: A Prospective Study of 2-Year-Old Toddlers

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Ouellet-Morin, Isabelle; Tremblay, Richard E.; Boivin, Michel; Meaney, Michael; Kramer, Michael; Cote, Sylvana M.

2010-01-01

Background: Previous studies indicate that children may experience disrupted cortisol secretion in child care. The extent to which this is a transient or long-term disruption is not known, as most studies have relied on cross-sectional designs, and age-heterogeneous small sample sizes. This study aims to (a) compare cortisol secretion measured at…

MicroRNAs as potential biomarkers in adrenocortical cancer: progress and challenges

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Nadia eCHERRADI

2016-01-01

Full Text Available Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of adrenocortical carcinoma. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors such as the IGF2 pathway, the Wnt pathway and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation and microRNA profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. MicroRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated microRNAs to the pathogenesis of adrenocortical carcinoma is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some microRNAs have been shown to carry potential diagnostic and prognostic values while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne microRNAs signatures, analyses of small cohorts of patients with adrenocortical carcinoma suggest that circulating microRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the microRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating microRNAs in adrenocortical carcinoma patients, while emphasizing their potential significance in adrenocortical carcinoma pathogenic

Cortisol Secretion and Change in Sleep Problems in Early Childhood: Moderation by Maternal Overcontrol

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Kiel, Elizabeth J.; Hummel, Alexandra C.; Luebbe, Aaron M.

2015-01-01

Childhood sleep problems are prevalent and relate to a wide range of negative psychological outcomes. However, it remains unclear how biological processes, such as HPA activity, may predict sleep problems over time in childhood in the context of certain parenting environments. Fifty-one mothers and their 18–20 month-old toddlers participated in a short-term longitudinal study assessing how shared variance among morning levels, diurnal change, and nocturnal change in toddlers’ cortisol secretion predicted change in sleep problems in the context of maternal overprotection and critical control. A composite characterized by low variability in, and, to a lesser extent, high morning values of cortisol, predicted increasing sleep problems from age 2 to age 3 when mothers reported high critical control. Results suggest value in assessing shared variance among different indices of cortisol secretion patterns and the interaction between cortisol and the environment in predicting sleep problems in early childhood. PMID:25766262

Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion.

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Debono, Miguel; Harrison, Robert F; Chadarevian, Rita; Gueroult, Carole; Abitbol, Jean-Louis; Newell-Price, John

2017-09-01

Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death. We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers. In a phase 1/2a, prospective study (Eudract no. 2012-002586-35), we recruited six patients with AI/ACS and two control groups of six sex-, age-, and body mass index-matched individuals: (1) patients with AI and no ACS (AI/NoACS) and (2) healthy volunteers with no AI [healthy controls (HC)]. Twenty-four-hour circadian cortisol analysis was performed to determine any differences between groups and timing of intervention for cortisol lowering using the 11β-hydroxylase inhibitor metyrapone. Circadian profiles of serum interleukin-6 (IL-6) were assessed. Serum cortisol levels in group AI/ACS were significantly higher than both group AI/NoACS and group HC from 6 pm to 10 pm [area under the curve (AUC) difference: 0.81 nmol/L/h; P = 0.01] and from 10 pm to 2 am (AUC difference: 0.86 nmol/L/h; P cortisol rhythms were reassessed. Postintervention evening serum cortisol was lowered, similar to controls [6 pm to 10 pm (AUC difference: -0.06 nmol/L/h; P = 0.85); 10 pm to 2 am (AUC difference: 0.10 nmol/L/h; P = 0.76)]. Salivary cortisone showed analogous changes. IL-6 levels were elevated before treatment [10 pm to 2 pm (AUC difference: 0.42 pg/mL/h; P = 0.01)] and normalized post treatment. In AI/ACS, the evening and nocturnal cortisol exposure is increased. Use of timed evening doses of metyrapone resets the cortisol rhythm to normal. This unique treatment paradigm is associated with a reduction in the cardiovascular risk marker IL-6. Copyright © 2017 Endocrine Society

Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

International Nuclear Information System (INIS)

Henry, I.; Grandjouan, S.; Couillin, P.

1989-01-01

The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

Maternal-child adrenocortical attunement in early childhood: continuity and change.

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Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

2015-01-01

This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. © 2014 Wiley Periodicals, Inc.

In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an increase of serum cortisol relative to other adrenal hormones.

Science.gov (United States)

Atzeni, F; Sarzi-Puttini, P; DePortu, S; Cutolo, M; Carrabba, M; Straub, R H

2008-01-01

In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

Science.gov (United States)

Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

2004-07-01

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

Childhood maltreatment and diurnal cortisol patterns in women with chronic pain.

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Nicolson, Nancy A; Davis, Mary C; Kruszewski, Denise; Zautra, Alex J

2010-06-01

To assess whether alleged childhood maltreatment is associated with daily cortisol secretion in women with chronic pain. Women with fibromyalgia (FM group, n = 35) or with osteoarthritis only (OA group, n = 35) completed diaries and collected three saliva samples daily for 30 days, with compliance monitored electronically. Childhood abuse and neglect were assessed by self-report (Childhood Trauma Questionnaire-short form [CTQ-sf]). Multilevel regression analyses estimated associations between maltreatment and diurnal cortisol levels and slopes, controlling for depressive symptoms, posttraumatic stress disorder (PTSD), and daily experience variables. Women reporting more severe childhood maltreatment had higher cortisol throughout the day. The estimated effect of CTQ on log cortisol (beta = 0.007, p = .001) represents a 0.7% increase in raw cortisol level for every unit increase in maltreatment score, which ranged from 25 (no maltreatment) to 106 in this sample. Although different forms of maltreatment were interrelated, emotional and sexual abuse were most closely linked to cortisol levels. Fibromyalgia and osteoarthritis groups showed similar secretory patterns, and maltreatment was associated with elevated cortisol in both. Although maltreatment was related to symptoms of depression, PTSD, and averaged daily reports of positive and negative affect, none of these variables mediated the link between maltreatment and cortisol. In women with chronic pain, self-reported childhood maltreatment was associated with higher diurnal cortisol levels. These results add to the evidence that abuse in childhood can induce long-term changes in hypothalamic-pituitary-adrenocortical activity. They further underscore the importance of evaluating childhood maltreatment in fibromyalgia and other chronic pain conditions.

Association between maternal childhood maltreatment and mother-infant attachment disorganization: Moderation by maternal oxytocin receptor gene and cortisol secretion.

Science.gov (United States)

Ludmer, Jaclyn A; Gonzalez, Andrea; Kennedy, James; Masellis, Mario; Meinz, Paul; Atkinson, Leslie

2018-04-24

This study examined maternal oxytocin receptor (OXTR, rs53576) genotype and cortisol secretion as moderators of the relation between maternal childhood maltreatment history and disorganized mother-infant attachment in the Strange Situation Procedure (SSP). A community sample of 314 mother-infant dyads completed the SSP at infant age 17 months. Self-reported maltreatment history more strongly predicted mother-infant attachment disorganization score and disorganized classification for mothers with more plasticity alleles of OXTR (G), relative to mothers with fewer plasticity alleles. Maltreatment history also more strongly predicted mother-infant attachment disorganization score and classification for mothers with higher SSP cortisol secretion, relative to mothers with lower SSP cortisol secretion. Findings indicate that maltreatment history is related to disorganization in the next generation, but that this relation depends on maternal genetic characteristics and cortisol. Copyright © 2018 Elsevier Inc. All rights reserved.

Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia.

Science.gov (United States)

McLean, Samuel A; Williams, David A; Harris, Richard E; Kop, Willem J; Groner, Kimberly H; Ambrose, Kirsten; Lyden, Angela K; Gracely, Richard H; Crofford, Leslie J; Geisser, Michael E; Sen, Ananda; Biswas, Pinaki; Clauw, Daniel J

2005-11-01

To compare the momentary association between salivary cortisol levels and pain, fatigue, and stress symptoms in patients with fibromyalgia (FM), and to compare diurnal cycles of cortisol secretion in patients with FM and healthy control subjects in a naturalistic environment. Twenty-eight patients with FM and 27 healthy control subjects completed assessments on salivary cortisol levels and pain, fatigue, and stress symptoms, 5 times a day for 2 consecutive days, while engaging in usual daily activities. Only those participants who adhered to the protocol (assessed via activity monitor) were included in the final analyses. Twenty FM patients and 16 healthy control subjects adhered to the protocol. There were no significant differences in cortisol levels or diurnal cortisol variation between FM patients and healthy controls. Among women with FM, a strong relationship between cortisol level and current pain symptoms was observed at the waking time point (t = 3.35, P = 0.008) and 1 hour after waking (t = 2.97, P = 0.011), but not at the later 3 time points. This association was not due to differences in age, number of symptoms of depression, or self-reported history of physical or sexual abuse. Cortisol levels alone explained 38% and 14% of the variation in pain at the waking and 1 hour time points, respectively. No relationship was observed between cortisol level and fatigue or stress symptoms at any of the 5 time points. Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic-pituitary-adrenal axis.

Renal tubular acidosis complicated with hyponatremia due to cortisol insufficiency

OpenAIRE

Izumi, Yuichiro; Nakayama, Yushi; Onoue, Tomoaki; Inoue, Hideki; Mukoyama, Masashi

2015-01-01

Adrenocortical insufficiency such as occurs in Addison's disease causes hyponatremia and renal tubular acidosis (RTA). Hyponatremia results from both aldosterone and cortisol insufficiency. RTA is due to aldosterone insufficiency. The involvement of cortisol in RTA is unclear. Here, we report a woman in her 70s who was admitted to our hospital with severe hyponatremia (106 mEq/l) and RTA. The patient exhibited low plasma cortisol levels with little response to rapid adrenocorticotropic hormon...

Genetic Moderation of Cortisol Secretion in Holocaust Survivors: A Pilot Study on the Role of ADRA2B

Science.gov (United States)

Fridman, Ayala; van IJzendoorn, Marinus H.; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J.

2012-01-01

In the current study we tested whether "ADRA2B" moderates stress regulation of Holocaust survivors as indexed by their diurnal cortisol secretion and cortisol reactivity to a stressor. Salivary cortisol levels of 54 female Holocaust survivors and participants in the comparison group were assessed during a routine day and in response to a…

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

International Nuclear Information System (INIS)

Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu

2000-01-01

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

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Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

2011-06-01

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

2008-04-15

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

International Nuclear Information System (INIS)

Pacella, Claudio M.; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico

2008-01-01

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival

Adrenocortical Regulation, Eating in the Absence of Hunger and BMI in Young Children

OpenAIRE

Francis, L. A.; Granger, D. A.; Susman, E. J.

2012-01-01

The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5 to 9 years (N = 43). Saliva was collected before and after the Trier Social Stress Test for children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60 minutes post-TSST-C. Age- and sex-specific BMI scores were cal...

The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

Science.gov (United States)

Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-09-17

We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

Science.gov (United States)

Raff, H; Kohandarvish, S

1990-08-01

Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

Association between burnout and cortisol secretion, perceived stress, and psychopathology in palliative care unit health professionals.

Science.gov (United States)

Fernández-Sánchez, José Carlos; Pérez-Mármol, José Manuel; Blásquez, Antonia; Santos-Ruiz, Ana María; Peralta-Ramírez, María Isabel

2018-06-01

ABSTRACTObjective:A high incidence of burnout has been reported in health professionals working in palliative care units. Our present study aims to determine whether there are differences in the secretion of salivary cortisol between palliative care unit health professionals with and without burnout, and to elucidate whether there is a relationship between burnout syndrome and perceived stress and psychopathological status in this population. A total of 69 health professionals who met the inclusion criteria participated in our study, including physicians, nurses, and nursing assistants. Some 58 were women (M = 29.65 years, SD = 8.64) and 11 men (M = 35.67 years, SD = 11.90). The level of daily cortisol was registered in six measurements taken over the course of a workday. Burnout syndrome was evaluated with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), the level of perceived stress was measured using the Perceived Stress Scale, and psychopathological status was gauged using the SCL-90-R Symptoms Inventory. There were statistically significant differences in secretion of cortisol in professionals with high scores on a single subscale of the MBI-HSS [F(3.5) = 2.48, p burnout showed higher scores on the psychopathology and stress subscales than professionals without it. A higher score in any dimension of the burnout syndrome in palliative care unit health professionals seems to be related to several physiological and psychological parameters. These findings may be relevant for further development of our understanding of the relationship between levels of burnout and cortisol secretion in the health workers in these units.

Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

Science.gov (United States)

Chen, Sue

2010-09-01

Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. Copyright 2010 Elsevier Inc. All rights reserved.

The relationship between Type D personality and physical health complaints is mediated by perceived stress and anxiety but not diurnal cortisol secretion.

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Smith, Michael A; Riccalton, Victoria C; Kelly-Hughes, Denise H; Craw, Olivia A; Allen, Sarah F; O'Connor, Daryl B; Wetherell, Mark A

2018-05-01

Type D personality has been associated with minor health complaints in the general population and dysregulation of basal cortisol secretion in coronary patients. The aims of the present study were to investigate (i) whether there is an association between Type D personality and basal cortisol secretion in the general population, and (ii) whether subjective measures of stress and anxiety, as well as indices of basal cortisol secretion, mediate the relationship between Type D personality and self-reported physical symptoms in this group. Self-report measures of stress, trait anxiety and physical symptoms were provided by 101 individuals aged 18-45 years. Saliva samples were also provided over two consecutive "typical" days, to enable indices of the cortisol awakening response and diurnal cortisol profile to be determined. There was a significant relationship between Type D personality and self-reported physical symptoms, which was fully mediated by subjective stress and anxiety. However, there were no significant relationships between Type D personality and the basal cortisol indices. These findings suggest that the association between Type D personality and minor health complaints in the general population can be explained by feelings of stress and anxiety, but a precise biological mechanism for this link is yet to be elucidated.

[Influence of pulsating magnetic field used in magnet therapy and magnet stimulation on cortisol secretion in human].

Science.gov (United States)

Woldańska-Okońska, Maria; Czernicki, Jan

2003-01-01

The aim of our study was to test the influence of magnetic fields during magnetotherapy and magnetostimulation over a longer period of time (like in physiotherapy) on cortisol secretion in humans. The study population was divided into two groups: magnetotherapy group (16 men) and magnetostimulation group (10 men). Magnetotherapy in the form of magnetic field induction (2.9 microT; frequency--40 Hz; square wave; bipolar; Magnetronic MF--10 apparatus) was applied for 20 min to the lumbar area in patients with chronic low back pain. Magnetostimulation (Viofor JPS system; M2P2 program; induction--25-80 microT; frequency--200 Hz, complex saw-like shape with a plateau halfway the height of the wave; bipolar) was applied every day for 12 min in patients with the same health problem. In both groups, the procedures were repeated 15 times (about 10:00 a.m.) with weekend breaks. Serum samples were collected at 6:00, 12:00, 16:00 and 24:00 and estimated by the micromethod of chemiluminescence (DPC Poland; Cat. No. LKC01). The circadian profile of cortisol was determined prior to the application, a day and a month after application. The data were analyzed statistically, using paired and unpaired Student's test. Magnetotherapy affects the cortisol secretion in the circadian profile by decreasing its level at 16:00 a day after 15 applications, whereas magnetostimulation by increasing its level at 12:00 a month after 15 applications, which may suggest its long-term effect on hypothalamic-pituitary axis. The comparison of the results indicated that a day after magnetotherapy and magnetostimulation, the circadian curves of cortisol secretion differed significantly by about 100%. All hormone oscillations did not exceed the physiological norms of the circadian cortisol level, not reaching the level so high as in an intense stress. This suggests rather their controlling effect on the cortisol level than their significant stressogenic nature.

The influence of the low-frequency magnetic fields of different parameters on the secretion of cortisol in men.

Science.gov (United States)

Woldańska-Okońska, Marta; Czernicki, Jan; Karasek, Michał

2013-03-01

The aim of this paper is to test the influence of long-term application of the low-frequency magnetic fields in magnetotherapy and magnetostimulation on cortisol secretion in men. Patients were divided into three groups: 16 men underwent magnetotherapy and 20 men (divided into two groups) underwent magnetostimulation. Magnetotherapy - 2 mT induction, 40 Hz, bipolar square wave, was applied for 20 min to lumbar area. Magnetostimulation (Viofor Jaroszyk, Paluszak, Sieroń (JPS) system, M2P2 program) was applied to 10 patients for 12 min each day. The third group (10 patients) underwent magnetostimulation (Viofor JPS system, M3P3) for 12 min each day using a different machine. All groups had 15 rounds of applications at approximately 10:00 a.m. with intermissions on the weekends. Blood serum was taken four times in a 24-hour period, before applications, the day after applications and a month later. Chemiluminescence micromethod was used to indicate hormone concentrations. Data was statistically analyzed with the analysis of variance (ANOVA) method. The statistically significant gains in the circadian cortisol profile at 4:00 p.m., be- fore and after application, were observed as a decrease in concentration during magnetotherapy. In magnetostimulation, with the M2P2 program, a significant increase in the cortisol concentration was observed in circadian profile at 12:00 p.m. one month after the last application. After magnetostimulation with the M3P3 program, a significant increase in concentration at 6:00 a.m. and a decrease in concentration at 12:00 p.m. were observed one month later. Statistically significant difference was demonstrated in the participants after the application of magnetotherapy and magnetostimulation with M3P3 program compared to the men submitted to magnetostimulation, with M2P2 program, at 4:00 p.m. after 15 applications. Biological hysteresis one month after magnetostimulation suggests long-term influence on the hypothalamo-hypophysial axis. The

The Effort-reward Imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women

Science.gov (United States)

Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-01-01

We examined the influence of work-related effort–reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort–Reward Imbalance (ERI) model, on the hypothalamic–pituitary–adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort–reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort–reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort–reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported. PMID:25228138

Longitudinal measurement of cortisol in association with mental health and experience of domestic violence and abuse: study protocol.

Science.gov (United States)

Lokhmatkina, Natalia V; Feder, Gene; Blake, Sarah; Morris, Richard; Powers, Victoria; Lightman, Stafford

2013-07-13

Domestic violence and abuse is threatening behavior, violence/abuse used by one person to control the other within an intimate or family-type relationship. Women experience more severe physical and sexual domestic violence and abuse and more mental health consequences than men. The current study aims at exploring of the role of hypothalamic-pituitary-adrenocortical axis activity in abuse impact on women's mental health. 1) To evaluate diurnal cortisol slope, cortisol awakening response, and the mean cortisol concentration in women with a current or recent experience of abuse; 2) To estimate whether cortisol secretion is associated with type, severity, duration and cessation of abuse; 3) To investigate whether cortisol acts as mediator between abuse and mental health condition; 4) To examine whether there is any distinction in cortisol levels between those women exposed to both childhood abuse and domestic violence and abuse and those experienced only the latter. 4) To explore whether cortisol secretion differs between women living in refuge and those still living in the community. To meet study objectives 128 women will be recruited in a domestic violence agency and local communities. Baseline and 3-month follow-up measures will be taken over 6 months after recruitment. Each assessment will include: (1) standardized self-administered questionnaires to evaluate socio-demographics, experience of violence and abuse, mental and physical health; (2) weight and height measurement; (3) self-completion of wakening, post-wakening and evening saliva samples. Saliva will be analysed for cortisol and cortisone using Ultra performance liquid chromatography-tandem mass spectrometry. We will compare diurnal cortisol parameters between non-abused controls and abuse survivors with and without mental health conditions. First following descriptive statistics for all the cortisol and mental health outcomes, relationships between them will be investigated using appropriate regression

The influence of the low-frequency magnetic fields of different parameters on the secretion of cortisol in men

Directory of Open Access Journals (Sweden)

Marta Woldańska-Okońska

2013-02-01

Full Text Available Objectives: The aim of this paper is to test the infl uence of long-term application of the low-frequency magnetic fi elds in magnetotherapy and magnetostimulation on cortisol secretion in men. Materials and Methods: Patients were divided into three groups: 16 men underwent magnetotherapy and 20 men (divided into two groups underwent magnetostimulation. Magnetotherapy – 2 mT induction, 40 Hz, bipolar square wave, was applied for 20 min to lumbar area. Magnetostimulation (Viofor Jaroszyk, Paluszak, Sieroń (JPS system, M2P2 program was applied to 10 patients for 12 min each day. The third group (10 patients underwent magnetostimulation (Viofor JPS system, M3P3 for 12 min each day using a different machine. All groups had 15 rounds of applications at approximately 10:00 a.m. with intermissions on the weekends. Blood serum was taken four times in a 24-hour period, before applications, the day after applications and a month later. Chemiluminescence micromethod was used to indicate hormone concentrations. Data was statistically analyzed with the analysis of variance (ANOVA method. Results: The statistically signifi cant gains in the circadian cortisol profi le at 4:00 p.m., before and after application, were observed as a decrease in concentration during magnetotherapy. In magnetostimulation, with the M2P2 program, a signifi cant increase in the cortisol concentration was observed in circadian profi le at 12:00 p.m. one month after the last application. After magnetostimulation with the M3P3 program, a signifi cant increase in concentration at 6:00 a.m. and a decrease in concentration at 12:00 p.m. were observed one month later. Statistically signifi cant difference was demonstrated in the participants after the application of magnetotherapy and magnetostimulation with M3P3 program compared to the men submitted to magnetostimulation, with M2P2 program, at 4:00 p.m. after 15 applications. Conclusions: Biological hysteresis one month after

Maternal DRD2, SLC6A3, and OXTR genotypes as potential moderators of the relation between maternal history of care and maternal cortisol secretion in the context of mother-infant separation.

Science.gov (United States)

Ludmer, Jaclyn A; Jamieson, Brittany; Gonzalez, Andrea; Levitan, Robert; Kennedy, James; Villani, Vanessa; Masellis, Mario; Basile, Vincenzo S; Atkinson, Leslie

2017-10-01

A mother's cortisol secretion is importantly associated with her own mental health and her infant's cortisol secretion. This study investigated the influences of maternal history of care and maternal DRD2, SLC6A3, and OXTR genotypes on maternal cortisol in the context of infant stress. A community sample of 296 mother-infant dyads completed a maternal separation at infant age 17 months. Maternal salivary cortisol, buccal cells, and self-reported history of care were collected. Multilevel models revealed that history of care had a greater influence on maternal baseline cortisol (but not cortisol trajectory) for mothers with more plasticity alleles of SLC6A3 (10R) and OXTR (G), relative to mothers with fewer or no plasticity alleles. Findings indicate that a mother's history of care is related to her cortisol secretion in anticipation of infant stress, but that this relation depends on her genetic characteristics. Findings are discussed in relation to the maternal protective system and anticipatory cortisol secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

Feminizing adrenocortical carcinoma with distant metastases: can surgery be considered?

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Alessandro Fancellu

2014-07-01

Full Text Available Functioning adrenocortical carcinomas are rare diseases with dismal prognosis. A 41-year-old man presenting with gynecomastia had a giant feminizing adrenocortical carcinoma at stage IV. Although surgical resection was controversial, we removed the primary tumor to reduce the mass effects. He lived for 12 months with an acceptable quality of life. Gynecomastia may be the first sign of feminizing adrenal malignancies. Surgery may ameliorate the quality of life in selected patients with metastatic disease.

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

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Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu [Kagoshima Univ. (Japan). Faculty of Medicine

2000-06-01

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

Relationship between temperament and transportation with rectal temperature and secretion of cortisol and epinephrine in bulls

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This study investigated whether temperament influences rectal temperature and the secretion of cortisol and epinephrine in response to transportation. Brahman bulls were selected based on temperament score (average of exit velocity, EV, and pen score, PS) measured 28 days prior to weaning with the 8...

Pre-schoolers suffering from psychiatric disorders show increased cortisol secretion and poor sleep compared to healthy controls.

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Hatzinger, Martin; Brand, Serge; Perren, Sonja; von Wyl, Anges; Stadelmann, Stephanie; von Klitzing, Kai; Holsboer-Trachsler, Edith

2012-05-01

Various studies of child cortisol secretion and sleep show a close association between poor sleep, deterioration of the HPA axis and unfavorable psychological functioning. However, there is little evidence as to whether these associations are clearly present in pre-school children suffering from psychiatric disorders. A total of 30 pre-schoolers suffering from psychiatric disorders (anxiety, adjustment disorders, emotional and attachment disorder; hyperactivity or oppositional disorder) and 35 healthy controls took part in the study. Saliva cortisol secretion was assessed both at baseline and under challenge conditions. Sleep was assessed via activity monitoring for seven consecutive days and nights, using a digital movement-measuring instrument. Parents and teachers completed questionnaires assessing children's cognitive, emotional and social functioning. The Berkeley Puppet Interview provided child-based reports of cognitive-emotional processes. Compared to healthy controls, children suffering from psychiatric disorders had much higher cortisol secretion both at baseline and under challenge conditions. Sleep was also more disturbed, and parents and teachers rated children suffering from psychiatric disorders as cognitively, emotionally and behaviorally more impaired, relative to healthy controls. Children with psychiatric disorders reported being more bullied and victimized. In five-year old children the presence of psychiatric disorders is reflected not only at psychological, social and behavioral, but also at neuroendocrine and sleep-related levels. It is likely that these children remain at increased risk for suffering from psychiatric difficulties later in life. Copyright © 2012 Elsevier Ltd. All rights reserved.

DNA methylation is an independent prognostic marker of survival in adrenocortical cancer

NARCIS (Netherlands)

Jouinot, Anne; Assie, Guillaume; Libe, Rossella; Fassnacht, Martin; Papathomas, Thomas; Barreau, Olivia; De La Villeon, Bruno; Faillot, Simon; Hamzaoui, Nadim; Neou, Mario; Perlemoine, Karine; Rene-Corail, Fernande; Rodriguez, Stephanie; Sibony, Mathilde; Tissier, Frederique; Dousset, Bertrand; Sbiera, Silviu; Ronchi, Cristina; Kroiss, Matthias; Korpershoek, Esther; De Krijger, Ronald; Waldmann, Jens; Bartsch, Detlef K.; Quinkler, Marcus; Haissaguerre, Magalie; Tabarin, Antoine; Chabre, Olivier; Sturm, Nathalie; Luconi, Michaela; Mantero, Franco; Mannelli, Massimo; Cohen, Regis; Kerlan, Veronique; Touraine, Philippe; Barrande, Gaelle; Groussin, Lionel; Bertagna, Xavier; Baudin, Eric; Amar, Laurence; Beuschlein, Felix; Clauser, Eric; Coste, Joel; Bertherat, Jerome

2017-01-01

Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective:

Delayed memory effects after intense stress in Special Forces candidates: exploring path processes between cortisol secretion and memory recall.

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Taverniers, John; Taylor, Marcus K; Smeets, Tom

2013-05-01

The aim of this paper is twofold. First, it explores delayed effects of high endogenously evoked cortisol concentrations on visuo-spatial declarative memory. Subsequently, it applies multiple mediation (MM) analyses to reveal path processes between stress and cognitive performance in a sample of 24 male Special Forces (SF) candidates (mean age = 27.0 years, SD = 4.1). The SF candidates were randomly assigned to a control (n = 12) or an intense stress group (n = 12), and cortisol secretion for the intense stress condition was triggered by a brusque 60 min prisoner of war exercise. Stress exposure provoked robust increases in cortisol concentrations and a significant decline in immediate recall performance, measured with the Rey-Osterrieth Complex Figure (ROCF). The relative retrieval differences in regard to the ROCF persisted even after a recovery period of 24 h, as both groups showed similar levels of memory decline over 24 h. Next, the study applied a MM design that involved distribution-independent asymptotic and resampling strategies to extend traditional bivariate analyses. MM results showed that ROCF performance was mediated by increases in cortisol concentrations. Considering the studied variables, the current analysis was the first to provide statistical support for the generally accepted thesis that cortisol secretion in itself, rather than subjective strain or the experimental treatment, affects cognitive performance. The revelation of such path processes is important because it establishes process identification and may refine existing paradigms.

Relative metabolic stability, but disrupted circadian cortisol secretion during the fasting month of Ramadan.

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Suhad Bahijri

Full Text Available BACKGROUND: Chronic feeding and sleep schedule disturbances are stressors that exert damaging effects on the organism. Practicing Muslims in Saudi Arabia go through strict Ramadan fasting from dawn till sunset for one month yearly. Modern era Ramadan practices in Saudi Arabia are associated with disturbed feeding and sleep patterns, namely abstaining from food and water and increasing daytime sleep, and staying awake and receiving food and water till dawn. HYPOTHESIS: Strict Ramadan practices in Saudi Arabia may influence metabolism, sleep and circadian cortisol secretion. PROTOCOL: Young, male Ramadan practitioners were evaluated before and two weeks into the Ramadan. Blood samples were collected at 9.00 am and 9.00 pm for measurements of metabolic parameters and cortisol. Saliva was collected serially during the day for cortisol determinations. RESULTS: Ramadan practitioners had relative metabolic stability or changes expected by the pattern of feeding. However, the cortisol circadian rhythm was abolished and circulating insulin levels and HOMA index were increased during this period. DISCUSSION: The flattening of the cortisol rhythm is typical of conditions associated with chronic stress or endogenous hypercortisolism and associated with insulin resistance. CONCLUSIONS: Modern Ramadan practices in Saudi Arabia are associated with evening hypercortisolism and increased insulin resistance. These changes might contribute to the high prevalence of chronic stress-related conditions, such as central obesity, hypertension, metabolic syndrome and diabetes mellitus type 2, and their cardiovascular sequelae observed in the Kingdom.

Childhood parental divorce and cortisol in young adulthood: evidence for mediation by family income.

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Kraft, Amy J; Luecken, Linda J

2009-10-01

Childhood parental divorce has been linked with negative physical and psychological health in adulthood, potentially due to alterations in adrenocortical activity resulting from chronic stress. The current study evaluated cortisol in 94 young adults (mean age 19.9) from families characterized by parental divorce (n=43) or intact parental marriages (n=51). Salivary cortisol was assessed prior to and at 3 time points after a challenging speech task. Participants from divorced families had significantly lower cortisol across the experimental period than those from intact families, even after controlling for family conflict and current depression and anxiety. Lower family income was also associated with lower cortisol, and partially mediated the relationship between parental divorce and cortisol. Findings suggest that childhood parental divorce is associated with attenuated cortisol in young adulthood, which may be explained by lower income in divorced families.

Adrenocortical cancer

DEFF Research Database (Denmark)

Payabyab, Eden C.; Balasubramaniam, Sanjeeve; Edgerly, Maureen

2016-01-01

The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection....... Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date......, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one...

Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

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Se Won Kim

2016-01-01

Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

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Gomez-Segovia, I; Gallowitsch, H J; Kresnik, E; Kumnig, G; Mikosch, P; Lind, P [Dept.of Nuclear Medicine and Endocrinology, LKH Klagenfurt (Austria)

2002-09-01

Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

International Nuclear Information System (INIS)

Gomez-Segovia, I.; Gallowitsch, H.J.; Kresnik, E.; Kumnig, G.; Mikosch, P.; Lind, P.

2002-01-01

Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

Effect of 5-azacytidine and cortisol on the P1798 cortisol-sensitive and non-resistant lymphosarcoma

International Nuclear Information System (INIS)

Chi, C.

1986-01-01

The P1798 lymphosarcoma is a tumor with both cortisol-sensitive (CS) and cortisol-resistant (CR) lines. Although differences between the CS and CR cells have been reported, none can fully explain the detailed mechanism of glucocorticoid resistance in CR tumors. Recently, it was shown that 5-azacytidine treatment could generate CS cells from CR SAK lymphoma cells in vitro. The present study examined the effect of combination treatment with 5-azacytidine and cortisol on the growth of the P1798 lymphosarcoma. 5-Azacytidine rendered the P1798 CR tumors partially cortisol-sensitive, and enhanced the cortisol-induced regression of the P1798 CS tumors. Survival of mice bearing both CS and CR P1798 tumors was increased by combination treatment. Similar whole cell and nuclear binding of 3 H-TA were observed in both 5-azacytidine-treated and control P1798 tumors. However, CR nuclei retained 64% of the whole cell binding of 3 H-TA compared to 25-29% nuclear retention in CS tumors. DNA methylation in tumors from 5-azacytidine-treated mice decreased to 53% (CS) and 42% (CR) of control. Since 5-azacytidine did not result in any change in thymidine labeling index or cell cycle distribution in P1798 tumors, it would appear to be cytostatic rather than cytotoxic to P1798 tumors. Three cell lines have been isolated from the P1798 lymphosarcoma: two are cortisol-sensitive both in vivo and in vitro, while the other is cortisol-resistant. Results from this study suggest that glucocorticoid resistance is a reversible process, and that the effect of 5-azacytidine on the P1798 CR tumor is at the gene expression level

The relationship between 63 days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals

NARCIS (Netherlands)

van Ockenburg, S. L.; Schenk, H. M.; van der Veen, A.; van Rossum, E. F. C.; Kema, I. P.; Rosmalen, J. G. M.

Background: Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. Methods: Ten

Cortisol and DHEA in development and psychopathology.

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Kamin, Hayley S; Kertes, Darlene A

2017-03-01

Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

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Parikh, Punam P; Rubio, Gustavo A; Farra, Josefina C; Lew, John I

2017-08-25

Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy. Patients with functional adrenocortical carcinoma (ACC) have significant preoperative comorbidities and experience higher rates of certain postoperative complications including wound complications, hematoma formation, adrenal insufficiency, pulmonary embolism and acute kidney injury. Functional ACC patients also necessitate longer hospitalizations. These patients should undergo appropriate preoperative counseling in preparation for adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects of Multivitamin Supplementation on Diurnal Cortisol Secretion and Perceived Stress

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Con Stough

2013-11-01

Full Text Available Recent evidence suggests that dietary intake of vitamins, in particular the B-vitamins including B6, B9 and B12 may have a number of positive effects on mood and stress. Given the effects of stress on a range of biological mechanisms including the endocrine system, it could be reasonably expected that multivitamin supplementation may also affect markers of these mechanisms such as diurnal cortisol secretion. In the current double-blind placebo-controlled study 138 adults (aged 20 to 50 years were administered a multivitamin containing B-vitamins versus placebo over a 16-week period. Salivary cortisol measurements were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16-weeks. Perceived Stress (PSS was measured at baseline, 8-weeks and 16-weeks, while blood serum measures of B6, B12 and homocysteine (HCy as well as red cell folate (B9 were also collected at these time points. A significant interaction was found between treatment group and study visit for the Cortisol Awakening Response (CAR. Compared to placebo, at 16-weeks multivitamin supplementation was found to be associated with a near-significant trend towards an increased CAR. No significant differences in PSS were found between groups, with PSS increasing in both groups across the course of the study. Red cell folate was found to be significantly correlated with the CAR response at 16-weeks while HCy levels were not found to be associated with the CAR response, although HCy significantly correlated with waking cortisol levels at 8-weeks. A possible interpretation of the elevation in CAR associated with multivitamin supplementation is that this represents an adaptive response to everyday demands in healthy participants.

A simple radioimmunoassay for plasma cortisol

International Nuclear Information System (INIS)

Seth, J.; Brown, L.M.

1978-01-01

A simple radioimmunoassay (RIA) for plasma cortisol is described which combines the advantages of (i) direct analysis of untreated plasma samples, (ii) use of solid-coupled anti-cortisol antibodies and (iii) use of a gamma-labelled radioligand. The reagents are relatively easily prepared and stable, and the analysis can be completed in 4 h. Inter-assay precision (C.V.) is 8-11%. Critical examination of specificity using high pressure liquid chromatography showed that 23-35% of the immunoassayable material in plasma was not cortisol. RIA results on samples collected under basal conditions were an average 40 nmol/l lower than fluorimetric results, while in insulin hypoglycaemia and synacthen (ACTH) stimulation tests, this difference increased to over 100 nmol/l. The RIA is technically more simple than fluorimetric, competitive-protein-binding, and many RIA methods, and can be used with advantage in the routine investigation of adrenocortical function. However, using the present antiserum, the RIA is not applicable to investigations on patients receiving metyrapone, nor in suspected cases of congenital adrenal hyperplasia. (Auth.)

Adrenocortical regulation, eating in the absence of hunger and BMI in young children.

Science.gov (United States)

Francis, L A; Granger, D A; Susman, E J

2013-05-01

The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5-9years (N=43). Saliva was collected before and after the Trier Social Stress Test for Children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60min post-TSST-C. Age- and sex-specific BMI scores were calculated from measured height and weight, and eating in the absence of hunger was assessed using weighed food intake during a behavioral procedure. We also included a measure of parents' report of child impulsivity, as well as family demographic information. Participants were stratified by age into younger (5-7years) and older (8-9years) groups. In younger children, parents' reports of child impulsivity were significantly and positively associated with BMI; cortisol AUCi was not associated with BMI or eating in the absence of hunger. In older children, however, greater stress-related cortisol AUCi was related to higher BMI scores and greater energy intake in the absence of hunger. The results suggest that cortisol AUCi in response to psychosocial stress may be linked to problems with energy balance in children, with some variation by age. Published by Elsevier Ltd.

Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

International Nuclear Information System (INIS)

Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

2011-01-01

Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

Virilization caused by an ectopic adrenal tumor located behind the iliopsoas muscle.

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Mavroudis, Konstantinos; Aloumanis, Kyriakos; Papapetrou, Peter D; Voros, Dionisios; Spanos, Iraklis

2007-06-01

Virilization due to androgen-secreting neoplasms in women is a result of androgen overproduction from benign or malignant tumors that are found in the ovaries or rarely in the adrenal glands. Virilizing tumors that arise from ectopic adrenal tissue are extremely rare. We describe a very rare case of an ectopic androgen-producing adrenal tumor. Case report study. Endocrinology outpatient department of university-affiliated teaching hospital. A 45-year-old woman with symptoms of virilization of abrupt onset and rapid progression, with high serum androgen hormone levels and normal glucocorticoid secretion. Basal hormonal levels, stimulation and suppression tests, imaging techniques, and selective venous sampling. Localization and surgical removal of the source of androgen production. An ectopic mass was detected behind the left iliopsoas muscle. The patient was operated on and an oblong-shaped lesion, weighing 6 g, was removed. Histologically, the tissue was identified to be of adrenal origin. Postoperatively the androgen levels decreased to normal levels. This case illustrates difficulties in detecting and localizing the rare contingence of an ectopic adrenocortical androgen-secreting tumor.

Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

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Vatroslav Čerina

2016-03-01

Full Text Available Only 4-9% of patients with Cushing’s disease (CD harbor pituitary macroadenomas. Clinical and biochemical features of macrocorticotropinomas are poorly understood. Some evidence exist that these tumors presents clinical features more similar to a non-functioning adenomas, being though defined silent corticotropinomas, rather than to ACTH-secreting adenomas. In this paper, we report a case of a 60-year old woman with a history of obesity, arterial hypertension and diabetes mellitus who presented with overt central hypothyroidism. Magnetic resonance imaging disclosed giant pituitary adenoma measuring 50 mm. Endocrinological evaluation confirmed CD: ACTH 50.3 pmol/L, urinary free-cortisol of 739 nmol/24h and cortisol of 639 nmol/L after 1 mg dexamethasone suppression test. Tumor mass was reduced by 50% using purely endoscopic transsphenoidal approach. Thirty-eight months after the partial resection, the patient had well controlled CD: ACTH 20.2 pmol/L, urinary free-cortisol of 238 nmol/24h, cortisol of 105 nmol/L after 1 mg dexamethasone suppression test. To the best of our knowledge, this is the largest ACTH-secreting adenoma ever reported. Our case suggests that tumor size does not necessarily correlate with aggressiveness of CD in patients with macrocorticotropinomas and that long-term control of CD may be achieved albeit incomplete surgical removal. Further studies are needed in order to determine the best treatment option for patients with macrocorticotropinomas.

Cortisol levels in hair of East Greenland polar bears.

Science.gov (United States)

Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Novak, M A; Henchey, E; Meyer, J S

2011-01-15

To demonstrate the ability to assess long-term hypothalamic-pituitary-adrenocortical (HPA) axis activity in polar bears (Ursus maritimus), a pilot study was conducted in which cortisol concentrations was analyzed in hair from 7 female (3-19 years) and 10 male (6-19 years) East Greenland polar bears sampled in 1994-2006. The hair was chosen as matrix as it is non-invasive, seasonally harmonized, and has been validated as an index of long-term changes in cortisol levels. The samples were categorized according to contamination: eight were clean (2 females, 6 males), 5 had been contaminated with bear blood (2 F, 3 M), and 4 with bear fat (3 F, 1 M). There was no significant difference in cortisol concentration between the three categories after external contamination was removed. However, contaminated hair samples should be cleaned before cortisol determination. Average hair cortisol concentration was 8.90 pg/mg (range: 5.5 to 16.4 pg/mg). There was no significant correlation between cortisol concentration and age (p=0.81) or sampling year (p=0.11). However, females had higher mean cortisol concentration than males (females mean: 11.0 pg/mg, males: 7.3 pg/mg; p=0.01). The study showed that polar bear hair contains measurable amounts of cortisol and that cortisol in hair may be used in studies of long-term stress in polar bears. Copyright © 2010 Elsevier B.V. All rights reserved.

Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout (Oncorhynchus mykiss)

International Nuclear Information System (INIS)

Dorval, J.; Hontela, A.

2003-01-01

The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout (Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), L-buthionine sulfoximine (L-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC 50 366 μM) and cortisol secretion (EC 50 19 μM) in a concentration-related manner. Pretreatment with ATA and L-BSO enhanced the toxicity of endosulfan (LC 50 and EC 50 , respectively, 302 and 2.6 μM with ATA, 346 and 3.1 μM with L-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC 50 of endosulfan to 51 μM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with L-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and L-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress

Daytime Secretion of Salivary Cortisol and Alpha-Amylase in Preschool-Aged Children with Autism and Typically Developing Children

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Kidd, Sharon A.; Corbett, Blythe A.; Granger, Douglas A.; Boyce, W. Thomas; Anders, Thomas F.; Tager, Ira B.

2012-01-01

We examined daytime salivary cortisol and salivary alpha-amylase (sAA) secretion levels and variability in preschool-aged children with autism (AUT) and typically developing children (TYP). Fifty-two subjects (26 AUT and 26 TYP) were enrolled. Salivary samples were obtained at waking, midday, and bedtime on two consecutive days at three phases…

Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

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Conforti, Valéria A; Morato, Ronaldo G; Augusto, Anderson M; de Oliveira e Sousa, Lúcio; de Avila, David M; Brown, Janine L; Reeves, Jerry J

2012-01-01

Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively. © 2011 Wiley Periodicals, Inc.

Release of β-endorphin, adrenocorticotropic hormone and cortisol in response to machine milking of dairy cows

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E. Fazio

2015-03-01

Full Text Available Aim: The present study was undertaken with the objective to obtain insight into the dynamics of the release of β-endorphin, adrenocorticotrophic hormone (ACTH and cortisol in response to machine milking in dairy cows. Materials and Methods: A total of 10 healthy multiparous lactating Italian Friesian dairy cows were used in the study. Animals were at the 4th-5th month of pregnancy and were submitted to machine milking 2 times daily. Blood samples were collected in the morning: In baseline conditions, immediately before milking and after milking; and in the early afternoon: In baseline conditions, before milking and after milking, for 2 consecutive days. Endocrine variables were measured in duplicate, using a commercial radioimmunoassay for circulating β-endorphin and ACTH concentrations and a competitive enzyme-linked immunoassay for cortisol concentration. Results: Data obtained showed a similar biphasic cortisol secretion of lactating dairy cows, with a significant increase of cortisol concentration after morning machine milking, at both the 1st and the 2nd day (p<0.05, and a decrease after afternoon machine milking at the 2nd day (p<0.01. One-way RM ANOVA showed significant effects of the machine milking on the cortisol changes, at both morning (f=22.96; p<0.001 and afternoon (f=15.10; p<0.01 milking, respectively. Two-way RM ANOVA showed a significant interaction between cortisol changes at the 1st and the 2nd day (f=7.94; p<0.0002, and between the sampling times (f=6.09; p<0.001. Conversely, no significant effects of the machine milking were observed on β-endorphin and ACTH changes, but only a moderate positive correlation (r=0.94; p<0.06 after milking stimuli. Conclusions: A wide range of cortisol concentrations reported in this study showed the complex dynamic patterns of the homeostatic mechanisms involved during machine milking in dairy cows, suggesting that β-endorphin and ACTH were not the main factors that caused the

Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

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Terry L. Levin, MD

2015-01-01

Full Text Available A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed.

Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood.

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Davis, Elysia Poggi; Head, Kevin; Buss, Claudia; Sandman, Curt A

2017-01-01

Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6-9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6-9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain. Copyright © 2016. Published by Elsevier Ltd.

The relationship between the menstrual cycle and cortisol secretion: Daily and stress-invoked cortisol patterns.

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Montero-López, Eva; Santos-Ruiz, Ana; García-Ríos, M Carmen; Rodríguez-Blázquez, Manuel; Rogers, Heather L; Peralta-Ramírez, María Isabel

2018-03-29

The menstrual cycle involves significant changes in hormone levels, causing physical and psychological changes in women that are further influenced by stress. The aim of this study was to understand the relationship between menstrual cycle phase and salivary cortisol patterns during the day as well as the salivary cortisol response to the Virtual Reality Version of the Trier Social Stress Test (TSST-VR). Forty two women not taking oral contraceptives (24 in follicular phase and 18 in luteal phase) participated in the study. Five samples of salivary cortisol collected during the day and another five samples of cortisol during the TSST-VR were analyzed. Psychological stress measures and psychopathological symptomatology were also evaluated. A 2 × 4 mixed ANCOVA showed an interaction between the two groups on the TSST-RV invoked cortisol response to the [F(3,42) = 3.681; p = 0.023) where women in luteal phase showed higher cortisol post exposure levels (5.96 ± 3.76 nmol/L) than women in follicular phase (4.31 ± 2.23 nmol/L). No other significant differences were found. Our findings provide evidence that menstrual cycle phase tended to influence cortisol response to laboratory-induced mental stress, with more reactivity observed in the luteal phase. Copyright © 2018 Elsevier B.V. All rights reserved.

Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

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Yin, Yuan; Cai, Xing; Chen, Xi; Liang, Hongwei; Zhang, Yujing; Li, Jing; Wang, Zuoyun; Chen, Xiulan; Zhang, Wen; Yokoyama, Seiji; Wang, Cheng; Li, Liang; Li, Limin; Hou, Dongxia; Dong, Lei; Xu, Tao; Hiroi, Takachika; Yang, Fuquan; Ji, Hongbin; Zhang, Junfeng; Zen, Ke; Zhang, Chen-Yu

2014-01-01

An increased population of CD4+CD25highFoxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles (MVs). In targeted mouse peripheral CD4+ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog (PTEN) and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides (ASOs) into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion. PMID:25223704

Pheochromocytoma and Adrenocortical Adenoma in the Same Gland

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Wei-Ren Hwang

2007-07-01

Full Text Available A right adrenal tumor was found incidentally during abdominal computed tomography exam in a 51-year-old female patient, who had had diabetes and hypertension for more than 10 years. The computed tomography scan was arranged for possible pancreatic lesion by a neurologist. Norepinephrine level was high in the plasma and urine. Vanillylmandelic acid level was elevated in the urine. Diurnal cortisol rhythm, plasma adrenocorticotropic hormone and urine free cortisol were all normal, but the plasma cortisol concentration could not be suppressed after a standard low-dose dexamethasone suppression test. Therefore, adrenal cortical adenoma with subclinical Cushing's syndrome was highly suspected; however, further imaging studies, including magnetic resonance image and 131I-6β-iodomethylnorcholesterol adrenal scintigraphy failed to discriminate an additional tumor. After right adrenalectomy, a small adrenal cortical adenoma and a large pheochromocytoma were noted. This is an extremely rare case of an adrenal incidentaloma consisting of both medullary and cortical tumors in the same gland.

Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

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Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L; Tasali, Esra; Leproult, Rachel; L'Hermite-Balériaux, Mireille; Van Cauter, Eve; Spiegel, Karine

2017-06-01

Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

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Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

2008-02-15

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

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Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Cardiovascular events in patients with mild autonomous cortisol secretion: analysis with artificial neural networks.

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Morelli, Valentina; Palmieri, Serena; Lania, Andrea; Tresoldi, Alberto; Corbetta, Sabrina; Cairoli, Elisa; Eller-Vainicher, Cristina; Arosio, Maura; Copetti, Massimiliano; Grossi, Enzo; Chiodini, Iacopo

2017-07-01

The independent role of mild autonomous cortisol secretion (ACS) in influencing the cardiovascular event (CVE) occurrence is a topic of interest. We investigated the role of mild ACS in the CVE occurrence in patients with adrenal incidentaloma (AI) by standard statistics and artificial neural networks (ANNs). We analyzed a retrospective record of 518 AI patients. Data regarding cortisol levels after 1 mg dexamethasone suppression (1 mg DST) and the presence of obesity (OB), hypertension (AH), type-2 diabetes (T2DM), dyslipidemia (DL), familial CVE history, smoking habit and CVE were collected. The receiver-operating characteristic curve analysis suggested that 1 mg DST, at a cut-off of 1.8 µg/dL, had the best accuracy for detecting patients with increased CVE risk. In patients with 1 mg-DST ≥1.8 µg/dL (DST+, n  = 223), age and prevalence of AH, T2DM, DL and CVE (66 years, 74.5, 25.9, 41.4 and 26.8% respectively) were higher than that of patients with 1 mg-DST ≤1.8 µg/dL (61.9 years, 60.7, 18.5, 32.9 and 10%, respectively, P  Cortisol after 1 mg-DST is independently associated with the CVE occurrence. The ANNs might help for assessing the CVE risk in AI patients. © 2017 European Society of Endocrinology.

Inhibition and Exuberance in Preschool Classrooms: Associations with Peer Social Experiences and Changes in Cortisol across the Preschool Year

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Tarullo, Amanda R.; Mliner, Shanna; Gunnar, Megan R.

2011-01-01

Associations between behavioral inhibition and activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a stress-sensitive neuroendocrine system indexed by salivary cortisol, have varied widely across studies. In the current study, we examined the role of peer social experiences in moderating patterns of association between…

Lifestyle, mental health status and salivary secretion rates.

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Toda, Masahiro; Morimoto, Kanehisa; Fukuda, Sanae; Hayakawa, Kazuo

2002-01-01

The relations between salivary variables, lifestyle and mental health status were investigated for 61 healthy female university students. The salivary secretion rates were significantly higher in the good lifestyle groups compared with the poor lifestyle groups. Among the 8 lifestyle items tested. "eating breakfast" and "mental stress" were significantly related to the salivary secretion rates. The present findings suggest that the acquisition of a good lifestyle is also very important from the viewpoint of the prevention of oral disease.A highly significant correlation (r=0.97; p<0.01) between the salivary cortisol levels and the cortisol secretion rates when controlled for the salivary secretion rates was also observed. This suggests that there is a high correlation between the intact salivary cortisol levels and the total cortisol quantity per unit time. Therefore, both these values can be used as a good index for the salivary cortisol determination.

Stress and cortisol responses in men: differences according to facial symmetry.

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Borráz-León, Javier I; Cerda-Molina, Ana Lilia; Mayagoitia-Novales, Lilian

2017-11-01

Stress response is associated with increased activity in the hypothalamic-pituitary-adrenocortical axis. Chronic stress-induced elevation in cortisol may alter its own negative regulation with multiple long-term consequences for physical and psychological health. One of the most reliable physical traits associated with mental, apparent physical health, and competitiveness is the degree of facial fluctuating asymmetry. However, to our knowledge there are no studies regarding the relationship between cortisol levels, facial symmetry and male competitiveness, and how cortisol changes after a stressful test depending on these traits. Here, a group of 100 college men were photographed to obtain their facial asymmetry levels. They then, answered the perceived stress scale and the intrasexual competition test and donated two saliva samples (pre-and post-test sample) to measure the change in their cortisol levels after a stressful test. We found that basal cortisol levels were positively correlated with both perceived stress and competitiveness, but not with facial fluctuating asymmetry. Cortisol levels increased in most symmetrical men after a short stressful test, but it decreased in most asymmetrical men. The results suggest differences in endocrine responses according to facial fluctuating asymmetry in men and how these responses could be related to the maintenance of social status.

High-density lipoprotein is a potential growth factor for adrenocortical cells

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Murao, Koji; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C.W.; Ishida, Toshihiko

2006-01-01

The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [ 3 H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

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Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

2016-12-01

Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report

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Horne John M

2011-08-01

Full Text Available Abstract Introduction Adrenocortical carcinomas are rare aggressive tumors. Their annual incidence is approximately one to two per million among the population of the United States of America. Patients with active endocrine tumors often present with Cushing's syndrome accompanied by virilizing features. Conversely, patients with non-functioning tumors may present with symptoms related to a mass-occupying lesion, such as abdominal pain and flank pain. Although varicoceles and acute kidney injuries are common problems in medicine, they are uncommon presentations of these rare tumors and easy to miss. We report a case of a large adrenocortical carcinoma that presented as testicular pain, varicocele, and acute kidney injury secondary to renal vein thrombosis. Case presentation A 54-year-old Caucasian man with a left-sided varicocele presented to our emergency department with lower abdominal pain and a decrease in urination. Four months previously, he had noticed pain and swelling in his left groin and had been diagnosed with left-sided varicocele. For one week, he began developing left-sided abdominal pain and decreased urination frequency, so he came to our emergency department for evaluation. His physical examination revealed a hard mass occupying the entire left side of his abdomen, crossing the midline, and extending to the pelvic brim. His blood tests showed acute kidney injury and mild anemia. Computed tomography of his abdomen showed a large retroperitoneal mass on the left side, displacing the left kidney inferiorly and the spleen superiorly with thoracic epidural compression. Thrombus was also identified in his left renal vein and inferior vena cava. Computed tomography of his chest showed bilateral pulmonary nodules. A computed tomography-guided abdominal mass biopsy was performed, and the diagnosis of adrenocortical carcinoma was made on the basis of pathology and immunohistochemistry. His hormonal evaluations were normal. His kidney

Extension of adrenocortical carcinoma into the right atrium – echocardiographic diagnosis: A case report

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Rozenman Yoseph

2003-05-01

Full Text Available Abstract Background Adrenocortical carcinoma is a rare, highly malignant tumor. Cardiac involvement of the tumor is very rare. Echocardiography facilitates the evaluation of the cardiac involvement of the tumor. Case Presentation We describe a patient with an adrenal tumor. Transthoracic echo showed its extension into the right atrium. Accordingly, a combined abdominal and cardiac operation was performed, monitored by transesophageal echocardiography. Conclusion This case highlights the importance of echocardiography in revealing the cardiac involvement by this tumor and in planning the operative procedure.

Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

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Kaltsas Gregory

2010-07-01

Full Text Available Abstract Introduction Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature. Case presentation A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease. Conclusions Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.

Automatic computer aided analysis algorithms and system for adrenal tumors on CT images.

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Chai, Hanchao; Guo, Yi; Wang, Yuanyuan; Zhou, Guohui

2017-12-04

The adrenal tumor will disturb the secreting function of adrenocortical cells, leading to many diseases. Different kinds of adrenal tumors require different therapeutic schedules. In the practical diagnosis, it highly relies on the doctor's experience to judge the tumor type by reading the hundreds of CT images. This paper proposed an automatic computer aided analysis method for adrenal tumors detection and classification. It consisted of the automatic segmentation algorithms, the feature extraction and the classification algorithms. These algorithms were then integrated into a system and conducted on the graphic interface by using MATLAB Graphic user interface (GUI). The accuracy of the automatic computer aided segmentation and classification reached 90% on 436 CT images. The experiments proved the stability and reliability of this automatic computer aided analytic system.

Effects of Mifepristone on Nonalcoholic Fatty Liver Disease in a Patient with a Cortisol-Secreting Adrenal Adenoma

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Enzo Ragucci

2017-01-01

Full Text Available Cushing syndrome (CS, a complex, multisystemic condition resulting from prolonged exposure to cortisol, is frequently associated with nonalcoholic fatty liver disease (NAFLD. In patients with adrenal adenoma(s and NAFLD, it is essential to rule out coexisting endocrine disorders like CS, so that the underlying condition can be properly addressed. We report a case of a 49-year-old woman with a history of hypertension, prediabetes, dyslipidemia, biopsy-confirmed steatohepatitis, and benign adrenal adenoma, who was referred for endocrine work-up for persistent weight gain. Overt Cushing features were absent. Biochemical evaluation revealed nonsuppressed cortisol on multiple 1-mg dexamethasone suppression tests, suppressed adrenocorticotropic hormone, and low dehydroepiandrosterone sulfate. The patient initially declined surgery and was treated with mifepristone, a competitive glucocorticoid receptor antagonist. In addition to improvements in weight and hypertension, substantial reductions in her liver enzymes were noted, with complete normalization by 20 weeks of therapy. This case suggests that autonomous cortisol secretion from adrenal adenoma(s could contribute to the metabolic and liver abnormalities in patients with NAFLD. In conclusion, successful management of CS with mifepristone led to marked improvement in the liver enzymes of a patient with long-standing NAFLD.

Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

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Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

2015-01-01

We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

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Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

2014-01-01

Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

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Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

2011-01-01

Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

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Marc Baay

2011-01-01

Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

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Bat-Chen eAmit-Cohen

2013-07-01

Full Text Available Tumor macrophages are generally considered to be alternatively/M2 activated to induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147, basigin is overexpressed in many tumor types, and has been shown to induce fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that tumor cell interactions with macrophages resulted in increased expression of EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7 breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell line in the presence of TNFalpha (1 ng/ml. Membranal EMMPRIN expression was increased in the co-cultures (by 3-4 folds, p<0.01, as was the secretion of MMP-9 and VEGF (by 2-5 folds for both MMP-9 and VEGF, p<0.01, relative to the single cultures with TNFalpha. Investigating the regulatory mechanisms, we show that EMMPRIN was post-translationally regulated by miR-146a, as no change was observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression of miR-146a was increased and its neutralization by its antagomir inhibited EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2-3 folds, p<0.05, only in the A498 co-culture via shedding off of the membranal protein by a serine protease that is yet to be identified, as demonstrated by the use of wide range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti-EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated pathway.

Analysis of the manifestation and feature of adrenal tumor on CT in 30 cases

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Xi Riquan; Xie Daohai; Guo Liang; Hu Chunhong; Fu Yingdi

2001-01-01

Objective: To analyze the manifestation and the feature of adrenal tumor with CT. Methods: The findings of various adrenal tumors with CT in 30 cases were analyzed retrospectively, the key to the diagnosis and differential diagnosis was suggested. Results: Usually, fibroxanthoma is inhomogeneous in density and moderate in size and was enhanced slightly after contrast medium administration. Pheochromocytoma is always larger and inhomogeneous in density and was enhanced markedly. The CT unit of myelo-lipoma simulated those of fluid or fat. Adrenal cyst has a low CT value and it showed cystic wall calcification. Aldosteronism adenoma was low in density and small in size, while cortisol adenoma was moderate in density and medium in size. Adrenocortical adenocarcinoma was the larger one with irregular margin and irregular hypodense areas inside. Metastatic carcinoma was larger and inhomogeneous in density. Conclusion: It is possible to increase the diagnostic rate by analysing the imaging feature of adrenal tumor

Development of cortisol circadian rhythm in infancy.

NARCIS (Netherlands)

Weerth, C. de; Zijl, R.H.

2003-01-01

BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not

A comparative assessment of the adrenotoxic effects of cadmium in two teleost species, rainbow trout, Oncorhynchus mykiss, and yellow perch, Perca flavescens

International Nuclear Information System (INIS)

Lacroix, Alexandra; Hontela, Alice

2004-01-01

Rainbow trout (Oncorhynchus mykiss) and yellow perch (Perca flavescens) have a different sensitivity to cadmium (Cd) in vivo (trout O.mykiss =175.6>LC50/EC50 P.flavescens =37.7). Adrenocortical cells of trout were more sensitive than those of perch and Cd had a higher endocrine-disrupting potential and specificity in trout than in perch. However, in both species, Cd had the same effect on ACTH, dbcAMP and pregnenolone-stimulated cortisol secretion, with pregnenolone maintaining cortisol secretion until cell viability was impaired. These results confirm that for both species, Cd interferes in the signalling pathway of cortisol synthesis in a step prior to the pregnenolone formation. Data provided by the present study revealed important differences in vulnerability of adrenal steroidogenesis between rainbow trout and yellow perch

A Late Onset of Adrenocortical Cancer Assosiated with Beckwith-Wiedemann Syndrome

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N S Kuznetsov

2014-06-01

Full Text Available Beckwith-Wiedemann syndrome (BWS is a genetic overgrowth disorder involving a predisposition to tumor development. The common features of Beckwith-Wiedemann syndrome include omphalocele, macroglos- sia and macrosomia. The increased risk for neoplasia is concentrated in the first eight years of life. However, this case presents a late onset of adrenocortical cancer assosiated with Beckwith-Wiedemann syndrome.

Links between early child maltreatment, mental disorders, and cortisol secretion anomalies.

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Bronsard, Guillaume; Auquier, Pascal; Boyer, Laurent

2016-11-01

Early child maltreatment has been widely associated with the development of mental disorders in both childhood and adulthood. However, such association cannot be systematically established, as only few factors are observed regularly, such as high prevalence of comorbidities and externalized disorders. Similarly, the association between early abuse and cortisol secretion anomalies has been well-documented. Whereas early hypercortisolism followed by hypocortisolism was often described, the results proved inconsistent and at times contradictory. The physiopathological mechanisms are quite complex and varied, including mixed neurotoxicity and stress response anomalies, linked to circadian rhythm disturbances. One of the difficulties inherent to research on this topic is to better define maltreatment in childhood. Studying children's groups at risk of maltreatment, such as children followed by juvenile justice or in child welfare systems, could be a very good tool, provided that social, judiciary, and mental health professionals are able to work together and implement common research objectives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.

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Chen, Shi; Li, Ran; Lu, Lin; Duan, Lian; Zhang, Xuebin; Tong, Anli; Pan, Hui; Zhu, Huijuan; Lu, Zhaolin

2018-01-01

To evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Retrospective study. The patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016. Serum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST). After LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity. The ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.

Autophagy-dependent secretion: contribution to tumor progression

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Tom Keulers

2016-11-01

Full Text Available Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies. In this review we discuss the current knowledge of the physiological roles of autophagy-dependent secretion, i.e. the effect on inflammation and insulin/ hormone secretion. Finally, we focus on the effects of autophagy-dependent secretion on the tumour microenvironment and tumour progression. The autophagy mediated secreted factors may stimulate cellular proliferation via auto- and paracrine signaling. The autophagy mediated release of immune modulating proteins change the immunosuppresive tumor microenvironment and may promote an invasive phenotype. These effects may be either direct or indirect through facilitating formation of the mobilized vesicle, aid in anterograde trafficking or alterations in homeostasis and/or autonomous cell signaling.

Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

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Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

1991-01-01

Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

Sleep duration partially accounts for race differences in diurnal cortisol dynamics.

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Peterson, Laurel M; Miller, Karissa G; Wong, Patricia M; Anderson, Barbara P; Kamarck, Thomas W; Matthews, Karen A; Kirschbaum, Clemens; Manuck, Stephen B

2017-05-01

Emerging research demonstrates race differences in diurnal cortisol slope, an indicator of hypothalamic-pituitary-adrenocortical (HPA)-axis functioning associated with morbidity and mortality, with African Americans showing flatter diurnal slopes than their White counterparts. Sleep characteristics are associated with both race and with HPA-axis functioning. The present report examines whether sleep duration may account for race differences in cortisol dynamics. Participants were 424 employed African American and White adults (mean age = 42.8 years, 84.2% White, 53.6% female) with no cardiovascular disease (Adult Health and Behavior Project-Phase 2 [AHAB-II] cohort, University of Pittsburgh). Cortisol slope was calculated using 4 salivary cortisol readings, averaged over each of 4 days. Demographic (age, sex), psychosocial (socioeconomic status [SES], affect, discrimination), and health behaviors (smoking, alcohol use, physical activity) variables were used as covariates, and sleep (self-report and accelerometry) was also assessed. African Americans had flatter slopes than Whites (F(1, 411) = 10.45, B = .02, p = .001) in models adjusting for demographic, psychosocial, and health behavior covariates. Shorter actigraphy-assessed total sleep time was a second significant predictor of flatter cortisol slopes (F(1, 411) = 25.27, B = -.0002, p race and diurnal slope [confidence interval = .05 (lower = .014, upper .04)]. African Americans have flatter diurnal cortisol slopes than their White counterparts, an effect that may be partially attributable to race differences in nightly sleep duration. Sleep parameters should be considered in further research on race and cortisol. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?

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Fureix Carole

2013-01-01

Full Text Available Abstract Background Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (NStudy1 = 55, NStudy2 = 58, kept in sub-optimal conditions (e.g. confinement, social isolation, and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1 and instantaneous scan sampling (study 2. Plasma samples (collected in study 1 but also non-invasive faecal samples (collected in both studies were retrieved in order to assess cortisol levels. Results Results showed that 1 plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2 both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. Conclusions Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure, therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity.

Adrenocortical scintigraphy with {sup 131}I-6-beta-iodomethyl-norcholesterol (NP 59) in bilateral adrenocortical carcinoma

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Ruiz Hernandez, G.; Pallares, F.J.C.; Avila y Avalos, C.R. de [Hospital Clinic Universitari de Valencia (Spain). Servei de Medicina Nuclear; Bartual, A.R.; Rodrigo, S.T.; Ampudia-Blasco, F.J. [Hospital Clinic Universitari de Valencia (Spain). Servei d`Endocrinologia

1998-06-01

A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma with local and secondary rapid progression is reported. The results of adrenocortical scintigraphy (NP 59) and histological findings allowed the diagnosis. This case report and a literature review showed the importance of using adrenocortical scintigraphy as a complementary imaging procedure of CT or MR images. (orig.) [Deutsch] Es wird ueber einen 49jaehrigen Mann berichtet, der an einem beidseitigen Nebennierenrinden-Karzinom mit schneller lokaler und sekundaerer Progression leidet. Die Ergebnisse der Nebennierenrinden-Szintigraphie (NP 59) und Histologie ermoeglichten die Diagnose: Dieser Fallbericht und ein Literaturueberblick zeigen die Bedeutung der Nebennierenrinden-Szintigraphie als ein zusaetzliches bildgebendes Verfahren neben CT und NMR. (orig.)

[Serum cortisol level variations in thyroid diseases].

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Seck-Gassama; Ndoye, O; Mbodj, M; Akala, A; Cisse, F; Niang, M; Ndoye, R

2000-01-01

This work studies the thyroid disorders impact on adrenals glands by measuring total cortisol. Radioimmunoassays of thyroid hormones and cortisol were performed in 108 subjects, aged 20-52 years, with thyroid diseases. Our results show low cortisol values (80.35 nmol/L) in 4.77% of hyperthyroids, high values in 3.57% of hyperthyroids (1348.18 nmol/L) and 12.5% of hypothyroids (969.05 nmol/L). In hyperthyroidism, thyroid hormone stimulates the secretion of 11 ceto metabolites biologically inactive, unable to slow pituitary activity, inducing an increased production of endogene cortisol. Excessive catabolism can lead to the exhausting of overstimulated adrenal glands, and therefore to a decreased cortisol. In hypothyroidism, high cortisol results of increase cortisol half life and decrease of metabolic clearance. Control mechanisms often allow normal cortisol values. These alterations in functional activity of adrenal glands, seen in nearly 10% of these subjects, sometimes command a specific attitude in diagnosis and therapy.

Cortisol levels and sleep patterns in infants with orofacial clefts undergoing surgery

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Mueller AA

2014-10-01

Full Text Available Andreas A Mueller,1,2 Nadeem Kalak,3 Katja Schwenzer-Zimmerer,1,2 Edith Holsboer-Trachsler,3 Serge Brand3,4 1Craniomaxillofacial Surgery, University of Basel and University Hospital of Basel, Basel, Switzerland; 2Hightech Research Center of Craniomaxillofacial Surgery, University of Basel, Basel, Switzerland; 3Psychiatric Clinics of the University of Basel, Center for Affective, Stress, and Sleep Disorders, Basel, Switzerland; 4Department of Sport and Health Science, Division of Sport Science, University of Basel, Basel, Switzerland Background: Traumatic events during early infancy might damage infants’ psychobiological functioning, such as sleep and cortisol secretion. Infants born with orofacial clefts (OFCs undergo functional, anatomical, and aesthetic surgery. The aim of the present study was to determine whether infants with OFC and undergoing OFC surgery show deteriorated sleep and cortisol secretion compared with healthy controls and with their presurgery status.Methods: A total of 27 infants with OFC (mean age: 22 weeks and 30 healthy controls (mean age: 23 weeks took part in the study. For infants with OFC, sleep actigraphy was performed and saliva cortisol was analyzed 5 days before, during, and 5 days after surgery. For controls, sleep and saliva cortisol were assessed similarly, except for the period taken up with surgery.Results: Compared with healthy controls, infants with OFC undergoing OFC surgery did not differ in sleep and cortisol secretion. Their sleep and cortisol secretion did deteriorate during the perisurgical period but recovered 5 days postsurgery. Conclusion: In infants with OFC undergoing corrective surgery, the pattern of results for sleep and cortisol suggests that OFC surgery does not seem to constitute a traumatic event with long-term consequences. Keywords: cortisol, sleep, orofacial cleft, surgery, infants

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

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Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

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Fox Bernard A

2007-11-01

Full Text Available Abstract Background The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5 melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-γ or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN, were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-γ or TNF-α was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO was determined using GRIES reagent. Results We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1α and MIP-1β following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-γ or TNF-α, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC, MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin

Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup final.

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van der Meij, Leander; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; Ijzerman, Hans; van Lange, Paul A M; Salvador, Alicia

2012-01-01

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.

Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup final.

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Leander van der Meij

Full Text Available This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50 watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.

FKBP5 methylation as a possible marker for cortisol state and transient cortisol exposure in healthy human subjects.

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Winkler, Britta K; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Harbeck, Birgit

2017-10-01

Current glucocorticoid replacement regimens, in adrenal insufficiency, fail to mimic the physiological cortisol secretion, thereby fostering serious side effects. To experimentally evaluate the impact of CpG methylation within the FKBP5 gene as a possible short- and long-term marker for cortisol exposure in humans. An ACTH-stimulation test was carried out and methylation status of the FKBP5 gene in leukocytes was determined. A negative correlation between basal levels of methylation and serum cortisol was observed. Individual changes in FKBP5 methylation after 24 h correlated with cortisol responses. Considering previous studies conducted with murine leucocytes, FKBP5 methylation may be suitable as a long-term biomarker, rather than acute glucocorticoid exposure, also in humans.

Deconvolution analysis of 24-h serum cortisol profiles informs the amount and distribution of hydrocortisone replacement therapy.

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Peters, Catherine J; Hill, Nathan; Dattani, Mehul T; Charmandari, Evangelia; Matthews, David R; Hindmarsh, Peter C

2013-03-01

Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m(2) body surface area/day in adults and 8.0 mg/m(2) body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen. © 2012 Blackwell Publishing Ltd.

Relationships of salivary cortisol and melatonin rhythms to sleep quality, emotion, and fatigue levels in patients with newly diagnosed lung cancer.

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Chang, Wen-Pei; Lin, Chia-Chin

2017-08-01

After being diagnosed with lung cancer, patients often experience sleep disturbance, anxiety, depression, and fatigue. These symptoms may occur because of changes in neurotransmitter secretion caused by tumors. This study investigated the correlation of cortisol and melatonin rhythms with sleep quality, anxiety, depression, and fatigue levels in patients with newly diagnosed lung cancer. We conducted a case-control study and recruited 40 patients with newly diagnosed lung cancer and 40 healthy adults. The patient group had a lower salivary melatonin level and flatter slope (p cortisol level and steeper slope (p cortisol slope (p = 0.005) and fatigue score (p = 0.032) predicted the sleep quality score (p = 0.011). Overall, the patients with newly diagnosed lung cancer had poorer sleep quality, higher depression levels, lower salivary melatonin levels, higher cortisol levels, and flatter melatonin and cortisol slopes than did the controls. The fatigue level and cortisol slope significantly predicted sleep quality. Therefore, the assessment of cortisol and melatonin rhythms and levels could provide crucial information that may be beneficial for managing symptoms in patients with newly diagnosed lung cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

International Nuclear Information System (INIS)

Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J.; Davenport, Matthew S.; Caoili, Elaine M.; Else, Tobias

2015-01-01

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

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Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Davenport, Matthew S.; Caoili, Elaine M. [University of Michigan Health System, Division of Abdominal Imaging, Department of Radiology, Ann Arbor, MI (United States); Else, Tobias [University of Michigan Health System, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Ann Arbor, MI (United States)

2015-08-15

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

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Zofia Ostrowska

2013-05-01

Full Text Available Background: It has been suggested that disturbances in melatonin (MEL secretion might play a role in osteoporosis development in females with anorexia nervosa (AN. It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue.Aim: We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system.Material/Methods: Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA, immunoradiometric assay (IRMA or enzyme-linked immunosorbent assay (ELISA methods.Discussion: Our study participants with AN showed a significant reduction in body mass and body mass index (BMI, a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00 as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a

Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary

International Nuclear Information System (INIS)

Ross, W.M.; Evered, D.C.; Hunter, P.; Benaim, M.; Cook, D.; Hall, R.

1979-01-01

Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethimide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients. (author)

Association Between Cortisol to DHEA-s Ratio and Sickness Absence in Japanese Male Workers.

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Hirokawa, Kumi; Fujii, Yasuhito; Taniguchi, Toshiyo; Takaki, Jiro; Tsutsumi, Akizumi

2017-11-21

This study aimed to investigate the association between serum levels of cortisol and dehydroepiandrosterone sulfate (DHEA-s) and sickness absence over 2 years in Japanese male workers. A baseline survey including questions about health behavior, along with blood sampling for cortisol and DHEA-s, was conducted in 2009. In total, 429 men (mean ± SD age, 52.9 ± 8.6 years) from whom blood samples were collected at baseline were followed until December 31, 2011. The hazard ratios (HR) and 95% confidence intervals (CI) for sickness absence were calculated using a Cox proportional hazard model, adjusted for potential confounders. Among 35 workers who took sickness absences, 31 had physical illness. A high cortisol to DHEA-s ratio increased the risk of sickness absence (crude HR = 2.68, 95% CI 1.12-6.41; adjusted HR = 3.33, 95% CI 1.35-8.20). The cortisol to DHEA-s ratio was linearly associated with an increased risk of sickness absence (p for trend sickness absences. This trend did not change when limited to absences resulting from physical illness. Hormonal conditions related to the hypothalamus-pituitary-adrenocortical axis and adrenal function should be considered when predicting sickness absence. The cortisol to DHEA-s ratio may be more informative than single effects of cortisol and DHEA-s levels.

The role of computed tomography in the localization of adrenal cortex tumors

International Nuclear Information System (INIS)

Baranowska, B.; Misiorowski, W.; Pacho, R.; Wysocki, M.; Kobuszewska, M.; Zgliczynski, S.; Medical Center of Postgraduate Education, Warsaw

1982-01-01

The aim of this study was to evaluate the usefulness of computed tomography in the localisation of adrenal tumors producing aldosterone and cortisol. One case each of Conn's and Cushing's syndrome are described. The diagnosis of Conn's syndrome was established by demonstrating an elevated plasma aldosterone level 'at rest' and its decrease after stimulation, the absence of plasma renin activity and a lowered plasma potassium level. The diagnosis of Cushing's syndrome due to adrenal adenoma was established by demonstrating the typical clinical features, an abnormal diurnal rhythm of cortisol and ACTH secretion and an increased urine excretion of 17-OHCS without suppression by large doses of dexamethasone. The localisation and the size of the tumors as determined by computed tomography were confirmed during surgery. (orig.) [de

Familial social support predicts a reduced cortisol response to stress in sexual minority young adults.

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Burton, C L; Bonanno, G A; Hatzenbuehler, M L

2014-09-01

Social support has been repeatedly associated with mental and physical health outcomes, with hypothalamic-pituitary-adrenocortical (HPA) axis activity posited as a potential mechanism. The influence of social bonds appears particularly important in the face of stigma-related stress; however, there is a dearth of research examining social support and HPA axis response among members of a stigmatized group. To address this gap in the literature, we tested in a sample of 70 lesbian, gay, and bisexual (LGB) young adults whether family support or peer support differentially predict cortisol reactivity in response to a laboratory stressor, the Trier Social Stress Test. While greater levels of family support were associated with reduced cortisol reactivity, neither peer support nor overall support satisfaction was associated with cortisol response. These findings suggest that the association between social support and neuroendocrine functioning differs according to the source of support among members of one stigmatized group. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

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Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

2013-10-01

Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

Effects of drugs on beta-endorphin and cortisol in smokers

International Nuclear Information System (INIS)

Du Tongxin; Wang Zizheng; Wang Shukui

2001-01-01

The authors observed the effects of drugs on beta-endorphin and cortisol in smokers and their correlation. The levels of plasma beta-endorphin and cortisol of smokers before and after cigarette withdrawal were detected by radioimmunoassay (RIA). The Levels of plasma beta-endorphin and cortisol in smokers is significantly higher than in controls. After natural withdrawal, the levels of plasma cortisol increased significantly, while beta-endorphin decreased significantly. After drug treatment, the levels of beta-endorphin and cortisol balanced. The drugs may play the role of cigarette withdrawal by improving the secretion of endogenous opium and the axis of hypothalamus-pituitary adrenal

Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

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Luciana Tock

2014-01-01

Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

The effect of a maternal history of childhood abuse on adrenocortical attunement in mothers and their toddlers.

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Fuchs, Anna; Moehler, Eva; Resch, Franz; Kaess, Michael

2017-07-01

We investigated circadian mother-child adrenocortical attunement in the context of a maternal history of childhood abuse (HoA). Mothers were screened after birth using the Childhood Trauma Questionnaire. Women reporting moderate or severe abuse formed the HoA group (n = 37; HoAG) and were compared with a non-maltreated comparison group (n = 45; CG). Three years later, cortisol awakening response (CAR) and diurnal slope (DSL) were assessed. Mother-child interaction was coded using the Emotional Availability Scales at 12 months of age. For the CAR, we found adrenocortical attunement only in the HoAG (2-way interaction: p = .004), particularly if mothers scored low on structuring (3-way interaction: p = .042) and children scored low on responsiveness (3-way interaction: p = .044). DSL-attunement was dependent on maternal sensitivity (3-way interaction: p = .012) and child involvement (3-way interaction: p = .012). In the context of a maternal HoA, it seems possible for mother-child-dyads to show less optimal interactional quality but be stronger attuned to each other biologically. © 2017 Wiley Periodicals, Inc.

Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin

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Laferrère, Blandine; Abraham, Cynthia; Awad, Marianne; Jean-Baptiste, Stephanie; Hart, Allison B.; Garcia-Lorda, Pilar; Kokkoris, Peter; Russell, Colleen D.

2010-01-01

Context Administration of glucocorticoids increases serum leptin levels in lean and obese individuals. A morning meal produces an increase in insulin, a cortisol peak, and an increase in leptin; these changes do not occur during fasting. Objective The objective of this study was to investigate whether inhibiting endogenous cortisol secretion with metyrapone decreases 24-h serum leptin levels and to determine whether a meal-related midmorning surge in cortisol is a prerequisite for the meal-entrained nocturnal rise in leptin. Design This was a randomized, cross-over study. Setting The study was performed at the General Clinical Research Center. Participants Lean males were studied. Intervention In study 1, seven lean men were studied for 24 h while their endogenous cortisol secretions were manipulated as follows: 1) CONTROL; 2) cortisol suppression by metyrapone (MET); and 3) MET and oral hydrocortisone (at 0900 h) (MET + CORT). Subjects were all fed a eucaloric diet (two meals at 1100 and 1700 h). In study 2, six men were studied without pharmacological intervention for 24 h on two occasions: once under a complete fast (FAST) and once in a feeding condition (one meal at 1100 h; FED). Main Outcome Measure The main outcome measure was serum leptin. Results MET significantly suppressed serum cortisol at 0800 h, midmorning, and over the 24-h period. As a result of cortisol suppression, 24-h serum leptin levels were decreased vs. control values despite similar insulin responses to meals. Administering a single dose of hydrocortisone to MET subjects potently stimulated serum leptin compared with the effect of MET alone. Conclusions Our data demonstrate that endogenous cortisol secretion is necessary for the maintenance of serum leptin levels over 24 h in lean, normally fed males. PMID:16537679

Monocytes/macrophages support mammary tumor invasivity by co-secreting lineage-specific EGFR ligands and a STAT3 activator

International Nuclear Information System (INIS)

Vlaicu, Philip; Mertins, Philipp; Mayr, Thomas; Widschwendter, Peter; Ataseven, Beyhan; Högel, Bernhard; Eiermann, Wolfgang; Knyazev, Pjotr; Ullrich, Axel

2013-01-01

Tumor-associated macrophages (TAM) promote malignant progression, yet the repertoire of oncogenic factors secreted by TAM has not been clearly defined. We sought to analyze which EGFR- and STAT3-activating factors are secreted by monocytes/macrophages exposed to tumor cell-secreted factors. Following exposure of primary human monocytes and macrophages to supernatants of a variety of tumor cell lines, we have analyzed transcript and secreted protein levels of EGFR family ligands and of STAT3 activators. To validate our findings, we have analyzed TAM infiltration levels, systemic and local protein levels as well as clinical data of primary breast cancer patients. Primary human monocytes and macrophages respond to tumor cell-derived factors by secreting EGFR- and STAT3-activating ligands, thus inducing two important oncogenic pathways in carcinoma cells. Tumor cell-secreted factors trigger two stereotype secretory profiles in peripheral blood monocytes and differentiated macrophages: monocytes secrete epiregulin (EREG) and oncostatin-M (OSM), while macrophages secrete heparin-binding EGF-like growth factor (HB-EGF) and OSM. HB-EGF and OSM cooperatively induce tumor cell chemotaxis. HB-EGF and OSM are co-expressed by TAM in breast carcinoma patients, and plasma levels of both ligands correlate strongly. Elevated HB-EGF levels accompany TAM infiltration, tumor growth and dissemination in patients with invasive disease. Our work identifies systemic markers for TAM involvement in cancer progression, with the potential to be developed into molecular targets in cancer therapy

Deconvolution of serum cortisol levels by using compressed sensing.

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Rose T Faghih

Full Text Available The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH from the hypothalamus, adrenocorticotropin hormone (ACTH from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i compressed sensing for recovering the amplitude and timing of the secretory events, and (ii generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R (2 above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii potentially designing optimal approaches for treating hormonal disorders.

Adrenocorticotropic Hormone and Cortisol Secretion Changes among the Law Enforcement Personnel during the Mission to the Areas of Armed Conflicts

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Roman V. Koubassov

2014-06-01

Full Text Available The adrenocorticotropic hormone and cortisol changes among law enforcement personnel during mission to the areas of armed conflicts were studied. At the beginning of the mission an increase of all hormones was detected, which corresponded to basic points of general adaptation syndrome theory. A further investigation revealed an imbalance of hormonal secretions in the hypophysis-adrenal system. Such an imbalance can lead to disregulation of interhormonal relations and can be a factor in decreasing the organism’s stress resistance.

Longitudinal measurement of cortisol in association with mental health and experience of domestic violence and abuse: study protocol

OpenAIRE

Lokhmatkina, Natalia V; Feder, Gene; Blake, Sarah; Morris, Richard; Powers, Victoria; Lightman, Stafford

2013-01-01

Background Domestic violence and abuse is threatening behavior, violence/abuse used by one person to control the other within an intimate or family-type relationship. Women experience more severe physical and sexual domestic violence and abuse and more mental health consequences than men. The current study aims at exploring of the role of hypothalamic-pituitary-adrenocortical axis activity in abuse impact on women's mental health. Study objectives: 1) To evaluate diurnal cortisol slope, corti...

Rapid appearance of transient secondary adrenocortical insufficiency after alpha-particle radiation therapy for Cushing's disease

International Nuclear Information System (INIS)

Cook, D.M.; Jordan, R.M.; Kendall, J.W.; Linfoot, J.A.

1976-01-01

A 17-year-old woman received 12,000 rads of alpha-particle radiation for the treatment of Cushing's disease. One day after the completion of therapy, the patient developed nausea, vomiting, headache, and postural hypotension. Laboratory evaluation demonstrated a marked fall of the previously elevated urinary 17-hydroxycorticosteroids (17-OHCS) and undetectable plasma cortisols. The urinary 17-OHCS transiently returned to supranormal levels but over a 2 1 / 2 -week period decreased and then remained low. The patient also demonstrated a subnormal urinary aldosterone excretion in relation to plasma renin activity (PRA) during 10 mEq/24 h sodium restriction. The remainder of the endocrine evaluation was normal, suggesting that pituitary function otherwise remained intact. One and one-half years after alpha-particle therapy, the patient's urinary 17-OHCS were normal and responded normally to metyrapone. The relationship between urinary aldosterone excretion and PRA also was normal. It is postulated that there was an infarction of an ACTH secreting pituitary tumor leaving the remainder of the pituitary intact. A chronically elevated circulating level of ACTH with sudden loss of ACTH secretion appeared to have been responsible for the initial low urinary aldosterone as well as the low urinary 17-OHCS. This is the first reported case of a presumed pituitary tumor infarction in association with alpha-particle pituitary radiation

Experience with surgical treatment for primary malignant adrenal tumors

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V. R. Latypov

2016-01-01

Full Text Available Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately.Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7 with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80 years (median age 51.0 years. The right and left adrenal glands were affected in 49 (36.9 % and 77 (57.9 % patients, respectively; both adrenal glands were involved in 7 (5.3 %. A group of 21 (15.8 % people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups.Results. The investigation analyzed treatment results in 21 (15.8 % patients with primary malignant adrenal lesions (Group 1. The most common morphological form was adrenocortical carcinoma in 15 (11.3 % patients (5 men and 10 women (1:2; their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

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Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

2017-03-01

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

Urinary free cortisol in the diagnosis of Cushing's syndrome: how useful?

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Odeniyi, I A; Ifedayo, A O; Fasanmade, O A; Olufemi, A F

2013-01-01

Cushing's syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. To confirm the clinical suspicion, biochemical tests are needed. These biochemical tests include the measurement of excess total endogenous cortisol secretion assessed by 24-hour urinary free cortisol (UFC), loss of the normal feedback of the hypothalamo-pituitary-adrenal axis assessed by suppressibility after dexamethasone testing, and disturbance of the normal circadian rhythm of cortisol secretion assessed by midnight serum or salivary cortisol. We searched the Medline, Pubmed, journal articles, WHO publications and reputable textbooks relating to Cushing's syndrome using publications from 1995 to 2011. UFC has been the classic screening test used to confirm hypercortisolemia as the first step in diagnostic work-up of Cushing's syndrome. Its long-term use in clinical practice has led to emergence of significant evidence regarding the utility of UFC in the diagnosis of Cushing's syndrome. UFC would have been a simple diagnostic tool to use but for the drawbacks in the sample collection, different laboratory methods of assay, not easily determined normal range. UFC use as a screening test is not strongly favoured because cortisol is not uniformly secreted during the day, and the increased prevalence of mild, preclinical or cyclic Cushing's syndrome. A very high level of UFC negates the need for other test procedures in patients with obvious symptoms and signs of Cushing's syndrome. We therefore suggest that UFC should be used with other screening tests for Cushing's syndrome to increase diagnostic yield.

Capturing effort and recovery: reactive and recuperative cortisol responses to competition in well-trained rowers

NARCIS (Netherlands)

Kallen, V.L.; Stubbe, J.H.; Zwolle, H.J.; Valk, P.

2017-01-01

Background/aim It is well known that physical strain is associated with increased cortisol production. And although mental stress elevates cortisol concentrations as well, little is known of the independent and/or combined effects of both on the secretion of cortisol. Aim of the study was to

Effect of the nature of subsequent environment on oxytocin and cortisol secretion in maltreated children

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Sakae G. Mizushima

2015-12-01

Full Text Available Childhood maltreatment (CM, including abuse and neglect is a crucial factor that distorts child development. CM is associated with alterations in numerous brain regions, and may be associated with neuropeptide hormonal dysregulation. This study aimed to investigate differences in secretion patterns of cortisol (CT and oxytocin (OT among children who experienced CM, children living in residential care facilities and in unstable environments. Among 38 maltreated children, 23 (mean age = 12.2 years, SD = 3.0 were categorized as Settled and 15 (mean age = 13.1 years, SD = 2.2 as Unsettled. Twenty-six age- and gender-matched (mean age = 12.6 years, SD = 2.1, typically developing (TD children were also included. Clinical and psychological assessments, including IQ and trauma evaluations were conducted for all participants. Age, gender and full-scale IQ were used as covariates in hormone analysis. Two saliva samples were collected, one on awakening, the other at bedtime. There were significant differences in the awakening CT levels of the Unsettled group, and in bedtime OT levels in the Settled group as compared with TD children, and between CM groups. Furthermore, there was a significant difference in trauma-symptomatic depression scores between the Settled and Unsettled CM group. These results suggest that CT diurnal secretions tend to be reactive to current stress rather previous experience. OT diurnal secretions are presumably hyper-regulated for coping with the environment to survive and thrive. By measuring salivary CT/OT diurnal patterns, hormonal dysregulation of CM children living in Settled environments and Unsettled environments was indicated.

Perception of academic examination stress: effects on serum leptin, cortisol, appetite and performance.

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Inam, Qurrat-ul-Aen; Shireen, Erum; Haider, Saida; Haleem, Darakhshan Jabeen

2011-01-01

Examination stress is a psychological stress that activate hypothalamic-pituitary adrenocortical (HPA) axis to increase circulating levels of glucocorticoids. The fat derived hormone leptin is also released in response to stress-inducing condition. To workout the role of leptin and cortisol in response to perceived levels of examination stress and their effects on academic performance. The present study was designed to monitor the relationship of self reported perceived levels of examination stress on serum levels of cortisol and leptin in female students going to appear in university examination. Fifty-six female undergraduate students participated in the study. Examination stress, appetite levels were assessed by a questionnaire and blood samples were collected one hour before appearing in the examination. Performance was evaluated from the marks obtained in that particular examination. Serum cortisol levels increased with an increase in the intensity of perceived examination stress. Serum leptin levels increased only in the group under moderate stress while increases in mild and severe stress group were not significant. Mild to moderate stress enhanced performance but severe stress decreased it. The present study shows an inverted U-shaped relationship between self reported different levels of perceived examination stress and academic performance.

Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

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Aschbacher, Kirstin; Derakhshandeh, Ronak; Flores, Abdiel J; Narayan, Shilpa; Mendes, Wendy Berry; Springer, Matthew L

2016-05-01

Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age=26years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Circulating Angiogenic Cell Function is Inhibited by Cortisol in Vitro and Associated with Psychological Stress and Cortisol in Vivo

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Aschbacher, Kirstin; Derakhshandeh, Ronak; Flores, Abdiel J.; Narayan, Shilpa; Mendes, Wendy Berry; Springer, Matthew L.

2016-01-01

Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age = 26 years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health. PMID:26925833

Development of the cortisol circadian rhythm in the light of stress early in life.

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Simons, Sterre S H; Beijers, Roseriet; Cillessen, Antonius H N; de Weerth, Carolina

2015-12-01

The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnosis and clinical genetics of Cushing syndrome in pediatrics

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Stratakis, Constantine A.

2016-01-01

SYNOPSIS Endogenous Cushing syndrome (CS) in pediatrics is rare; it may be caused by tumors that produce corticotropin (ACTH) in the pituitary gland (this form of CS is called Cushing disease) or elsewhere (ectopic CS), tumors that produce corticotropin-releasing hormone (CRH) anywhere (mostly neuroendocrine tissues), and finally adrenocortical masses that produce cortisol, such as adrenocortical cancer (ACC) or adenomas, and bilateral adrenocortical hypeprlasia (BAHs). ACC is a very rare cause of CS in children but should be excluded first, especially among younger patients. CS in children is often caused by germline or somatic mutations in an expanding list of genes with implications for the prognosis of the patients and for their families. CS should be early recognized in children; otherwise, it can lead to significant morbidity and mortality. All patients with suspected CS should be referred to specialized clinical centers for work-up; these centers should have access to experienced endocrine and neurological surgeons. PMID:27241967

A longitudinal study of the effects of child-reported maternal warmth on cortisol stress response 15 years after parental divorce

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Luecken, Linda J.; Hagan, Melissa J.; Wolchik, Sharlene A.; Sandler, Irwin N.; Tein, Jenn-Yun

2015-01-01

Objective Childhood parental divorce is associated with an increased risk of behavioral and physical health problems. Alterations in adrenocortical activity may be a mechanism in this relation. Parent-child relationships have been linked to cortisol regulation in children exposed to adversity, but prospective research is lacking. We examined maternal warmth in adolescence as a predictor of young adults’ cortisol stress response 15 years after parental divorce. Methods Participants included 240 youth from recently divorced families. Mother and child reports of maternal warmth were assessed at 6 time points across childhood, adolescence, and young adulthood. Offspring salivary cortisol was measured in young adulthood before and after a social stress task. Structural equation modeling was used to predict cortisol response from maternal warmth across early and late adolescence. Results Higher child-reported maternal warmth in early adolescence predicted higher child-reported maternal warmth in late adolescence (std. regression = .45, SE = .065, p children from divorced families, a warm mother-child relationship post-divorce and across development, as perceived by the child, may promote efficient biological regulation later in life. PMID:26465217

Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation.

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Hannibal, Kara E; Bishop, Mark D

2014-12-01

Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to

Cortisol-binding globulin and meat quality in five European lines of pigs

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Geverink, N.A.; Foury, A.; Plastow, G.S.; Gil, L.; Gispert, M.; Hortós, M.; Font I Furnols, M.; Gort, G.; Moisan, M.P.; Mormède, P.

2006-01-01

The gene (Cbg) encoding cortisol-binding globulin (CBG) has been proposed as a candidate gene to explain genetic variation in cortisol secretion and carcass composition in pigs. The objective of this study was to evaluate the association between CBG and pork quality in 5 European breeding lines,

Diagnosis of bilateral adrenocortical hemorrhage by computed tomography

International Nuclear Information System (INIS)

Liu, L.; Haskin, M.E.; Rose, L.I.; Bemis, C.E.

1982-01-01

Adrenocortical hemorrhage has been diagnosed on the basis of the clinical presentation and response to steroids or autopsy findings. Prompt recognition of the disease has been difficult because of its similarity to other disorders. We report the diagnosis of a bilateral adrenocortical hemorrhage by computed tomography (CT), followed by biochemical confirmation of the diagnosis

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing’s disease

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Regina Streuli

2017-06-01

Full Text Available Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS. We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease.

Hyperthyroidism caused by an ectopic thyrotropin-secreting tumor of the nasopharynx: a case report and review of the literature.

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Tong, Anli; Xia, Weibo; Qi, Fang; Jin, Zimeng; Yang, Di; Zhang, Zhuhua; Li, Fang; Xing, Xiaoping; Lian, Xiaolan

2013-09-01

Ectopic thyrotropin (TSH)-secreting tumors are extremely rare. To our knowledge, only three cases have previously been reported so far, but the tumors were not studied ultrastructurally and in vitro. We present a case that was extensively examined to gain deeper insights in terms of the histopathological features and hormonal secretion profile of the tumor. A 49-year-old female complained of nasal obstruction for 15 years and thyrotoxicosis for one and a half years. Except for a high basal TSH with concomitantly elevated free tri-iodothyronine (FT3) and free thyroxine (FT4) levels, her pituitary hormone profile yielded normal results. Magnetic resonance imaging revealed a 2 cm × 2 cm mass in the nasopharynx, which showed an increased tracer uptake on octreotide scintigraphy. Preoperative treatment with octreotide effectively reduced serum TSH, FT3, and FT4 to normal levels. The mass was endoscopically removed via an endonasal approach. Immunophenotyping and hormone determination of cultured cells confirmed that the mass was a plurihormonal TSH-/growth hormone (GH)-/prolactin (PRL)-producing adenoma. Co-expression of TSH and GH was found in most cells. Electron microscopy showed that the adenoma was formed by a single cell type, with secretory granules of small size. In vitro studies demonstrated that octreotide reduced both TSH and GH secretion. We report an ectopic TSH-secreting tumor, which had plurihormonal secretion in vitro, including TSH, GH, and PRL. Histologically, it mimicked a TSH-secreting pituitary adenoma. Octreotide was useful in the diagnosis and treatment of this ectopic TSH-secreting tumor. Ectopic TSH-secreting tumors are extremely rare. In terms of hormone secretion profile, histological characteristics, and response to octreotide, they are similar to pituitary TSH-secreting adenomas, suggesting that they are of identical cell origin.

Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

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Hewedi Doaa H

2010-10-01

Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

Cortisol secretion after adrenocorticotrophin (ACTH and Dexamethasone tests in healthy female and male dogs

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Castillo Victor

2009-08-01

Full Text Available Abstract Background For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs. Methods Seven healthy adult Cocker Spaniels (4 females and 3 males were assigned to a two by two factorial design: 4 dogs (2 females and 2 males received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group. Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal to 4 dogs (2 female and 2 males while the rest was treated with saline solution (control group. Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits. Results and Discussion No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection. Conclusion We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.

Association of copeptin and cortisol in newly diagnosed multiple sclerosis patients.

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Baranowska-Bik, Agnieszka; Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Martynska, Lidia; Wolinska-Witort, Ewa; Baranowska, Boguslawa; Bik, Wojciech

2015-05-15

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Obesity may increase the risk of developing MS. The aim of this study was to evaluate copeptin and cortisol plasma levels in newly diagnosed untreated MS patients and to determine whether copeptin and cortisol are related to the patients' clinical statuses. We report that copeptin and cortisol were higher in overweight/obese MS patients. Positive correlations were observed between the two parameters. We conclude that alterations of copeptin and cortisol levels in multiple sclerosis patients may be related to adiposity. An increase in cortisol may also be associated with copeptin secretion. Copyright © 2015 Elsevier B.V. All rights reserved.

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women.

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Lovallo, William R; Farag, Noha H; Vincent, Andrea S; Thomas, Terrie L; Wilson, Michael F

2006-03-01

Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (psrelease in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

International Nuclear Information System (INIS)

Hatano, Yu; Nakahama, Ken-ichi; Isobe, Mitsuaki; Morita, Ikuo

2014-01-01

Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These

Clinical applications of cortisol measurements in hair.

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Wester, Vincent L; van Rossum, Elisabeth F C

2015-10-01

Cortisol measurements in blood, saliva and urine are frequently used to examine the hypothalamus-pituitary-adrenal (HPA) axis in clinical practice and in research. However, cortisol levels are subject to variations due to acute stress, the diurnal rhythm and pulsatile secretion. Cortisol measurements in body fluids are not always a reflection of long-term cortisol exposure. The analysis of cortisol in scalp hair is a relatively novel method to measure cumulative cortisol exposure over months up to years. Over the past years, hair cortisol concentrations (HCC) have been examined in association with a large number of somatic and mental health conditions. HCC can be used to evaluate disturbances of the HPA axis, including Cushing's syndrome, and to evaluate hydrocortisone treatment. Using HCC, retrospective timelines of cortisol exposure can be created which can be of value in diagnosing cyclic hypercortisolism. HCC have also been shown to increase with psychological stressors, including major life events, as well as physical stressors, such as endurance exercise and shift work. Initial studies show that HCC may be increased in depression, but decreased in general anxiety disorder. In posttraumatic stress disorder, changes in HCC seem to be dependent on the type of traumatic experience and the time since traumatization. Increased hair cortisol is consistently linked to obesity, metabolic syndrome and cardiovascular disease. Potentially, HCC could form a future marker for cardiovascular risk stratification, as well as serve as a treatment target. © 2015 European Society of Endocrinology.

Poverty-alleviation program participation and salivary cortisol in very low-income children.

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Fernald, Lia C H; Gunnar, Megan R

2009-06-01

Correlational studies have shown associations between social class and salivary cortisol suggestive of a causal link between childhood poverty and activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a quasi-experimental design, we evaluated the associations between a family's participation in a large-scale, conditional cash transfer program in Mexico (Oportunidades, formerly Progresa) during the child's early years of life and children's salivary cortisol (baseline and responsivity). We also examined whether maternal depressive symptoms moderated the effect of program participation. Low-income households (income Mexico were enrolled in a large-scale poverty-alleviation program between 1998 and 1999. A comparison group of households from demographically similar communities was recruited in 2003. Following 3.5 years of participation in the Oportunidades program, three saliva samples were obtained from children aged 2-6 years from intervention and comparison households (n=1197). Maternal depressive symptoms were obtained using the Center for Epidemiologic Studies-Depression Scale (CES-D). Results were that children who had been in the Oportunidades program had lower salivary cortisol levels when compared with those who had not participated in the program, while controlling for a wide range of individual-, household- and community-level variables. Reactivity patterns of salivary cortisol did not differ between intervention and comparison children. Maternal depression moderated the association between Oportunidades program participation and baseline salivary cortisol in children. Specifically, there was a large and significant Oportunidades program effect of lowering cortisol in children of mothers with high depressive symptoms but not in children of mothers with low depressive symptomatology. These findings provide the strongest evidence to date that the economic circumstances of a family can influence a child's developing stress

Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

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Poorman, Caroline E; Postlewait, Lauren M; Ethun, Cecilia G; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Staley, Charles A; Poultsides, George A; Maithel, Shishir K

2017-07-01

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P 2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

Direct immune-detection of cortisol by chemiresistor graphene oxide sensor.

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Kim, Yo-Han; Lee, Kyungmin; Jung, Hunsang; Kang, Hee Kyung; Jo, Jihoon; Park, In-Kyu; Lee, Hyun Ho

2017-12-15

In this study, a biosensor to detect a stress biomarker of cortisol using cortisol monoclonal antibody (c-Mab) covalently immobilized on reduced graphene oxide (rGO) channel as electrical sensing element was demonstrated. Highly specific immune-recognition between the c-Mab and the cortisol was identified and characterized on a basis of resistance change at the rGO channel based chemiresistor sensor achieving the limit of detection of 10pg/mL (27.6 pM). In addition, cortisol concentrations of real human salivary sample and buffer solution of rat adrenal gland acute slices, which could secret the cortisol induced by adrenocorticotropic hormone (ACTH), were directly measured by the chemiresistor corresponding to the specific sensing of the cortisol. The rGO chemiresistor could selectively measure the cortisol levels in spite of diverse neuroendocrine's existence. The potential perspective of this study can be a protocol of new cortisol sensor development, which will be applicable to point-of-care testing (POCT) targeted for salivary cortisol, in vitro psychobiological study on cortisol induction, and implantable sensor chip in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Parent Cortisol and Family Relatedness Predict Anxious Behavior in Emerging Adults

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Johnson, Vanessa Kahen; Gans, Susan E.

2016-01-01

Emerging adult cortisol response during family interaction predicts change in EA anxious behavior during the transition to college (Gans & Johnson, in press). In the present study, we take an additional step toward integrating family systems research and physiology by including assessment of parent physiology. We collect salivary cortisol from parents and emerging-adults during triadic family interaction. Emerging adults (N = 101) between the ages of 17 and 19 were assessed at three time points across their first college year: the summer before college, fall and spring semesters. Two parents accompanied the emerging adult child to the summer assessment; all family members provided four saliva samples each at 20-minute intervals. Later assessments of emerging adults included measures of internalizing behaviors. Parents’ cortisol secretion patterns during family interaction predict their emerging adult child’s cortisol secretion pattern, parent perceptions of the family environment, and emerging adult children’s internalizing behavior during the college transition. Different patterns of results emerged for mothers’ and fathers’ cortisol response to family interaction, and for families with sons or with daughters. The approach taken by this study provides a first step toward understanding how interrelationships among elements of physiology and family functioning contribute to adjustment during major life transitions. PMID:27536860

Attenuation of cortisol across development for victims of sexual abuse.

Science.gov (United States)

Trickett, Penelope K; Noll, Jennie G; Susman, Elizabeth J; Shenk, Chad E; Putnam, Frank W

2010-01-01

Inconsistencies exist in literature examining hypothalamic-pituitary-adrenal (HPA) axis activity in children and adults who have experienced childhood abuse. Hence, the extent and manner to which childhood abuse may disrupt HPA axis development is largely unknown. To address these inconsistencies, the developmental course of nonstress cortisol in a long-term longitudinal study was assessed at six time points from childhood through adolescence and into young adulthood to determine whether childhood abuse results in disrupted cortisol activity. Nonstress, morning cortisol was measured in 84 females with confirmed familial sexual abuse and 89 nonabused, comparison females. Although dynamically controlling for co-occurring depression and anxiety, hierarchical linear modeling (HLM) showed that relative to comparison females, the linear trend for abused females was significantly less steep when cortisol was examined across development from age 6 to age 30, t (1, 180) = -2.55, p cortisol activity starting in adolescence with significantly lower levels of cortisol by early adulthood, F (1, 162) = 4.78, p cortisol activity was initially significantly higher, t (1, 425) = 2.18, p cortisol hyposecretion subsequent to a period of heightened secretion.

Genetics of Beckwith-Wiedemann syndrome-associated tumors: common genetic pathways

NARCIS (Netherlands)

Steenman, M.; Westerveld, A.; Mannens, M.

2000-01-01

A specific subset of solid childhood tumors-Wilms' tumor, adrenocortical carcinoma, rhabdomyosarcoma, and hepatoblastoma-is characterized by its association with Beckwith-Wiedemann syndrome. Genetic abnormalities found in these tumors affect the same chromosome region (11p15), which has been

Ectopic corticotroph syndrome

Directory of Open Access Journals (Sweden)

Penezić Zorana

2004-01-01

Full Text Available INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally

Cognitive control moderates parenting stress effects on children's diurnal cortisol

OpenAIRE

Raffington, Laurel; Schmiedek, Florian; Heim, Christine; Shing, Yee Lee

2018-01-01

This study investigated associations between parenting stress in parents and self-reported stress in children with children's diurnal cortisol secretion and whether these associations are moderated by known stress-regulating capacities, namely child cognitive control. Salivary cortisol concentrations were assessed from awakening to evening on two weekend days from 53 6-to-7-year-old children. Children completed a cognitive control task and a self-report stress questionnaire with an experiment...

Analysis of adrenocortical tumours morphology as regards their structure and potential malignancy

International Nuclear Information System (INIS)

Kajor, M.; Ciupinska-Kajor, M.; Dobrosz, Z.; Ziaja, J.; Krol, R.; Heitzman, M.; Cierpka, L.

2006-01-01

Introduction: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. Material and methods: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 ± 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. Results: In routine histopathological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4 - 9 features of malignancy were present, among ACA - 0 - 3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). Conclusion: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma. (author)

Cortisol plays central role in biochemical changes during pregnancy

African Journals Online (AJOL)

McRoy

Background: Pregnancy is known to alter the feedback effect of cortisol on ACTH secretion and .... ANOVA and LSD test, superscripts (*) depict significant differences between cases and controls, analyzed by ..... Influence of brain angiotensin ...

Putting a finger on the problem: Finger stick blood draw and immunization at the well-child exam elicit a cortisol response to stress among one-year-old children.

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Kertes, Darlene A; Kamin, Hayley S; Liu, Jingwen; Bhatt, Samarth S; Kelly, Maria

2018-07-01

Research examining stress reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis in young children has historically been hampered by a lack of reliable methods to invoke a cortisol stress response. This report details an effective method of eliciting a cortisol rise in one-year-old children (N = 83) by modifying and combining two naturalistic stressors previously used with infants and children. Salivary cortisol levels were collected from children before and after a finger stick blood draw and immunizations performed during their one year well-child checkup at their pediatrician's office. Results indicated that the stressor was successful at eliciting a significant cortisol response. An extensive set of potential demographic and clinical confounds were also assessed in order to identify methodological considerations important in studies of infant cortisol. The stress paradigm presented here provides a promising alternative for studies of infant HPA activity to enable investigators to more effectively evaluate early functioning of the biological stress system during this developmentally important life stage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of changes in functional status of hypothalamic-pituitary-adrenocortical axis in immunoenhancement after low dose radiation

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Liu Shuzheng; Zhao Yong; Han Zhenbo

1994-01-01

Whole-body irradiation (WBI) of mice with 75 mGy X-rays caused increase in 5-hydroxytryptamine (5HT) content of hypothalamus and decrease in serum adrenocorticotropic hormone (ACTH) and corticosterone (CS) level, accompanied with potentiation of immune functions, expressed as increased spontaneous incorporation of 3 H-TdR into thymocytes, augmented proliferative reaction of the splenocytes to Con A and increased production of interleukin-2 by the splenocytes. After intra hypothalamic injection of 5HT there occurred a lowering of serum ACTH level and enhancement of immune reactivity of the splenic and thymic lymphocytes. It is assumed that low dose radiation could influence the central 5-hydroxytryptaminergic neurons causing increase in hypothalamic 5HT content and this, in turn, decreases pituitary secretion of ACTH with a down-regulation of the adrenocortical function. This would partially release the tonic suppression normally exerted on the immune organs by the hypothalamic-pituitary-adrenocortical axis, thus leading to potentiation of immune functions. These neuroendocrine changes should be considered as an important factor in the analysis of the mechanism of immunoenhancement after WBI with low doses

Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

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Kuehl, Linn K; Hinkelmann, Kim; Muhtz, Christoph; Dettenborn, Lucia; Wingenfeld, Katja; Spitzer, Carsten; Kirschbaum, Clemens; Wiedemann, Klaus; Otte, Christian

2015-01-01

Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, pcortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oncocytic adrenocortical neoplasms--a clinicopathologic study of 13 new cases emphasizing the importance of their recognition.

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Wong, Daniel D; Spagnolo, Dominic V; Bisceglia, Michele; Havlat, Marek; McCallum, Dugald; Platten, Michael A

2011-04-01

Oncocytic adrenocortical neoplasms (OANs) are a rare but important subtype of adrenal tumors with unique clinical and morphological features. We present 13 previously unpublished cases, of which 3 were classified as benign, 2 as having borderline malignant potential, and 8 as malignant according to the Lin-Weiss-Bisceglia criteria. Seven tumors (54%) showed evidence of endocrine activity. All were composed of more than 90% oncocytes confirmed immunohistochemically using the antimitochondrial antibody mES-13 and ultrastructurally in 4 cases. Small oncocytes were a frequent finding that challenges the conventional notion of oncocytes as necessarily having abundant cytoplasm. Most cases were immunoreactive for vimentin, synaptophysin, inhibin-α, melan A, and calretinin, the latter being a novel finding in this group of neoplasms. Cytokeratin positivity with AE1/AE3 and CAM5.2 was variable. The literature was comprehensively reviewed to identify all cases of OANs reported to date. Hormone production is not as uncommon as previously believed, occurring in 30%. The Lin-Weiss-Bisceglia criteria were retrospectively applied to all published cases with sufficient information and were shown to effectively separate tumors according to their future risk of recurrence and survival using Kaplan-Meier survival curves (log-rank test, P interval = 27.5-88.5 months), providing the first preliminary evidence that the prognosis of malignant OANs is likely to be more favorable than conventional adrenocortical carcinomas, in which the reported median survival is between 14 and 32 months. Copyright © 2011 Elsevier Inc. All rights reserved.

Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

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Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-05-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

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Figueiredo B.C.

2000-01-01

Full Text Available Adrenocortical tumors (ACT in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72. Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.

The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood.

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Inga Schalinski

Full Text Available Inconsistent findings exist for the activity of the hypothalamic-pituitary-adrenal (HPA axis in patients with stress related disorders. Recent studies point towards early life stress as a potential modulator.We investigated the impact of childhood sexual abuse on phasic (saliva cortisol reactivity and tonic (hair cortisol regulation. Furthermore, we assessed predictors on cortisol accumulation in hair. Women (N = 43 with stress-related disorders underwent a standardized assessment of idiographic adverse and traumatic experiences and psychopathology, while measuring salivary cortisol and, heart rate and blood pressure.Comparing women with and without childhood sexual abuse revealed lower rates of responders and distinct levels of salivary cortisol to the interview in conjunction with a lower heart rate for the abused group. Childhood adversities, traumatic experiences, and depression contributed to higher hair cortisol levels.Our finding of lower response rate and distinct salivary cortisol pattern in individuals with childhood sexual abuse compared to individuals without early sexual abuse supports the role of environmental programming for the HPA axis. Both, childhood adversities and traumatic stress emerge as crucial factors for long-term cortisol secretion. Lower or suppressed phasic cortisol responses to trauma-related stimuli may therefore be associated with higher tonic values. Thus, early exposure to adversities may result in a biological distinct phenotype in adult patients with stress-related disorders.

The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood.

Science.gov (United States)

Schalinski, Inga; Elbert, Thomas; Steudte-Schmiedgen, Susann; Kirschbaum, Clemens

2015-01-01

Inconsistent findings exist for the activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with stress related disorders. Recent studies point towards early life stress as a potential modulator. We investigated the impact of childhood sexual abuse on phasic (saliva cortisol reactivity) and tonic (hair cortisol) regulation. Furthermore, we assessed predictors on cortisol accumulation in hair. Women (N = 43) with stress-related disorders underwent a standardized assessment of idiographic adverse and traumatic experiences and psychopathology, while measuring salivary cortisol and, heart rate and blood pressure. Comparing women with and without childhood sexual abuse revealed lower rates of responders and distinct levels of salivary cortisol to the interview in conjunction with a lower heart rate for the abused group. Childhood adversities, traumatic experiences, and depression contributed to higher hair cortisol levels. Our finding of lower response rate and distinct salivary cortisol pattern in individuals with childhood sexual abuse compared to individuals without early sexual abuse supports the role of environmental programming for the HPA axis. Both, childhood adversities and traumatic stress emerge as crucial factors for long-term cortisol secretion. Lower or suppressed phasic cortisol responses to trauma-related stimuli may therefore be associated with higher tonic values. Thus, early exposure to adversities may result in a biological distinct phenotype in adult patients with stress-related disorders.

Children's diurnal cortisol responses to negative events at school and home.

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Bai, Sunhye; Robles, Theodore F; Reynolds, Bridget M; Repetti, Rena L

2017-09-01

This study examined the within-and between-person associations between daily negative events - peer problems, academic problems and interparental conflict - and diurnal cortisol in school-age children. Salivary cortisol levels were assessed four times per day (at wakeup, 30min later, just before dinner and at bedtime) on eight days in 47 youths ages 8-13 years old (60% female; M age=11.28, SD=1.50). The relative contributions of within- and between-person variances in each stressor were estimated in models predicting same-day diurnal cortisol slope, same-day bedtime cortisol, and next morning wakeup cortisol. Children who reported more peer problems on average showed flatter slopes of cortisol decline from wakeup to bedtime. However, children secreted more cortisol at wakeup following days when they had reported more peer or academic problems than usual. Interparental conflict was not significantly associated with diurnal cortisol. Findings from this study extend our understanding of short-term cortisol responses to naturally occurring problems in daily life, and help to differentiate these daily processes from the cumulative effects of chronic stress. Copyright © 2017. Published by Elsevier Ltd.

Salivary cortisol assessment in the evaluation of hypothalamic-pituitary-adrenal function

International Nuclear Information System (INIS)

Kahn, S.E.; Maxwell, J.U.; Barron, J.L.

1984-01-01

A simple, short and sensitive direct radio-immunoassay technique for the determination of salivary cortisol concentration was employed to assess saliva as a medium for evaluating cortisol response during endocrine testing in 9 controls and 40 patients. Results in controls suggested that an adequate salivary cortisol response to insulin hypoglycaemia was an increase of 150% above the basal value with a minimum peak of 15 nmol/l. Thirty-three patients were classified as being either good or poor responders to insulin hypoglycaemia on the basis of criteria for plasma cortisol levels. When the defined salivary cortisol response was used for assessment, all 33 patients were correctly categorized into the same response groups. The salivary cortisol response to intramuscular tetracosactin in 3 patients and an intravenous dexamethasone infusion in 4 patients confirmed the value of saliva as an assay medium. These studies show that the salivary cortisol response parallels that of total plasma cortisol in all cases. However, with sampling at short intervals a lag in secretion of the free fraction from the plasma into the saliva becomes apparent. The relative change in cortisol levels from the basal value is greater in saliva than in plasma

Does cortisol moderate the environmental association between peer victimization and depression symptoms? A genetically informed twin study.

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Brendgen, Mara; Ouellet-Morin, Isabelle; Lupien, Sonia; Vitaro, Frank; Dionne, Ginette; Boivin, Michel

2017-10-01

Many youths who are victimized by peers suffer from depression symptoms. However, not all bullying victims show depression symptoms and individuals' biological sensitivity may play an important moderating role in this regard. In line with this notion, peer victimization has been associated with increased depressive symptoms in youth with higher basal cortisol secretion. It is unclear, however, whether this moderating effect of cortisol really concerns the environmental effect of peer victimization on depression. Indeed, genetic factors can also influence individuals' environmental experiences, including peer victimization, and part of these genetic factors may be those associated with depression. Using a genetically informed design based on 159 monozygotic and 120 dizygotic twin pairs (52% girls) assessed at age 14 years, this study examined whether cortisol secretion moderates the environmental or the genetic association between peer victimization and depression symptoms. Salivary cortisol at awakening was obtained with buccal swabs during four school week days. Peer victimization and depression were assessed via self-reports. Cholesky modeling revealed that peer victimization was associated with depression symptoms via both genetic and environmental pathways. Moreover, the environmental association between peer victimization and depression symptoms steadily increased with increasing levels of morning cortisol. The genetic association between peer victimization and depression symptoms also varied, albeit less, as a function of individuals' cortisol secretion. These findings support the hypothesis that peer victimization increases internalizing psychopathology mainly in youth with heightened biological reactivity to environmental conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro quantitative analysis of Salmonella typhimurium preference for amino acids secreted by human breast tumor

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Choi, Eunpyo; Maeng, Bohee; Lee, Jae-hun; Chang, Hyung-kwan; Park, Jungyul

2016-12-01

Bacterial therapies have been paid significant attentions by their ability to penetrate deep into the solid tumor tissue and its propensity to naturally accumulate in tumors of living animals. Understanding the actual mechanism for bacteria to target the tumor is therapeutically crucial but is poorly understood. We hypothesized that amino acids released from the specific tumors induced bacteria to those tumors and the experiments for chemotactic response of bacteria toward the cancer secreting amino acids was then performed by using the diffusion based multiple chemical gradient generator constructed by in situ self-assembly of microspheres. The quantitative analysis was carried out by comparison of intensity using green fluorescent protein (GFP) tagged Salmonella typhimurium ( S. typhimurium) in the gradient generator, which showed the clear preference to the released amino acids, especially from breast cancer patients. The understanding chemotaxis toward the cancer secreting amino acids is essential for controlling S. typhimurium targeting in tumors and will allow for the development of bacterial therapies.

Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGFβ1-induced macrophages

International Nuclear Information System (INIS)

Machado, Camila Maria Longo; Andrade, Luciana Nogueira Sousa; Teixeira, Verônica Rodrigues; Costa, Fabrício Falconi; Melo, Camila Morais; Santos, Sofia Nascimento dos; Nonogaki, Suely; Liu, Fu-Tong; Bernardes, Emerson Soares; Camargo, Anamaria Aranha; Chammas, Roger

2014-01-01

In order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGFβ1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68 + -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68 + cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGFβ1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGFβ1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGFβ1, increased Arginase I protein levels and galectin-3 expression in WT- BMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGFβ1 signaling pathways

A Longitudinal Study of the Effects of Child-Reported Maternal Warmth on Cortisol Stress Response 15 Years After Parental Divorce.

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Luecken, Linda J; Hagan, Melissa J; Wolchik, Sharlene A; Sandler, Irwin N; Tein, Jenn-Yun

2016-01-01

The experience of parental divorce during childhood is associated with an increased risk of behavioral and physical health problems. Alterations in adrenocortical activity may be a mechanism in this relation. Parent-child relationships have been linked to cortisol regulation in children exposed to adversity, but prospective research is lacking. We examined maternal warmth in adolescence as a predictor of young adults' cortisol stress response 15 years after parental divorce. Participants included 240 youth from recently divorced families. Mother and child reports of maternal warmth were assessed at 6 time points across childhood, adolescence, and young adulthood. Offspring salivary cortisol was measured in young adulthood before and after a social stress task. Structural equation modeling was used to predict cortisol response from maternal warmth across early and late adolescence. Higher child-reported maternal warmth in early adolescence predicted higher child-reported maternal warmth in late adolescence (standardized regression = 0.45, standard error = 0.065, p < .01), which predicted lower cortisol response to a challenging interpersonal task in young adulthood (standardized regression = -0.20, standard error = 0.094, p = .031). Neither mother-reported warmth in early adolescence nor late adolescence was significantly related to offspring cortisol response in young adulthood. Results suggest that for children from divorced families, a warm mother-child relationship after divorce and across development, as perceived by the child, may promote efficient biological regulation later in life. ClinicalTrials.gov Identifier: NCT01407120.

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

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Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

School start time influences melatonin and cortisol levels in children and adolescents - a community-based study.

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Carissimi, Alicia; Martins, Alessandra Castro; Dresch, Fabiane; da Silva, Lilian Corrêa; Zeni, Cristian Patrick; Hidalgo, Maria Paz

2016-01-01

School start time influences sleep parameters. Differences between circadian sleep parameters on weekends and weekdays have been associated with obesity, sleep, and psychiatric disorders. Moreover, circadian rhythm dysregulation affects the secretion of some hormones, such as melatonin and cortisol. In the current study, we investigate the effect of school start time on cortisol and melatonin levels in a community sample of Brazilian children and adolescents. This was a cross-sectional study of 454 students (mean age, 12.81 ± 2.56 years; 58.6% female). From this sample, 80 participants were randomly selected for saliva collection to measure melatonin and cortisol levels. Circadian sleep parameters were assessed by self-reported sleep and wake up schedules and the Morningness-Eveningness Questionnaire. The outcomes, salivary melatonin and cortisol levels, were measured in morning, afternoon and night saliva samples, and behavior problems were assessed using the Child Behavior Checklist (CBCL). The main results revealed that morning school start time decreased the secretion of melatonin. Morning melatonin levels were significantly positively correlated with the sleep midpoint on weekdays and on weekends. Afternoon melatonin levels were positively correlated with the sleep midpoint on weekends in the morning school students. Conversely, in the afternoon school students, night melatonin levels were negatively correlated with the sleep midpoint on weekdays. Cortisol secretion did not correlate with circadian sleep parameters in any of the school time groups. In conclusion, school start time influences melatonin secretion, which correlated with circadian sleep parameters. This correlation depends on the presence of psychiatric symptoms. Our findings emphasize the importance of drawing attention to the influence of school start time on the circadian rhythm of children and adolescents.

Hair cortisol concentrations and cortisol stress reactivity predict PTSD symptom increase after trauma exposure during military deployment.

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Steudte-Schmiedgen, Susann; Stalder, Tobias; Schönfeld, Sabine; Wittchen, Hans-Ulrich; Trautmann, Sebastian; Alexander, Nina; Miller, Robert; Kirschbaum, Clemens

2015-09-01

Previous evidence on endocrine risk markers for posttraumatic stress disorder (PTSD) has been inconclusive. Here, we report results of the first prospective study to investigate whether long-term hair cortisol levels and experimentally-induced cortisol stress reactivity are predictive of the development of PTSD symptomatology in response to trauma during military deployment. Male soldiers were examined before deployment to Afghanistan and at a 12-month post-deployment follow-up using dimensional measures for psychopathological symptoms. The predictive value of baseline (i) hair cortisol concentrations (HCC, N=90) and (ii) salivary cortisol stress reactivity (measured by the Trier Social Stress Test, N=80) for the development of PTSD symptomatology after being exposed to new-onset traumatic events was analyzed. Baseline cortisol activity significantly predicted PTSD symptom change from baseline to follow-up upon trauma exposure. Specifically, our results consistently revealed that lower HCC and lower cortisol stress reactivity were predictive of a greater increase in PTSD symptomatology in soldiers who had experienced new-onset traumatic events (explaining 5% and 10.3% of variance, respectively). Longitudinal analyses revealed an increase in HCC from baseline to follow-up and a trend for a negative relationship between HCC changes and the number of new-onset traumatic events. Additional pre-deployment analyses revealed that trauma history was reflected in lower HCC (at trend level) and that HCC were negatively related to stressful load. Our data indicate that attenuated cortisol secretion is a risk marker for subsequent development of PTSD symptomatology upon trauma exposure. Future studies are needed to confirm our findings in other samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gamma camera imaging of bilateral adrenocartical hyperplasia and adrenal tumors in the dog

International Nuclear Information System (INIS)

Mulnix, J.A.; Van den Brom, W.E.; Lubberink, A.A.; de Bruijne, J.J.; Rijnberk, A.

1976-01-01

Gamma camera imaging of the adrenal glands was done in 8 dogs with hyperadrenocorticism and 4 normal dogs given intravenous injections of 131I-19-iodocholesterol. In normal dogs, both adrenal glands could be visualized separately, and there was no difficulty in distinguishing among the images of normal glands, hyperplastic glands, and functional adrenal tumors. In addition, gamma camera imaging enabled the correct surgical site to be selected for removal of adrenal tumors. Hyperadrenocorticism was diagnosed in 8 dogs by evaluation of urinary 17-hydroxycorticosteroid (OHCS) excretion rates, urinary 17-OHCS and plasma 11 beta-OHCS responses to dexamethasone suppression of endogenous adrenocorticotropin (ACTH) secretion, and plasma 11 beta-OHCS response to intravenous administration of ACTH. Base line 17-OHCS excretion increased in 5 of the 8 dogs. Plasma 11 beta-OHCS concentrations were not decreased by dexamethasone administration in the 4 dogs subsequently found to have adrenal tumors; however, there was an exaggerated increase in plasma 11 beta-OHCS concentration after administration of ACTH in 3 of the 4 dogs which had bilateral adrenocortical hyperplasia

Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas

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Eu Jeong Ku

2013-06-01

Full Text Available A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.

Gamma knife radiosurgery for secreting pituitary tumors

International Nuclear Information System (INIS)

Noren, G.; Jackson, I.M.D.; Chougule, P.; Zheng, Z.; Epstein, M.H.

1998-01-01

Transsphenoidal surgery usually represents first line treatment for pituitary adenomas with the aim of removing the tumor, decompressing the optic apparatus and, in secreting tumors, eliminating the hypersecretion. Gamma Knife radiosurgery is indicated for tumor remnants or recurrences in or above the sella including those invading the cavernous sinus and also as initial treatment in patients who are unable to tolerate an open surgical procedure and where medication has failed. In this study, the target definition was retrospectively studied and when necessary corrected in 10 acromegalic patients, 8 with Cushing's disease, and 12 with prolactinomas undergoing Gamma Knife radiosurgery. The dose plan was analyzed and the volume of the target covered by a minimum of 15, 20, 25, 30 and 35 Gy was estimated. A dose/volume profile for each treatment was created and correlated to the endocrinological and clinical outcome. Cure, according to strict endocrinological criteria, was seen in 6 of the acromegalic patients, in 2 of the patients with ACTH hypersecretion, and in 2 of the patients with prolactinomas. Analysis of these profiles, also for the patients with partial effect, show that a minimum radiation dose of 20 Gy may be adequate to eliminate the hypersecretion in acromegalic patients whereas a dose of at least 25 Gy may be required in patients with Cushing's disease and prolactinoma. (author)

Associations of long-term shift work with waking salivary cortisol concentration and patterns among police officers.

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Fekedulegn, Desta; Burchfiel, Cecil M; Violanti, John M; Hartley, Tara A; Charles, Luenda E; Andrew, Michael E; Miller, Diane B

2012-01-01

The objective of this study was to evaluate whether long-term shift work is associated with both the total hormonal secretion after awakening and the pattern of the cortisol levels during the first hour following awakening, among 65 randomly selected police officers who represent a high stress occupation. Dominant shift (Day, Afternoon, or Midnight) was ascertained using daily payroll records of each participant's work activities during the 6-8 yrs prior to saliva sampling. Four salivary samples were collected at 15 min intervals upon first awakening. After accounting for potential confounders, salivary cortisol concentrations averaged across all four time points and total area under the curve differed significantly across shift with midnight shift workers showing suppressed awakening cortisol response relative to the afternoon and day shift. The percent of hours worked on midnight shift was inversely correlated with total awakening cortisol output. In contrast, the pattern of cortisol secretion during the first hour following waking appeared not to be affected as no significant interaction effect was found between time since awakening and shift work. The results show that long-term midnight shift work is associated with decreased absolute mean level and total volume of cortisol released over the waking period.

Associations of Long-term Shift Work with Waking Salivary Cortisol Concentration and Patterns among Police Officers

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FEKEDULEGN, Desta; BURCHFIEL, Cecil M.; VIOLANTI, John M.; HARTLEY, Tara A.; CHARLES, Luenda E.; ANDREW, Michael E.; MILLER, Diane B.

2015-01-01

The objective of this study was to evaluate whether long-term shift work is associated with both the total hormonal secretion after awakening and the pattern of the cortisol levels during the first hour following awakening, among 65 randomly selected police officers who represent a high stress occupation. Dominant shift (Day, Afternoon, or Midnight) was ascertained using daily payroll records of each participant’s work activities during the 6–8 yrs prior to saliva sampling. Four salivary samples were collected at 15 min intervals upon first awakening. After accounting for potential confounders, salivary cortisol concentrations averaged across all four time points and total area under the curve differed significantly across shift with midnight shift workers showing suppressed awakening cortisol response relative to the afternoon and day shift. The percent of hours worked on midnight shift was inversely correlated with total awakening cortisol output. In contrast, the pattern of cortisol secretion during the first hour following waking appeared not to be affected as no significant interaction effect was found between time since awakening and shift work. The results show that long-term midnight shift work is associated with decreased absolute mean level and total volume of cortisol released over the waking period. PMID:23047078

Isolation of rat adrenocortical mitochondria

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Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

2012-10-12

Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

Differences in cortisol profiles and circadian adjustment time between nurses working night shifts and regular day shifts: A prospective longitudinal study.

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Niu, Shu-Fen; Chung, Min-Huey; Chu, Hsin; Tsai, Jui-Chen; Lin, Chun-Chieh; Liao, Yuan-Mei; Ou, Keng-Liang; O'Brien, Anthony Paul; Chou, Kuei-Ru

2015-07-01

This study explored the differences in the circadian salivary cortisol profiles between nurses working night shifts and regular day shifts following a slow rotating shift schedule to assess the number of days required for adjusting the circadian rhythm of salivary cortisol levels in nurses working consecutive night shifts and the number of days off required to restore the diurnal circadian rhythm of salivary cortisol levels. This was a prospective, longitudinal, parallel-group comparative study. The participants were randomly assigned to night and day-shift groups, and saliva samples were collected to measure their cortisol levels and circadian secretion patterns. Significant differences were observed in the overall salivary cortisol pattern parameters (cortisol awakening response, changes in cortisol profiles between 6 and 12h after awakening, and changes in cortisol profiles between 30 min and 12 h after awakening) from Days 2 to 4 of the workdays between both groups. However, on Day 2 of the days off, both groups exhibited similar cortisol profiles and the cortisol profiles in the night-shift group were restored. Nurses working night shifts require at least 4 days to adjust their circadian rhythms of cortisol secretions. Moreover, on changing from night shift to other shifts, nurses must be allowed more than 2 days off work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of acupuncture on adrenocortical hormone production in rabbits with a central lesion

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Liao, Y.Y.; Seto, K.; Saitoh, H.; Kawakami, M.

A study was made of adrenocortical hormone production under electroacupuncture stimulation of the Tsu-San-Li locus in rabbits with a lesion in the fornix, stria terminalis, ventromedial nucleus or arcuate nucleus. In rabbits with a lesion in the stria terminalis or ventromedial nucleus, electroacupuncture stimulation of Tsu-San-Li resulted in no increase in phase 1 but an increase in phase 2 of adrenocortical hormone production. In rabbits with a lesion in the fornix or arcuate nucleus electroacupuncture stimulation of Tsu-San-Li was followed by increased adrenocortical hormone production in the both phases. These results show that the stria terminalis and the ventromedial nucleus play a major role in the augmentation of adrenocortical hormone production by electroacupuncture stimulation of Tsu-San-Li.

Medición de cortisol y sus fracciones: Una puesta al día

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Patricia Maidana

2013-12-01

Full Text Available La determinación del cortisol sérico total forma parte fundamental de la exploración bioquímica de la función adrenocortical. Dado que esta hormona circula en plasma, en parte unida a proteínas de transporte y en parte en estado libre, existe la posibilidad de realizar la determinación de sus diferentes fracciones no solo en sangre sino también en orina, saliva y otros fluidos biológicos. Es posible realizar tanto determinaciones basales como pruebas funcionales y de esta manera evaluar la secreción de cortisol en un momento dado del día, estudiar su variación circadiana y analizar su relación con el resto de los componentes del eje hipotálamo-hipófiso-adrenal. Las mediciones habituales de cortisol en sangre, saliva y orina reflejan los niveles de esta hormona en el momento de la recolección o durante un período de 24 horas. Recientemente han aparecido trabajos en los cuales se propone la determinación de cortisol en cabello y uñas como potenciales marcadores del estatus hormonal en períodos más prolongados. El objetivo de esta revisión es realizar una puesta al día acerca de la metodología disponible actualmente en nuestro medio para la evaluación del eje adrenal, haciendo hincapié en su aplicación para el diagnóstico clínico.

Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-KV Transmission Line

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Lee, Jack Monroe, Jr.

There is ongoing controversy about the possibility of adverse biological effects from environmental exposures to electric and magnetic fields. These fields are produced by all electrical equipment and appliances including electrical transmission lines. The objective of this environmental science study was to investigate the possible effects of a high voltage transmission line on domestic sheep (Ovis aries L.), a species that can often be found near such lines. The study was primarily designed to determine whether a specific effect of electric and magnetic fields found in laboratory animals also occurs in livestock under natural environmental conditions. The effect is the ability of fields, at levels found in the environment, to significantly depress the normally high nocturnal concentrations of the pineal hormone-melatonin. Ten female Suffolk lambs were penned for 10 months directly beneath a 500-kV transmission line near Estacada, Oregon. Ten other lambs of the same type were penned in a control area away from the transmission line where electric and magnetic fields were at ambient levels. Serum melatonin was analyzed by radioimmunoassay (RIA) from 6618 blood samples collected at 0.5 to 3-hour intervals over eight 48-hour periods. Serum progesterone was analyzed by RIA from blood samples collected twice weekly. Serum cortisol was also assayed by RIA from the blood samples collected during the 48-hour samples. Results showed that lambs in both the control and line groups had the typical pattern of melatonin secretion consisting of low daytime and high nighttime serum concentrations. There were no statistically significant differences between groups in melatonin levels, or in the phase or duration of the nighttime melatonin elevation. Age at puberty and number of reproductive cycles also did not differ between groups. Serum cortisol showed a circadian rhythm with highest concentrations during the day. There were, however, no differences in cortisol concentrations

The activity of 11β-hydroxysteroid dehydrogenase type 2 enzyme and cortisol secretion in patients with adrenal incidentalomas.

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Morelli, Valentina; Polledri, Elisa; Mercadante, Rosa; Zhukouskaya, Volha; Palmieri, Serena; Beck-Peccoz, Paolo; Spada, Anna; Fustinoni, Silvia; Chiodini, Iacopo

2016-09-01

In adrenal incidentaloma (AI) patients, beside the cortisol secretion, a different 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) activity, measurable by 24-h urinary cortisol/cortisone ratio (R-UFF/UFE) (the higher R-UFF/UFE the lower HSD11B2 activity), could influence the occurrence of the subclinical hypercortisolism (SH)-related complications (hypertension, type 2 diabetes, obesity). We evaluated whether in AI patients, UFF levels are associated to UFE levels, and the HSD11B2 activity to the complications presence. In 156 AI patients (93F, age 65.2 ± 9.5 years), the following were measured: serum cortisol after 1 mg-dexamethasone test (1 mg-DST), ACTH, UFF, UFE levels, and R-UFF/UFE (by liquid chromatography-tandem mass spectrometry), the latter was also evaluated in 63 matched-controls. We diagnosed SH (n = 22) in the presence of ≥2 among ACTH levels, and 1 mg-DST >83 nmol/L. Patients showed higher UFF levels and R-UFF/UFE than controls (75.9 ± 43.1 vs 54.4 ± 22.9 nmol/24 h and 0.26 ± 0.12 vs 0.20 ± 0.07, p levels (291 ± 91.1 vs 268 ± 61.5, p = 0.069). The R-UFF/UFE was higher in patients with high (h-UFF, n = 28, 0.41 ± 0.20) than in those with normal (n-UFF, 0.22 ± 0.10, p levels and in patients with SH than in those without SH (0.30 ± 0.12 vs 0.25 ± 0.12, p = 0.04). UFF levels were associated with R-UFF/UFE (r = 0.849, p levels in n-UFF patients but not in h-UFF patients, and it is not associated with the SH complications.

Overweight and obese children have lower cortisol levels than normal weight children.

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Kjölhede, E Allansson; Gustafsson, P E; Gustafsson, P A; Nelson, N

2014-03-01

The stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex. Salivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6-12 years using Salivette(®) tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the children's height and weight, and these measurements were used to calculate their BMI. The children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex. Our findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

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Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

2014-08-01

The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

Sexual orientation and diurnal cortisol patterns in a cohort of U.S. young adults.

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Austin, S Bryn; Rosario, Margaret; McLaughlin, Katie A; Roberts, Andrea L; Gordon, Allegra R; Sarda, Vishnudas; Missmer, Stacey; Anatale-Tardiff, Laura; Scherer, Emily A

2016-07-01

Sexual minorities in the United States are at elevated risk of bullying, discrimination, and violence victimization, all stressors that have been linked to psychological and behavioral stress responses including depressive and anxious symptoms and substance use. Acute and chronic stressors may also elicit physiologic stress responses, including changes in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Few studies, however, have examined the relationship between minority sexual orientation and diurnal cortisol patterns. The present study included 1670 young adults ages 18-32 years (69% female, 31% male) from the Growing Up Today Study, a prospective cohort of U.S. youth. Participants provided five saliva samples over one day to estimate diurnal cortisol patterns. Sexual orientation groups included: completely heterosexual with no same-sex partners (referent), completely heterosexual with same-sex partners/mostly heterosexual, and gay/lesbian/bisexual. Covariates included perceived stress and stressful life events in the past month. Sex-stratified multilevel models of log-transformed cortisol values were used to model diurnal cortisol patterns, and generalized estimating equations were used to model area under the curve (AUC), both with respect to ground (AUCg) and increase (AUCi). Among females, sexual minorities reported significantly more stressful life events in the past month than their heterosexual counterparts. In adjusted multilevel models, sexual orientation was not significantly associated with diurnal cortisol patterns or with AUCg or AUCi in either females or males. There were no significant interactions between sexual orientation and stressful life events. Time-varying negative mood was significantly associated with higher cortisol levels across the day for both female and male participants, after adjusting for all covariates. This study from a large cohort of U.S. young adults did not detect a relationship between sexual

CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.

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Cristina L Ronchi

Full Text Available Adrenocortical tumors comprise frequent adenomas (ACA and rare carcinomas (ACC. Human cytochrome P450 2W1 (CYP2W1 is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC.CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples.CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues. Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1 in 72% of non-adrenal normal tissues, but high (H-score 2-3 in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues, being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively, and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01 or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01.CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.

Stress-related cortisol response and laboratory eating behavior in obese women.

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Lorig, Fabian; Kießl, Gundula Rebecca Raphaela; Laessle, Reinhold Gustav

2016-06-01

Stress-related cortisol secretion has been linked to increased appetite and subsequent food intake in overweight individuals. The present study addresses this relationship in a repeated-measures randomized controlled laboratory experiment. Nineteen obese women were compared to 36 normal weight controls with respect to stress-induced salivary cortisol and laboratory eating behavior, measured by a universal eating monitor. The trier social stress test served as stressor. Stress-induced cortisol levels were significantly higher in the obese compared to the normal weight controls. Unexpectedly, a corresponding increase in laboratory food intake was not detected. The results are interpreted and discussed with regard to restrained eating, which was found to be present to a significant degree in the obese women.

Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

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Bush, Nicole R; Obradović, Jelena; Adler, Nancy; Boyce, W Thomas

2011-11-01

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

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Jones Janette JL

2009-03-01

Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

Clinical significance of the changes of plasma cortisol levels in patients with acute cerebral hemorrhage

International Nuclear Information System (INIS)

Wu Zhiqiang

2005-01-01

Objective: To explore the changes of plasma cortisol levels in patients with acute cerebral hemorrhage. Methods: Plasma cortisol levels were measured with RIA at 24:00 and 8:00 right after admission in 68 patients with acute cerebral hemorrhage and the tests were repeated in 61 patients one week later 40 controls entered this study. Results: The plasma cortisol levels were significantly higher in the patients than the corresponding readings in controls (P<0.001) with obliteration of the normal diurnal rhythm of secretion. The increase of the cortisol levels was positively correlated with the severity of the disease. As the condition of the patients improved, the cortisol levels dropped gradually. Conclusion: The plasma cortisol levels in patients with acute cerebral hemorrhage were closely related to the severity of the disease and were of prognostic value. (authors)

Marked cortisol production by intracrine ACTH in GIP-treated cultured adrenal cells in which the GIP receptor was exogenously introduced.

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Hiroko Fujii

Full Text Available The ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR in the human adrenal gland causes significant hypercortisolemia after ingestion of each meal and leads to Cushing's syndrome, implying that human GIPR activation is capable of robustly activating adrenal glucocorticoid secretion. In this study, we transiently transfected the human GIPR expression vector into cultured human adrenocortical carcinoma cells (H295R and treated them with GIP to examine the direct link between GIPR activation and steroidogenesis. Using quantitative RT-PCR assay, we examined gene expression of steroidogenic related proteins, and carried out immunofluorescence analysis to prove that forced GIPR overexpression directly promotes production of steroidogenic enzymes CYP17A1 and CYP21A2 at the single cell level. Immunofluorescence showed that the transfection efficiency of the GIPR gene in H295R cells was approximately 5%, and GIP stimulation enhanced CYP21A2 and CYP17A1 expression in GIPR-introduced H295R cells (H295R-GIPR. Interestingly, these steroidogenic enzymes were also expressed in the GIPR (- cells adjacent to the GIPR (+ cells. The mRNA levels of a cholesterol transport protein required for all steroidogenesis, StAR, and steroidogenic enzymes, HSD3β2, CYP11A1, CYP21A2, and CYP17A1 increased 1.2-2.1-fold in GIP-stimulated H295R-GIPR cells. These changes were reflected in the culture medium in which 1.5-fold increase in the cortisol concentration was confirmed. Furthermore, the levels of adenocorticotropic hormone (ACTH receptor and ACTH precursor proopiomelanocortin (POMC mRNA were upregulated 2- and 1.5-fold, respectively. Immunofluorescence showed that ACTH expression was detected in GIP-stimulated H295R-GIPR cells. An ACTH-receptor antagonist significantly inhibited steroidogenic gene expression and cortisol production. Immunostaining for both CYP17A1 and CYP21A2 was attenuated in cells treated with ACTH receptor antagonists

Primary pigmented nodular adrenocortical disease

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Marie T Manipadam

2011-01-01

Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of ACTH-independent Cushing′s syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney′s complex. Bilateral adrenalectomy is the treatment of choice.

Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis

International Nuclear Information System (INIS)

Li, L.-A.; Lin, Tsu-Chun Emma

2007-01-01

Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10 -5 M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10 -7 M and CYP11B2 at 10 -9 M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis

Feminizing adrenal tumors: Our experience about three cases

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Chentli Farida

2013-01-01

Full Text Available Feminizing adrenal tumors (FATs are very rare as they account for less than 2% of all the adrenal neoplasms. Their prognosis is deemed to be very poor. We aimed to present a mono centre (adult and pediatric experience over a long period of time (January 1980 to Jun 2012. During the study period, we observed only three cases in men aged 22 (2 cases and 45 (1 case. They all consulted for a painful gynecomastia, decreased libido and impotency. Estradiol was high in two cases at presentation, and after a relapsing tumor in the third one. All had big adrenal tumors (5.9, 6, and 17 cm, and a mixed secretion composed by high estradiol and cortisol. The pathological study argued for malignancy in two cases. But, only one had diffuse metastasis and died 4 years after diagnosis; the others diagnosed one and three years ago are still alive without any metastasis or relapsing.

Job satisfaction and cortisol awakening response in teachers scoring high and low on burnout.

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Moya-Albiol, Luis; Serrano, Miguel Angel; Salvador, Alicia

2010-11-01

The burnout syndrome is an important psychosocial risk in the job context, especially in professions with a strong social interaction, as in the case of teaching. High levels of burnout have been related to negative psychological indicators and hormonal alterations. This study compares job satisfaction and the cortisol awakening response (CAR) in teachers scoring high (HB) and low (LB) on burnout. HB teachers showed lower job satisfaction and no significant differences in the CAR when compared with the LB group. The results of the study suggest a general dissatisfaction with work along with a different functioning of the hypothalamo-pituitary-adrenocortical axis in HB teachers. Although non significantly, they showed a lower magnitude of the CAR than LB teachers. When considering the whole sample, emotional exhaustion and depersonalization correlated negatively and personal accomplishment positively with each subscale of the job satisfaction questionnaire whereas cortisol levels or CAR did not correlate significantly with both burnout subscales and job satisfaction. These results should be taken into account when working to prevent burnout in teachers, as the modified parameters could be considered indicators of the onset or development of the syndrome.

Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

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Martin Regina M

2004-07-01

Full Text Available Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM and 10 metastasizing/recurrent (MR tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in

Circulating β-endorphin, adrenocorticotrophic hormone and cortisol levels of stallions before and after short road transport: stress effect of different distances

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Grasso Loredana

2008-03-01

Full Text Available Abstract Background Since transport evokes physiological adjustments that include endocrine responses, the objective of this study was to examine the responses of circulating β-endorphin, adrenocorticotrophic hormone (ACTH and cortisol levels to transport stress in stallions. Methods Forty-two healthy Thoroughbred and crossbred stallions were studied before and after road transport over distances of 100, 200 and 300 km. Blood samples were collected from the jugular vein: first in a single box immediately before loading (pre-samples, then immediately after transport and unloading on arrival at the breeding stations (post-samples. Results An increase in circulating β-endorphin levels after transport of 100 km (P P P P P > 0.05 between horses of different ages and different breeds were observed for β-endorphin, ACTH and cortisol levels. Conclusion The results obtained for short term transportation of stallions showed a very strong reaction of the adrenocortical system. The lack of response of β-endorphin after transport of 200–300 km and of ACTH after transport of 300 km seems to suggest a soothing effect of negative feedback of ACTH and cortisol levels.

The Role of the Pituitary-Adrenocortical Axis System in the Regulation of Secretion of Digestive Glands of Wrestlers during Sports and Postsports Ontogenesis

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Panov, Sergei F.; Panova, Irina P.; Volunskaya, Elena V.; Chebotarev, Andrei V.

2016-01-01

According to many researchers its necessary to research a hormonal profile in order to determine mechanisms of regulation of functions of the digestive conveyor during sports activities. In the paper the results of the carried out research on studying of a role of pituitary-adrenocortical axis system of adaptive reactions in activities of the…

SINGLE AND AGGREGATE SALIVARY CORTISOL MEASURES IN WORKING WOMEN LIVING IN HIGH AND LOW STATUS NEIGHBORHOODS IN SWEDEN.

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Lindfors, Petra; Riva, Roberto; Lundberg, Ulf

2015-10-01

Contextual factors including neighborhood status have consistently been associated with health disparities. This may relate to a poorer neighborhood status involving an exposure to chronic stressors, which dysregulates cortisol secretion. This study investigated single and aggregate cortisol measures in 88 working women living in high and low status neighborhoods. Results showed significantly lower waking cortisol among women in low status neighborhoods. However, there were no group differences in aggregate cortisol measures. The lower morning cortisol among women in the low status neighborhoods follows previous research suggesting hypocortisolism as a pathway linking neighborhood status and health disparities, albeit a less consistent finding across cortisol measures in this sample. This may relate to the Swedish welfare state and its fostering of equality.

Thyrotropin-secreting pituitary tumor presenting with congestive heart failure and good response to dopaminergic agonist cabergoline

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Yu-Hsi Kao

2013-11-01

Full Text Available Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects

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Gilpin Heather

2008-08-01

Full Text Available Abstract Background Diurnal rhythm-mediated endogenous cortisol levels in humans are characterised by a peak in secretion after awakening that declines throughout the day to an evening trough. However, a significant proportion of the population exhibits an atypical cycle of diurnal cortisol due to shift work, jet-lag, aging, and mental illness. Results The present study has demonstrated a correlation between elevation of cortisol in the evening and deterioration of visual object recognition memory. However, high evening cortisol levels have no effect on spatial memory. Conclusion This study suggests that atypical evening salivary cortisol levels have an important role in the early deterioration of recognition memory. The loss of recognition memory, which is vital for everyday life, is a major symptom of the amnesic syndrome and early stages of Alzheimer's disease. Therefore, this study will promote a potential physiologic marker of early deterioration of recognition memory and a possible diagnostic strategy for Alzheimer's disease.

Reactive thymic hyperplasia following treatment of ACTH-producing tumors

International Nuclear Information System (INIS)

Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J.; Frank, M.; Ehlenz, K.; Kisker, O.

1997-01-01

Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism's recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the 'rebound' enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing's disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [de

The impact of negative family-work spillover on diurnal cortisol.

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Zilioli, Samuele; Imami, Ledina; Slatcher, Richard B

2016-10-01

Both dimensions of the work-family interface, work-to-family and family-to-work spillover, have important implications for health and well-being. Despite the importance of these associations, very little is known about the physiological mechanisms through which the interplay between family and work experiences are translated into long-lasting consequences for health. This study investigated both positive and negative aspects of each spillover dimension on diurnal cortisol secretion patterns in a large panel study of working adults between the ages of 33 and 80. Greater negative family-to-work (NFW) spillover predicted lower wake-up cortisol values and a flatter (less "healthy") diurnal cortisol slope. This effect was evident even after controlling for the effects of the other spillover dimensions. These findings indicate that not all aspects of the work-family interface might impact stress physiology to the same extent and suggest that diurnal cortisol may be an important pathway through which negative aspects of the work-family interface leave their mark on health. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Abnormal secretion of melatonin and cortisol in relation to sleep disturbances in children with Williams syndrome.

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Sniecinska-Cooper, Anna Maria; Iles, Ray Kruse; Butler, Stephen Andrew; Jones, Huw; Bayford, Richard; Dimitriou, Dagmara

2015-01-01

A high rate of sleep disturbances has been reported in individuals with Williams syndrome (WS) but the underlying aetiology has yet to be identified. Melatonin and cortisol levels display circadian rhythmicity and are known to affect and regulate sleep/wake patterns. The current study examined the levels of these two endocrine markers and explored a possible relationship with sleep patterns in children with WS. Twenty-five children with WS and 27 typically developing age- and gender-matched comparison children were recruited. Saliva was collected from each child at three time points: 4-6 pm, before natural bedtime, and after awakening. The levels of salivary melatonin and cortisol were analysed by specific enzyme-linked immunoassays. Sleep patterns were examined using actigraphy and the Children's Sleep Habit Questionnaire. The WS group had shallower drops in cortisol and less pronounced increase in melatonin at bedtime compared to the controls. Furthermore, they also had significantly higher levels of cortisol before bedtime. Increased bedtime cortisol and less pronounced rise in melatonin levels before sleep may play a role in the occurrence of sleep disturbances, such as delayed sleep onset, observed in children with WS. As both markers play a significant role in our circadian rhythm and sleep/wake cycle, it is necessary to examine sleep using multi-system analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Five year remission of GHRH secreting bronchial neuroendocrine tumor with symptoms of acromegaly. Utility of chromogranin A in the monitoring of the disease

International Nuclear Information System (INIS)

Bolanowski, M.; Zatonska, K.; Kos-Kudla, B.; Rzeszutko, M.; Marciniak, M.

2006-01-01

Acromegaly is usually caused by excess GH (growth hormone) secretion by pituitary adenoma. Extremely rare (< 1% of cases) acromegaly can be a result of ectopic GHRH (growth hormone releasing hormone) secretion by bronchial tubes, lung, pancreatic or intestinal tumor. The aim of this description is to present the case of successfully treated acromegaly caused by ectopic GHRH secretion by bronchial neuroendocrine tumor and the usefulness of chromogranin A assay in the disease monitoring. The diagnosis of acromegaly in 61-year old woman was based on typical clinical picture and elevated GH and IGF-1(insulin-like growth factor-1) levels. MRI (magnetic resonance imaging) images revealed no tumor in the pituitary but only the pituitary enlargement. Moreover, the right lung tumor (10 cm size) and elevated GHRH level were documented. The secretion of GH, IGF-1 and GHRH were normalized and progression of acromegaly was stopped after the carcinoid tumor surgery. Currently, 5 year after surgery, acromegaly is still in the remission, as the normal levels of GH, IGF-1, chromogranin A and normal chest and pituitary images confirm. The authors emphasize usefulness of measurement of chromogranin A concentration for the evaluation of the tumor remission in case the routine GHRH assay is not accessible. (authors)

Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism

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Lu Tang

2018-01-01

Full Text Available Aldosterone- and cortisol-coproducing adrenal adenoma (A/CPA cases have been observed in patients with primary aldosteronism (PA. This study investigated the incidence, clinical characteristics, and molecular biological features of patients with A/CPAs. We retrospectively identified 22 A/CPA patients from 555 PA patients who visited the Chinese People’s Liberation Army General Hospital between 2004 and 2015. Analysis of clinical parameters revealed that patients with A/CPAs had larger tumors than those with pure APAs (P<0.05. Moreover, they had higher proportions of cardiovascular complications, glucose intolerance/diabetes, and osteopenia/osteoporosis compared to the pure APA patients (P<0.001. In the molecular biological findings, quantitative real-time PCR analysis revealed similar CYP11B1 and CYP17A1 mRNA expressions in resected A/CPA specimens and in pure APA specimens. Western blot and immunochemical analyses showed CYP11B1, CYP11B2, and CYP17A1 expressions in both A/CPAs and pure APAs. Seventeen cases with KCNJ5 mutations were detected among the 22 A/CPA DNA samples, but no PRKACA or other causative mutations were observed. Each patient improved following adrenalectomy. In conclusion, A/CPAs were not rare among PA patients. These patients associated with high incidences of cardiovascular events and metabolic disorders. Screening for excess cortisol secretion is necessary for PA patients.

The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

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Ghaly, Maurice; Teplitz, Dale

2004-10-01

Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

Direct assay for urine cortisol with cortisol kit TFB

Energy Technology Data Exchange (ETDEWEB)

Manaka, Yukiko; Watanabe, Michiko; Hosoya, Takaaki [Yamagata Univ. (Japan). Hospital

2002-05-01

We examined Cortisol Kit TFB for direct assay of urine cortisol. And the multiplication by dilution factor of urine cortisol values in this kit was examined. The coefficient of correlation of cortisol levels (46 urine samples) between Cortisol Kit TFB and Chemilumi ACS-Cortisol II, which is another kit for direct assay of urine cortisol, was r=0.858, y=1.86x+38.2 (p<0.001). There were differences between the both cortisol levels of each urine sample in spite of the good coefficient of correlation. The urine cortisol values obtained from the standard curve in addition of 50 {mu}l of zero standard were 50-80% of the values obtained from the standard curve in the package insert. These results suggest that the specificity of the antibodies of both direct assay kits for urine cortisol may be different each other, and the multiplication by 1.09, the dilution factor due to the addition of zero standard to only urine sample, is unnecessary although it is indispensable for urine samples to add zero standard. Cortisol Kit TFB was very convenient for its easy assay procedure and short incubation. (author)

Direct assay for urine cortisol with cortisol kit TFB

International Nuclear Information System (INIS)

Manaka, Yukiko; Watanabe, Michiko; Hosoya, Takaaki

2002-01-01

We examined Cortisol Kit TFB for direct assay of urine cortisol. And the multiplication by dilution factor of urine cortisol values in this kit was examined. The coefficient of correlation of cortisol levels (46 urine samples) between Cortisol Kit TFB and Chemilumi ACS-Cortisol II, which is another kit for direct assay of urine cortisol, was r=0.858, y=1.86x+38.2 (p<0.001). There were differences between the both cortisol levels of each urine sample in spite of the good coefficient of correlation. The urine cortisol values obtained from the standard curve in addition of 50 μl of zero standard were 50-80% of the values obtained from the standard curve in the package insert. These results suggest that the specificity of the antibodies of both direct assay kits for urine cortisol may be different each other, and the multiplication by 1.09, the dilution factor due to the addition of zero standard to only urine sample, is unnecessary although it is indispensable for urine samples to add zero standard. Cortisol Kit TFB was very convenient for its easy assay procedure and short incubation. (author)

Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

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Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

2012-02-01

CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

International Nuclear Information System (INIS)

Cheng, Li-Chuan; Li, Lih-Ann

2012-01-01

CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

Cortisol level

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... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

Serum cortisol level and its correlation to serum insulin and fasting blood sugar levels in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Chen Jianzhong; Zhang Jun

2004-01-01

Objective: To investigate the change of serum cortisol levels and its correlation to blood sugar and serum insulin levels in patients with type 2 diabetes mellitus. Methods: Blood sugar with oxidase method and serum cortisol insulin levels with RIA (8 AM fasting specimen) were measured in 26 patients with type 2 diabetes mellitus and 30 controls. Results: The serum cortisol levels in the diabetic patients were significantly higher than those in the controls (P<0.01). The cortisol levels were positively correlated to the blood sugar levels (r=0.32, p<0.01), but not correlated to insulin levels. Conclusion: There were cortisol secretion disturbances in patients with type 2 diabetes

Endogenous Cushing’s Syndrome with Precocious Puberty in an 8-Year-Old Boy due to a Large Unilateral Adrenal Adenoma

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Muhammad Rajib Hossain

2013-01-01

Full Text Available Adrenocortical tumors (ACTs causing Cushing’s syndrome are extremely rare in children and adolescents. Bilateral macronodular adrenocortical disease which is a component of the McCune-Albright syndrome is the most common cause of endogenous Cushing’s syndrome. We report the case of a boy with Cushing’s syndrome who presented with obesity and growth retardation. The child was hypertensive. The biochemical evaluation revealed that his serum cortisol levels were 25.80 g/dL, with a concomitant plasma ACTH level of 10.0 pg/mL and nonsuppressed serum cortisol on high-dose dexamethasone suppression test (HDDST to be 20.38 g/dL. Computed tomography of the abdomen demonstrated a 8 × 6 × 5 cm left adrenal mass with internal calcifications. Following preoperative stabilization, laparotomy was carried out which revealed a lobulated left adrenal mass with intact capsule weighing 120 grams. Histopathological examination revealed a benign cortical neoplastic lesion, suggestive of adrenal adenoma; composed of large polygonal cells with centrally placed nuclei and prominent nucleoli without capsular and vascular invasion. On the seventh postoperative day, cortisol levels were within normal range indicating biochemical remission of Cushing’s syndrome. On followup after three months, the patient showed significant clinical improvement and had lost moderate amount of weight and adrenal imaging was found to be normal.

Evidence for a positive correlation between serum cortisol levels and IL-1beta production by peripheral mononuclear cells in anorexia nervosa.

Science.gov (United States)

Limone, P; Biglino, A; Bottino, F; Forno, B; Calvelli, P; Fassino, S; Berardi, C; Ajmone-Catt, P; Bertagna, A; Tarocco, R P; Rovera, G G; Molinatti, G M

2000-01-01

A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in anorexia nervosa (AN), together with some immunological abnormalities, involving citokine - and particularly Tumor Necrosis-Factor-alpha (TNF-alpha) - production by polymorphonuclear cells. The ability of pro-inflammatory cytokines to activate the HPA axis is well known; however, there are no data demonstrating an interdependence between immunological and endocrine response in AN. To investigate the presence of a correlation between immune response and pituitary-adrenal function, plasma ACTH and serum cortisol concentrations were measured in 13 AN patients and in the same number of controls. TNF-alpha and interleukin (IL)-1beta production by ex-vivo unstimulated and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating cortisol concentrations were higher (p<0.01) in AN (156.7 +/- 45.1 microg/l, mean +/- SD) than in controls (105.9 +/- 25.7 microg/l). Unstimulated IL-1beta release in supernatants of mononuclear cell cultures was slightly but not significantly higher in AN than in controls, while TNF-alpha release was similar in the two groups. A positive correlation was found between IL-1beta concentrations in unstimulated culture supranatants and serum cortisol levels in AN (r=0.782, p=0.002), while in normal subjects there was a trend toward a negative correlation; a slight positive correlation, while not significant, between IL-1beta and plasma ACTH, as well as between TNF-alpha and serum cortisol was also found in AN. These data suggest that the normal relationship between pro-inflammatory cytokines release, particularly IL-1beta, and cortisol secretion is deranged in AN.

Blood-ACTH, cortisole and aldosterone levels following complex radiation treatment for cancer of the uterine cervix

International Nuclear Information System (INIS)

Modnikov, O.P.

1984-01-01

Blood-ACTH, cortisole and aldosterone levels in patients with cancer of the uterine cervix were measured radioimmunologically prior to complex radiotherapy, following a half-dose exposure of tumor focus and immediately on completion of the treatment course. Patients showed a rise in cortisole and aldosterone levels and a slight increase in ACTH. Radiation therapy inhibited production of cortisole and aldosterone matched by a rise in ACTH output

Psychological pathways from racial discrimination to cortisol in African American males and females.

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Lee, Daniel B; Peckins, Melissa K; Heinze, Justin E; Miller, Alison L; Assari, Shervin; Zimmerman, Marc A

2018-04-01

The association between racial discrimination (discrimination) and stress-related alterations in the neuroendocrine response-namely, cortisol secretion-is well documented in African Americans (AAs). Dysregulation in production of cortisol has been implicated as a contributor to racial health disparities. Guided by Clark et al. (Am Psychol 54(10):805-816, 1999. doi: 10.1037/0003-066X.54.10.805 ) biopsychosocial model of racism and health, the present study examined the psychological pathways that link discrimination to total cortisol concentrations in AA males and females. In a sample of 312 AA emerging adults (45.5% males; ages 21-23), symptoms of anxiety, but not depression, mediated the relation between discrimination and total concentrations of cortisol. In addition, the results did not reveal sex differences in the direct and indirect pathways. These findings advance our understanding of racial health disparities by suggesting that the psychological consequences of discrimination can uniquely promote physiologic dysregulation in AAs.

A black adrenocortical adenoma causing Cushing's syndrome not imaged by radiocholesterol scintigraphy

International Nuclear Information System (INIS)

Reschini, E.; Baldini, M.; Cantalamessa, L.

1990-01-01

In a 33-year-old female patient with left adrenal tumour and Cushing's syndrome, adrenocortical scintigraphy with radiocholesterol did not image the tumour nor the suppressed contralateral gland. Histology showed a black adrenocortical adenoma composed only of compact cells; there was no evidence of malignancy. This demonstrates that non-visualization of the adrenal glands in a patient with Cushing's syndrome is not invariably due to adrenal carcinoma. The literature on black adrenal adenomas causing Cushing's syndrome is reviewed. (orig.)

Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

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Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

2015-01-01

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

On psychobiology in psychoanalysis - salivary cortisol and secretory IgA as psychoanalytic process parameters

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Euler, Sebastian; Schimpf, Heinrich; Hennig, Jürgen; Brosig, Burkhard

2005-01-01

This study investigates the psychobiological impact of psychoanalysis in its four-hour setting. During a period of five weeks, 20 subsequent hours of psychoanalysis were evaluated, involving two patients and their analysts. Before and after each session, saliva samples were taken and analysed for cortisol (sCortisol) and secretory immunoglobuline A (sIgA). Four time-series (n=80 observations) resulted and were evaluated by "Pooled Time Series Analysis" (PTSA) for significant level changes and setting-mediated rhythms. Over all sessions, sCortisol levels were reduced and sIgA secretion augmented parallel to the analytic work. In one analytic dyad a significant rhythm within the four-hour setting was observed with an increase of sCortisol in sessions 2 and 3 of the week. Psychoanalysis may, therefore, have some psychobiological impact on patients and analysts alike and may modulate immunological and endocrinological processes. PMID:19742067

Adrenocortical function in hospitalised patients with active ...

African Journals Online (AJOL)

2006-05-17

May 17, 2006 ... Tuberculosis (TB) is a major cause of morbidity and mortality in sub-Sah aran Africa, ... To assess whether adrenocortical function was compromised in patients with active tuberculosis. (TB) during the first 5 days of ..... Hernandez-Pando R, de la Luz Streber M, Orozco H, et al. Emergent immunoregulatory.

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

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Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

2003-01-01

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma

Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion.

Science.gov (United States)

Iranmanesh, Ali; Veldhuis, Johannes D

2008-11-01

ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (Pfeedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging.

Adrenocortical zonation, renewal, and remodeling

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Marjut ePihlajoki

2015-03-01

Full Text Available The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones. Some of these pools appear to be activated only during specific developmental windows or in response to extreme physiological demand. Senescent cells can also be replenished through direct lineage conversion; for example, cells in the zona glomerulosa can transform into cells of the zona fasciculata. Adrenocortical cell differentiation, renewal, and function are regulated by a variety of endocrine/paracrine factors including adrenocorticotropin, angiotensin II, insulin-related growth hormones, luteinizing hormone, activin, and inhibin. Additionally, zonation and regeneration of the adrenal cortex are controlled by developmental signaling pathways, such as the sonic hedgehog, delta-like homologue 1, fibroblast growth factor, and WNT/β-catenin pathways. The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation.

Night Shift Work and Levels of 6-Sulfatoxymelatonin and Cortisol in Men

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Mirick, Dana K.; Bhatti, Parveen; Chen, Chu; Nordt, Frank; Stanczyk, Frank Z.; Davis, Scott

2016-01-01

Background Nightshift work is associated with cancer among men, but the biological mechanism is unclear. We investigated whether male nightshift workers demonstrated changes in levels of melatonin and cortisol, potential biomarkers of cancer risk. Methods Urine was collected from 185 nightshift and 158 dayshift-working male healthcare providers, aged 22-55, throughout work and sleep periods and assayed for 6-sulfatoxymelatonin and cortisol. Morning serum was collected within 90 minutes of completing the night and assayed for cortisol. Results Nightshift workers had significantly lower 6-sulfatoxymelatonin levels during daytime sleep, nighttime work, and nighttime sleep on off-nights (57%, 62% and 40% lower, respectively), relative to the dayshift workers during nighttime sleep (pnights (pnight work and daytime sleep, and levels remain low when nightshift workers sleep at night. Chronic reduction in melatonin among nightshift workers may be an important carcinogenic mechanism. Cortisol secretion patterns may be impacted by night shift work, which could affect cancer risk. Impact Shiftwork could be an important risk factor for many types of cancer. PMID:23563887

Weather conditions: a neglected factor in human salivary cortisol research?

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Milas, Goran; Šupe-Domić, Daniela; Drmić-Hofman, Irena; Rumora, Lada; Klarić, Irena Martinović

2018-02-01

There is ample evidence that environmental stressors such as extreme weather conditions affect animal behavior and that this process is in part mediated through the elevated activity of the hypothalamic pituitary adrenal axis which results in an increase in cortisol secretion. This relationship has not been extensively researched in humans, and weather conditions have not been analyzed as a potential confounder in human studies of stress. Consequently, the goal of this paper was to assess the relationship between salivary cortisol and weather conditions in the course of everyday life and to test a possible moderating effect of two weather-related variables, the climate region and timing of exposure to outdoors conditions. The sample consisted of 903 secondary school students aged 18 to 21 years from Mediterranean and Continental regions. Cortisol from saliva was sampled in naturalistic settings at three time points over the course of a single day. We found that weather conditions are related to salivary cortisol concentration and that this relationship may be moderated by both the specific climate and the anticipation of immediate exposure to outdoors conditions. Unpleasant weather conditions are predictive for the level of salivary cortisol, but only among individuals who anticipate being exposed to it in the immediate future (e.g., in students attending school in the morning shift). We also demonstrated that isolated weather conditions or their patterns may be relevant in one climate area (e.g., Continental) while less relevant in the other (e.g., Mediterranean). Results of this study draw attention to the importance of controlling weather conditions in human salivary cortisol research.

Classic congenital adrenal hyperplasia and puberty.

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Charmandari, Evangelia; Brook, Charles G D; Hindmarsh, Peter C

2004-11-01

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.

Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

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Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

2012-01-01

Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress.

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Brummelte, Susanne; Chau, Cecil M Y; Cepeda, Ivan L; Degenhardt, Amanda; Weinberg, Joanne; Synnes, Anne R; Grunau, Ruth E

2015-01-01

Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function. Differences in cortisol levels have been found in preterm infants exposed to substantial procedural stress during neonatal intensive care, compared to infants born full-term, but only a few studies investigated whether altered programming of the HPA axis persists past toddler age. Further, there is a dearth of knowledge of what may contribute to these changes in cortisol. This prospective cohort study examined the cortisol profiles in response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol, in children (n=129) born at varying levels of prematurity (24-32 weeks gestation) and at full-term (38-41 weeks gestation), at age 7 years. Further, we investigated the relationships among cortisol levels and neonatal procedural pain-related stress (controlling for multiple medical confounders), concurrent maternal factors (parenting stress, depressive and anxiety symptoms) and children's behavioral problems. For each aim we investigate acute cortisol response profiles to a cognitive challenge as well as diurnal cortisol patterns at home. We hypothesized that children born very preterm will differ in their pattern of cortisol secretion from children born full-term, possibly depended on concurrent child and maternal factors, and that exposure to neonatal pain-related stress would be associated with altered cortisol secretion in children born very preterm, possibly in a sex-dependent way. Saliva samples were collected from 7-year old children three times during a laboratory visit for assessment of cognitive and executive functions (pretest, mid-test, end-study day acute stress profile) and at four times over two consecutive non-school days at home (i.e. morning, mid-morning, afternoon and bedtime-diurnal rhythm profile). We found that cortisol profiles were similar in preterm and full-term children, albeit preterms had slightly higher cortisol at bedtime compared to

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

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Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El

2016-01-01

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

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Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

2016-06-15

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.

The secretion, synthesis, and metabolism of cortisol and its downstream genes in the H-P-I axis of rare minnows (Gobiocypris rarus) are disrupted by acute waterborne cadmium exposure.

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Liu, Xiao-Hong; Xie, Bi-Wen; Wang, Zhi-Jian; Jin, Li; Zhang, Yao-Guang

2016-01-01

The H (hypothalamic)-P (pituitary)-I (interrenal) axis plays a critical role in the fish stress response and is regulated by several factors. Cadmium (Cd) is one of the most toxic heavy metals in the world, but its effects on the H-P-I axis of teleosts are largely unknown. Using rare minnow (Gobiocypris rarus) as an experimental animal, we found that Cd only disrupted the secretion and synthesis of cortisol. Neither hormones at the H or P level nor the expressions of their receptor genes (corticotropin-releasing hormone receptor (CRHR) and melanocortin receptor 2 (MC2R)) were affected. Steroidogenic acute regulator (StAR), CYP11A1 and CYP11B1, which encode the key enzymes in the cortisol synthesis pathway, were significantly up-regulated in the kidney (including the head kidney). The level of 11β-HSD2, which is required for the conversion of cortisol to cortisone, was increased in the kidney, intestine, brain, and hepatopancreas, whereas the expression of 11β-HSD1, which encodes the reverse conversion enzyme, was increased in the gill, kidney and almost unchanged in other tissues. The enzyme activity concentration of 11β-HSD2 was increased in the kidney as well. The level of glucocorticoid receptor (GR) decreased in the intestine, gill and muscle, and the key GR regulator FK506 binding protein5 (FKBP5) was up-regulated in the GR-decreased tissues, whereas the level of nuclear receptor co-repressor 1 (NCoR1), another GR regulator remained almost unchanged. Thus, GR, FKBP5 and 11β-HSD2 may be involved in Cd-induced cortisol disruption. Copyright © 2016 Elsevier Inc. All rights reserved.

Salivary cortisol and alpha-amylase levels during an assessment procedure correlate differently with risk-taking measures in male and female police recruits

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Ruud eVan Den Bos

2014-01-01

Full Text Available Recent laboratory studies have shown that men display more risk-taking behaviour in decision-making tasks following stress, whilst women are more risk-aversive or become more task-focussed. In addition, these studies have shown that sex differences are related to levels of the stress hormone cortisol (indicative of activation of the hypothalamus-pituitary-adrenocortical-axis: the higher the levels of cortisol the more risk-taking behaviour is shown by men, whereas women generally display more risk-aversive or task-focussed behaviour following higher levels of cortisol. Here, we assessed whether such relationships hold outside the laboratory, correlating levels of cortisol obtained during a job-related assessment procedure with decision-making parameters in the Cambridge Gambling Task (CGT in male and female police recruits. The CGT allows for discriminating different aspects of reward-based decision-making. In addition, we correlated levels of alpha-amylase (indicative for activation of the sympatho-adrenomedullary-axis and decision-making parameters. In line with earlier studies men and women only differed in risk-adjustment in the CGT. Salivary cortisol levels correlated positively and strongly with risk-taking measures in men, which was significantly different from the weak negative correlation in women. In contrast, and less strongly so, salivary alpha-amylase levels correlated positively with risk-taking in women, which was significantly different from the weak negative correlation with risk-taking in men. Collectively, these data support and extend data of earlier studies indicating that risky decision-making in men and women is differently affected by stress hormones. The data are briefly discussed in relation to the effects of stress on gambling.

Cortisol production rate is similarly elevated in obese women with or without the polycystic ovary syndrome.

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Roelfsema, Ferdinand; Kok, Petra; Pereira, Alberto M; Pijl, Hanno

2010-07-01

The pituitary-adrenal axis in obesity and polycystic ovary syndrome (PCOS) is marked by increased urinary excretion of cortisol and its metabolites. It is not as yet clear whether the increased cortisol production in PCOS is related to obesity per se. We investigated 15 obese PCOS women with a body mass index of 30-54 kg/m(2) and 15 healthy obese controls (body mass index 31-60 kg/m(2)) with a regular menstrual cycle. Patients and control women underwent 24-h blood sampling at 20-min intervals. Cortisol concentrations were measured with a sensitive assay. Data were analyzed with a new deconvolution program, approximate entropy, and cosinor regression. Basal, pulsatile, and total cortisol production expressed per liter distribution volume, per square meter body surface, and as absolute amount per 24 h was similar in PCOS patients and matched healthy control women. In addition, the regularity of cortisol secretion and the diurnal properties were identical. Compared with 10 lean control women, mean cortisol production per liter distribution volume was similar in the three groups, but the total 24-h cortisol production was increased in obese control women and PCOS women. This study demonstrates equally increased cortisol production in PCOS women and obese healthy control women.

Morning cortisol is lower in obese individuals with normal glucose tolerance

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Praveen EP

2011-09-01

Full Text Available Edavan P Praveen1, Jaya Prakash Sahoo1, Bindu Kulshreshtha2, Madan L Khurana3, Nandita Gupta1, Sada Nand Dwivedi3, Guresh Kumar3, Ariachery C Ammini11Department of Endocrinology, All India Institute of Medical Sciences, 2Ram Manohar Lohia Hospital, 3Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, IndiaBackground: There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS. This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH levels with body mass index (BMI and glucose tolerance.Subjects and methods: The sample frame was the “Offspring of individuals with diabetes study” database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were ≥10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT, and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.Results: Four hundred and ninety-five participants (305 males [62%] and 190 females [38%] were included in the analysis. ACTH and cortisol levels were higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and cortisol increased as fasting plasma glucose increased. Cortisol levels were significantly lower in offspring of T2DM subjects with MS than in offspring of T2DM subjects without MS. When adjusted for BMI, the significance was marginal. In males, cortisol levels were negatively correlated with early insulin secretion during OGTT (insulinogenic index [0–30] and positively with waist circumference and serum high-density lipoprotein cholesterol. In females, fasting

Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report

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Kabayegit Ozlem

2008-07-01

Full Text Available Abstract Introduction Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. Case presentation We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. Conclusion Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.

Depression differed by midnight cortisol secretion, alexithymia and anxiety between diabetes types: a cross sectional comparison.

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Melin, Eva O; Thunander, Maria; Landin-Olsson, Mona; Hillman, Magnus; Thulesius, Hans O

2017-09-20

Increased prevalence of depression is found in both type 2 diabetes (T2D) and type 1 diabetes (T1D). Melancholia and atypical depression differ by cortisol secretion and clinical features. The aim was to compare the clinical presentation of T1D and T2D patients in relation to self-reported depression, self-reported anxiety, alexithymia, obesity, and midnight salivary cortisol (MSC). Comparative cross-sectional design. The participants were consecutively recruited from one hospital diabetes outpatient clinic: 24 T2D patients (31-59 years) and 148 T1D patients (32-59 years). Self-reported depression, anxiety and alexithymia were assessed by Hospital Anxiety and Depression scale and Toronto Alexithymia Scale-20. MSC, HbA1c, anthropometrics and data from medical records were collected. Multiple logistic regression analyses were performed. Comparisons of prevalence between diabetes types showed for T2D/T1D: depression 25%/12% (P = 0.10); high MSC (≥9.3 nmol/L) 38%/22% (P = 0.13); alexithymia 25%/13% (P = 0.12); anxiety 38%/35% (P = 0.82). The prevalence of high MSC did not differ between depressed and non-depressed T2D patients (17% vs. 44%, P = 0.35), but differed between depressed and non-depressed T1D patients (53% vs. 18%, P = 0.003). The alexithymia prevalence differed between depressed and non-depressed T2D patients (67% vs.11%, P = 0.018), and between depressed and non-depressed T1D patients (47% vs. 11%, P foot complications (AOR 8.5), HbA1C >70 mmol/mol (AOR 6.4), and high MSC (≥9.3 nmol/L) (AOR 4.8). The depressed T2D patients had traits of atypical depression, without associated high MSC (≥9.3 nmol/L) and anxiety, but the association with alexithymia was strong. The depressed T1D patients had traits of melancholia with associated high MSC and anxiety. The obesity prevalence was high in depressed T2D patients and low in depressed T1D patients.

Adrenal scintigraphy with 131I-19-iodocholesterol in the diagnosis of Cushing's syndrome associated with adrenal tumor

International Nuclear Information System (INIS)

Barliev, G.B.

1979-01-01

Seven patients with Cushing's syndrome secondary to adrenocortial tumors were studied using 131 I-19-iodocholesterol. The diagnoses of all cases were verified histologically. In three cases with adenoma the uptake of the tracer was in the tumor only, while the two patients with adrenocortical carcinoma failed to show adrenal accumulation of the labelled compound. In two patients there was a hyperplasia-like scintigraphic pattern, while the stimulation and suppression biochemical tests suggested adrenal tumor. One of these cases was verified as a mixed form (adenoma plus hyperplasia), and the tumor bearing gland was significantly larger on the scan which helped the preoperative localization. In the other case, verified as bilateral multiple adrenocortical adenomas, the autonomus function of both adrenals was proved by dexamethasone suppression scanning. It seems reasonable to use the latter as an adjunctive diagnostic procedure in patients where there is a discrepancy between the standard scintiscan and the biochemical indexes of adrenal hyperfunction. (orig.) 891 MG/orig. 892 MBE [de

Surgical management and clinical prognosis of adrenocortical carcinoma.

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Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

2012-01-01

To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

Regulation of Corticosteroidogenic Genes by MicroRNAs

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Stacy Robertson

2017-01-01

Full Text Available The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

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Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

2014-06-01

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

Night traffic and health: Results of laboratory and field studies; Naechtlicher Verkehrslaerm und Gesundheit: Ergebnisse von Labor- und Feldstudien

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Maschke, C. [Technische Univ. Berlin (Germany). Inst. fuer Technische Akustik; Ising, H. [Umweltbundesamt, Berlin (Germany). Inst. fuer Wasser-, Boden-, und Lufthygiene; Arndt, D. [Robert Koch-Institut, Medizinische Diagnostik - Umweltmedizin, Berlin (Germany)

1995-04-01

The present article summarizes the results obtained in the Berlin laboratory and field studies on `noise-induced stress reactions`. Unaccustomed air-traffic noise at night leads to elevated epinephrine and cortisol levels. If road traffic noise at night rises above the accustomed level, this leads to enhanced renal cortisol secretion. Noise at night deserves to be termed a stressor because it is able to activate both the hypothalamic-pituitary-adrenocortical and the hypothalamic-adrenomedullar control loop. Elevation of epinephrine secretion was more distinct in the air-traffic field study than it was in the laboratory study. The relative elevation of cortisol secretion in the field study was of the same order as that of epinephrine secretion. Noise-induced noctural elevation of epinephrine secretion seems only to occur in the case of unaccustomed noise levels. If exposure to noise is prolonged, it subsides in an adaptive process and gives way to an elevated cortisol secretion. Elevation of both cortisol and epinephrine secretion is indicative of a stressing traffic noise situation. Air-traffic noise was found to impair subjective sleep quality and lead to a rise in epinephrine secretion both in the laboratory and the field study. No correlation was found between noise emission from low-flying aircraft and epinephrine or cortisol secretion in the field study. Neither the field nor the laboratory study showed a correlation between the number of night flights and catecholamine secretion. Cortisol secretion remained equally unaffected by the number of flights. The present results confirm the hypothesis that air and road traffic noise cause bodily distress. Chronic exposure to noise at night must therfore be regarded as a health hazard. (orig./MG) [Deutsch] Ungewohnter naechtlicher Fluglaerm fuehrt zu einer erhoehten Adrenalin-und Cortisolausscheidung. Wird die Intensitaet eines gewohnten naechtlichen Strassenverkehrslaerms erhoeht, ist eine vermehrte renale

Shift work at young age is associated with elevated long-term cortisol levels and body mass index.

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Manenschijn, Laura; van Kruysbergen, Rulanda G P M; de Jong, Frank H; Koper, Jan W; van Rossum, Elisabeth F C

2011-11-01

The incidence of obesity and other features of the metabolic syndrome is increased in shift workers. This may be due to a misalignment between the internal circadian rhythm and the behavioral rhythm. The stress hormone cortisol could play a role in this phenomenon because it is secreted in a circadian rhythm, and long-term elevated cortisol leads to components of the metabolic syndrome. We compared cortisol levels in scalp hair of shift and day workers to study changes in long-term cortisol due to shift work. Hair samples were collected from 33 shift workers and 89 day workers. Cortisol was extracted from the hair samples with methanol, and cortisol levels were measured using ELISA. Height and weight were measured, and body mass index (BMI) was calculated. Shift workers had higher hair cortisol levels than day workers: 47.32 pg/mg hair [95% confidence interval (CI) = 38.37-58.21] vs. 29.72 pg/mg hair (95% CI = 26.18-33.73) (P cortisol levels were present only in younger shift workers: 48.53 pg/mg hair (95% CI = 36.56-64.29) vs. 26.42 pg/mg hair (95% CI = 22.91-30.55) (P cortisol and BMI were positively correlated (β = 0.262; P = 0.005). Shift work at a young adult age is associated with elevated long-term cortisol levels and increased BMI. Elevated cortisol levels and BMI may contribute to the increased cardiovascular risk found in shift workers.

Evaluation of steroid laboratory tests and adrenal gland imaging with radiocholesterol in the aetiological diagnosis of Cushing's syndrome

International Nuclear Information System (INIS)

Barbarino, A.; De Marinis, L.; Liberale, I.; Menini, E.

1979-01-01

Basal values of the urinary excretion of 17-oxogenic steroids and serum levels of cortisol were not satisfactory in the differentiation of 'suspected' subjects from patients with true Cushing's syndrome. With a RIA method for serum cortisol determination, the overnight dexamethasone suppression test provided the most reliable single test in establishing adrenocortical hyperfunction. Thirty-five normal subjects, fifty-nine obese patients, thirteen 'suspected' patients and thirteen patients with disease states other than Cushing's syndrome had suppressed values below 4.0 μg/100 ml. None of the ten patients with Cushing's syndrome had a cortisol concentration less than 16.3 μg/100ml. Adrenal gland scintigraphy after radiocholesterol injection is a more valuable tool than the metyrapone test and the high-dose dexamethasone suppression test in the localization and differential diagnosis of adrenocortical lesions causing Cushing's syndrome. It obviates the need for angiographic procedure in the localization of adenomas. It is a reliable technique for identifying functioning adrenal remnants. Therefore a schedule is proposed for studying patients with suspected adrenocortical hyperfunction. (author)

Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

International Nuclear Information System (INIS)

Esteban, N.V.; Loughlin, T.; Yergey, A.L.; Zawadzki, J.K.; Booth, J.D.; Winterer, J.C.; Loriaux, D.L.

1991-01-01

Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5 mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day. A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed

Yawning, fatigue and cortisol: expanding the Thompson Cortisol Hypothesis.

OpenAIRE

Thompson, Simon

2014-01-01

Yawning and its involvement in neurological disorders has become the new scientific conundrum. Cortisol levels are known to rise during stress and fatigue; yawning may occur when we are under stress or tired. However, the link between yawning, fatigue, and cortisol has not been fully understood. Expansion of the Thompson Cortisol Hypothesis proposes that the stress hormone, cortisol, is responsible for yawning and fatigue especially in people with incomplete innervation such as multiple sclero...

A case of Addison's disease accompanied with bilateral adrenal calcification on CT

International Nuclear Information System (INIS)

Lee, Li-Chik; Fujita, Naohisa; Ohba, Yachiyo

1985-01-01

A 62-year-old woman was admitted to our hospital with complaints of general malaise and hyperpigmentation. We diagnosed her case as primary adrenocortical insufficiency (Addison's disease) by endocrinological studies. CT demonstrated dense calcification in both adrenal beds without evidence of normal glandular remnants. Calcified adrenal is not specific to tuberculosis, but some points of CT findings are useful for pathogenetic approach. Recently, there have been several reports that ACTH producing pituitary tumors develop in patients treated with conventional corticosteroid replacement. Corticosteroid should be administered by monitoring of plasma cortisol and ACTH concentrations. (author)

The effect of physical activity on psychological distress, cortisol and obesity: results of the Farming Fit intervention program.

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Brumby, Susan; Chandrasekara, Ananda; Kremer, Peter; Torres, Susan; McCoombe, Scott; Lewandowski, Paul

2013-10-28

Rural and regional Australians have a higher likelihood of mental illness throughout their lifetime than people living in major cities, although the underlying reasons are not yet well defined. Additionally, rural populations experience more lifestyle associated co-morbidities including obesity, diabetes and cardiovascular disease. Research conducted by the National Centre for Farmer Health between 2004 and 2009 revealed a positive correlation between obesity and psychological distress among the farming community. Chronic stress is known to overstimulate the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol secretion which are associated with abdominal adiposity. Increasing physical activity may normalise cortisol secretion and thereby positively impact both physical and mental health. This paper assesses the effects of increasing physical activity on obesity, health behaviors and mental health in Victorian farming men and women. Farming Fit was a six month quasi-experimental (convenience sample) longitudinal design control-intervention study. Overweight or obese (BMI ≥25 kg/m2) farm men (n = 43) and women (n = 29) were recruited with demographic, health behaviors, anthropometric, blood pressure and biochemistry data collected at baseline and at a six months. Salivary cortisol and depression anxiety stress scale results were collected at baseline, three and six months. The intervention group (n = 37) received a personalized exercise program and regular phone coaching to promote physical activity. The intervention group showed significant reductions in body weight and waist circumference. Results indicated that following the six month exercise program, the intervention group were 2.64 ± 0.65 kg lighter (p physical activity altered measures of obesity in farm men and women but did not affect mental health measures or cortisol secretion levels. ACTRN12610000827033.

Lower immunglobulin A levels but not lower cortisol or α-amylase activity in children with chronic tension-type headache.

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Fernández-de-Las-Peñas, César; Fernández-Mayoralas, Daniel M; Arroyo-Morales, Manuel; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; Díaz-Rodríguez, Lourdes; Pareja, Juan A

2011-03-01

The study was designed to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), immunoglobulin A (IgA) (immune system) concentrations and α-amylase (sympathetic nervous system [SNS]) activity between children with chronic tension-type headache (CTTH) and healthy children. Thirty-six children, 10 boys and 26 girls (age: 9 ± 2 years) with CTTH and 36 age- and sex-matched healthy children were recruited. Salivary cortisol, α-amylase activity, salivary flow rate, IgA concentration and IgA rate were collected from non-stimulated saliva. A headache diary was used for collecting data on intensity, frequency and duration of headache for four weeks. Children with CTTH showed lower IgA concentration (p = .008) and IgA rate (p = .039), but not lower cortisol concentration (p = .447), salivary flow rate (p = .289) or α-amylase activity (p = .559), as compared to healthy children. Neither age (p > .582) nor gender (p > .227) influenced salivary markers. A significant association between the number of years with headache and IgA concentration (r(s) = - 0.385; p = .023) was found: the greater the number of years with headache, the lower the IgA concentration. These results suggest that children with CTTH present with deficits in the immune system, but not dysfunction in the HPA axis or SNS. Future studies are needed to elucidate the direction of these relationships.

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

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Orlander, Philip R.

2011-01-01

Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants.

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Ivars, Katrin; Nelson, Nina; Theodorsson, Annette; Theodorsson, Elvar; Ström, Jakob O; Mörelius, Evalotte

2015-01-01

Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

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Carlotta Pozza

2012-01-01

Full Text Available Cushing’s syndrome (CS is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing’s disease, CD or an ectopic source (ectopic ACTH secretion, EAS. The remaining causes (20% are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”. Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors which have a significant activity against aggressive pituitary or ectopic tumors.

Cortisol rapidly reduces prolactin release and cAMP and 45Ca2+ accumulation in the cichlid fish pituitary in vitro

International Nuclear Information System (INIS)

Borski, R.J.; Helms, L.M.H.; Richman, N.H. III; Grau, E.G.

1991-01-01

During in vitro incubation, prolactin release is inhibited in a dose-related manner by cortisol. This action is mimicked by the synthetic glucocorticoid agonist dexamethasone but not by other steroids tested. Perifusion studies indicate that the inhibition of [ 3 H]prolactin release by cortisol occurs within 20 min. Cortisol (50 nM) also inhibits cAMP accumulation and reduces 45 Ca 2+ accumulation in the tilapia rostral pars distalis within 15 min. Cortisol's action on prolactin release is blocked in the presence of either the Ca 2+ ionophore A23187 or a combination of dibutyryl cAMP and 3-isobutyl-1-methylxanthine, which increase intracellular Ca 2+ and cAMP, respectively. Taken together, these findings suggest that cortisol may play a physiologically relevant role in the rapid modulation of prolactin secretion in vivo. These studies also suggest that the inhibition of prolactin release by cortisol is a specific glucocorticoid action that may be mediated, in part, through cortisol's ability to inhibit intracellular cAMP and Ca 2+ metabolism

Facebook behaviors associated with diurnal cortisol in adolescents: Is befriending stressful?

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Morin-Major, Julie Katia; Marin, Marie-France; Durand, Nadia; Wan, Nathalie; Juster, Robert-Paul; Lupien, Sonia J

2016-01-01

Facebook(©) is changing the way people interact and socialize. Despite great interest in psychology and sociology, little is known about Facebook behaviors in relation to physiological markers of stress. Given that the brain undergoes important development during adolescence and that glucocorticoids--a major class of stress hormones-are known to modulate its development, it is important to study psychosocial factors that may influence secretion of stress hormones during adolescence. The goal of the present study was to explore the associations between Facebook behaviors (use frequency, network size, self-presentation and peer-interaction) and basal levels of cortisol among adolescent boys and girls. Eighty-eight adolescents (41 boys, 47 girls) aged between 12 and 17 (14.5 ± 1.8) were recruited. Participants provided four cortisol samples per day for two non-consecutive weekdays. Facebook behaviors were assessed in accordance with the existing literature. Well-validated measures of perceived stress, perceived social support, self-esteem, and depressive symptoms were also included. A hierarchical regression showed that after controlling for sex, age, time of awakening, perceived stress, and perceived social support, cortisol systemic output (area under the curve with respect to ground) was positively associated with the number of Facebook friends and negatively associated with Facebook peer-interaction. No associations were found among depressive symptoms, self-esteem, and cortisol. These results provide preliminary evidence that Facebook behaviors are associated with diurnal cortisol concentrations in adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma

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Kuai R

2017-09-01

Full Text Available Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs, which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative – withalongolide A 4,19,27-triacetate (WGA-TA – which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA1 mimetic peptide (22A, which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm, discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC50] 0.26±0.045 µM than free WGA-TA (IC50 0.492±0

Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

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Dean A. Myers

2012-01-01

Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients.

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Sartorio, A; Agosti, F; Patrizi, A; Gattico, A; Tringali, G; Giunta, M; Muller, E E; Rigamonti, A E

2013-03-01

It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that

Radioimmunoassay of glicagon secretion in diabetes mellitus

International Nuclear Information System (INIS)

Milanova, St.; Koparanova, O.; Milkov, V.; Visheva, N.; Kurtev, I.; Maleeva, A.

1988-01-01

Radioimunoassay of glucagon, lh, fsh, aldosterone, cortisol, acth, sth and lth was performed using preparations from the firms SORIN, AMERSHAM and HOECHST. The basal glucagon secretion was estimated in 403 diabetic patients and 84 normal subjects. It was transitorily suppressed by glucose. The alpha-cellular reactivity in diabetic patients was stimulated by insulin-induced hypoglycemia and with arginine and vasopressin. The tested group of diabetic patients had absolute hyperglucagonemia, despite the hyperglycemia, which is an evidence of abnormal alpha-cellular function. The insulin-dependent nature of hyperglucagonemia in diabetes mellitus and the hyperreactivity of glucagon secretion after protein stimulation was demonstrated. The correlation of these results leads to essential diagnostic inferences

Stimulation of corticosterone secretion in vitro by brief ACTH exposure

International Nuclear Information System (INIS)

Keith, L.D.; Tam, B.; Greer, M.A.

1986-01-01

The authors examined the relationship between ACTH concentration and exposure duration on stimulation of corticosterone (B) secretion in vitro using perifused enzymatically dispersed rat adrenocortical cells. A modular perifusion apparatus was used that permitted evaluation of 20-24 cell chambers per experimental session. In expt 1,20-1000 pg/ml concentrations of synthetic ACTH-(1-24) were presented to cells for 1 min. In expt 2, 100 pg ACTH-(1-24) was presented to adrenal cells in five dose-duration regimens ranging from 5 pg/min for 20 min to 100 pg/min for 1 min. Perifusal rate was 1 ml/min in all sessions. B was determined by radioimmunoassay. In expt 1 (constant-duration paradigm), 1-min presentation of ACTH-(1-24) produced log-linear dose-response effects across these concentrations. In expt 2 (constant-mass paradigm), identical masses administered in different dose-duration regimens had different steroidogenic efficacies: low-dose long-duration regimens provoked greater total release than high-dose short-duration regimens. Overall, every dose-duration regimen was associated with stimulation of B secretion. These results indicate that 1) very brief exposure to physiological concentrations of ACTH-(1-24) is a significant stimulus for corticosteroid secretion; 2) variations in the dose-duration regimen over the physiological range modifies both the maximum rate of secretion and the duration of secretion, but not the response latency; and 3) ACTH-(1-24) presentation mass is not the sole determinant of B secretion

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

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Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

Science.gov (United States)

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

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Sherri Z. Millis

2015-01-01

Full Text Available Purpose Current first-line chemotherapy for patients with metastatic adrenocortical cancer (ACC includes doxorubicin, etoposide, cisplatin, and mitotane with a reported response rate of only 23.2%. New therapeutic leads for patients with refractory tumors are needed; there is no standard second-line treatment. Methods Samples from 135 ACC tumors were analyzed by immunohistochemistry, in situ hybridization (FISH or CISH, and/or gene sequencing at a single commercial reference laboratory (Caris Life Sciences to identify markers associated with drug sensitivity and resistance. Results Overexpression of proteins related to demonstrated chemotherapy sensitivity or resistance included topoisomerase 1, progesterone receptor, and topoisomerase 2-alpha in 46%, 63%, and 42% of cases, respectively. Loss of excision repair cross-complementary group 1 (ERCC1, phosophatase and tensin homolog, O(6-methylguanine-methyltransferase, and ribonucleotide reductase M1 (RRM1 was identified in 56%, 59%, 71%, and 58% of cases, respectively. Other aberrations included overexpression of programmed death-ligand 1 or programmed cell death protein 1 tumor-infiltrating lymphocytes in >40% of cases. In all, 35% of cases had a mutation in the canonical Wnt signaling pathway (either CTNNB1 or APC and 48% had a mutation in TP53. No other genomic alterations were identified. Conclusion Biomarker alterations in ACC may be used to direct therapies, including recommendations for and potential resistance of some patients to traditional chemotherapies, which may explain the low response rate in the unselected population. Limited outcomes data support the use of mitotane and platinum therapies for patients with low levels of the proteins RRM1 and ERCC1.

Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

International Nuclear Information System (INIS)

Pepe, G.J.; Waddell, B.J.; Albrecht, E.D.

1990-01-01

We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of [3H]F/[14C]E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production

Cortisol and somatization.

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Rief, W; Auer, C

2000-05-01

Somatization symptoms are frequently associated with depression, anxiety, and feelings of distress. These features interact with the activity of the HPA-axis. Therefore we investigated relationships between somatization symptoms and cortisol. Seventy-seven participants were classified into three groups: somatization syndrome (at least eight physical symptoms from the DSM-IV somatization disorder list), somatization syndrome combined with major depression, and healthy controls. The following data were collected: salivary cortisol at three time points (morning, afternoon, evening), nighttime urinary cortisol, serum cortisol after the dexamethasone suppression test (DST), and psychological variables such as depression, anxiety, somatization, and hypochondriasis. Salivary cortisol showed typical diurnal variations. However, the groups did not differ on any of the cortisol variables. A possible explanation may be counteracting effects of somatization and depression. Exploratory correlational analyses revealed that associations between cortisol and psychopathological variables were time-dependent. DST results correlated with psychological aspects of somatization, but not with the number of somatoform symptoms per se.

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

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Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

1991-03-01

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; Ppituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

Science.gov (United States)

Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W

2018-05-02

Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of

In vivo and in vitro evaluation of [18F]FETO with respect to the adrenocortical and GABAergic system in rats

International Nuclear Information System (INIS)

Mitterhauser, Markus; Wadsak, Wolfgang; Wabnegger, Leila; Sieghart, Werner; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert

2003-01-01

11β-Hydroxylase (CYP11B1, P450 11β ) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [ 11 C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[ 18 F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA A receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [ 3 H]flunitrazepam in the absence or presence of 10 μM diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%±1.19% ID/g at 30 min), followed by lung (1.18%±0.19% ID/g, 10 min), liver (0.59%±0.13% ID/g, 10 min) and duodenum (0.7%±0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [ 3 H]flunitrazepam with similar potencies and to a comparable extent. It is concluded that FETO shows characteristics suitable for the imaging of

Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism

Directory of Open Access Journals (Sweden)

Herve eLefebvre

2015-04-01

Full Text Available It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia, a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events which cause the disease favor abnormal adrenal differenciation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms which are likely to play a role in the pathophysiology of bilateral macronodular adrenal hyperplasia-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

Hair cortisol and self-reported stress in healthy, working adults.

Science.gov (United States)

Gidlow, Christopher J; Randall, Jason; Gillman, Jamie; Silk, Steven; Jones, Marc V

2016-01-01

Chronic stress can be important in the pathology of chronic disease. Hair cortisol concentrations (HCC) are proposed to reflect long term cortisol secretion from exposure to stress. To date, inconsistencies in the relationship between HCC and self-reported stress have been attributed to variation and limitations of perceived stress measurement. We report data from employees of two large public sector worksites (n=132). Socio-demographic, health, lifestyle, perceived stress scale (PSS), and work-related effort reward imbalance (ERI) were collected at baseline. Participants were asked to respond to mobile text messages every two days, asking them to report current stress levels (Ecological momentary assessment, EMA), and mean stress was determined overall, during work hours, and out of work hours. At 12 weeks, the appraisal of stressful life events scale (ALES) was completed and 3 cm scalp hair samples were taken, from which HCC was determined (to reflect cortisol secretion over the past 12 weeks). Mean response rate to EMA was 81.9 ± 14.9%. Associations between HCC and the various self-reported stress measures (adjusted for use of hair dye) were weak (allwork hours (ρ=.196, p=.013) and ALES Loss subscale (ρ=.241, p=.003), and two individual items from ERI (relating to future work situation). In regression analysis adjusting for other possible confounders, only the HCC-ALES Loss association remained significant (p=.011). Overall, our study confirms that EMA provides a useful measurement tool that can gather perceived stress measures in real-time. But, there was no relationship between self-reported stress collected in this way, and HCC. The modest association between HCC and stress appraisal does however, provide some evidence for the role of cognitive processes in chronic stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

When endocrinology and democracy collide: emotions, cortisol and voting at national elections.

Science.gov (United States)

Waismel-Manor, Israel; Ifergane, Gal; Cohen, Hagit

2011-11-01

Faced with stressful experiences, such as uncertainty or novelty, the adrenal glands secrete glucocorticoid hormones to help us cope with stress. Since many decision-making situations are stressful, there is reason to believe that voting is a stressful event. In this study, we asked voters in Israel's national election (N=113) to report on their general affective state immediately before entering the polling place using the Positive Affect Negative Affect Schedule (PANAS) and to provide us with a saliva sample through which we could evaluate their cortisol levels. Compared to a second sample of voters who reported their affective state on election night (N=70), we found that voters at the ballot box had higher positive and negative affect. Moreover, our voters at the polling place exhibited cortisol levels that were significantly higher than their own normal levels obtained on a similar day, and significantly higher than those of a second control group sampled the day after the elections (N=6). Our data demonstrate that elections are exciting, yet stressful events, and it is this stress, among other factors, that elevates the cortisol levels of voters. Since elevated cortisol has been found to affect memory consolidation, impair memory retrieval and lead to risk-seeking behavior, we discuss how these outcomes of elevated cortisol levels may affect voting in general and the field of electoral studies in particular. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

International Nuclear Information System (INIS)

Okada, H.

1979-01-01

Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

Combined Ovarian and Adrenal Venous Sampling in the Localization of Adrenocorticotropic Hormone-Independent Ectopic Cushing Syndrome.

Science.gov (United States)

Chen, Shi; Li, Ran; Zhang, Xiaobo; Lu, Lin; Li, Ji; Pan, Hui; Zhu, Huijuan

2018-03-01

Cushing syndrome is rarely caused by the secretion of cortisol from ovarian tumors. In clinical decision-making, it is important to determine whether the ovarian tumor is capable of secreting cortisol. Selective ovarian and adrenal venous sampling is scarcely reported in the localization of ACTH-independent ectopic Cushing syndrome. We present a case of 40-year-old Chinese woman who had weight gain, hirsutism, hypertension, and menstrual disorder over 6 months. Her physical examination and biochemical assessment revealed adrenocorticotropic hormone-independent Cushing syndrome. Adrenal computed tomography scan indicated no abnormality. A mass of 5.7 cm × 4.2 cm × 3.4 cm was discovered by pelvic ultrasonography. Somatostatin receptor scintigraphy revealed no abnormal radioactivity intake. Combined ovarian and adrenal venous sampling together with a cortisol assay were conducted. Results revealed cortisol concentration of the right-side ovarian vein, left-side ovarian vein, and peripheral vein of 268.60, 29.00, and 35.18 μg/dL, respectively, suggesting a right-side ovarian origin. A right-side salpingo-oophorectomy was performed and the pathological diagnosis revealed ovarian steroid cell tumor, not otherwise specified. The cortisol level was substantially lower after the patient underwent surgery and symptoms of Cushing syndrome disappeared. At 3-year follow-up, the patient remained disease free, and no tumor was observed on pelvic ultrasonogram. Combined ovarian and adrenal venous sampling is valuable in the localization of adrenocorticotropic hormone-independent ectopic Cushing syndrome.

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes.

Science.gov (United States)

Liu, Peter Y; Pincus, Steven M; Keenan, Daniel M; Roelfsema, Ferdinand; Veldhuis, Johannes D

2005-02-01

The hypothalamo-pituitary-testicular and hypothalamo-pituitary-adrenal axes are prototypical coupled neuroendocrine systems. In the present study, we contrasted in vivo linkages within and between these two axes using methods without linearity assumptions. We examined 11 young (21-31 yr) and 8 older (62-74 yr) men who underwent frequent (every 2.5 min) blood sampling overnight for paired measurement of LH and testosterone and 35 adults (17 women and 18 men; 26-77 yr old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements every 10 min for 24 h. To mirror physiological interactions, hormone secretion was first deconvolved from serial concentrations with a waveform-independent biexponential elimination model. Feedforward synchrony, feedback synchrony, and the difference in feedforward-feedback synchrony were quantified by the cross-approximate entropy (X-ApEn) statistic. These were applied in a forward (LH concentration template, examining pattern recurrence in testosterone secretion), reverse (testosterone concentration template, examining pattern recurrence in LH secretion), and differential (forward minus reverse) manner, respectively. Analogous concentration-secretion X-ApEn estimates were calculated from ACTH-cortisol pairs. X-ApEn, a scale- and model-independent measure of pattern reproducibility, disclosed 1) greater testosterone-LH feedback coordination than LH-testosterone feedforward synchrony in healthy men and significant and symmetric erosion of both feedforward and feedback linkages with aging; 2) more synchronous ACTH concentration-dependent feedforward than feedback drive of cortisol secretion, independent of gender and age; and 3) enhanced detection of bidirectional physiological regulation by in vivo pairwise concentration-secretion compared with concentration-concentration analyses. The linking of relevant biological input to output signals and vice versa should be useful in the dissection of the reciprocal control of

Diurnal cortisol rhythm

DEFF Research Database (Denmark)

Harris, Anette; Endresen Reme, Silje; Tangen, Tone

2015-01-01

with different instruments, and cortisol in a population with LBP. Participants (n=305) sick-listed 2-10 months due to non-specific LBP were included in the study. The screening instruments were the MINI-interview, HADS and HSCL-25. Saliva cortisol were measured on 2 consecutive days; at awakening, 30min later......, at 15:00h and 22:00h. Results showed no associations between any of the main diagnostic categories from the MINI-interview, or anxiety/depression measured with HADS or HSCL-25 and cortisol. However, significant associations were found between low cortisol awakening response, low cortisol slope during...... the day and the somatization scale from HSCL-25 (dizziness or lack of energy, lack of sexual interest, the feeling that everything requires substantial efforts, difficulties to fall asleep, headache). The results indicate that cortisol, may not be directly associated with psychopathology, such as anxiety...

Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris)

Science.gov (United States)

Tripp, K.M.; Verstegen, J.P.; Deutsch, C.; Bonde, Robert K.; de Wit, M.; Manire, Charles A.; Gaspard, J.; Harr, K.E.

2011-01-01

The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ≤23.5 and ≤16.7%; and ACTH: ≤6.9 and ≤8.5%. Accuracy resulted in a mean adjusted R(2)≥0.87 for serum cortisol and ≥0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1 µg/dl) and ACTH (10.0 pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ≥1.0 µg/dl were diagnostic of chronic stress; ACTH concentrations ≥87.5 pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4±0.2 µg/dl) and ACTH (47.7±15.9 pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate.

TSH-induced hyperthyroidism caused by a pituitary tumor.

Science.gov (United States)

Beck-Peccoz, Paolo; Persani, Luca

2006-09-01

A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Endoscopic Endonasal Surgery for Remission of Cushing Disease Caused by Ectopic Intracavernous Macroadenoma: Case Report and Literature Review.

Science.gov (United States)

Koutourousiou, Maria; Winstead, Welby I

2017-02-01

Complete surgical resection of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the gold standard of treatment of Cushing disease. Ectopic location of these adenomas is an extremely rare condition that may compromise the diagnosis and surgical success. We present the first case of an ectopic intracavernous ACTH-secreting macroadenoma totally resected with endoscopic endonasal surgery (EES). A 36-year-old woman presented with Cushing syndrome. Increased ACTH, serum cortisol, and free urine cortisol levels were identified; however, pituitary magnetic resonance imaging failed to show a pituitary tumor; instead, a parasellar lesion in the left cavernous sinus (CS) was noticed. Inferior petrosal sinus sampling showed a significant central to peripheral and lateralized left-sided ACTH gradient. The patient underwent EES. No tumor was found in the sella; however, the left CS was widely explored and a tumor was found lateral to the paraclival segment of the carotid artery. There were no complications after EES. Pathology confirmed the diagnosis of an ACTH-secreting adenoma. During the immediate postoperative course, serum cortisol levels decreased lower than 5 μg/dL. Postoperative magnetic resonance imaging showed complete tumor resection. At 20 months follow-up, the patient remained in clinical and biochemical remission of Cushing disease. Only 12 cases of ectopic intracavernous ACTH-secreting adenomas have been reported and all were microadenomas. The presence of an ectopic ACTH-secreting macroadenoma in the CS represents a surgical challenge. EES is the ideal approach for complete resection of ectopic intracavernous adenomas, allowing for a wide exploration of the CS with no surgical complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

Directory of Open Access Journals (Sweden)

Santosh Kumar Mondal

2014-01-01

Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

In vivo and in vitro evaluation of [{sup 18}F]FETO with respect to the adrenocortical and GABAergic system in rats

Energy Technology Data Exchange (ETDEWEB)

Mitterhauser, Markus [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna (Austria); Wadsak, Wolfgang [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Inorganic Chemistry, University of Vienna (Austria); Ludwig-Boltzmann-Institute for Nuclear Medicine, Vienna (Austria); Wabnegger, Leila; Sieghart, Werner [Institute for Brain Research, University of Vienna (Austria); Viernstein, Helmut [Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Kletter, Kurt [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Dudczak, Robert [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria)

2003-10-01

11{beta}-Hydroxylase (CYP11B1, P450{sub 11{beta}}) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [{sup 11}C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[{sup 18}F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA{sub A} receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [{sup 3}H]flunitrazepam in the absence or presence of 10 {mu}M diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%{+-}1.19% ID/g at 30 min), followed by lung (1.18%{+-}0.19% ID/g, 10 min), liver (0.59%{+-}0.13% ID/g, 10 min) and duodenum (0.7%{+-}0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [{sup 3}H]flunitrazepam with similar potencies and to a comparable extent. It is concluded

Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish

OpenAIRE

Faught, Erin; Best, Carol; Vijayan, Mathilakath M.

2016-01-01

Abnormal embryo cortisol level causes developmental defects and poor survival in zebrafish (Danio rerio). However, no study has demonstrated that maternal stress leads to higher embryo cortisol content in zebrafish. We tested the hypothesis that maternal stress-associated elevation in cortisol levels increases embryo cortisol content in this asynchronous breeder. Zebrafish mothers were fed cortisol-spiked food for 5 days, to mimic maternal stress, followed by daily breeding for 10 days to mon...

The relationship between cortisol responses to laboratory stress and cortisol profiles in daily life

OpenAIRE

Kidd, Tara; Carvalho, Livia A.; Steptoe, Andrew

2014-01-01

Relationships between cortisol responses to laboratory stress and cortisol output over the day have not been studied extensively. We tested associations between cortisol responses to a set of laboratory challenges (colour/word interference and mirror tracing) and three aspects of cortisol output over the day, namely total area under the curve (AUCday), the cortisol awakening response (CAR) and the slope of cortisol decline over the day. Participants were 466 men and women aged 54–76 years. We...

Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

NARCIS (Netherlands)

Molenaar, N.; Groeneveld, A.B.J.; Dijstelbloem, H.M.; de Jong, M.F.C.; Girbes, A.R.J.; Heijboer, A.C.; Beishuizen, A.

2011-01-01

Purpose: To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. Methods: A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63

High cortisol awakening response is associated with impaired error monitoring and decreased post-error adjustment.

Science.gov (United States)

Zhang, Liang; Duan, Hongxia; Qin, Shaozheng; Yuan, Yiran; Buchanan, Tony W; Zhang, Kan; Wu, Jianhui

2015-01-01

The cortisol awakening response (CAR), a rapid increase in cortisol levels following morning awakening, is an important aspect of hypothalamic-pituitary-adrenocortical axis activity. Alterations in the CAR have been linked to a variety of mental disorders and cognitive function. However, little is known regarding the relationship between the CAR and error processing, a phenomenon that is vital for cognitive control and behavioral adaptation. Using high-temporal resolution measures of event-related potentials (ERPs) combined with behavioral assessment of error processing, we investigated whether and how the CAR is associated with two key components of error processing: error detection and subsequent behavioral adjustment. Sixty university students performed a Go/No-go task while their ERPs were recorded. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive days following ERP data collection. The results showed that a higher CAR was associated with slowed latency of the error-related negativity (ERN) and a higher post-error miss rate. The CAR was not associated with other behavioral measures such as the false alarm rate and the post-correct miss rate. These findings suggest that high CAR is a biological factor linked to impairments of multiple steps of error processing in healthy populations, specifically, the automatic detection of error and post-error behavioral adjustment. A common underlying neural mechanism of physiological and cognitive control may be crucial for engaging in both CAR and error processing.

Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

NARCIS (Netherlands)

Molenaar, Nienke; Johan Groeneveld, A. B.; Dijstelbloem, Hilde M.; de Jong, Margriet F. C.; Girbes, Armand R. J.; Heijboer, Annemieke C.; Beishuizen, Albertus

2011-01-01

To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with

Global gene expression response to telomerase in bovine adrenocortical cells

International Nuclear Information System (INIS)

Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.

2005-01-01

The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

Pulsatile thyrotropin secretion in patients with Addison's disease during variable glucocorticoid therapy

DEFF Research Database (Denmark)

Hangaard, J; Andersen, M; Grodum, E

1996-01-01

, increasing significantly (P glucocorticoids, when the pulse frequency was also significantly reduced (P ... of glucocorticoids on the TSH response to TRH, our data indicate that even physiological serum levels of cortisol have an influence on endogenous TSH secretion, probably caused by regulation of the pituitary sensitivity to TRH....

Tributyltin (TBT) and Dibutyltin (DBT) Alter Secretion of Tumor Necrosis Factor Alpha (TNFα) from Human Natural Killer (NK) Cells and a Mixture of T cells and NK Cells

Science.gov (United States)

Hurt, Kelsi; Hurd-Brown, Tasia; Whalen, Margaret

2012-01-01

Butyltins (BTs) have been in widespread use. Tributyltin (TBT) has been used as a biocide in a variety of applications and is found in human blood samples. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride plastics and as a de-worming agent in poultry. DBT, like TBT, is found in human blood. Human natural killer (NK) cells are the earliest defense against tumors and viral infections and secrete the cytokine tumor necrosis factor (TNF) alpha (α). TNFα is an important regulator of adaptive and innate immune responses. TNFα promotes inflammation and an association between malignant transformation and inflammation has been established. Previously, we have shown that TBT and DBT were able to interfere with the ability of NK cells to lyse tumor target cells. Here we show that BTs alter cytokine secretion by NK cells as well as a mixture of T and NK lymphocytes (T/NK cells). We examined 24 h, 48 h, and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 µM) on TNFα secretion by highly enriched human NK cells and T/NK cells. The results indicate that TBT (200 - 2.5 nM) decreased TNFα secretion from NK cells. In the T/NK cells 200 nM TBT decreased secretion while 100-5 nM TBT increased secretion of TNFα. NK cells or T/NK cells exposed to higher concentrations of DBT showed decreased TNFα secretion while lower concentrations showed increased secretion. The effects of BTs on TNFα secretion are seen at concentrations present in human blood. PMID:23047847

Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency.

Science.gov (United States)

Geiger, Ashley M; Pitts, Kenneth P; Feldkamp, Joachim; Kirschbaum, Clemens; Wolf, Jutta M

2015-11-01

Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes. To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST. CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects--NE: F=1.05, p=.41; E: F=2.56, p=.045; cortisol: F=13.28, pcortisol's central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens. Copyright © 2015. Published by Elsevier Inc.

When we test, do we stress? Impact of the testing environment on cortisol secretion and memory performance in older adults.

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Sindi, Shireen; Fiocco, Alexandra J; Juster, Robert-Paul; Pruessner, Jens; Lupien, Sonia J

2013-08-01

The majority of studies find that older adults have worse memory performance than young adults. However, contextual features in the testing environment may be perceived as stressful by older adults, increasing their stress hormone levels. Given the evidence that older adults are highly sensitive to the effects of stress hormones (cortisol) on memory performance, it is postulated that a stressful testing environment in older adults can lead to an acute stress response and to memory impairments. The current study compared salivary cortisol levels and memory performance in young and older adults tested in environments manipulated to be stressful (unfavourable condition) or not stressful (favourable condition) for each age group. 28 young adults and 32 older adults were tested in two testing conditions: (1) a condition favouring young adults (constructed to be less stressful for young adults), and (2) a condition favouring older adults (constructed to be less stressful for older adults). The main outcome measure was salivary cortisol levels. Additionally, immediate and delayed memory performances were assessed during each condition. In older adults only, we found significantly high cortisol levels and low memory performance in the condition favouring young adults. In contrast, cortisol levels were lower and memory performance was better when older adults were tested in conditions favouring them. There was no effect of testing condition in young adults. The results demonstrate that older adults' memory performance is highly sensitive to the testing environment. These findings have important implications for both research and clinical settings in which older adults are tested for memory performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Massive weight loss decreases corticosteroid-binding globulin levels and increases free cortisol in healthy obese patients: an adaptive phenomenon?

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Manco, Melania; Fernández-Real, José M; Valera-Mora, Maria E; Déchaud, Henri; Nanni, Giuseppe; Tondolo, Vincenzo; Calvani, Menotti; Castagneto, Marco; Pugeat, Michel; Mingrone, Geltrude

2007-06-01

Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women. Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.

High Cardiorespiratory Fitness Is Negatively Associated with Daily Cortisol Output in Healthy Aging Men.

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Francesco Lucertini

Full Text Available Physical fitness has salutary psychological and physical effects in older adults by promoting neuroplasticity and adaptation to stress. In aging, however, the effects of fitness on the hypothalamic-pituitary-adrenal (HPA axis are mixed. We investigated the association between cardiorespiratory fitness and HPA activity in healthy elderly men (n = 22, mean age 68 y; smokers, obese subjects, those taking drugs or reporting recent stressful events were excluded, by measuring in saliva: i daily pattern of cortisol secretion (6 samples: 30' post-awakening, and at 12.00, 15.00, 18.00, 21.00, 24.00 h; and ii the cortisol response to a mental challenge. Cardiorespiratory fitness (VO2max was estimated using the Rockport Walking Test and the participants were assigned to high-fit (HF, ≥60°, n = 10 and low-fit (LF, ≤35°, n = 12 groups according to age-specific percentiles of VO2max distribution in the general population. At all daytimes, basal cortisol levels were lower in the HF than the LF group, most notably in the evening and midnight samples, with a significant main effect of physical fitness for cortisol levels overall; the area-under-the-curve for total daily cortisol output was significantly smaller in the HF group. Among the subjects who responded to mental stress (baseline-to-peak increment >1.5 nmol/L; n = 13, 5 LF, 8 HF, the amplitude of cortisol response and the steepness of recovery decline displayed an increasing trend in the HF subjects, although between-group differences failed to reach the threshold for significance. In conclusion, cardiorespiratory fitness in healthy aging men is negatively correlated with daily cortisol output and contributes to buffering the HPA dysregulation that occurs with advancing age, thus possibly playing a beneficial role in contrasting age-related cognitive and physical decline.

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)].

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Linquette, M; Lefebvre, J; Racadot, A; Cappoen, J P

1975-01-01

The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is

CD4+ T cell-mediated rejection of MHC class II-positive tumor cells is dependent on antigen secretion and indirect presentation on host APCs.

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Haabeth, Ole Audun Werner; Fauskanger, Marte; Manzke, Melanie; Lundin, Katrin U; Corthay, Alexandre; Bogen, Bjarne; Tveita, Anders Aune

2018-05-11

Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4+ T cell-driven anti-tumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4+ T cells in vivo. These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4+ T cell-mediated rejection, and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4+ T cells. Copyright ©2018, American Association for Cancer Research.

Pituitary gland tumors

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Jesser, J.; Schlamp, K.; Bendszus, M.

2014-01-01

This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [de

[Pituitary gland tumors].

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Jesser, J; Schlamp, K; Bendszus, M

2014-10-01

This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

Hair cortisol concentrations exhibit a positive association with salivary cortisol profiles and are increased in obese prepubertal girls.

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Papafotiou, Chrysanthe; Christaki, Eirini; van den Akker, Erica L T; Wester, Vincent L; Apostolakou, Filia; Papassotiriou, Ioannis; Chrousos, George P; Pervanidou, Panagiota

2017-03-01

Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.

Cortisol and finfish welfare

NARCIS (Netherlands)

Ellis, T.; Yildiz, H.Y.; López-Olmeda, J.; Spedicato, M.T.; Tort, L.; Overli, O.; Martins, C.I.

2012-01-01

Previous reviews of stress, and the stress hormone cortisol, in fish have focussed on physiology, due to interest in impacts on aquaculture production. Here, we discuss cortisol in relation to fish welfare. Cortisol is a readily measured component of the primary (neuroendocrine) stress response and

Role of cortisol in stocking density-induced changes in growth and metabolism of brook charr (Salvelinus fontinalis)

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Vijayan, M.M.

1990-01-01

Brook charr (Salvelinus fontinalis) held at high stocking density (SD) (120 kg/m{sup 3}) had a lower growth rate, food consumption and food conversion efficiency, and plasma thyroxine (T4) than those held at low SD (30 kg/m{sup 3}). SD had no effect on plasma triiodothyronine (T3) levels. Plasma cortisol levels in fish maintained at high SD were variable, being either lower with increased SD or not different from the low SD group. Head kidney tissue (containing the interrenal cells) preparations of brook charr held at high SD showed a higher spontaneous cortisol secretion rate. There was no difference in the clearance rate of ({sup 3}H)-cortisol from plasma, but liver from fish held at high SD showed higher cortisol uptake and catabolism, indicative of altered hepatic metabolic activity. High SD appears to alter the energy metabolism of brook charr. This was evident from significant changes between densities in levels of metabolites (plasma glucose and liver glycogen) and activities of key hepatic enzymes (PFK, HK, FBPase, G6PDH, HOAD, GK and G3PDH). These results suggests that high SD has the effect of mobilizing triglycerides, and promoting gluconeogenesis from glycerol, but has little effect on protein metabolism. When cortisol was administered to brook charr in the form of slow release intraperitoneal implants, the metabolic changes evident were similar to those observed in fish held at high SD. There was no consistent increase in plasma cortisol levels of cortisol implanted fish over a 90 day period. Nevertheless, there were significant effects, apparently cortisol-related, on certain metabolite levels (plasma glycerol, plasma glucose, hepatic glycogen), and activities of key hepatic enzymes.

Antepartum depression severity is increased during seasonally longer nights: relationship to melatonin and cortisol timing and quantity.

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Meliska, Charles J; Martínez, Luis F; López, Ana M; Sorenson, Diane L; Nowakowski, Sara; Kripke, Daniel F; Elliott, Jeffrey; Parry, Barbara L

2013-11-01

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than

Long-term follow-up results of combination therapy of surgery and gamma knife on pituitary tumor

International Nuclear Information System (INIS)

Ikeda, Hidetoshi; Yoshimoto, Takashi; Shirokura, Hideshi

1997-01-01

Usefulness of the combination therapy for invasive pituitary tumor with surgery and gamma knife (GK) was evaluated on 17 cases followed for >2 years. Tumors involved ACTH cell adenoma, GH cell adenoma, mixed GH and PRL, purihormonal adenoma, gonadotrophic cell adenoma, GH cell adenoma and null cell adenoma, which were divided into I and II group since adverse effects by GK on the normal pituitary tissues could be evaluated according to tumor growth and abnormal hormone secretion. Irradiation was carried out to make the marginal dose of around 30 (15-35) Gy and center dose of 25-70 Gy on the gland, and marginal dose of <10 Gy on optic nerve. After GK, follow-up was done by pituitary hormone values, tests for sight and visual field and MRI examination. Hypopituitarism was seen in 67% with 100% remission of Cushing's disease. MRI revealed that the adenoma changed to fibrosis (type 1) with increasing Gd-enhancement or to cystic necrosis (type 2) without Gd-enhancement. Values for GH, cortisol and ACTH turned to normal ones. Thus the combination therapy was found useful. (K.H.)

Myxoid variant of adrenocortical tumors. Report of two cases with unique entity

International Nuclear Information System (INIS)

Suzuki, Rumi; Ito, Yukio; Okamoto, Takahiro; Iihara, Masatoshi; Obara, Takao; Tsuiki, Mika; Takano, Kazue; Nishikawa, Toshio; Aiba, Motohiko

2007-01-01

Cases in the title are reported. Case 1, a 57-year old female, had fracture and reduced limbic muscular force due to Cushing syndrome. CT image gave a big tumor in the left adrenal and 131 I-adosterol scintigraphy revealed the increased and decreased 131 I accumulation in the left and right adrenal, respectively: the carcinoma suspected. Only tumor portion was dissected out and was found to be an adenoma in histology. Case 2, a 50-year old male, had Cushing syndrome and extreme obesity. Previous CT presented a big tumor in the left adrenal; biopsy was performed under CT; and before surgery, the tumor was partly calcified in CT, which was found to be a carcinoma. In both cases, histology gave findings of the interstitial and extracellular disposition of myxoid material and of pseudoglandular pattern. (R.T.)

A Case of Cushing’s Syndrome due to Ectopic Adrenocorticotropic Hormone Secretion from Esthesioneuroblastoma with Long Term Follow-Up after Resection

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Leslee N. Matheny

2018-01-01

Full Text Available We present a case of a 52-year-old male who developed Cushing’s Syndrome due to ectopic adrenocorticotrophic hormone (ACTH secretion from a large esthesioneuroblastoma (ENB of the nasal sinuses. The patient initially presented with polyuria, polydipsia, weakness, and confusion. Computed tomography scan of the head and magnetic resonance imaging showed a 7 cm skull base mass centered in the right cribriform plate without sella involvement. Work-up revealed ACTH-dependent hypercortisolemia, which did not suppress appropriately after high-dose dexamethasone. Subsequent imaging of the chest, abdomen, and pelvis did not reveal other possible ectopic sources of ACTH secretion besides the ENB. His hospital course was complicated by severe hypokalemia and hyperglycemia before successful surgical resection of the tumor, the biopsy of which showed ENB. Postoperatively, his ACTH level dropped below the limit of detection. In the ensuing 4 months, he underwent adjuvant chemoradiation with carboplatin and docetaxel with good response and resolution of hypokalemia and hyperglycemia, with no sign of recurrence as of 30 months postoperatively. His endogenous cortisol production is rising but has not completely recovered.

ADRENOCORTICOTROPIN HORMONE AND CORTISOL DYNAMIC VARIATION IN CASE OF CHILDREN›S NEUROINFECTIONS

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T. N. Malyugina

2016-01-01

Full Text Available The  data  presented in the  article  deal  with  research  of hormone changes in hypophysial-paranephric system in the course  of neuroinfections. The  given  work  was  carried  out with  the  purpose of detection of dependence of the  cortisol and adrenocorticotropin hormone level on aetiology, gender, severity and  period  (cycle  of the  disease.A comprehensive clinical  and  laboratorial checkup of 109 children with  different  nosological forms of neuroinfections was carried  out: meningitis: viral, enteroviral, purulent and  cerebromeningitis. Control board group was composed of 10 healthy children of the identical age. All the patients underwent the Adrenocorticotropin Hormone and  Cortisol  blood  serum  level,  IFA technique being  used,  during acuity and  reconvalesence. It has  been  determined that  in  case  of neuroinfections  irrrespective of the ethiology, hypophysis trophic funtction undergoes arrest during the whole disease period. While studying adrenal gland  functioning during the  acuity the  increased cortisol secretion is observed, the degree of which  is authentically  higher  in case  of purulent meningitis and  meningoencephalitis compared to hydromeningitis. On recovery  the cortisol values decrease to healthy children’s level. A reliable dependence of the  ACTH  and  cortisol  level  on the  severity degree in case of purulent meningitis and meningoencephalitis was discovered ( brought to light. It is also satisfactorily brought to light that ACTH and cortisol levels depend on the severity degree in case of purulent meningitis and meningoencephalitis. It is proved that adrenal gland  system function does  not depend on the patients’ gender and  age in case of neuroinfections.

The diurnal patterns of cortisol and dehydroepiandrosterone in relation to intense aerobic exercise in recreationally trained soccer players.

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Labsy, Z; Prieur, F; Le Panse, B; Do, M C; Gagey, O; Lasne, F; Collomp, K

2013-03-01

Diurnal patterns of cortisol and dehydroepiandrosterone (DHEA) secretion, the two main peripheral secretory products of the hypothalamic-pituitary-adrenal neuroendocrine stress axis, have been well characterized in rest conditions but not in relation to physical exercise. The purpose of this investigation was therefore to determine the effects of an intense 90-min aerobic exercise on the waking diurnal cortisol and DHEA cycles on three separate days [without exercise, with morning exercise (10:00-11:30 h), and with afternoon exercise (14:00-15:30 h)] in nine recreationally trained soccer players. Saliva samples were collected at awakening, 30 min after awakening, and then every 2 h from 08:00 to 22:00 h. A burst of secretory activity was found for cortisol (p exercise days under all conditions. However, there was a significant increase in salivary cortisol concentrations on the morning-exercise and afternoon-exercise days at, respectively, 12:00 h (p exercise was not evident for DHEA. The results of this investigation indicate that 90 min of intense aerobic exercise does not affect the circadian pattern of salivary adrenal steroids in recreationally trained athletes over a 16-h waking period, despite a transitory increase in post-exercise cortisol concentration. Further studies are necessary to determine whether these results are applicable to elite athletes or patients with cortisol or DHEA deficiency.

The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle

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Emma J. Brown

2017-04-01

Full Text Available The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal’s ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human–cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

Relationship between oxygen free radicals, cytokines, cortisol and stress complications in patients with acute cerebrovascular disease

International Nuclear Information System (INIS)

Zhu Yingbin; Wang Bingjie; Li Yunchao

2010-01-01

Objective: To investigate the relationship between oxygen free radicals, cytokines, cortisol and stress complications in patients with acute cerebrovascular disease (ACVD). Methods: Serum levels of superoxide dismutases (SOD), malonaldehyde (MDA) (with biochemistry) interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and cortisol (with RIA) were measured in 32 patients with acute cerebrovascular disease (ACVD) plus stress complications and 48 patients without stress complications as well as 36 controls. Results: Serum SOD contents in non-stressed group were higher than those in stressed group (P<0.05) but lower than those of the controls (P<0.05). However the levels of MDA, IL-6, TNF-α and cortisol were highest in the stressed group and lowest in the controls (all P<0.05). Conclusion: Oxygen free radicals, IL-6, TNF-α and cortisol were involved in stress complications in patients with ACVD. Monitoring the levels of serum SOD, MDA, IL-6, TNF-α and cortisol could be useful for predicting stress complications and evaluating the therapeutic effect. (authors)

Extraction-free cortisol assay

International Nuclear Information System (INIS)

1980-01-01

A method for determining the concentration of cortisol in a serum sample comprises: (a) incubating the sample, labelled cortisol and an effective amount of deblocking agent in an aqueous medium with a composite comprising anti-cortisol antibodies fixed in active form onto the surfaces of a negatively charged support material, the incubation being carried out at a pH of from 4.0 to 6.5 and under conditions sufficient to result in the formation of immunochemical complexes on the composite, some of which complexes comprise labelled cortisol; (b) separating the composite from the incubation medium; (c) determining the amount of label on the separated composite or in the remaining incubation medium; and (d) relating the determination of (c) to a standard to determine the cortisol concentration in the sample. (author)

Stress and stereotypic behaviour in mink (Mustela vison)

DEFF Research Database (Denmark)

Malmkvist, Jens; Jeppesen, Leif Lau; Palme, R.

2011-01-01

We examined whether female mink with low (LS) and high (HS) occurrence of stereotypic behaviour differ in their adrenocortical activity in baseline conditions or in response to immobilisation (Experiment 1), handling, adrenocorticotropic hormone (ACTH) challenge (Experiment 2) and excretion...... 4-20 h after the handling (P = 0.001). In Experiment 3 (n = 16), the excretion of infused (3)H-cortisol did not differ between LS and HS mink. Stereotypic behaviour is concurrent with higher baseline concentrations of FCM, which cannot be explained by a greater adrenocortical reactivity...... or a different excretion of the circulating cortisol. Instead, we conclude that mink with a high level of stereotypic behaviour have a greater perception of stress, or increased sensitivity to stressors at the pituitary level....

Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

Science.gov (United States)

Puar, Troy; Engels, Manon; van Herwaarden, Antonius E; Sweep, Fred C G J; Hulsbergen-van de Kaa, Christina; Kamphuis-van Ulzen, Karin; Chortis, Vasileios; Arlt, Wiebke; Stikkelbroeck, Nike; Claahsen-van der Grinten, Hedi L; Hermus, Ad R M M

2017-02-01

Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 × 105 (CYP11B1), 1.8 × 102 (CYP11B2), and 6.3 × 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 × 101 (LHCGR) and 9.3 × 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia. Copyright © 2017 by the Endocrine Society

Effect of aerobic and anaerobic exercise on anxiety and, blood cortisol secretion rate of young wrestlers

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bahram Delfan

2013-09-01

Conclusion: Regarding the results of the research it can be said that one session of aerobic exercise was effective in decreasing anxiety of wrestlers and also a long-term continuation of these exercises reduces anxiety and the cortisol hormone level which leads to mental and emotional balance of athletes.

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

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Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

2008-01-01

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice.

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Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Sugaya, Nagisa; Nomura, Shinobu

2012-06-01

This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

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Qin L

2016-03-01

effective in restraining SW13 cell proliferation. DDP could promote cell apoptosis and induce autophagy in SW13 cells. Concomitant therapy further promoted cell apoptosis by inhibiting autophagy. In vivo, we found that concomitant therapy was more potent than DDP monotherapy in inhibiting the growth of xenografted tumors and prolonging the survival of tumor-bearing mice.Conclusion: The antitumor ability of DDP was related to autophagy activity, and the concomitant therapy (DDP and CQ could be an optimal strategy for treating ACC. Keywords: adrenocortical carcinoma, chloroquine, cisplatin, apoptosis, autophagy

Cortisol response and desire to binge following psychological stress: comparison between obese subjects with and without binge eating disorder.

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Rosenberg, Noa; Bloch, Miki; Ben Avi, Irit; Rouach, Vanessa; Schreiber, Shaul; Stern, Naftali; Greenman, Yona

2013-07-30

While stress and negative affect are known to precede "emotional eating", this relationship is not fully understood. The objective of this study was to explore the relationship between induced psychological stress, hypothalamic-pituitary-adrenal (HPA) axis activity, and eating behavior in binge eating disorder (BED). The Trier Social Stress Test (TSST) was applied in obese participants with (n=8) and without BED (n=8), and normal weight controls (n=8). Psychological characteristics, eating-related symptoms, and cortisol secretion were assessed. Baseline stress, anxiety and cortisol measures were similar in all groups. At baseline desire to binge was significantly higher among the BED group. While the TSST induced an increase in cortisol levels, a blunted cortisol response was observed in the BED group. In the BED group, a positive correlation was found between cortisol (area under the curve) levels during the TSST and the change in VAS scores for desire to binge. Post-TSST desire to binge and sweet craving were significantly higher in the BED group and correlated positively with stress, anxiety, and cortisol response in the BED group only. These results suggest chronic down-regulation of the HPA axis in participants with BED, and a relationship between psychological stress, the acute activation of the HPA axis, and food craving. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasis

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J Khare

2018-01-01

Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS. Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml and 87.56 μg/dl (n < 7.5 μg/ml, respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 μg/dl (n < 1.8 μg/ml, respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.

Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

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Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

2014-01-01

Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, pcortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward

Cortisol Measures Across the Weight Spectrum.

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Schorr, Melanie; Lawson, Elizabeth A; Dichtel, Laura E; Klibanski, Anne; Miller, Karen K

2015-09-01

There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated. This study aimed to investigate cortisol measures across the weight spectrum. This was a cross-sectional study at a clinical research center. This study included 60 women, 18-45 years of age: overweight/obese (OB; N = 21); AN (N = 18); and normal-weight controls (HC; N = 21). HPA dynamics were assessed by urinary free cortisol, mean overnight serum cortisol obtained by pooled frequent sampling every 20 minutes from 2000-0800 h, 0800 h serum cortisol and cortisol-binding globulin, morning and late-night salivary cortisol, and dexamethasone-CRH testing. Body composition and bone mineral density (BMD) were assessed by dual-energy x-ray absorptiometry. Cortisol measures demonstrated a U-shaped relationship with BMI, nadiring in the overweight-class I obese range, and were similarly associated with visceral adipose tissue and total fat mass. Mean cortisol levels were higher in AN than OB. There were weak negative linear relationships between lean mass and some cortisol measures. Most cortisol measures were negatively associated with postero-anterior spine and total hip BMD. Cortisol measures are lowest in overweight-class I obese women-lower than in lean women. With more significant obesity, cortisol levels increase, although not to as high as in AN. Therefore, extreme underweight and overweight states may activate the HPA axis, and hypercortisolemia may contribute to increased adiposity in the setting of caloric excess. Hypercortisolemia may also contribute to decreased BMD and muscle wasting in the setting of both caloric restriction and excess.

Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours

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Helwig, J; Bertram, S; Sheu, S Y; Suttorp, A C; Seggewiß, J; Willscher, E; Walz, M K; Worm, K; Schmid, K W

2011-01-01

Background For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours. Methods In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16). Results Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist. Conclusion miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential. PMID:21471143

Clinical and prognostic aspects of adrenocortical neoplasms in childhood.

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Teinturier, C; Pauchard, M S; Brugières, L; Landais, P; Chaussain, J L; Bougnères, P F

1999-02-01

A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.

Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line

International Nuclear Information System (INIS)

Furuta, Chie; Noda, Shiho; Li Chunmei; Suzuki, Akira K; Taneda, Shinji; Watanabe, Gen; Taya, Kazuyoshi

2008-01-01

Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo. However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17β and modulation of nine major enzyme genes involved in the synthesis of steroid hormones (CYP11A, CYP11B1, CYP17, CYP19, 17βHSD1, 17βHSD4, CYP21, 3βHSD2, StAR) in human adrenal H295R cells supplied with cAMP. Exposure to 10 -7 to 10 -5 M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17β levels and increased progesterone secretion. At 10 -5 M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17βHSD4 and significantly suppressed expression of 3βHSD2. In comparison, 10 -7 to 2 x 10 -5 M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17β, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19. Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols

Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: the Multi-Ethnic Study of Atherosclerosis.

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Golden, Sherita Hill; Sánchez, Brisa N; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V; Seeman, Teresa; Wand, Gary S

2013-11-01

Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Non-cell autonomous or secretory tumor suppression.

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Chua, Christelle En Lin; Chan, Shu Ning; Tang, Bor Luen

2014-10-01

Many malignancies result from deletions or loss-of-function mutations in one or more tumor suppressor genes, the products of which curb unrestrained growth or induce cell death in those with dysregulated proliferative capacities. Most tumor suppressors act in a cell autonomous manner, and only very few proteins are shown to exert a non-cell autonomous tumor suppressor function on other cells. Examples of these include members of the secreted frizzled-related protein (SFRP) family and the secreted protein acidic and rich in cysteine (SPARC)-related proteins. Very recent findings have, however, considerably expanded our appreciation of non-cell autonomous tumor suppressor functions. Broadly, this may occur in two ways. Intracellular tumor suppressor proteins within cells could in principle inhibit aberrant growth of neighboring cells by conditioning an antitumor microenvironment through secreted factors. This is demonstrated by an apparent non-cell autonomous tumor suppressing property of p53. On the other hand, a tumor suppressor produced by a cell may be secreted extracellularly, and taken up by another cell with its activity intact. Intriguingly, this has been recently shown to occur for the phosphatase and tensin homolog (PTEN) by both conventional and unconventional modes of secretion. These recent findings would aid the development of therapeutic strategies that seek to reinstate tumor suppression activity in therapeutically recalcitrant tumor cells, which have lost it in the first place. © 2014 Wiley Periodicals, Inc.

Diet choice, cortisol reactivity, and emotional feeding in socially housed rhesus monkeys.

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Arce, Marilyn; Michopoulos, Vasiliki; Shepard, Kathryn N; Ha, Quynh-Chau; Wilson, Mark E

2010-11-02

Chronic psychosocial stress produces an array of adverse health consequences that are highly comorbid, including emotional eating, affective disorders, and metabolic syndrome. The consumption of high caloric diets (HCDs) is thought to provide comfort in the face of unrelenting psychosocial stress. Using social subordination in female rhesus monkeys as a model of continual exposure to daily stressors in women, we tested the hypothesis that subordinate females would consume significantly more calories from a HCD compared to dominant females, and this pattern of food intake would be associated with reduced cortisol release and reduced frequency of anxiety-like behaviors. Food intake, parameters of cortisol secretion, and socio-emotional behavior were assessed for 3 weeks during a no choice phase when only a low caloric diet (LCD) was available and during a choice condition when both a LCD and HCD were available. While all animals preferred the HCD, subordinate females consumed significantly more of the HCD than did dominant females. A flattening of the diurnal cortisol rhythm and a greater increase in serum cortisol to an acute social separation occurred during the diet choice condition in all females. Furthermore, the rate of anxiety-like behavior progressively declined during the 3-week choice condition in subordinate but not dominant females. These data provide support for the hypothesis that daily exposure to psychosocial stress increases consumption of calorically dense foods. Furthermore, consumption of HCDs may be a metabolic stressor that synergizes with the psychosocial stress of subordination to further increase the consumption of these diets. Copyright © 2010 Elsevier Inc. All rights reserved.

Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: The Multi-Ethnic Study of Atherosclerosis

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Golden, Sherita Hill; Sánchez, Brisa N.; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V.; Seeman, Teresa; Wand, Gary S.

2013-01-01

Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and B...

Contribution of the TP53 R337H mutation to the cancer burden in southern Brazil: Insights from the study of 55 families of children with adrenocortical tumors.

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Mastellaro, Maria J; Seidinger, Ana L; Kang, Guolian; Abrahão, Renata; Miranda, Eliana C M; Pounds, Stanley B; Cardinalli, Izilda A; Aguiar, Simone S; Figueiredo, Bonald C; Rodriguez-Galindo, Carlos; Brandalise, Silvia R; Yunes, José A; Barros-Filho, Antônio de A; Ribeiro, Raul C

2017-08-15

The tumor protein p53 (TP53) arginine-to-histidine mutation at codon 337 (R337H) predisposes children to adrenocortical tumors (ACTs) and, rarely, to other childhood tumors, but its impact on adult cancer remains undetermined. The objective of this study was to investigate the frequency and types of cancer in relatives of children with ACT who carry the TP53 R337H mutation. TP53 R337H testing was offered to relatives of probands with ACT. The parental lineage segregating the R337H mutation was identified in all families. The frequency and distribution of cancer types were compared according to R337H status. The authors' data also were compared with those publicly available for children with TP53 mutations other than R337H. The mean and median follow-up times for the probands with ACT were 11.2 years and 9.7 years (range, 3-32 years), respectively. During this time, cancer was diagnosed in 12 of 81 first-degree relatives (14.8%) carrying the R337H mutation but in only 1 of 94 noncarriers (1.1%; P = .0022). At age 45 years, the cumulative risk of cancer was 21% (95% confidence interval, 5%-33%) in carriers and 2% (95% confidence interval, 0%-4%) in noncarriers (P = .008). The frequency of cancer was higher in the R337H segregating lineages than in the nonsegregating lineages (249 of 1410 vs 66 of 984 individuals; P cancer were the most common types. TP53 R337H carriers have a lifelong predisposition to cancer with a bimodal age distribution: 1 peak, represented by ACT, occurs in the first decade of life, and another peak of diverse cancer types occurs in the fifth decade. The current findings have implications for genetic counseling and surveillance of R337H carriers. Cancer 2017;123:3150-58. © 2017 American Cancer Society. © 2017 American Cancer Society.

Reduced Cortisol Metabolism during Critical Illness

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Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

2015-01-01

BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (Pcortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian

Stress hormones in health and illness: the roles of work and gender.

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Lundberg, Ulf

2005-11-01

Two neuroendocrine systems are of specific interest in the study of stress and health; the sympathetic adrenomedullary system with the secretion of epinephrine and norepinephrine, and the hypothalamic pituitary adrenocortical (HPA) system with the secretion of cortisol. These hormones have often been used as objective indicators of stress in the individual. However, through their bodily effects, they are also a link between the psychosocial environment and various health outcomes. From a series of studies of women and men, it was concluded that gender roles and psychological factors are more important than biological factors for the sex differences in stress responses. The stress responses have been important for human and animal survival and for protection of the body. However, in modern society, some of these bodily responses may cause harm rather than protection. The catecholamines have been linked to cardiovascular disorders such as hypertension, myocardial infarction and stroke, cortisol to cardiovascular disease, Type 2 diabetes, reduced immune function and cognitive impairment. An adequate balance between catabolic (mobilization of energy) and anabolic processes (growth, healing) is considered necessary for long term health and survival. In modern society, which is characterized by a rapid pace of life, high demands, efficiency and competitiveness in a global economy, it is likely that lack of rest, recovery and restitution is a greater health problem than the absolute level of stress.

Adolescent Adrenocortical Activity and Adiposity: Differences by Sex and Exposure to Early Maternal Depression

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Ruttle, Paula L.; Klein, Marjorie H.; Slattery, Marcia J.; Kalin, Ned H.; Armstrong, Jeffrey M.; Essex, Marilyn J.

2014-01-01

Summary Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations. PMID:25001956

Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

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Moorkens, G; Berwaerts, J; Wynants, H; Abs, R

2000-07-01

Previous studies have revealed that hormonal disturbances may accompany the chronic fatigue syndrome (CFS). Changes in the secretion of the pituitary-adrenal axis have been demonstrated, as well as abnormalities in the GH-IGF-I axis. However, data have not always been well characterized and were sometimes conflicting. The small number of CFS patients investigated in earlier studies may have played a role in the interpretation of the results. Hormonal testing was performed in 73 nonobese CFS patients and nonobese 21 age-and gender-matched healthy controls. We investigated GH, ACTH and cortisol responses to insulin-induced hypoglycaemia. In a subgroup of patients arginine and clonidine stimulation for GH was also performed. Nocturnal secretion of GH, ACTH and cortisol were determined. Serum levels of IGF-I, prolactin, TSH, and free thyroxine were also measured. Visceral fat mass was assessed by CT scanning. GH response to insulin induced hypoglycaemia assessed by peak value (17.0 +/- 13.1 microg/l vs. 22. 1 +/- 9.8 microg/l; P = 0.01) and by AUC (450.0 +/- 361.3 microg/l vs. 672.3 +/- 393.0 microg/l; P = 0.002) was significantly decreased in CFS patients vs. controls. Nocturnal GH secretion assessed by GH peak value (5.4 +/- 3.7 vs. 9.0 +/- 5.1 microg/l; P = 0.44) and by AUC (34.4 +/- 20.2 vs. 67.4 +/- 43.1; P = 0.045) was also significantly impaired in CFS patients. Arginine and clonidine administration showed no differences in GH secretion between CFS patients and controls. In the CFS group, GH peak values were significantly higher after ITT than after arginine (P = 0.017) or clonidine (P = 0.001). No differences in serum IGF-I levels were found between CFS patients and controls. Except for a significantly lower nocturnal cortisol peak value, no differences were found in ACTH and cortisol secretion between CFS patients and controls. Significantly higher serum prolactin levels (7.4 +/- 4.7 microg/l vs. 4.4 +/- 1.3 microg/l; P = 0.004) and significantly higher serum

Circadian secretion patterns of ß-endorphin and leucine enkephalin

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E. H. de Wet

1992-07-01

Full Text Available ß-endorphin and leucine enkephalin are neuropeptides with potent opioid activity. In a study to investigate the circadian secretion patterns of the above-mentioned, blood samples were collected hourly from 12 healthy males who were subjected to the experiment for 24 hours. Radioimmunoassays were used in the analysis of plasma samples for ß-endorphin and leucine enkephalin. Peak concentrations of ß-endorphin were demonstrated from 08:00-09:00, while peak concentrations of leucine enkephalin occured from 23:00-07:00. Trough concentrations of ß-endorphin occurred from 24:00-05:00, while trough con­centrations of leucine enkephalin were demonstrated from 09:00-12:00. The illustrated circadian secretion pattern for ß-endorphin simulates the well-known circadian rhythm of cortisol. The answer to this may be in the fact that ß-endorphin and corticotropin stem from the same precursor. The illustrated circadian secretion pattern for leucine enkephalin simulates that of melatonin. The reason for this is unclear.

Antigen localization controls T cell-mediated tumor immunity.

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Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

2011-08-01

Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

Plasma cortisol radioimmunoassay with 125I-cortisol and polyethylene glycol

International Nuclear Information System (INIS)

Nishi, Keiko; Ogihara, Toshio; Miyai, Kiyoshi; Kumahara, Yuichi; Ishibashi, Kaichiro.

1976-01-01

A new, convenient, and less time-consuming plasma cortisol radioimmunoassay was set up. An antibody raised to cortisol-21-hemisuccinate-BSA was used at a 1: 6400 dilution. Because of its relatively high specificity, direct assay was possible. The main points of improvement were as follows, 125 I-cortisol was used as the labelled compound, B-F separation was done with polyethylene glycol, the effect of endogeneous corticosteroid binding globulin (CBG) was avoided by the use of 0.6% glutamate buffer pH 3.3 treatment. It was found that by the omission of heat treatment it was possible to avoid this CBG effect. The minimum detectable concentration was 0.1 mg/tube, and the assay range was 1 to 80 μg/dl plasma when a 10 μl sample was used. Precision and accuracy were satisfactory. Coefficient of variance for intraassay and interassay were 6.0% at 12.1 μg/dl, 3.8% at 36.6 μg/dl and 7.5% at 10.2 μg/dl, 6.7% at 41.8 μg/dl respectively. Data obtained by this method, by Murphy's CPBA method, and by other commercial RIA methods were quite comparable. The mean value of serum cortisol (8:30 - 11:30) in normal subjects was 7.7 +- 3.4 μg/dl (m +- S.D., n=102). Mean value of serum cortisol was decreased slightly but significantly with age. (auth.)

Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli

OpenAIRE

Oei, Nicole Y. L.; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

2014-01-01

Summary Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain’s ‘‘reward system’’, and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PETstudies indicate that the stress hormone cortisol may be crucial in the interaction between st...

Associations between circadian and stress response cortisol in children.

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Simons, Sterre S H; Cillessen, Antonius H N; de Weerth, Carolina

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (M age  = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

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Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

1993-10-01

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

A Cushing's syndrome patient's severe insomnia and morning blood pressure surge both improved after her left adrenal tumor resection.

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Imaizumi, Yuki; Ibaraki, Ai; Asada, Satoshi; Tominaga, Mitsuhiro; Hayashi, Hiroyuki; Tsuchihashi, Takuya; Eguchi, Kazuo; Kario, Kazuomi; Taketomi, Akira

2016-12-01

Underlying mechanisms of the elevated risks of hypertension and cardiovascular disease (CVD) in Cushing's syndrome (CS) are unclear. We treated an adult woman with CS because of a cortisol-secreting adrenal tumor. After tumor resection, the 24-h blood pressure (BP) level improved from 156/91 to 131/84 mmHg; the morning BP surprisingly improved from 174/98 to 127/93 mmHg, although we reduced her antihypertensive medication. Her sleep quality (by the Pittsburgh Sleep Quality Index) improved from 7 to 2 points. Disturbed circadian BP rhythm is often observed in CS, but was reported only as altered nocturnal BP fall. This is the first report showing the disappearance of the morning BP surge evaluated by ambulatory BP monitoring with postsurgery sleep quality improvement. Poor-quality sleep, followed by exaggerated morning BP surge may thus be a cause of CS-related cardiovascular events. Sleep quality and BP circadian rhythm evaluations may clarify hypertension and high CVD risk in CS.

Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies.

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Gaffey, Allison E; Wirth, Michelle M; Hoks, Roxanne M; Jahn, Allison L; Abercrombie, Heather C

2014-07-01

Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants' cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 h. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 h. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications: (1) when given a controlled dose of hydrocortisone, cortisol levels may increase more dramatically in women taking HBC versus women not on HBC or men; and (2) in studies manipulating cortisol levels, women on hormonal contraceptives should be investigated as a separate group.

Tumor interstitial fluid - a treasure trove of cancer biomarkers.

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Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J; Timmermans-Wielenga, Vera; Talman, Mai-Lis; Serizawa, Reza R; Moreira, José M A

2013-11-01

Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secretion, non-classical secretion, secretion via exosomes and membrane protein shedding. Consequently, the interstitial aqueous phase of solid tumors is a highly promising resource for the discovery of molecules associated with pathological changes in tissues. Firstly, it allows one to delve deeper into the regulatory mechanisms and functions of secretion-related processes in tumor development. Secondly, the anomalous secretion of molecules that is innate to tumors and the tumor microenvironment, being associated with cancer progression, offers a valuable source for biomarker discovery and possible targets for therapeutic intervention. Here we provide an overview of the features of tumor-associated interstitial fluids, based on recent and updated information obtained mainly from our studies of breast cancer. Data from the study of interstitial fluids recovered from several other types of cancer are also discussed. This article is a part of a Special Issue entitled: The Updated Secretome. Copyright © 2013 Elsevier B.V. All rights reserved.

Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: Comparison to salivary cortisol

OpenAIRE

D’Anna-Hernandez, Kimberly L.; Ross, Randal G.; Natvig, Crystal L.; Laudenslager, Mark L.

2011-01-01

Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair corti...

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

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Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

The Relations between Bullying Exposures in Middle Childhood, Anxiety, and Adrenocortical Activity

Science.gov (United States)

Carney, JoLynn V.; Hazler, Richard J.; Oh, Insoo; Hibel, Leah C.; Granger, Douglas A.

2010-01-01

This exploratory study investigated how exposure to bullying at school in middle childhood is associated with student anxiety levels and adrenocortical activity at a time preceding lunch when anxiety about potential bullying would potentially be higher. Ninety-one sixth-grade students (55 female and 36 male) reported being exposed one or more…

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

Science.gov (United States)

Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

2000-09-01

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

Hair cortisol detection in dairy cattle by using EIA: protocol validation and correlation with faecal cortisol metabolites.

Science.gov (United States)

Tallo-Parra, O; Manteca, X; Sabes-Alsina, M; Carbajal, A; Lopez-Bejar, M

2015-06-01

Hair may be a useful matrix to detect cumulative cortisol concentrations in studies of animal welfare and chronic stress. The aim of this study was to validate a protocol for cortisol detection in hair from dairy cattle by enzyme immunoassay (EIA). Seventeen adult Holstein-Friesian dairy cows were used during the milking period. Hair cortisol concentration was assessed in 25-day-old hair samples taken from the frontal region of the head, analysing black and white coloured hair separately. Concentrations of cortisol metabolites were determined in faeces collected twice a week during the same period of time. There was a high correlation between cortisol values in faeces and cortisol in white colour hair samples but such correlation was not significant with the black colour hair samples. The intra- and inter-assay coefficients of variation were 4.9% and 10.6%, respectively. The linearity showed R 2=0.98 and mean percentage error of -10.8 ± 1.55%. The extraction efficiency was 89.0 ± 23.52% and the parallelism test showed similar slopes. Cortisol detection in hair by using EIA seems to be a valid method to represent long-term circulating cortisol levels in dairy cattle.

WISP3 (CCN6 Is a Secreted Tumor-Suppressor Protein that Modulates IGF Signaling in Inflammatory Breast Cancer

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Celina G. Kleer

2004-03-01

Full Text Available Inflammatory breast cancer (IBC is the most lethal form of locally advanced breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that belongs to the CCN family. It contains a signal peptide at the N-terminus and four highly conserved motifs. Here, for the first time, we investigate the function of WISP3 protein in relationship to its structural features. We found that WISP3 is secreted into the conditioned media and into the lumens of normal breast ducts. Once secreted, WISP3 was able to decrease, directly or through induction of other molecule(s, the IGF-1-induced activation of the IGF-IR, and two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC cells. Furthermore, WISP3 containing conditioned media decreased the growth rate of SUM149 cells. This work sheds light into the mechanism of WISP3 function by demonstrating that it is secreted and that, once in the extracellular media, it induces a series of molecular events that leads to modulation of IGF-IR signaling pathways and cellular growth in IBC cells.

Screening for Cushing's syndrome in obese patients

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Ozay Tiryakioglu

2010-01-01

Full Text Available OBJECTIVES: The aim of this study was to examine the frequency of Cushing's syndrome (CS in obese patients devoid of specific clinical symptoms of Cushing's syndrome. METHODS: A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13 were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC. An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 μg/24 h were considered to be abnormal. Suppression of serum cortisol 100 μg/24 h were recorded in 37 patients (24%. Cushing's syndrome was diagnosed in 14 of the 150 patients (9.33%. Etiologic reasons for Cushing's syndrome were pituitary microadenoma (9 patients, adrenocortical adenoma (3 patients, and adrenocortical carcinoma (1 patient. CONCLUSION: A significant proportion (9.33% of patients with simple obesity were found to have Cushing's syndrome. These findings argue that obese patients should be routinely screened for Cushing's syndrome.

Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

OpenAIRE

Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-01-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was...

The role of anxiety in cortisol stress response and cortisol recovery in boys with oppositional defiant disorder/conduct disorder.

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Schoorl, Jantiene; Rijn, Sophie van; Wied, Minet de; van Goozen, Stephanie; Swaab, Hanna

2016-11-01

Children with antisocial and aggressive behaviors have been found to show abnormal neurobiological responses to stress, specifically impaired cortisol stress reactivity. The role of individual characteristics, such as comorbid anxiety, in the stress response is far less studied. Furthermore, this study extended previous studies in that not only baseline and reactivity to a psychosocial stressor were examined, but also recovery from a stressor. These three phases of cortisol could be impacted differentially in boys with oppositional defiant disorder/conduct disorder (ODD/CD) with (+ANX) and without anxiety (-ANX). The results revealed that cortisol patterns in response to psychosocial stress were different for boys with ODD/CD+ANX (n=32), ODD/CD-ANX (n=22) and non-clinical controls (NC) (n=34), with age range of 7.8-12.9 years. The ODD/CD-ANX group showed lower overall cortisol levels than the NC group. When considering the three phases of cortisol separately, the ODD/CD-ANX group had lower baseline cortisol levels relative to the other groups, whereas the ODD/CD+ANX showed an impaired cortisol recovery response. Within those with ODD/CD, callous-unemotional traits were predictive of high baseline cortisol levels. Also, anxiety predicted high baseline and recovery cortisol levels, whereas a high number of CD symptoms predicted reduced cortisol stress reactivity. These results clearly indicate that comorbid anxiety is an important factor in explaining differences in stress response profiles in boys with ODD/CD; although boys with CD/ODD are generally characterized by an impaired cortisol stress response, we found that those with comorbid anxiety showed impaired cortisol recovery, whereas those without anxiety showed reduced baseline cortisol levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

International Nuclear Information System (INIS)

Sandhu, Navdeep; Vijayan, Mathilakath M.

2011-01-01

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

Energy Technology Data Exchange (ETDEWEB)

Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

2011-05-15

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Cortisol in human milk predicts child BMI.

Science.gov (United States)

Hahn-Holbrook, Jennifer; Le, Tran Bao; Chung, Anna; Davis, Elysia Poggi; Glynn, Laura M

2016-12-01

Breastfeeding has been linked to lower rates of childhood obesity. Human milk contains cortisol, known to regulate glucose storage and metabolism. The aim of this study was to to test the hypothesis that early exposure to cortisol in human breast milk helps to modulate infant body mass index (BMI) trajectories over the first 2 years of life. Growth curve modeling was used to examine whether infant exposure to cortisol in human milk at 3 months predicted changes in child body mass index percentile (BMIP) at 6, 12, and 24 months of age in 51 breastfeeding mother-child pairs. Infants exposed to higher milk cortisol levels at 3 months were less likely to exhibit BMIP gains over the first 2 years of life, compared with infants exposed to lower milk cortisol. By age 2, infants exposed to higher milk cortisol levels had lower BMIPs than infants exposed to lower milk cortisol. Milk cortisol was a stronger predictor of BMIP change in girls than boys. Cortisol exposure through human milk may help to program metabolic functioning and childhood obesity risk. Further, because infant formula contains only trace amounts of glucocorticoids, these findings suggest that cortisol in milk is a novel biological pathway through which breastfeeding may protect against later obesity. © 2016 The Obesity Society.

Stress, cortisol, and obesity: a role for cortisol responsiveness in identifying individuals prone to obesity.

Science.gov (United States)

Hewagalamulage, S D; Lee, T K; Clarke, I J; Henry, B A

2016-07-01

There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Papel de la testosterona y el cortisol en el síndrome metabólico y la diabetes mellitus tipo 2 Role of testosterone and cortisol in metabolic syndrome and type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Aimée M. Álvarez Álvarez

2010-04-01

énicos de la resistencia a la insulina es el flujo aumentado de ácidos grasos que llega al hígado a partir del metabolismo de la grasa visceral. La relación cortisol/testosterona modula, entre otras hormonas, la acumulación de la grasa visceral; ha sido asociada, en hombres, a la mortalidad y la incidencia de enfermedades cardiovasculares isquémicas, a través de una alteración de los componentes del síndrome metabólico. Esta razón pudiera ser un indicador temprano de la resistencia a la insulina y del síndrome metabólico. Este elemento introduce una nueva dimensión dentro de la fisiopatogenia del síndrome metabólico que merece ser estudiada, con la finalidad de incrementar las potencialidades diagnósticas y terapéuticas en este campo.INTRODUCTION: metabolic syndrome and the type 2 diabetes mellitus are metabolic disorders fully approached in scientific literature due to its high incidence, as well as its association with a high morbidity and mortality. In past years new elements of potential impact in its physiopathology have been reviewed including the sexual steroids and the glucocorticoids. In present paper were reviewed and discussed the more current knowledges on the testosterone and cortisol role in the physiopathology of metabolic syndrome and type 2 diabetes mellitus in men. DEVELOPMENT: testosterone plays a significant role in modulation of sensitivity to insulin and in glucose homeostasis because of in men the low levels of testosterone are a predictor element of type 2 diabetes mellitus and of the metabolic syndrome. A bidirectional and reversible relation between androgen deficiency and the adiposity, as well as between the androgen deficiency and insulin resistance have been established. Authors suggest that low levels of testosterone could predispose to abdominal obesity provoking an alteration of fat acid metabolism, which at the same time will promote the insulin resistance. Cortisol and testosterone secretion are interrelated and have

Adrenocortical neoplasia: Evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

NARCIS (Netherlands)

R.R. de Krijger (Ronald); T.G. Papathomas (Thomas)

2012-01-01

textabstractAdrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of

Comparison between Salivary Cortisol Release in Rest and Training Days in Male Fitness Trainee

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Ardalan Shariat

2013-03-01

Full Text Available Background: The aim behind the current study was a comparison between salivary cortisol release in rest and training days in male fitness trainers. Methods: In such balanced crossover research, 15 healthy fitness-trained participants (with the mean age, weight and Height of 20.35 ± 1.20 years, 74.15 ± 3.20 kg and 177.30 ± 3.45 cm, respectively who had a four-year-previous experience in fitness exercise were chosen. While performing the research, the subjects were involved in a fitness training. The protocol contained three times of fitness training in a week, which would totally be alternative days of “rest” and “exercise” in the period of training. It means that they did training on Monday, Wednesday and Friday, and rested on the other days. To ensure the validity of this study, the participants were selected randomly, in both control and experimental groups. In the meantime, the protocol for fitness exercise was made up of four sets of 15 repetitions utilizing 65% of 1 repetition maximum (1 RM. Within each testing time, saliva samples were taken once in two hours for a maximum of 16 hours. In this study, the ANOVA was followed by a Post-hoc LSD test. Also, the significance level was deemed as (P≤0.05. Results: It was shown that there was a statistically significant addition in the salivary cortisol level right away after the fitness exercise session (P ≤ 0.05. However, no statistically significant difference was observed between exercise and control days in the circadian rhythm of salivary cortisol (P > 0.05. Conclusion: The present research demonstrated that while there was a significant influence of fitness exercise on cortisol right away after exercise, no statistically significant effect has been observed on the circadian secretion of cortisol in fitness sportsmen.

Does cortisol influence core executive functions? A meta-analysis of acute cortisol administration effects on working memory, inhibition, and set-shifting.

Science.gov (United States)

Shields, Grant S; Bonner, Joseph C; Moons, Wesley G

2015-08-01

The hormone cortisol is often believed to play a pivotal role in the effects of stress on human cognition. This meta-analysis is an attempt to determine the effects of acute cortisol administration on core executive functions. Drawing on both rodent and stress literatures, we hypothesized that acute cortisol administration would impair working memory and set-shifting but enhance inhibition. Additionally, because cortisol is thought to exert different nongenomic (rapid) and genomic (slow) effects, we further hypothesized that the effects of cortisol would differ as a function of the delay between cortisol administration and cognitive testing. Although the overall analyses were nonsignificant, after separating the rapid, nongenomic effects of cortisol from the slower, genomic effects of cortisol, the rapid effects of cortisol enhanced response inhibition, g+ = 0.113, p=.016, but impaired working memory, g+ = -0.315, p=.008, although these effects reversed over time. Contrary to our hypotheses, there was no effect of cortisol administration on set-shifting. Thus, although we did not find support for the idea that increases in cortisol influence set-shifting, we found that acute increases in cortisol exert differential effects on working memory and inhibition over time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Flavonoid metabolites reduce tumor necrosis factor‐α secretion to a greater extent than their precursor compounds in human THP‐1 monocytes

Science.gov (United States)

di Gesso, Jessica L.; Kerr, Jason S.; Zhang, Qingzhi; Raheem, Saki; Yalamanchili, Sai Krishna; O'Hagan, David; Kay, Colin D.; O'Connell, Maria A.

2015-01-01

1 Scope Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti‐inflammatory effects of flavonoid metabolites relative to their precursor structures. 2 Methods and results Six flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1–10 μM) were screened for their ability to reduce LPS‐induced tumor necrosis factor‐α (TNF‐α) secretion in THP‐1 monocytes. One micromolar peonidin‐3‐glucoside, cyanidin‐3‐glucoside, and the metabolites isovanillic acid (IVA), IVA‐glucuronide, vanillic acid‐glucuronide, protocatechuic acid‐3‐sulfate, and benzoic acid‐sulfate significantly reduced TNF‐α secretion when in isolation, while there was no effect on TNF‐α mRNA expression. Four combinations of metabolites that included 4‐hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF‐α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS‐induced IL‐1β and IL‐10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL‐1β secretion but none of the flavonoids or metabolites significantly modified IL‐10 secretion. 3 Conclusion This study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites. PMID:25801720

Measurements and signification of unbound cortisol in plasma

International Nuclear Information System (INIS)

Heyns, W.; Coolens, J.L.; Van Baelen, H.; De Moor, P.

1984-01-01

It is generally accepted that transcortin-bound cortisol in plasma has no direct hormonal activity. For that reason unbound cortisol, rather than total cortisol will reflect hormonal impregnation. In this communication we present a method to calculate unbound cortisol from total cortisol and from the concentration of transcortin based on the binding equilibrium. The results of this technique correlate very well with those obtained by centrifugal ultrafiltration at 37 0 C (R=0.988, y=0.986+0.862xX; n=20) showing the validity of this technique. The diurnal variation of transcortin and of total or unbound cortisol was studied in normal adult volunteers. No diurnal variation was observed for transcortin and the concentration of this protein was identical in normal men [38.3+-3.1(SD)mg/l, n=17] and women (38.9+-4.6 mg/l; n=5) but markedly higher (89.9+-14.6 mg/l, n=9) in estrogen-treated women. As expected both total and unbound cortisol showed marked diurnal variation with relatively high levels at 8 AM (total cortisol 23.5+-2.7 μg% in men and 25.8+-6.1 μg% in women); unbound cortisol 2.3+-0.5 μg% in men; 3.0+-1.6 μg% in women) and low levels at 10 PM (total cortisol 4.9+-3.3 μg% in men, 5.7+-2.8 μg% in women; unbound cortisol 0.2+-0.1 μg% in men; 0.3+-0.1μg% in women). In estrogen-treated women the levels of total cortisol were about twice as high at all timepoints, but the unbound cortisol concentrations were similar. These results indicate that the unbound cortisol is not affected by the changed concentration of transcortin. In patients with Cushing's disease, on the other hand, the unbound cortisol is relatively more elevated than the total cortisol due to a high degree of saturation of this protein, which is often present at relatively low concentrations [fr

Glucocorticoid receptor, but not mineralocorticoid receptor, mediates cortisol regulation of epidermal ionocyte development and ion transport in zebrafish (danio rerio.