Infrasellar pituitary gangliocytoma causing Cushing's syndrome.

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Domingue, Marie-Eve; Marbaix, Etienne; Do Rego, Jean-Luc; Col, Vincent; Raftopoulos, Christian; Duprez, Thierry; Vaudry, Hubert; Maiter, Dominique

2015-10-01

Pituitary gangliocytomas are uncommon neuronal tumours that may present with endocrine disorders, the most frequent being acromegaly caused by growth hormone hypersecretion. Cushing's syndrome is very rarely seen with gangliocytomas. We report the unique case of a 62 year-old woman whose clinical picture and endocrine testing clearly demonstrated adrenocorticotropin (ACTH)-dependent Cushing's syndrome. Pituitary magnetic resonance imaging showed a 12-mm homogeneous, infra- and retrosellar mass first diagnosed as pituitary macroadenoma. Transsphenoidal surgery was performed and allowed complete resection of the tumour with sparing of normal anterior pituitary. Very low postoperative serum cortisol and ACTH levels were observed in the early postoperative period and the patient is still in remission 18 months after surgery, thus demonstrating that the resected lesion was entirely responsible for the clinical picture. Histological and immunocytochemical analyses demonstrated a benign tumour composed of mature neuronal cells suggestive of a gangliocytoma, expressing both ACTH and corticotropin-releasing hormone (CRH). The tumour was surrounded by a rim of pituitary tissue containing ACTH-producing endocrine cells. Careful analysis of the resected lesion did not reveal any pituitary microadenoma. We search literature for similar cases and retraced only nine cases of gangliocytomas associated with Cushing's syndrome. In most of them, the tumour was combined with either pituitary corticotroph adenoma or hyperplasia. Our case represents a unique case of an infrasellar pituitary gangliocytoma which was able to cause Cushing's syndrome by both direct ACTH production and CRH-induced stimulation of neighbour normal corticotroph cells.

Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia

Directory of Open Access Journals (Sweden)

Valeria de Miguel

2010-06-01

Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

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Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

2016-07-01

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

Staged Bilateral Laparoscopic Adrenalectomy for Infantile ACTH-independent Cushing's Syndrome (Bilateral Micronodular Non-pigmented Adrenal Hyperplasia): A Case Report.

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Simforoosh, Nasser; Razzaghy Azar, Maryam; Soltani, Mohmmad Hossein; Nourbakhsh, Mona; Shemshaki, Hamidreza

2017-08-29

ACTH-independent Cushing's syndrome is an uncommon disorder in children. While laparoscopic adrenalectomy is well-established in adults, it is rarely used in infants and is associated with some concerns. A seven-month infant was referred to our hospital due to progressive signs and symptoms of Cushing's syndrome. Laboratory data confirmed ACTH-independent hypercortisolism. No history of exogenous corticosteroid contact was observed. The patient underwent left transperitoneal laparoscopic adrenalectomy when she was 7 months old, nevertheless,complete response was not seen. The patient underwent right laparoscopic adrenalectomy (contra-lateral adrenal gland) when she was 20 months old. The signs and symptoms of Cushing's syndrome began to resolve and serum and urine cortisol levels became normal 3 months after the second surgery. laparoscopic adrenalectomy is safe and feasible in infants, and in this case, relieved patient of the symptoms and saved her life.

Imaging in Cushing's syndrome; Imagem em sindrome de Cushing

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Sahdev, Anju; Evanson, Jane [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Diagnostic Imaging; Reznek, Rodney H. [St. Bartholomew' s Hospital, London (United Kingdom). Institute of Cancer. Cancer Imaging; Grossman, Ashley B. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Endocrinology]. E-mail: anju.sahdev@bartsandthelondon.nhs.uk

2007-11-15

Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80% of CS is due to ACTH-dependent causes and 20% due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas. (author)

Bilateral catheterization of inferior petrosal sinous: Utility in Cushing syndrome

International Nuclear Information System (INIS)

Ferrer, Maria D; Fajardo, Carmen; Esteban Enrique; Cosin Octavio, Valldecabres Carmen; Reig, Marian

2010-01-01

The aim of this study is to present our experience on bilateral and simultaneous inferior petrous sinus catheterization, on those patients with ACTH -dependent Cushing's syndrome. We describe the procedure and our results. Material and Method: A retrospective study was held between January 2003 and September 2009, including nine patients (2 men, 7 women) presenting ACTH - dependent Cushing's syndrome. Simultaneous inferior petrosal sinus catheterization was performed in all of them, sampling basal ACTH and after CRH stimulation. ACTH levels gradient in different pituitary locations and peripheral blood levels was recorded. Diagnosis was suggested when inappropriate and maintained hypercortisolemia. High urinary free cortisol levels and no response to dexamethasone suppression were detected. Eight out of nine patients had a prior negative imaging test result. Results: Inferior petrosal sinus bilateral catheterization was successfully performed in all cases, with no evidence of further complications. The results showed definitive diagnosis in all cases. In four patients ACTH levels gradient was lateralized to the left, leading to a specific surgical approach. One patient presented pituitary ACTH - secreting adenoma. Two other patients showed ectopic ACTH production, one showed suprarenal adenoma secreting ACTH and other one showed response to pituitary stimulation without side lateralisation, presenting a histological diagnosis of pituitary hyperplasia. Conclusion: Petrosal sinus catheterization is shown to be an efficient procedure to manage Cushing's syndrome differential diagnosis and to obtain specific anatomical information.

An unusual case of ectopic ACTH syndrome.

Science.gov (United States)

Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C

2012-02-01

Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Selenium-75-cholesterol imaging and computed tomography of the adrenal glands in differentiating the cause of Cushing's syndrome

International Nuclear Information System (INIS)

Miller, J.L.; Smith, J.A.; Mervis, B.; Roman, T.

1983-01-01

Measurement of 75 Se-cholesterol (Scintadren) uptake and computed tomography (CT) of the adrenal glands were compared as a means of differentiating the cause of Cushing's syndrome in 11 patients over a 2-year period. Quantitative Scintadren imaging differentiated adrenocorticotrophic hormone (ACTH)-dependent disease from local adrenocortical lesions as the cause of Cushing's syndrome in all the patients studied. CT of the adrenal glands rapidly and accurately detected the adrenal mass lesions in 2 cases and was effective in documenting bilateral hyperplasia due to ectopic ACTH-dependent disease. However, in entopic ACTH (pituitary)-dependent disease the adrenal glands were of normal thickness in all but 2 patients, who had bilateral hyperplasia. Scintadren imaging and CT are useful non-invasive procedures for differentiating local adrenal disease from ACTH-dependent disease as the cause of Cushing's syndrome and should be the initial investigations once a firm clinical and biochemical diagnosis of Cushing's syndrome has been made

Cushing's syndrome in pregnancy.

Science.gov (United States)

Nassi, Rossella; Ladu, Cristina; Vezzosi, Chiara; Mannelli, Massimo

2015-02-01

Cushing's syndrome is a rare condition in the general population and is even less common during pregnancy with only a few cases reported in literature. The diagnosis of Cushing's syndrome may be difficult during pregnancy because the typical features of the disorder and pregnancy may overlap. However, Cushing's syndrome results in increased fetal and maternal complications, and diagnosis and treatment are critical. This report describes a case of 26-year-old female at the 19th week of pregnancy with symptoms and signs of hypercortisolism, where ACTH-independent Cushing's syndrome was diagnosed and treated by robotic laparoscopic adrenalectomy at the 21th week of gestation.

Profound amplification of secretory-burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease

NARCIS (Netherlands)

van Aken, Maarten O.; Pereira, Alberto M.; van den Berg, Gerrit; Romijn, Johannes A.; Veldhuis, Johannes D.; Roelfsema, Ferdinand

2004-01-01

As described originally, Nelson's syndrome is characterized by grossly elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging in the course of Cushing's disease after bilateral adrenalectomy. No detailed studies have defined whether the mechanisms directing ACTH secretion

E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

Science.gov (United States)

Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

2016-11-01

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

Cushing's syndrome complicated by multiple opportunistic infections

NARCIS (Netherlands)

Bakker, R. C.; Gallas, P. R.; Romijn, J. A.; Wiersinga, W. M.

1998-01-01

The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and

ACTH-producing pheochromocytoma: clinical considerations and concise review of the literature

NARCIS (Netherlands)

Nijhoff, M. F.; Dekkers, O. M.; Vleming, L. J.; Smit, J. W. A.; Romijn, J. A.; Pereira, A. M.

2009-01-01

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It

A rare cause of Cushing's syndrome

DEFF Research Database (Denmark)

Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg

2014-01-01

Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH...

Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules.

Science.gov (United States)

Tating, Dan Louie Renz P; Montevirgen, Natasha Denise S; Cajucom, Loyda

2016-03-01

Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome.

A case of adrenal Cushing's syndrome with bilateral adrenal masses.

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Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

2016-01-01

A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

Severe Hypertension Secondary to Renal Artery Stenosis and Cushing's Syndrome

International Nuclear Information System (INIS)

Al-Zahrani, Ali S.; Al-Hajjaj, Alya; Al-Watban, Jehad; Kanaan, Imaduddin

2005-01-01

We present an unusual patient who simultaneously had severe renal artery stenosis RAS and Cushings syndrome. The case highlights the difficulty of reaching a specific diagnosis of Cushings syndrome and the possible interaction between Cushings syndrome and some other concurrent illnesses that this patient had. A 37-year old man presented with severe hypertension HTN and uncontrolled diabetes mellitus DM without clear physical signs of Cushings syndrome. He was found to have severe osteoporosis, proximal myopathy, several cutaneous warts, tinea versicolor, and chronic viral hepatitis. Captopril-stimulated renal scan and renal artery angiogram revealed severe RAS. Partial balloon dilatation of RAS led to improvement in HTN. Unexpectedly, urine free cortisol 24 hour was found extremely high. Serum adrenocorticotropic hormone ACTH was also elevated and high dose dexamethasone suppression tests were inconclusive. Several imaging studies failed to localize the source of ACTH. Despite normal MRI of the pituitary gland, bilateral inferior petrosal sinus sampling IPSS localized the source of ACTH secretion to the right side of the pituitary gland and right anterior hemihypophysectomy resulted in cure of Cushings disease, HTN, DM, and tinea versicolor with significant improvement in cutaneous warts, osteoporosis, and chronic hepatitis. In conclusion, RAS and Cushings syndrome may occur together. Significant hypercortisolemia can occur without clear signs of Cushings syndrome. Controlling hypercortisolemia is of paramount importance when treating chronic infections in patients with Cushing's syndrome. (author)

ACTH blood test

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... thyroid, or pancreas) making too much ACTH ( ectopic Cushing syndrome ) A lower-than-normal level of ACTH may ... Disease Read more Adrenal Gland Disorders Read more Cushing's Syndrome Read more A.D.A.M., Inc. is ...

Clinicopathological correlates of adrenal Cushing's syndrome.

Science.gov (United States)

Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

2015-03-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome

Directory of Open Access Journals (Sweden)

Christina E. Brzezniak

2017-04-01

Full Text Available Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS. Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

Incompatibility between fasting and postprandial plasma glucose in patients with Cushing's syndrome.

Science.gov (United States)

Otsuki, Michio; Kitamura, Tetsuhiro; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi

2016-11-30

It is shown that glucocorticoids have discordant effects on plasma glucose concentration through their effects on hepatic glycogen deposition, gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by cortisol overproduction is frequently accompanied with diabetes mellitus, but fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not examined in patients with Cushing's syndrome. The aim of this study was to investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their relationship in patients with Cushing's syndrome, in comparison with control subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH-independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI) were enrolled in this study. HbA1c and FPG in the patients with Cushing's syndrome were not different from the controls, whereas the FPG/HbA1c ratio was significantly lower in the patients with Cushing's syndrome than the controls. OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's syndrome than the non-diabetic controls, while HbA1c was not different between both groups and FPG was significantly lower in the patients with Cushing's syndrome than the controls. HOMA-β but not HOMA-R was significantly higher in the patients with Cushing's syndrome than the controls. In conclusion, FPG was rather lower in the patients with Cushing's syndrome than the controls. Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the abnormality of glucose metabolism in patients with Cushing's syndrome.

Ectopic ACTH syndrome complicated by multiple opportunistic infections treated with percutaneous ablation of the adrenal glands.

Science.gov (United States)

Chan, Chrystal; Roberts, James Mark

2017-11-14

Ectopic adrenocorticotropic hormone (ACTH)-related Cushing's syndrome can lead to multiple complications including severe immunosuppression. If the ACTH-secreting tumour cannot be found, definitive treatment is surgical adrenalectomy, typically followed by glucocorticoid replacement. Here, we present a case of fulminant respiratory failure secondary to coinfection with Pneumocystis jirovecii and cytomegalovirus in a patient with ectopic ACTH-dependent Cushing's syndrome with occult primary. Due to significant deconditioning, she was unable to undergo definitive adrenalectomy and instead underwent percutaneous microwave ablation of the adrenal glands. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cyclical Cushing's syndrome due to an atypical thymic carcinoid

NARCIS (Netherlands)

Meinardi, [No Value; van den Berg, G; Wolffenbuttel, BHR; Kema, IP; Dullaart, RPF

A 43-year-old man presented with fluctuating symptoms of weight gain, shortness of breath, pretibial oedema, associated with anxiety and memory disturbances. Laboratory investigation revealed an adrenocorticotropin (ACTH)-dependent cyclical Cushing's syndrome characterised by remarkable variations

Menstrual Abnormalities in a Woman with Acth-Dependent Pituitary Macroadenoma Mimicking Polycystic Ovary Syndrome

OpenAIRE

Chun-Cheng Liao; Shih-Yi Lin; Hsin-Wang Lin; Kuang-Hua Chen; Lan-Hua Chang; Shun-Tien Chen; John Wang

2006-01-01

Objective: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). Case Report: A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year...

Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation.

Science.gov (United States)

Wagner-Bartak, Nicolaus A; Baiomy, Ali; Habra, Mouhammed Amir; Mukhi, Shalini V; Morani, Ajaykumar C; Korivi, Brinda R; Waguespack, Steven G; Elsayes, Khaled M

2017-07-01

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent. Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

ACTH overexpressing pituitary hyperplasia in a patient with ectopic ACTH-syndrome due to carcinoid of the lung

Directory of Open Access Journals (Sweden)

Larisa Konstantinovna Dzeranova

2015-01-01

Full Text Available Ectopic ACTH-syndrome is the most diagnostically challenging  variant of endogenous hypercortisolism. Particularly difficult differential diagnosis of this syndrome is from Cushing's disease (CD, as currently there is no single test sufficiently accurate to differentiate accurately ectopic ACTH production from the pituitary. The main functional tests are based on the fact that the vast majority of ectopic ACTH production is autonomous and suppresses one from pituitary. But in some cases this is not observed, and then the data obtained all necessary laboratory and instrumental research evidence in favor of central genesis of CD in a patient with ACTH ectopic secretion, which can lead to inappropriate treatment. If you confirm the ectopic ACTH-syndrome, it may take quite a long time of searching for the pathological focus, as there is no sufficiently precise imaging and diagnostic method for determining the localization of ectopic source of ACTH production. Thus, the differential diagnosis of ACTH-dependent hypercortisolism and localization of the ectopic tumor is the cornerstone of early and radical treatment of patients. We present a difficult clinical case of a patient having a pituitary hyperplasia with excessive ACTH expression with primary ectopic ACTH syndrome caused by lung carcinoid.

Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia Expresion aberrante de receptores de glucagón en tejido adrenal de un paciente con síndrome de Cushing e hiperplasia adrenal macronodular indedependiente de ACTH

Directory of Open Access Journals (Sweden)

Valeria de Miguel

2010-06-01

Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

Science.gov (United States)

Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

2015-09-01

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all Pdisease, especially when the plasma ACTH level alone is not conclusive.

Relationship of serum lipids to adrenal-gland uptake of 6β-[131I] iodomethyl-19-norcholesterol in Cushing's syndrome

International Nuclear Information System (INIS)

Valk, T.W.; Gross, M.D.; Freitas, J.E.; Swanson, D.P.; Schteingart, D.E.; Beierwaltes, W.H.

1980-01-01

An alteration in serum cholesterol levels has been suggested as a possible modifier of adrenal uptake of the cholesterol analog, 6β-[ 131 I]iodomethyl-19-norcholesterol (NP-59). To assess the effect of hypercholesterolemia upon NP-59 adrenal uptake, patients with Cushing's syndrome (eight with pituitary-dependent, four with ACTH-independent, and two with ectopic-ACTH syndrome) were selected for retrospective analysis based on the availability of serum cholesterol (n = 14) and triglyceride (n = 10) concentrations obtained at the time of adrenal scintigraphy. A negative correlation (r = -0.78, p < 0.01) was found between NP-59 uptake and serum cholesterol levels in patients with pituitary-dependent Cushing's disease. Compared with pituitary-dependent disease, the ectopic-ACTH syndrome and ACTH-independent states demonstrated equal or greater adrenal uptake of NP-59 at similar serum cholesterol concentrations. Serum triglyceride concentrations did not correlate with total adrenal uptake of NP-59 in any of the patient groups studied. Increased serum cholesterol concentrations are associated with diminished adrenal uptake of NP-59, and in some cases may limit the diagnoic efficacy of adrenal scintigraphy in Cushing's syndrome

Medical treatment of Cushing's syndrome: Adrenal-blocking drugs and ketaconazole

NARCIS (Netherlands)

R.A. Feelders (Richard); L.J. Hofland (Leo); W.W. de Herder (Wouter)

2010-01-01

textabstractCushing's syndrome is associated with serious morbidity and increased mortality. Irrespective of its cause, i.e. a pituitary adenoma, ectopic ACTH production or an adrenal neoplasia, Cushing's syndrome is primarily treated surgically. However, when surgery is unsuccessful or

Cushing's syndrome: from physiological principles to diagnosis and clinical care

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Raff, Hershel; Carroll, Ty

2015-01-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic–pituitary–adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism – Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. PMID:25480800

A case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome.

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Chen, Y; Zhang, Y; Wang, L; Yang, X

2017-01-01

To date, cervical carcinoma complicated with Cushing's syndrome were all diagnosed as small cell carcinoma histo- logically, but not adenosquamous carcinoma. Here the authors present the diagnosis, management, and prognosis of a case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome. A 28-year-old woman was admitted with the chief complaint of post-coital bleeding for one month. Gynecological examination revealed a nodular yellowish-pigmented vegetation (6x5 cm) on the cervix. Laboratory findings proved the diagnosis of Cushing's syndrome. Histopathological diagnosis showed the adenosquamous carcinoma with melanoma differentiation. Immunohistochemical stainings for melanoma A and anti- adrenocorticotropic hormone (ACTH) were positive in the majority of the tumor cells, which indicated that this melanocytic cervical carcinoma lesion was the source of ectopic ACTH production resulting in Cushing's syndrome. This is a unique case of a rare type of cervical carcinoma.

Diagnosis and Management of 253 Cases with Cushing's syndrome in Imam Khomeini Hospital

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Esteghamati A.R

2007-09-01

Full Text Available Background: Definite diagnosis and treatment of Cushing's syndrome is still a dilemma. The aim of this study was to evaluate the accuracy of diagnostic tests and follow-up of patients with Cushing's syndrome."nMethods: Two hundred and fifty three consecutive cases with Cushing's syndrome during 1370-78 were studied. The screening tests were performed in all patients. High dose dexamethasone suppression test (HDDST and ACTH measurement were carried out. MRI/CT Scan were performed and compared with laboratory data and pathologic specimens as a gold standard test."nResults: The age range was 32±11 yrs. The most frequent symptoms were weakness; hypertension, typical striae, and depression .The frequency of hypertension in ACTH-dependent case were 77% vs. 36% in adrenal tumors (P< 0.001. HDDST was positive in 99% of micro and 71% of macroadenomas. Adrenal tumors showed 3.6% suppression but none in ectopic cases. HDDST had a sensitivity of 98%, specificity of 97% and accuracy equals to 98%. The frequency of different etiologies was as following: Cushing's disease in 64.8%, adrenal tumors in 32.8% and ectopic ACTH in 2.4% of patients. Trans-sphenoidal surgery (TSS was performed in 120 patients .The patients were followed for 53±25 months whose remission periods were 46.7±23.8 months (range 4-114 months. Survival analysis showed 93% remission rate in 12mo, 82% in 2yr and only 33% after 5yr.This recurrence didn't have any platue level."nConclusion: In our study, hypertension was more prevalent in ACTH-dependent Cushing's syndrome. HDDST had acceptable sensitivity, specificity and accuracy. Lifelong follow up of pituitary adenomas is inevitable in the case of progressive and gradual nature of recurrence in these tumors.

Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist

International Nuclear Information System (INIS)

Charbonnel, B.; Chatal, J.F.; Ozanne, P.

1981-01-01

An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland

131I-19-iodocholesterol adrenal scanning in Cushing's syndrome

International Nuclear Information System (INIS)

Charbonnel, B.; Chatal, J.F.; Chupin, M.; Guillon, J.

1976-01-01

7 patients were investigated: 2 bilateral hyperplasia due to pituitary ACTH excess showed bilateral adrenal activity. 1 post-surgical remnant with recurrent Cushing's syndrome was detected. 1 adenoma showed unilateral intense activity and absent activity in the controlateral gland, even after ACTH treatment. 2 carcinomas were weakly imaged. In 1 case, hepatic metastasis showed 131 I-19-iodocholesterol uptake. Adrenal imaging with 131 I-19-iodocholesterol is not a good procedure for assessing hormonal function. It is a valuable and safe tool in the localization and diagnosis of adrenal lesions causing Cushing's syndrome, perhaps better than radiologic procedures. Radiation dosimetry is acceptable [fr

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

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Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

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Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

2017-08-01

Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

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Sharma, Susmeeta T

2017-06-01

Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS. ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.

Hyperthyroidism due to thyroid-stimulating hormone secretion after surgery for Cushing's syndrome: a novel cause of the syndrome of inappropriate secretion of thyroid-stimulating hormone.

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Tamada, Daisuke; Onodera, Toshiharu; Kitamura, Tetsuhiro; Yamamoto, Yuichi; Hayashi, Yoshitaka; Murata, Yoshiharu; Otsuki, Michio; Shimomura, Iichiro

2013-07-01

Hyperthyroidism with the syndrome of inappropriate secretion of TSH (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushing's syndrome. This is a novel cause of SITSH. The aim of this study was to describe and discuss 2 cases of SITSH patients that were found after surgery for Cushing's syndrome. We also checked whether SITSH occurred in 7 consecutive patients with Cushing's syndrome after surgery. A 45-year-old Japanese woman with ACTH-independent Cushing's syndrome and a 37-year-old Japanese man with ACTH-dependent Cushing's syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/d within 18 days after surgery, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T₃ and TSH were normalized by the hydrocortisone dose increase of 30 mg/d, and these were elevated by the dose decrease of 10 mg/d. We also checked TSH and thyroid hormone levels of the 7 consecutive patients with Cushing's syndrome after surgery. Six (66.6 %) of 9 patients showed SITSH. This is the first report that insufficient replacement of hydrocortisone after surgery for Cushing's syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. We need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

Refractory Post-Herpetic Neuralgia As An Initial Presentation Of Olfactory Neuroblastoma-Related Ectopic ACTH Syndrome

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Hsiang-Hung Lin

2009-03-01

Full Text Available We report a woman aged 64 years with ectopic adrenocorticotropic hormone (ACTH syndrome caused by olfactory neuroblastoma as an initial presentation of refractory post-herpetic neuralgia. The manifestations such as cushingoid appearance and endocrine abnormalities are compatible with Cushing's syndrome. Brain computed tomography revealed a sellar mass. A biopsy revealed olfactory neuroblastoma. Immunohistochemical staining further defined the tumor as an ACTH-secreting neuroblastoma. Subsequent opportunistic infections by Candida glabrata fungemia and multiple drug-resistant Acinetobacter baumannii pneumonia occurred during hospitalization as a complication of severe hypercortisolism. Before any therapy for Cushing's syndrome and neuroblastoma could be initiated, the patient died from sepsis and multiorgan failure. We propose that Cushing's syndrome is more complex than what clinicians thought, and that meticulous cerebral imaging studies are crucial.

Gamma knife radiosurgery for Cushing's disease and Nelson's syndrome.

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Marek, Josef; Ježková, Jana; Hána, Václav; Kršek, Michal; Liščák, Roman; Vladyka, Vilibald; Pecen, Ladislav

2015-06-01

This paper presents our 18 years of experience in treating ACTH secreting adenomas (Cushing's disease and Nelson's syndrome) using the Leksell gamma knife (LGK) irradiation. Twenty-six patients with Cushing's disease were followed-up after LGK irradiation for 48-216 months (median 78 months). Seventeen patients had undergone previous surgery, in nine patients LGK irradiation was the primary therapy. Furthermore, 14 patients with Nelson's syndrome were followed-up for 30-204 months (median 144 months). LGK treatment resulted in hormonal normalization in 80.7 % of patients with Cushing's disease. Time to normalization was 6-54 months (median 30 months). The volume of the adenoma decreased in 92.3% (in 30.7% disappeared completely). There was no recurrence of the disease. In all 14 patients with Nelson's syndrome ACTH levels decreased (in two patients fully normalized) their ACTH levels. When checked up 5-10 years after irradiation regrowth of the adenoma was only detected in one patient (9.1%), in 27.3% adenoma volume remained unchanged, in 45.4% adenoma volume decreased and in 18.2% adenoma completely disappeared. Hypopituitarism did not develop in any patient where the critical dose to the pituitary and distal infundibulum was respected. LGK radiation represents an effective and well-tolerated option for the treatment of patients with Cushing's disease after unsuccessful surgery and may be valuable even as a primary treatment in patients who are not suitable for, or refuse, surgery. In the case of Nelson's syndrome it is possible to impede tumorous growth and control the size of the adenoma in almost all patients.

Resposta do ACTH plasmático ao estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH- dependente submetidos a cateterismo bilateral simultâneo dos seios petrosos inferiores Response of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTHdependent Cushing's syndrome submitted to simultaneous bilateral petrosal sinuses sampling

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Daniella Maria Carneiro do Rêgo

2007-12-01

Full Text Available OBJETIVO: Comparar a resposta do ACTH plasmático após estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH-dependente que realizaram cateterismo bilateral simultâneo dos seios petrosos inferiores. MATERIAIS E MÉTODOS: O procedimento foi realizado em 21 pacientes - 14 mulheres e 7 homens - com síndrome de Cushing ACTH-dependente no período de janeiro de 1998 a dezembro de 2003. Após a cateterização de ambos os seios petrosos, amostras de sangue para ACTH foram colhidas, simultaneamente, nos seios petrosos e veia periférica, tanto no estado basal como após três e cinco minutos da administração de CRH humano (100 mg (6 pacientes ou CRH + desmopressina (100 mg + 10 mg (15 pacientes. RESULTADOS: Aos três minutos, houve aumento percentual do ACTH tanto no grupo CRH (257,77 ± 240,36 no seio petroso direito e 718,78 ± 1.358,82 no seio petroso esquerdo [média ± desvio-padrão] como no grupo CRH + desmopressina (1.263,35 ± 1.842,91 no seio petroso direito [p = 0,06] e 583,93 ± 1.020,03 no seio petroso esquerdo [p = 0,83]. Aos cinco minutos houve declínio percentual do ACTH no grupo do CRH (181,07 ± 217,39 no seio petroso direito e 188,25 ± 270,15 no seio petroso esquerdo e aumento progressivo no grupo do CRH + desmopressina (1.365,29 ± 1.832,31 no seio petroso direito [p = 0,03] e 866,43 ± 1.431,72 no seio petroso esquerdo [p = 0,11]. Nos três pacientes com secreção ectópica não houve gradiente. CONCLUSÃO: A estimulação combinada CRH + desmopressina induziu maior produção de ACTH em adenomas corticotróficos em comparação ao CRH, o que pode melhorar a sensibilidade diagnóstica deste procedimento.OBJECTIVE: To compare the responses of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTH-dependent Cushing's syndrome submitted to simultaneous, bilateral inferior petrosal sinuses sampling. MATERIALS AND METHODS: The procedure was performed in 21 patients - 14

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.

The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

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Chabre, Olivier

2018-06-01

Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

The role of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology.

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Pecori Giraldi, Francesca; Cavallo, Luigi Maria; Tortora, Fabio; Pivonello, Rosario; Colao, Annamaria; Cappabianca, Paolo; Mantero, Franco

2015-02-01

In the management of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%-100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.

Laparoscopic bilateral transperitoneal adrenalectomy for Cushing syndrome: surgical challenges and lessons learnt.

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Aggarwal, Sandeep; Yadav, Kunal; Sharma, Aditya P; Sethi, Vrishketan

2013-06-01

Laparoscopic adrenalectomy is well established for treatment of adrenal lesions. However, bilateral adrenalectomy for Cushing syndrome is a challenging and time-consuming operation. We report our experience of laparoscopic bilateral adrenalectomy for this disease in 19 patients. From September 2009 to August 2012, we have operated 19 patients with Cushing syndrome and performed bilateral laparoscopic adrenalectomy using the transperitoneal approach; synchronous in 15 patients and staged in 4 patients. In 15 patients, the surgery was carried out sequentially on both the sides in lateral position with intraoperative change in position. Complete adrenalectomy including periadrenal fat was carried out on both the sides. Nineteen patients were referred from Department of Endocrinology for bilateral adrenalectomy for adrenocorticotropin hormone (ACTH)-dependent and ACTH-independent Cushing syndrome. The indications for surgery were Cushing disease in 15 patients, occult/ectopic source of ACTH in 2 patients, and primary adrenal hyperplasia in 2 patients. Fifteen patients underwent bilateral adrenalectomy during the same operation. Four patients underwent staged procedures. All procedures were completed laparoscopically with no conversions. The mean operating time for simultaneous bilateral adrenalectomy was 210 minutes (range, 150 to 240 min). This included the repositioning and reprepping time. There were no major intraoperative complications. The average blood loss was 100 mL (range, 50 to 200 mL). None of the patients required blood transfusions in the postoperative period. The postoperative complications included minor port-site infection in 2 patients. One severely debilitated patient died on the 14th postoperative day because of hospital-acquired pneumonia. The remaining 18 patients have done well in terms of impact on the disease. Laparoscopic bilateral adrenalectomy for Cushing syndrome is feasible and safe. It confers all the advantages of minimally invasive

ECTOPIC CUSHING SYNDROME: A 10-YEAR EXPERIENCE FROM A TERTIARY CARE CENTER IN SOUTHERN INDIA.

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Sathyakumar, Samantha; Paul, Thomas Vizhalil; Asha, Hesargatta Shyamsunder; Gnanamuthu, Birla Roy; Paul, M J; Abraham, Deepak Thomas; Rajaratnam, Simon; Thomas, Nihal

2017-08-01

Ectopic adrenocorticotropic hormone (ACTH) secretion is a less common cause of Cushing syndrome and is seen in 5 to 10% of cases with endogenous hypercortisolemia. We hereby describe our experience of patients with ectopic ACTH syndrome, who have been managed over the past 10 years at a tertiary care center in Southern India. The inpatient and outpatient records of patients from 2006 to 2015 were retrospectively reviewed. The clinical features, clinical history, biochemical values, imaging features, including radiologic findings and positron emission tomography scans, management, details of follow-up, and outcomes, were documented. We compared the biochemical findings in these patients with 20 consecutive patients with Cushing disease (Cushing syndrome of pituitary origin). A total of 21 patients were studied. The median age at presentation was 34 years (range, 19 to 55 years). Seven patients had thymic carcinoid, 7 had bronchial carcinoid, 3 had lung malignancies, 2 had medullary carcinoma thyroid, 1 patient had a pancreatic neuroendocrine tumor, and 1 patient had an occult source of ACTH. The most common clinical features at presentation were muscle weakness (95%), hyperpigmentation (90%), facial puffiness (76%), easy bruising (61%), edema (57%), and striae (52%). Extensive acne was seen in a large number of patients (43%). Only 3 patients (14%) had central obesity. The median 8 am cortisol was 55.5 μg/dL (range, 3.8 to 131 μg/dL), median 8 am ACTH was 207 pg/mL (range, 31.1 to 703 pg/mL), and the median 24-hour urinary free cortisol was 2,484 μg (range, 248 to 25,438 μg). Basal cortisol and ACTH, as well as midnight cortisol and ACTH level, were markedly higher in patients with ectopic Cushing syndrome as compared to patients with Cushing disease. Twelve of 21 patients had developed life-threatening infections by follow-up. Nine patients had undergone surgical intervention to address the primary tumor. However, only 1 patient exhibited a complete cure on

Diagnosis in the cushing's syndrome revisited

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De Marinis, L; Mancini, A; D' Amico, C and others

1986-01-01

The diagnostic procedure for the differential diagnosis of Cushing's syndrome is reported in this paper based on the experience of 23 cases. Inappropiate cortisol secretion was established by an absent cortisol circadian rhythm and absent cortisol suppression after overnight dexamethasone suppression test. The ACTH serum levels were then determined in basal conditions and after insulin-induced hypoglycemia (0.15 U/kg b.w. insulin i.v.). ACTH was low or undetectable in 9 patients, and high or normal-high in 14 patients. In the first group of patients an adrenal trasmission computed tomography (CT) was performed and showd an adrenal adenima in 6 patients, adrenal carcinoma in 2 patients and hyperplasia of residual adrenal gland in 1 patient, who had previously undergone monolateral adrenalectomy. These patients underwent surgical treatment, except the patient with adrenal hyperplasia. In the second group of patients, negative in 4 patients, doubtful in 1 patient. Surgical exploration by transsphenoidal route was performed, and an ACTH-producing adenima removed in all cases. Radicalization with hypophysectomy was necessary in 2 patients, while other 2 patients are under observation for the suspicion of a recurrent pituitary tumor. In all patients adrenal scintiscan was also performed, and confirmed the suspicion pointed out by CT scan. A relatively simple protocol with a functional test (ACTH determination) and a morphological one (computed tomography), can be reliably applied in the differential diagnosis of Cushing syndrome. 62 refs.

Diagnosis in the cushing's syndrome revisited

International Nuclear Information System (INIS)

De Marinis, L.; Mancini, A.; D'Amico, C.

1986-01-01

The diagnostic procedure for the differential diagnosis of Cushing's syndrome is reported in this paper based on the experience of 23 cases. Inappropiate cortisol secretion was established by an absent cortisol circadian rhythm and absent cortisol suppression after overnight dexamethasone suppression test. The ACTH serum levels were then determined in basal conditions and after insulin-induced hypoglycemia (0.15 U/kg b.w. insulin i.v.). ACTH was low or undetectable in 9 patients, and high or normal-high in 14 patients. In the first group of patients an adrenal trasmission computed tomography (CT) was performed and showd an adrenal adenima in 6 patients, adrenal carcinoma in 2 patients and hyperplasia of residual adrenal gland in 1 patient, who had previously undergone monolateral adrenalectomy. These patients underwent surgical treatment, except the patient with adrenal hyperplasia. In the second group of patients, negative in 4 patients, doubtful in 1 patient. Surgical exploration by transsphenoidal route was performed, and an ACTH-producing adenima removed in all cases. Radicalization with hypophysectomy was necessary in 2 patients, while other 2 patients are under observation for the suspicion of a recurrent pituitary tumor. In all patients adrenal scintiscan was also performed, and confirmed the suspicion pointed out by CT scan. A relatively simple protocol with a functional test (ACTH determination) and a morphological one (computed tomography), can be reliably applied in the differential diagnosis of Cushing syndrome

The utility of preoperative acth/cortisol ratio for the diagnosis and prognosis of cushing's disease

Directory of Open Access Journals (Sweden)

Alev Selek

2018-01-01

Full Text Available Purpose: Cushing's syndrome (CS is a rare disease having diagnostic difficulties. Many diagnostic tests have been defined but none of these are diagnostic alone. Determination of the cause is another problem which sometimes requires more sophisticated and invasive procedures. Therefore, we aimed to evaluate the utility of pretreatment plasma adrenocorticotropic hormone (ACTH/cortisol ratios in patients with confirmed endogenous CS for the diagnosis and differential diagnosis of CS. Materials and Methods: This retrospective evaluation included 145 patients with the diagnosis of CS, 119 patients with Cushing's disease (CD, and 26 patients with ACTH-independent CS (AICS, in a university hospital. Furthermore, 114 individuals in whom CS diagnosis was excluded with at least one negative screening test were enrolled to the study as control group. The clinical, laboratory, imaging, postsurgical pathologic records and also clinical follow-up data of all patients were evaluated. Results: The median basal ACTH/cortisol ratio of the patients with CD was significantly higher than AICS and controls. A cutoff ACTH/cortisol ratio >2.5 was found to be diagnostic for CD with 82% specificity and 63% sensitivity. Among CD group, patients with recurrent disease had higher preoperative ACTH levels and ACTH/cortisol ratio than patients with sustained remission. Furthermore, these patients had more invasive, atypical, and larger tumors. Conclusion: An ACTH/cortisol ratio >2.5 would be beneficial to diagnose CD together with other diagnostic tests. It is a simple test with no additional cost. Higher ratios might be related with larger, invasive, and atypical adenoma and also might be helpful to predict recurrence.

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

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

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Petersenn Stephan

2006-04-01

Full Text Available Abstract Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide

Adrenalectomy for Cushing's syndrome: do's and don'ts.

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Paduraru, D N; Nica, A; Carsote, M; Valea, A

2016-01-01

Aim. To present specific aspects of adrenalectomy for Cushing's syndrome (CS) by introducing well established aspects ("do's") and less known aspects ("don'ts"). Material and Method. This is a narrative review. Results. The "do's" for laparoscopic adrenalectomy (LA) are the following: it represents the "gold standard" for secretor and non-secretor adrenal tumors and the first line therapy for CS with an improvement of cardio-metabolic co-morbidities; the success rate depending on the adequate patients' selection and the surgeon's skills. The "don'ts" are large (>6-8 centimeters), locally invasive, malignant tumors requiring open adrenalectomy (OA). Robotic adrenalectomy is a new alternative for LA, with similar safety and conversion rate and lower pain drugs use. The "don'ts" are the following: lack of randomized controlled studies including oncologic outcome, different availability at surgical centers. Related to the sub-types of CS, the "do's" are the following: adrenal adenomas which are cured by LA, while adrenocortical carcinoma (ACC) requires adrenalectomy as first line therapy and adjuvant mitotane therapy; synchronous bilateral adrenalectomy (SBA) is useful for Cushing's disease (only cases refractory to pituitary targeted therapy), for ectopic Cushing's syndrome (cases with unknown or inoperable primary site), and for bilateral cortisol producing adenomas. The less established aspects are the following: criteria of skilled surgeon to approach ACC; the timing of surgery in subclinical CS; the need for adrenal vein catheterization (which is not available in many centers) to avoid unnecessary SBA. Conclusion. Adrenalectomy for CS is a dynamic domain; LA overstepped the former OA area. The future will improve the knowledge related to RA while the cutting edge is represented by a specific frame of intervention in SCS, children and pregnant women. Abbreviations: ACC = adrenocortical carcinoma, ACTH = Adrenocorticotropic Hormone, CD = Cushing's disease, CS

Radioimmunoassay for human ACTH

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Matsumura, S; Oyama, H; Tenku, A; Horino, M [Kawasaki Medicial School, Kurashiki, Okayama (Japan); Kobayashi, K

1977-03-01

A radioimmunoassay method for human adrenocorticotropic hormone (ACTH) is described. The antiserum was produced in a guinea pig by multiple injections of a total of 1 mg of porcine ACTH adsorbed with CM-cellulose and mixed with complete Freund's adjuvant. The antiserum used for this study at a final dilution of 1:500,000 was obtained from a guinea pig after 10 immunizations. A highly purified native ACTH (Li, ..cap alpha.. sub(h)sup(1-39) ACTH) was used as an assay standard and a tracer hormone. Separation of free and bound hormone was achieved by dextran coated charcoal. Extraction of ACTH from plasma samples was performed by Donald's method modified with silicic acid. The antibody appeared to be directed against the C-terminal portion of the hormone molecule and showed no significant reaction with other pituitary hormones (GH, TSH, LH, FSH, Hpr, Oxytocin, Arginine-and Lysine-Vasopressin). Plasma ACTH levels of 5 healthy subjects at nine o'clock averaged 32 +- 8.5 pg/ml (M +- SD). Plasma ACTH concentrations in a case of Sheehan's syndrome and of an untreated adrenogenital syndrome at nine o'clock were less than 20 and 194 pg/ml, respectively. A case of Cushing's syndrome accompanied with bilateral nodular hyperplasia of the adrenal cortex showed diminished diurnal variation and normal levels of plasma ACTH. In contrast, elevated plasma ACTH levels and lack of diurnal rhythm of ACTH secretion were observed in a suspected case of Cushing's disease.

Bilateral catheterization of the inferior petrosal sinuses in 23 cases of ACTh-dependent hypercoarisolism

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Castro, E.; Nombela, L.; Brasa, J.

1996-01-01

Our purpose is to assess the results of catheterization of the inferior petrosal sinuses, a measure that is included in the diagnostic protocol for ACTH-dependent hypercortisolism. We analyzed retrospectively the data obtained for 23 patients (20 women and 3 men) subjected to this procedure. The test was complete (catheterization both inferior petrosal sinuses) in 21 patients (91%). The sensitivity in differentiating between Cushing's disease (n=21) and ectopic ACTH syndrome (n=21) was 95.2% after administration of CRH, with a specificity of 100%, and the positive predictive value for the intra pituitary localization of the micro adenoma (confirmed by histological study in 19 cases) was 61%. Catheterization of the inferior petrosal sinuses shows an elevated sensitivity and specificity in the diagnosis of Cushing's disease, although the positive predictive value for determining the intrapituitary localization of the adenoma is low. (Author) 12 refs

Cushing's syndrome associated with a bronchial adenoma. Possible periodic hormonogenesis.

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Shapiro, M S; Gutman, A; Bruderman, I; Myers, B; Griffel, W B

1975-09-01

Diagnostic and therapeutic problems in a patient with ectopic ACTH syndrome caused by a malignant bronchial adenoma are discussed. Persistent Cushing's syndrome was present following apparent total adrenalectomy, but radioactive scanning with 131I-19-iodocholesterol showed the presence of residual adrenal tissue in the right suprarenal bed. Amelioration of the hypercortisolism occurred after removal of the bronchial adenoma. A paradoxical elevation of adrenocortical activity followed administration of dexamethasone and data are presented which suggest that periodic secretion of ACTH accounted for this phenomenon.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

International Nuclear Information System (INIS)

Fasshauer, Mathias; Paschke, Ralf; Koch, Christian A; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen

2006-01-01

ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111 In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from

Cushing syndrome

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Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... Cushing syndrome . Prednisone, dexamethasone, and prednisolone ...

Prognosis of patients treated for Cushing syndrome.

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Aulinas, Anna; Valassi, Elena; Webb, Susan M

2014-01-01

Cushing syndrome (CS), due to an ACTH-secreting pituitary adenoma, adrenal tumors, or ectopic ACTH secretion, causes hypercortisolism. CS is associated with major morbidity, especially metabolic and cardiovascular complications, osteoporosis, psychiatric changes, and cognitive impairment. Despite biochemical "cure" of hypercortisolism and clinical improvement after effective treatment, these complications are only partially reversible. Exacerbation of prior autoimmune diseases is also seen. All of these lead to quality of life impairment and increased mortality. This review addresses the main comorbidities and long-term consequences of CS despite clinical and biochemical "cure". Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

HIV infection and Cushing's disease

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Lalić Tijana

2014-01-01

Full Text Available Introduction: People with AIDS can have a dysfunction of the hypothalamic - pituitary-adrenal axis. With regard to HIV infection, most often mentioned is iatrogenic Cushing's syndrome or Pseudo-Cushing's Syndrome. So far there are described only two cases of Cushing disease in HIV -infected persons. Case report: A 48-year-old patient, after eleven years of HIV infection and a year since the introduction of HAART, was diagnosed with Cushing's disease based on cushingoid habitus, lack of suppression of cortisol in screening, elevated ACTH and pituitary tumor. She had transfenoidal surgery and histopathologic findings corresponded to basophilic adenoma. After the operation, short time on hydrocortisone substitution, she generally felt well with regular ART. Four years later, again easily bruising, facial redness, oily skin with acne, weight gain, uneven distribution of stomach adipose tissue, sweating, oligomenorrhea and high blood pressure. There was no rest/relapse of tumor on control pituitary MRI. Initially, elevated ACTH, valid cortisol in daily profiles, later the absence of the suppression of cortisol after 4 mg (LDST and 8 mg (HDST of dexamethasone along with maintenance of higher ACTH, indicate recurrence of clinical and laboratory relapse wherefore ketoconazole was introduced. Despite increasing doses of ketoconazole, she held slightly higher morning cortisol, ACTH and with persisting Cushing's syndrome. Conclusion: The coexistence of the two entities could lead to overlapping metabolic and phenotypic characteristics and the interaction between and/or synergism.

Cushing's Syndrome

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宗, 友厚; 伊藤, 勇; 諏訪, 哲也; 武田, 純; MUNE, Tomoatsu

2003-01-01

Sixteen cases of verified Cushing's syndrome, and twelve cases of probable Cushing's syndrome were reviewed and data on them were compared with various reports on Cushing's syndrome in the literature.

Exogenous Cushing syndrome

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Cushing syndrome - corticosteroid induced; Corticosteroid-induced Cushing syndrome; Iatrogenic Cushing syndrome ... Cushing syndrome is a disorder that occurs when your body has a higher than normal level of the hormone ...

21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

Science.gov (United States)

2010-04-01

... and serum. ACTH measurements are used in the differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushing's syndrome, adrenocortical insufficiency, and the ectopic ACTH...

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome.

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Trott, M J; Farah, G; Stokes, V J; Wang, L M; Grossman, A B

2016-01-01

We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases.

Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing's syndrome

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Oosterhuis, J. K.; van den Berg, G.; Monteban-Kooistra, W. E.; Ligtenberg, J. J. M.; Tulleken, J. E.; Zijlstra, J. G.; Meertens, John

We describe two patients with a severe Cushing's syndrome due to ectopic production of ACTH. Both patients developed a life-threatening Pneumocystis jiroveci pneumonia (PCP) shortly after treatment of the hypercortisolism was started by means of inhibition of production of glucocorticoids and

The diagnostic value of late-night salivary cortisol for diagnosis of subclinical Cushing's syndrome.

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Kuzu, Idris; Zuhur, Sayid Shafi; Demir, Nazan; Aktas, Gokce; Yener Ozturk, Feyza; Altuntas, Yuksel

2016-01-01

Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC). The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 μg/dL and ACTH Cushing's syndrome were significantly higher than in subjects with non-functioning adrenal adenoma and the control group (p Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 μg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively. Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492).

What Are the Treatments for Cushing's Syndrome?

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... Pinterest Email Print What are the treatments for Cushing syndrome? Treatment for Cushing syndrome depends on the reason for the extra cortisol in the body. 1 , 2 Medicine If Cushing syndrome is caused by glucocorticoid medicine taken to treat ...

Pathophysiology of Cushing's disease.

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Fehm, H L; Voigt, K H

1979-01-01

The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by

Clinical Characteristics of Endogenous Cushing's Syndrome at a Medical Center in Southern Taiwan

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Tung, Shih-Chen; Wang, Pei-Wen; Liu, Rue-Tsuan; Chen, Jung-Fu; Hsieh, Ching-Jung; Kuo, Ming-Chun; Yang, Joseph W.; Lee, Wei-Ching; Cheng, Min-Hsiung; Lee, Tao-Chen

2013-01-01

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy. PMID:24062770

Cushing's like syndrome in typical bronchial carcinoid a case report and review of the literature.

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Pedicelli, Ilaria; Patriciello, Giuseppina; Scala, Giovanni; Sorrentino, Antonietta; Gravino, Gennaro; Patriciello, Pasquale; Zeppa, Pio; Di Crescenzo, Vincenzo; Vatrella, Alessandro

2016-01-01

Cushing's syndrome occurred in 1-5% of cases of bronchial carcinoids. In this paper we describe a case of typical bronchial carcinoid in a nonsmoker young male with clinical manifestations mimicking a Cushing's syndrome. The patient performed chest radiograph and computed tomography. Fiberoptic bronchoscopy revealed the presence of an endobronchial mass occluding the bronchus intermedius. A rigid bronchoscopy was necessary for the conclusive diagnosis and for partial resection of the intraluminal tumor. Despite of the presence of Cushingoid features, the normal blood levels of ACTH and cortisol excluded the coexistence of a Cushing's syndrome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

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Lacroix A.

2000-01-01

Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

LENUS (Irish Health Repository)

McDermott, J H

2008-09-01

We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome.

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Kang, Seol-Hee; Lee, Hae-Ahm; Kim, Mina; Lee, Eunjo; Sohn, Uy Dong; Kim, Inkyeom

2017-06-01

Cushing's syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing's syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing's syndrome. For establishment of a Cushing's syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg -1 ·day -1 ). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing's syndrome. Copyright © 2017 the American Physiological Society.

Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

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Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

1994-11-01

We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

Diagnosis application of ACTH radioimmunoassay in diseases of hypothalamus, hypophysis and adrenal axis

International Nuclear Information System (INIS)

Moreira, A.C.; Foss, M.C.; Iazigi, N.

1988-01-01

The diagnostic value of 900-1,100 am plasma ACTH radioimmunoassay were studied in 10 patients with Cushing's disease before and after treatment, three patients with Cushing's syndrome with adrenal tumours, one Nelson's syndrome patient; 13 patients with Addison's disease and 12 patients with hypo-pituitarism. Twenty-seven normal subjects were controls. The measurement of basal plasma ACTH gave good differentiation between: a. pituitary Cushing's disease from adrenal tumors; b. Addison's disease from hypo-pituitarism. However this assay has a limited value for the differentiation between Cushing's disease from normal subjects and it is often unhelpful in the differential diagnosis of hypo-pituitarism from normal subjects. (author)

Bilateral inferior petrosal sinus sampling in the diagnosis of Cushing disease

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Deipolyi AR

2015-04-01

Full Text Available Amy R Deipolyi,1 Rahmi Oklu21Vascular and Interventional Radiology, NYU Langone Medical Center, New York, NY, USA; 2Division of Vascular and Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAAbstract: Bilateral inferior petrosal sinus sampling (BIPSS is a minimally invasive procedure performed in the workup of adrenocorticotropic hormone (ACTH-dependent Cushing syndrome (CS. Because noninvasive tests in the evaluation of CS patients lack sensitivity, BIPSS is the gold standard in diagnosing Cushing disease (CD, which is a pituitary source of excess ACTH. Here, the pathophysiology of CD and procedural details of BIPSS are reviewed.Keywords: pituitary adenoma, Cushing disease, inferior petrosal sinus, venous sampling

VENOUS SAMPLING FOR CUSHING DISEASE: COMPARISON OF INTERNAL JUGULAR VEIN AND INFERIOR PETROSAL SINUS SAMPLING.

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Radvany, Martin G; Quinones-Hinojosa, Alfredo; Gallia, Gary L; Wand, Gary S; Salvatori, Roberto

2016-09-01

Because magnetic resonance imaging (MRI) fails to detect many adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, inferior petrosal sinus sampling (IPSS) is considered the gold standard to differentiate Cushing disease (CD) from ectopic ACTH secretion syndrome (EAS). Some authors have suggested internal jugular vein sampling (IJVS) as an alternative to IPSS. We simultaneously compared IJVS to IPSS in 30 consecutive patients referred for ACTH-dependent Cushing syndrome and equivocal MRI exams. Five sites were simultaneously sampled in each patient (right and left IPS, right and left IJV, and femoral vein) before and after the administration of corticotrophin-releasing hormone or desmopressin. The test was considered consistent with CD when the IPS to peripheral ratio was >2 at baseline or >3 after stimulus and the IJV to peripheral ratio was >1.7 at baseline or >2 after stimulus. In 27 of 30 patients, IPSS results were consistent with a central source of ACTH. Two of the other 3 patients had EAS (one lung carcinoid and one occult), and 1 patient had pathology-proven CD. The sensitivity of IPSS was 96.4%. Only 64.2% of these patients had results meeting criteria for a central source of ACTH by IJVS criteria. Twenty patients with centralizing IPPS have undergone pituitary surgery. Of these, the central origin of excessive ACTH was confirmed with certainty in 16 patients. Among these 16 patients, the IPSS sensitivity was 93.8%, whereas 5 patients had false-negative IJVS (68.7% sensitivity). These results do not support the routine use of IJVS in establishing if the pituitary is the source of excessive ACTH. ACTH = adrenocorticotropic hormone CD = Cushing disease CRH = corticotrophin-releasing hormone CS = Cushing syndrome DDAVP = desmopressin EAS = ectopic ACTH secretion IJVS = internal jugular vein sampling IPSS = inferior petrosal sinus sampling JVS = jugular venous sampling MRI = magnetic resonance imaging.

Syndroom van Cushing. II. Nieuwe behandelingen

NARCIS (Netherlands)

van Aken, M. O.; Feelders, R. A.; van der Lely, A. J.; Romijn, J. A.; Lamberts, S. W. J.; de Herder, W. W.

2006-01-01

Several new therapeutic options both medicinal and surgical, have emerged for the treatment of Cushing's syndrome. In Cushing's disease caused by an adrenocorticotropin (ACTH) secreting pituitary adenoma, the introduction ofendoscopic pituitary surgery offers better visualization of the sella than

Latest diagnostic approaches to determine the cause of ACTH ...

African Journals Online (AJOL)

A case of a 50-year-old woman who was referred for the evaluation of possible ACTH-dependent Cushing's syndrome (CS) is described. The localisation of ... and facial plethora. On bone mineral density assessment she had ..... the source of EC, PET/CT using 68 Ga-DOTA-labelled octreotide analogues had the best ...

Cushing disease revealed by bilateral atypical central serous chorioretinopathy: case report.

Science.gov (United States)

Giovansili, Iama; Belange, Georeges; Affortit, Aude

2013-01-01

We report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR). We present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed. A 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient's morning cortisol remains undetectable, and serous retinal detachments had regressed. CSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing's syndrome.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

Directory of Open Access Journals (Sweden)

Joo Hee Lim

2016-03-01

Full Text Available A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report.

Science.gov (United States)

Lim, Joo Hee; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

2016-03-01

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

ACTH-Secreting tumor of cecum. Case report

Directory of Open Access Journals (Sweden)

N S Kuznetsov

2013-06-01

Full Text Available Ectopic hormonesecreting of cecum are rare. We report the case of a 52yearold woman with a typical clin ical picture of Cushing disease. Diagnostic tests confirmed ACTH dependent Cushing’s syndrome, which is caused by neuroendocrine tumor of the cecum. Due to the rarity of the disease, we believe it appropriate to share our experience of this group of patients.

Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor

Directory of Open Access Journals (Sweden)

Volmar KeithE

2009-09-01

Full Text Available Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor (ACT. We report an infant with Cushing syndrome due to adrenocortical carcinoma. The patient presented at six months of age with a three-month history of growth failure, rapid weight gain, acne, and irritability. Physical examination showed obesity, hypertension, and Cushingoid features. Biochemical evaluation showed very high serum cortisol, mildly elevated testosterone, and suppressed ACTH. Abdominal MRI revealed a heterogeneous right adrenal mass extending into the inferior vena cava. Evaluation for metastases was negative. The tumor was removed surgically en bloc. Pathologic examination demonstrated low mitotic rate, but capsular and vascular invasion. She received no adjuvant therapy. Her linear growth has improved and Cushingoid features resolved. Hormonal markers and quarterly PET scans have been negative for recurrence 24 months postoperatively. In conclusion, adrenocortical neoplasms in children are rare, but should be considered in the differential diagnosis of Cushing syndrome.

Cushing's Syndrome

Science.gov (United States)

Cushing's syndrome is a hormonal disorder. The cause is long-term exposure to too much cortisol, a hormone that ... your body to make too much cortisol. Cushing's syndrome is rare. Some symptoms are Upper body obesity ...

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)

[Paraneoplastic Cushing's syndrome, a real diagnostic and therapeutic challenge: A case report and literature review].

Science.gov (United States)

Meftah, A; Moumen, A; Massine El Hammoumi, M; Hajhouji, S; El Jadi, H; Anas Guerboub, A; Elmoussaoui, S; Mayaudon, H; Hassane Kabiri, E; Hakkou, K; Belmejdoub, G

2015-12-01

Paraneoplastic Cushing's syndrome is a rare cause of endogenous hypercortisolism attributable to ectopic ACTH secretion by non-pituitary tumors. Imaging and biochemical results are often inconclusive and differential diagnosis with Cushing's disease can then be challenging. Moreover, these tumors may be occult and difficult to find and thus the need of new imaging tools such as (18)FDG-PET scan and (18)DOPA-PET scan. We report a 50-year-old man who presented with very aggressive clinical features related to Cushing's syndrome. Biological work-up confirmed the hypercortisolism and was consistent with an ectopic ACTH secretion. Conventional localization techniques failed to show any tumor and bilateral adrenalectomy was performed because of life-threatening complications. Two years later, thoracic computed tomography reveals an 11 mm mass in the left lower pulmonary lobe, (18)FDG-PET scan found a non-specific mild hypermetabolism of the lung nodule, and the (18)DOPA-PET scan confirmed the high uptake of this nodule suggesting an endocrine carcinoma. Histology confirmed a typical carcinoid tumor. The tumor cells stained positive for ACTH, CD56, chromogranin and synaptophysin. This case illustrates the dilemma between the need for morphological diagnosis of the ectopic ACTH source and control of the life-threatening hypercortisolism. (18)FDG-PET scan and (18)DOPA-PET scan should be considered early as a secondary diagnostic tool when conventional imagery fails to show any tumor. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

What Causes Cushing's Syndrome?

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... Share Facebook Twitter Pinterest Email Print What causes Cushing syndrome? Cushing syndrome can develop for two reasons: Medication ... uhs ), thyroid, or thymus How Tumors Can Cause Cushing Syndrome Normally, the pituitary gland in the brain controls ...

Cushing's disease; inferior petrosal sinus venography and samplings

International Nuclear Information System (INIS)

Chung, Tae Sub; Suh, Jung Ho; Kim, Dong Ik; Lee, Hyun Chul; Huh, Kap Bum; Kim, Young Soo; Chung, Sang Sup

1991-01-01

Hypersecretion of ACTH in patients with Cushing's syndrome originates from either a pituitary tumor (Cushing's disease) or an ectopic ACTH-secreting tumor. These 2 entities may be clinically indistinguishable, and additional difficulty arise because pituitary microadenomas may be radiologically occult. Recently, bilateral selective venous sampling from the inferior petrosal sinuses became the procedure of choice for confirming a false negative study of a combined hormonal test and pituitary ACTH hypersecretion. We performed selective venous catheterization and sampling for ACTH. The central location of the lesion was detected in 1 case (intersinus gradient = 1.1 : 1), and the remaining 5 cases revealed lateralization of the lesions (intersinus gradient = 3.7 - 20.1 : 1), which correlated well with transsphenoidal microadenomectomies in all the cases. We concluded that selective venous ACTH sampling from the inferior petroal sinus is a reliable and useful aid in the diagnosis of Cushing's disease when standard clinical and biochemical studies are inconclusive

Multiple endocrine adenomatosis with Cushing's disease and the amenorrhea-galactorrhea syndrome responsive to proton beam irradiation

International Nuclear Information System (INIS)

Veseley, D.L.; Fass, F.H.

1981-01-01

Multiple endocrine adenomatosis (MEA) or neoplasia is a hereditary disorder consisting of tumors of hyperplasia of several endocrine glands. In MEA-1 the pituitary, parathyroids, and pancreatic islets are most frequently involved, while in MEA-2 the thyroid (medullary carcinoma of the thyroid), parathyroids,and adrenals (pheochromocytomas) are the endocrine glands most likely to be involved. Cushings's syndrome may occur in MEA-1 and has also been found in patients with MEA-2, where the cause of Cushing's syndrome is usually ectopic ACTH production from medullary carcinoma of the thyroid. Recently, there have been reports of amenorrhea-galactorrhea syndrome in patients with MEA-1, and confirmation that hyperprolactinemia is associated with this syndrom has been found in patients with MEA-1. The present report details a patient who has been followed up for 20 years since she first presented with amenorrhea and galactorrhea. Ten years after first being seen she was noted to have Cushing's syndrom and hyperparathyroidism due to parathyroid hyperplasia. Both the amenorrhea-galactorrhea syndrome and Cushing's sydrome disappeared with proton beam irradiation to the pituitary

Progestogens and Cushing's syndrome.

LENUS (Irish Health Repository)

Harte, C

2012-02-03

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing\\'s syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg\\/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg\\/day but Cushing\\'s syndrome has been reported in patients taking 400 mg\\/day. Neither the glucocorticoid-like effects or Cushing\\'s syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing\\'s syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing\\'s syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.

Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk.

Science.gov (United States)

Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno

2014-01-01

We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.

Unmasking sarcoidosis following surgery for Cushing disease

DEFF Research Database (Denmark)

Diernæs, Jon Erik; Bygum, Anette; Poulsen, Per L

2016-01-01

We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman pr...... successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.......We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman...... for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed...

Residual manifestations of hypercortisolemia following surgical treatment in a patient with Cushing syndrome.

Science.gov (United States)

Bartz, Sara K; Karaviti, Lefkothea P; Brandt, Mary L; Lopez, Monica E; Masand, Prakash; Devaraj, Sridevi; Hicks, John; Anderson, Lauren; Lodish, Maya; Keil, Meg; Stratakis, Constantine A

2015-01-01

Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist. To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention. A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis. This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later.

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

Science.gov (United States)

Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

2017-01-01

Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

Psychiatric phenomenology in Cushing's disease.

Science.gov (United States)

Loosen, P T; Chambliss, B; DeBold, C R; Shelton, R; Orth, D N

1992-07-01

We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria. The diagnosis of Generalized Anxiety Disorder (GAD) was most common in Cushing's disease (79%), followed by MDD (68%), and Panic Disorder (PD) including subthreshold PD (53%). The combination of MDD and GAD and/or PD was also common in Cushing's disease (63%). Behavioral symptoms, if present, usually first occurred at or after the onset of the first physical symptoms. However, the onset of PD was associated with more chronic stages of Cushing's disease. In both Cushing's disease and MDD, more female than male relatives suffered from MDD, whereas more male than female relatives suffered from substance abuse. The data demonstrate a syndrome of anxious depression in patients with active Cushing's disease; such comorbidility has not been previously noted. The data also point to intriguing epidemiological, clinical, and biological associations between Cushing's disease, MDD and substance abuse.

Performance of the 4-mg intravenous dexamethasone suppression test in differentiating Cushing disease from pseudo-Cushing syndrome.

Science.gov (United States)

Nouvel, Migueline; Rabilloud, Muriel; Raverot, Véronique; Subtil, Fabien; Vouillarmet, Julien; Thivolet, Charles; Jouanneau, Emmanuel; Borson-Chazot, Françoise; Pugeat, Michel; Raverot, Gérald

2016-02-01

Discriminating Cushing disease (CD) from pseudo-Cushing syndrome (PCS) is a challenging task that may be overcome with the 4-mg intravenous (IV) dexamethasone suppression test (DST). Assess the performance of the 4-mg IV DST in the differential diagnosis between CD and PCS in well-characterized patients. Retrospective comparative study of subjects seen in a tertiary care unit (November 2008 to July 2011). Thirty-six patients with PCS and 32 patients with CD underwent 4-mg IV dexamethasone infusions from 11 am to 3 pm. Areas Under ROC Curves (AUCs) were estimated and compared for ACTH and cortisol measured at 4 pm the same day (day 1) and 8 am the next day (day 2). The ROC curve of the marker with the highest AUC was used to determine the threshold with the highest specificity for 100% sensitivity. The AUC of ACTH at 8 am on day 2 was estimated at 98.4% (95% CI: [92.1-100]), which is significantly greater than that of ACTH at 4 pm on day 1 (P=0.04) and that of cortisol at 8 am on day 2 (P=0.05). For ACTH at 8 am on day 2, the threshold with the highest specificity for 100% sensitivity was estimated at 14.8 ng/L. At this threshold, the sensitivity was estimated at 100% [89-100] and the specificity at 83.3% [67-94]. The 4-mg IV DST is an easy and accurate tool in distinguishing CD from PCS. It deserves thus a better place in establishing the diagnosis of CD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Psychiatric disorders associated with Cushing's syndrome.

Science.gov (United States)

Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Górniak, Eliza; Krysta, Krzysztof

2015-09-01

Cushing's syndrome is the term used to describe a set of symptoms associated with hypercortisolism, which in most cases is caused by hypophysial microadenoma over-secreting adrenocorticotropic hormone. This endocrine disorder is often associated with psychiatric comorbidities. The most important include mood disorders, psychotic disorders, cognitive dysfunctions and anxiety disorders. The aim of this article was to review the prevalence, symptoms and consequences of psychiatric disorders in the course of Cushing's syndrome. We therefore performed a literature search using the following keywords: Cushing's syndrome and psychosis, Cushing's syndrome and mental disorders, Cushing's syndrome and depression, Cushing's syndrome and anxiety. The most prevalent psychiatric comorbidity of Cushing's syndrome is depression. Psychiatric manifestations can precede the onset of full-blown Cushing's syndrome and therefore be misdiagnosed. Despite the fact that treatment of the underlying endocrine disease in most cases alleviates psychiatric symptoms, the loss of brain volume persists. It is important to be alert to the symptoms of hypercortisolism in psychiatric patients to avoid misdiagnosis and enable them receiving adequate treatment.

Six controversial issues on subclinical Cushing's syndrome.

Science.gov (United States)

Chiodini, Iacopo; Albani, Adriana; Ambrogio, Alberto Giacinto; Campo, Michela; De Martino, Maria Cristina; Marcelli, Giorgia; Morelli, Valentina; Zampetti, Benedetta; Colao, Annamaria; Pivonello, Rosario

2017-05-01

Subclinical Cushing's syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing's syndrome is not rare, being estimated to be between 0.2-2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing's syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing's syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing's syndrome viewpoint regarding the following controversial issues on Subclinical Cushing's syndrome (SCS): (1) Who has to be screened for subclinical Cushing's syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing's syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing's syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing's syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing's syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing's syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing's syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing's syndrome.

The diagnostic value of CT scan and selective venous sampling in Cushing's syndrome

International Nuclear Information System (INIS)

Negoro, Makoto; Kuwayama, Akio; Yamamoto, Naoto; Nakane, Toshichi; Yokoe, Toshio; Kageyama, Naoki; Ichihara, Kaoru; Ishiguchi, Tsuneo; Sakuma, Sadayuki

1986-01-01

We studied 24 patients with Cushing's syndrome in order to find the best way to confirm the pituitary adenoma preoperatively. At first, the sellar content was studied by means of a high-resolution CT scan in each patient. Second, by selective catheterization in the bilateral internal jugular vein and the inferior petrosal sinus, venous samples (c) were obtained for ACTH assay. Simultaneously, peripheral blood sampling (P) was made at the anterior cubital vein for the same purpose, and the C/P ratio was carefully calculated in each patient. If the C/P ratio exceeded 2, it was highly suggestive of the presence of pituitary adenoma. Even by an advanced high-resolution CT scan with a thickness of 2 mm, pituitary adenomas were detected in only 32 % of the patients studied. The result of image diagnosis in Cushing disease was discouraging. As for the chemical diagnosis, the results were as follows. At the early stage of this study, the catheterization was terminated in the jugular veins of nine patients. Among these, in five patients the presence of pituitary adenoma was predicted correctly in the preoperative stage. Later, by means of inferior petrosal sinus samplings, pituitary microadenomas were detected in ten patients among the twelve. Selective venous sampling for ACTH in the inferior petrosal sinus or jugular vein proved to be useful for the differential diagnosis of Cushing's syndrome when other diagnostic measures such as CT scan were inconclusive. (author)

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease.

Science.gov (United States)

Srinivasan, Lakshmi; Laws, Edward R; Dodd, Robert L; Monita, Monique M; Tannenbaum, Christyn E; Kirkeby, Kjersti M; Chu, Olivia S; Harsh, Griffith R; Katznelson, Laurence

2011-12-01

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.

Multiple endocrine adenomatosis with Cushing's disease and the amenorrhea-galactorrhea syndrome responsive to proton beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Veseley, D.L.; Fass, F.H.

1981-09-01

Multiple endocrine adenomatosis (MEA) or neoplasia is a hereditary disorder consisting of tumors of hyperplasia of several endocrine glands. In MEA-1 the pituitary, parathyroids, and pancreatic islets are most frequently involved, while in MEA-2 the thyroid (medullary carcinoma of the thyroid), parathyroids,and adrenals (pheochromocytomas) are the endocrine glands most likely to be involved. Cushings's syndrome may occur in MEA-1 and has also been found in patients with MEA-2, where the cause of Cushing's syndrome is usually ectopic ACTH production from medullary carcinoma of the thyroid. Recently, there have been reports of amenorrhea-galactorrhea syndrome in patients with MEA-1, and confirmation that hyperprolactinemia is associated with this syndrom has been found in patients with MEA-1. The present report details a patient who has been followed up for 20 years since she first presented with amenorrhea and galactorrhea. Ten years after first being seen she was noted to have Cushing's syndrom and hyperparathyroidism due to parathyroid hyperplasia. Both the amenorrhea-galactorrhea syndrome and Cushing's sydrome disappeared with proton beam irradiation to the pituitary.

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)

Structural brain abnormalities in Cushing's syndrome.

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Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

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

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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.

Case report of a bilateral adrenal myelolipoma associated with Cushing disease.

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Park, Se Yoon; Kwak, Mi Kyung; Kim, Hye Jeong; Park, Hyeong Kyu; Suh, Kyo-Il; Yoo, Myung Hi; Jin, So Young; Yun, Sumi; Byun, Dong Won

2017-12-01

Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Pulmonary mineralization in four dogs with Cushing's syndrome

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Berry, C.R.; Ackerman, N.; Monce, K.

1994-01-01

The clinical and imaging features of four dogs with Cushing's syndrome and pulmonary mineralization are reviewed. Three dogs presented with a primary complaint of respiratory distress/dyspnea. Three dogs had pituitary dependent Cushing's syndrome, while the remaining one dog had iatrogenic Cushing's syndrome. Each dog had clinical features typical for Cushing's syndrome. Two of the dogs were euthanized due to progressive hypoxemia. In each dog, the serum calcium, phosphorous, blood urea nitrogen and creatinine were normal. A generalized increase in unstructured interstitial pulmonary opacity with diffuse mineralization was noted on thoracic radiographs of all dogs. In one dog, an ill-defined nodular interstitial pattern of mineralization was present. Delayed bone phase scintigraphy using 99m Technetium methylene diphosphonate documented generalized pulmonary uptake in two dogs. 99m Technetium labeled microaggregated albumin lung perfusion scans were normal in these two dogs. 99m Tc-MDP scintigraphy can provide useful information in diagnosing pulmonary mineralization in Cushingoid dogs

Cushing's syndrome: a model for sarcopenic obesity.

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Drey, Michael; Berr, Christina M; Reincke, Martin; Fazel, Julia; Seissler, Jochen; Schopohl, Jochen; Bidlingmaier, Martin; Zopp, Stefanie; Reisch, Nicole; Beuschlein, Felix; Osswald, Andrea; Schmidmaier, Ralf

2017-09-01

Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known to be associated with obesity and muscle atrophy. We compared Cushing's syndrome with matched obese controls regarding body composition, physical performance, and biochemical markers to test the hypothesis that Cushing's syndrome could be a model for sarcopenic obesity. By propensity score matching, 47 controls were selected by body mass index and gender as obese controls. Fat mass and muscle mass were measured by bioelectrical impedance analysis. Muscle function was assessed by chair rising test and hand grip strength. Biochemical markers of glucose and lipid metabolism and inflammation (hsCRP) were measured in peripheral blood. Muscle mass did not differ between Cushing's syndrome and obese controls. However, Cushing's syndrome patients showed significantly greater chair rising time (9.5 s vs. 7.3 s, p = 0.008) and significantly lower hand grip strength (32.1 kg vs. 36.8 kg, p = 0.003). Cushing's syndrome patients with impaired fasting glucose have shown the highest limitations in hand grip strength and chair rising time. Similar to published data in ageing medicine, Cushing's syndrome patients show loss of muscle function that cannot be explained by loss of muscle mass. Impaired muscle quality due to fat infiltration may be the reason. This is supported by the observation that Cushing's syndrome patients with impaired glucose metabolism show strongest deterioration of muscle function. Research in sarcopenic obesity in elderly is hampered by confounding comorbidities and polypharmacy. As Cushing's syndrome patients are frequently free of comorbidities and as Cushing's syndrome is potentially curable we suggest Cushing's syndrome as a clinical model for further research in sarcopenic obesity.

Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

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Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

2017-03-01

Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

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

Is There a Cure for Cushing's Syndrome?

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... Pinterest Email Print Is there a cure for Cushing syndrome? Untreated Cushing syndrome can be life-threatening—fortunately, most people with ... their previous strength. People who no longer have Cushing syndrome might be more likely to develop diabetes, high ...

Ambulatory Arterial Stiffness Indexes in Cushing's Syndrome.

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Battocchio, Marialberta; Rebellato, Andrea; Grillo, Andrea; Dassie, Francesca; Maffei, Pietro; Bernardi, Stella; Fabris, Bruno; Carretta, Renzo; Fallo, Francesco

2017-03-01

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushing's syndrome. Twenty-four patients with Cushing's syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushing's disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearman's rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified. © Georg Thieme Verlag KG Stuttgart · New York.

What Are the Symptoms of Cushing's Syndrome?

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... Pinterest Email Print What are the symptoms of Cushing syndrome? Most people with Cushing syndrome have a range of symptoms, 1 and one ... of other conditions. 3 , 4 Physically, someone with Cushing syndrome might: Be heavy or obese above the waist ...

PRKAR1A-negative familial Cushing's syndrome: two case reports.

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Lim, Lee Ling; Kitan, Normayah; Paramasivam, Sharmila Sunita; Ratnasingam, Jeyakantha; Ibrahim, Luqman; Chan, Siew Pheng; Tan, Alexander Tong Boon; Vethakkan, Shireene Ratna

2015-12-01

Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood. A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex. The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

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Erfe, J Mark; Perry, Avital; McClaskey, John; Inzucchi, Silvio E; James, Whitney Sheen; Eid, Tore; Bronen, Richard A; Mahajan, Amit; Huttner, Anita; Santos, Florecita; Spencer, Dennis

2017-10-13

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient

[Cyclic Cushing's Syndrome - rare or rarely recognized].

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Kiałka, Marta; Doroszewska, Katarzyna; Mrozińska, Sandra; Milewicz, Tomasz; Stochmal, Ewa

2015-01-01

Cyclic Cushing's syndrome is a type of Cushing's disease which is characterized by alternating periods of increasing and decreasing levels of cortisol in the blood. The diagnostic criteria for cyclic Cushing's syndrome are at least three periods of hypercortisolism alternating with at least two episodes of normal levels of serum cortisol concentration. The epidemiology, signs, symptoms, pathogenesis and treatment of cyclic Cushing's syndrome have been discussed.

Mutiple Spontaneous Rib Fractures in Patient with Cushing's Syndrome.

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Lee, Hyun Jung; Je, Ji Hye; Seo, Ji Hye; Na, Young Ju; Yoo, Hye Jin

2014-11-01

Glucocorticoid (GC) excess, including Cushing's syndrome, is a common cause of secondary osteoporosis. Thirty to fifty percent of Cushing's syndrome patients experience non-traumatic fractures, which is often the presenting manifestation of Cushing's syndrome. However, there have been rare cases of Cushing's syndrome diagnosed only based upon bone manifestations. We describe a case of Cushing's syndrome that was diagnosed in a 44-year-old woman who initially visited our hospital due to multiple non-traumatic rib fractures. She did not exhibit any other manifestations of Cushing's syndrome such as moon face, buffalo hump or abdominal striae. Initially, we evaluated her for bone metastases from a cancer of unknown origin, but there was no evidence of metastatic cancer. Instead, we found a left adrenal incidentaloma. As a result of the hormone study, she was diagnosed as having Cushing's syndrome. Interestingly, her bony manifestation of Cushing's syndrome, which was evident in the bone scan and bone mineral densitometry, completely recovered after a left adrenalectomy. Therefore, the possibility of Cushing's syndrome as a cause of secondary osteoporosis should be considered in young patients with non-traumatic multiple fractures, with or without any other typical features of Cushing's syndrome.

Sustained remission of Cushing's disease with mitotane and pituitary irradiation

International Nuclear Information System (INIS)

Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.; McKenzie, A.; Victoria, R.; Therrien, B.A.

1980-01-01

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest

How Do Health Care Providers Diagnose Cushing's Syndrome?

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... Email Print How do health care providers diagnose Cushing syndrome? Diagnosing Cushing syndrome can be complex and difficult. This syndrome is ... health care provider may try different tests. Diagnosing Cushing syndrome often requires several steps. If you are being ...

Menstrual Abnormalities in a Woman with Acth-Dependent Pituitary Macroadenoma Mimicking Polycystic Ovary Syndrome

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Chun-Cheng Liao

2006-06-01

Conclusion: PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.

Endocrine hypertension – Cushing's syndrome

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Singh, Yashpal; Kotwal, Narendra; Menon, A. S.

2011-01-01

Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This review discusses the etiology and pathophysiology of hypertension in Cushing's syndrome, while suggesting methods of management of this condition. It also provides an overview of diagnosis and management strategies in this disease. PMID:22145133

Screening for Cushing's syndrome in obese patients

Directory of Open Access Journals (Sweden)

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.

Mortality in Patients with Endogenous Cushing's Syndrome.

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Javanmard, Pedram; Duan, Daisy; Geer, Eliza B

2018-06-01

Cushing's syndrome is associated with increased morbidity and mortality. Cardiovascular events, sepsis, and thromboembolism are the leading causes of mortality. Patient's with Cushing's due to a pituitary adenoma and those with Cushing's due to benign adrenal adenoma have relatively good survival outcomes often mirroring that of the general population. Persistent or recurrent disease is associated with high mortality risk. Ectopic Cushing's syndrome and Cushing's due to adrenocortical carcinoma confer the highest mortality risk among Cushing's etiologies. Prompt diagnosis and treatment, and specific monitoring for and treatment of associated comorbidities are essential to decrease the burden of mortality from Cushing's. Copyright © 2018 Elsevier Inc. All rights reserved.

Course of depression in Cushing's syndrome: response to treatment and comparison with Graves' disease.

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Sonino, N; Fava, G A; Belluardo, P; Girelli, M E; Boscaro, M

1993-01-01

Depression in a common, life-threatening complication of Cushing's syndrome and may occur in several other endocrine disorders. It is not clear, however, whether distinct features pertain to hypercortisolism. We studied depression in Cushing's syndrome differentiating pituitary-dependent and pituitary-independent forms, its incidence compared to Graves' disease, and its appearance in the prodromal phase of both conditions. To 66 consecutive patients with Cushing's syndrome and 70 with Graves' disease, after treatment, a semistructured interview for depressive symptoms based on Paykel's clinical interview for depression was administered. In Cushing's syndrome, the response of depression to normalization of urinary cortisol levels was evaluated by Kellner's global rating method. There was a significant difference in the occurrence of depression (p Cushing's syndrome (62%) and Graves' disease (23%). Depression appeared in the prodromal phase in 27% of patients with Cushing's syndrome and in 14% of those with Graves' disease, but the difference was not significant. In Cushing's syndrome, there were no significant differences in depression between patients with pituitary-dependent (n = 41) and pituitary-independent (n = 20) forms, or in their response to treatment. About 70% of patients fully recovered from their depression, whereas there was no substantial change in the others and even worsening in 2. Our findings in Cushing's syndrome and Graves' disease are in agreement with previous investigations using specific diagnostic criteria for depression. We found a tendency for this symptom to manifest in the prodromal phase of both illnesses. An endocrine etiology should be, therefore, considered in depressed patients not responding to standard psychiatric treatment.

Surgical outcomes of laparoscopic adrenalectomy for patients with Cushing's and subclinical Cushing's syndrome: a single center experience.

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Miyazato, Minoru; Ishidoya, Shigeto; Satoh, Fumitoshi; Morimoto, Ryo; Kaiho, Yasuhiro; Yamada, Shigeyuki; Ito, Akihiro; Nakagawa, Haruo; Ito, Sadayoshi; Arai, Yoichi

2011-12-01

We retrospectively examined the outcome of patients who underwent laparoscopic adrenalectomy for Cushing's/subclinical Cushing's syndrome in our single institute. Between 1994 and 2008, a total of 114 patients (29 males and 85 females, median age 54 years) with adrenal Cushing's/subclinical Cushing's syndrome were studied. We compared the outcome of patients who underwent laparoscopic adrenalectomy between intraperitoneal and retroperitoneal approaches. Surgical complications were graded according to the Clavien grading system. We also examined the long-term results of subclinical Cushing's syndrome after laparoscopic adrenalectomy. Laparoscopic surgical outcome did not differ significantly between patients with Cushing's syndrome and those with subclinical Cushing's syndrome. Patients who underwent laparoscopic intraperitoneal adrenalectomy had longer operative time than those who received retroperitoneal adrenalectomy (188.2 min vs. 160.9 min). However, operative blood loss and surgical complications were similar between both approaches. There were no complications of Clavien grade III or higher in either intraperitoneal or retroperitoneal approach. We confirmed the improvement of hypertension and glucose tolerance in patients with subclinical Cushing's syndrome after laparoscopic adrenalectomy. Laparoscopic adrenalectomy for adrenal Cushing's/subclinical Cushing's syndrome is safe and feasible in either intraperitoneal or retroperitoneal approach. The use of the Clavien grading system for reporting complications in the laparoscopic adrenalectomy is encouraged for a valuable quality assessment.

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

Cushing's syndrome in childhood: update on genetics, treatment, and outcomes.

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Lodish, Maya

2015-02-01

To provide an update on the genes associated with Cushing's syndrome in children, as well as to familiarize the clinician with recent treatment guidelines and outcome data for children with Cushing's syndrome. The list of genes associated with Cushing's syndrome continues to grow. In addition, treatment for childhood Cushing's syndrome is evolving. As long-term follow-up data on children becomes available, clinicians need to be aware of the issues that require attention. Knowledge of the specific genetic causes of Cushing's syndrome has potential implications for treatment, surveillance, and counseling. Advances in surgical technique, radiation modalities, and medical therapies offer the potential for additional treatment options in Cushing's syndrome. Early identification and management of post-treatment morbidities in children treated for Cushing's syndrome is crucial in order to optimize care.

Unmasking sarcoidosis following surgery for Cushing disease.

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Diernaes, Jon E F; Bygum, Anette; Poulsen, Per L

2016-01-01

We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.

Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

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McKeever, P E; Koppelman, M C; Metcalf, D; Quindlen, E; Kornblith, P L; Strott, C A; Howard, R; Smith, B H

1982-09-01

A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

Paraneoplastic Cushing Syndrome Due To Wilm's Tumor.

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Faizan, Mahwish; Manzoor, Jaida; Saleem, Muhammad; Anwar, Saadia; Mehmood, Qaiser; Hameed, Ambreen; Ali, Agha Shabbir

2017-05-01

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, along with histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed.

Paraneoplastic cushing syndrome due to wilm's tumor

International Nuclear Information System (INIS)

Faizan, M.; Anwar, S.; Hameed, A.; Manzoor, J.; Saleem, M.; Mehmood, Q.; Ali, A. S.

2017-01-01

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, alongwith histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed. (author)

Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome.

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Abe, Ichiro; Sugimoto, Kaoru; Miyajima, Tetsumasa; Ide, Tomoko; Minezaki, Midori; Takeshita, Kaori; Takahara, Saori; Nakagawa, Midori; Fujimura, Yuki; Kudo, Tadachika; Miyajima, Shigero; Taira, Hiroshi; Ohe, Kenji; Ishii, Tatsu; Yanase, Toshihiko; Kobayashi, Kunihisa

2018-04-27

Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas. Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning ACTH level (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly lower rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index. Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

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Dogansen, Sema Ciftci; Yalin, Gulsah Yenidunya; Canbaz, Bulent; Tanrikulu, Seher; Yarman, Sema

2018-01-01

The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing's syndrome

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Andereggen, Lukas; Schroth, Gerhard; Gralla, Jan; Ozdoba, Christoph; Seiler, Rolf; Mariani, Luigi; Beck, Juergen; Widmer, Hans-Rudolf; Andres, Robert H.; Christ, Emanuel

2012-01-01

Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma. We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation. In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing's disease patients. BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor. (orig.)

Therapeutic compounds for Cushing's syndrome: a patent review (2012-2016).

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Ma, Li; Yin, Lina; Hu, Qingzhong

2016-11-01

Endogenous Cushing's syndrome (CS) is a set of disorders caused by chronic exposure to excess glucocorticoids induced by neuroendocrine tumors in pituitary, adrenals, and infrequently other sites (ectopic ACTH syndrome). Due to various comorbidities, CS patients exhibit higher risks of cardiovascular diseases and thus increased mortality. Pharmaceutical therapy is an important constituent of treatment regimen. Areas covered: Patents published since 2012 are reviewed, which claim therapeutic compounds interfering with ACTH secretion and down-stream signal transduction, inhibiting cortisol biosynthesis and antagonizing glucocorticoid receptors. Advances focus on a) new analogues with improved efficacy and PK properties or less off-target toxicity; b) existing drugs (candidates) being repurposed to treat CS; and c) novel strategies such as selective inhibition of CYP11B1. Expert opinion: New compounds against established targets need to be developed because current drugs lack selectivity leading to off-target toxicity. Selective inhibition of CYP11B1 is a novel alternative strategy and is potentially versatile in controlling all types of hypercortisolism. Selective multi-targeting enzymes in steroidogenesis network is promising due to potential synergistic effects. However, doses toward each targets are not feasible to adjust because the corresponding intrinsic potencies are rigid. Targeting PRKACA mutations is promising in treating CS caused by adrenal adenomas.

Personality characteristics and quality of life in patients treated for Cushing's syndrome.

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Sonino, Nicoletta; Bonnini, Stefano; Fallo, Francesco; Boscaro, Marco; Fava, Giovanni A

2006-03-01

Psychological distress does not always disappear upon proper endocrine treatment of Cushing's syndrome, and quality of life may still be compromised. Little is known on the personality correlates that may be involved. The aim of this study was to provide a controlled assessment of personality characteristics and quality of life in patients successfully treated for Cushing's syndrome. A single-centred, controlled, prospective study. Twenty-four consecutive outpatients who were in remission upon proper treatment of Cushing's syndrome for at least 1 year and no more than 3 years (20 with pituitary-dependent Cushing's disease and four with a cortisol-secreting adrenal adenoma; 5 M/19 F; mean age 34.5, SD = 10.6; range 18-57 years) were compared with 24 healthy control subjects matched for sociodemographic variables. Both patients and controls were administered two self-rating scales: (a) tridimensional personality questionnaire (TPQ), a 100-item inventory that yields three scales: novelty seeking, harm avoidance and reward dependence. (b) symptom rating test (SRT), a 46-item scale for assessing psychological distress and quality of life with six subscales (anxiety, depression, somatic symptoms, anger-hostility, cognitive symptoms, psychotic symptoms). There were no significant differences in personality dimensions, as measured by the TPQ, between patients and controls. The results did not change when the four patients with an adrenal adenoma were excluded and only the 20 with pituitary-dependent Cushing's disease were considered. As to the SRT scale, patients with Cushing's syndrome displayed significantly higher scores in anxiety (P= 0.046), depression (P= 0.013), and psychotic symptoms (P= 0.006), with a generalized compromised quality of life (P= 0.02). Again, no differences were found in evaluating the 20 patients with Cushing's disease separately. Even though personality traits other than those explored here may be involved, the results seem to exclude the

Inhalational Steroids and Iatrogenic Cushing's Syndrome.

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A V, Raveendran

2014-01-01

Bronchial asthma (BA) and Allergic rhinitis (AR) are common clinical problems encountered in day to day practice, where inhalational corticosteroids (ICS) or intranasal steroids (INS) are the mainstay of treatment. Iatrogenic Cushing syndrome (CS) is a well known complication of systemic steroid administration. ICS /INS were earlier thought to be safe, but now more and more number of case reports of Iatrogenic Cushing syndrome have been reported, especially in those who are taking cytochrome P450 (CYP 450) inhibitors. Comparing to the classical clinical features of spontaneous Cushing syndrome, iatrogenic Cushing syndrome is more commonly associated with osteoporosis, increase in intra-ocular pressure, benign intracranial hypertension, aseptic necrosis of femoral head and pancreatitis, where as hypertension, hirsuitisum and menstrual irregularities are less common. Endocrine work up shows low serum cortisol level with evidence of HPA (hypothalamo-pituitary-adrenal) axis suppression. In all patients with features of Cushing syndrome with evidence of adrenal suppression always suspect iatrogenic CS. Since concomitant administration of cytochrome P450 inhibitors in patients on ICS/INS can precipitate iatrogenic CS, avoidance of CYP450 inhibitors, its dose reduction or substitution of ICS are the available options. Along with those, measures to prevent the precipitation of adrenal crisis has to be taken. An update on ICS-/INS- associated iatrogenic CS and its management is presented here.

Primary thyroid disorders in endogenous Cushing's syndrome.

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Niepomniszcze, Hugo; Pitoia, Fabian; Katz, Silvia B; Chervin, Raul; Bruno, Oscar D

2002-09-01

To study the prevalence of primary thyroid disorders in patients who underwent endogenous hypercortisolism. Retrospective evaluation of 59 patients with Cushing's syndrome (CS) who had, at least, a record of thyroid palpation by expert endocrinologists and basal measurements of TSH by second generation assays. When available, tri-iodothyronine and thyroxine serum levels, TRH-TSH tests and anti-thyroid antibodies were also analyzed. There were two age- and gender-matched control groups. The 'goiter control group' comprised 118 healthy subjects who underwent thyroid palpation. The 'antibody control group' was composed of 40 individuals who attended the blood bank of our hospital. Antibodies against thyroperoxidase and measurements of TSH were analyzed in their blood samples. Available files of 83 CS patients admitted to our endocrine unit from 1985 to 1998 were examined. Fifty-nine patients (52 women and 7 men) with a mean age of 36.2 years (range 14-61 years) met the above requirements. Diagnosis of hypercortisolism had been established by a standard 1-mg overnight dexamethasone suppression test and urinary free cortisol (UFC). Etiological diagnosis involved dynamic testing, measurements of ACTH levels and imaging techniques. After treatment, all but one of the patients were cured or controlled of their hypercortisolism. This was established by the finding of subnormal serum cortisol concentrations and/or subnormal 24-h UFC levels. Primary thyroid disorders were defined by the presence of one or more of the following diagnostic criteria: (i) goiter, (ii) positive anti-thyroid antibodies and/or (iii) primary thyroid function abnormalities. Eighteen (30.5%) patients had goiter (diffuse in 78% and nodular in 22%), 14 (23.7%) had primary subclinical hypothyroidism and 5 (8.4%) had hyperthyroidism. In 41 patients evaluated for antithyroid antibodies, it was found that 23 (56.1%) had positive titers. In a group of patients in which thyroid autoantibodies were measured

Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome

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Hiraishi, Kiichiro; Yoshimoto, Takanobu; Tsuchiya, Kyoichiro; Minami, Isao; Doi, Masaru; Izumiyama, Hajime; Hirata, Yukio; Sasano, Hironobu

2011-01-01

Primary aldosteronism (PA), an autonomous aldosterone hypersecretion from adrenal adenoma and/or hyperplasia, and subclinical Cushing syndrome (SCS), a mild but autonomous cortisol hypersecretion from adrenal adenoma without signs or symptoms of Cuhing's syndrome, are now well-recognized clinical entities of adrenal incidentaloma. However, the clinicopathological features of PA associated with SCS (PA/SCS) remain unknown. The present study was undertaken to study the prevalence of PA/SCS among PA patients diagnosed at our institute, and characterize their clinicopathlogical features. The prevalence of PA/SCS was 8 of 38 PA patients (21%) studied. These 8 PA/SCS patients were significantly older and had larger tumor, higher serum potassium levels, lower basal plasma levels of aldosterone, adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) as well as lower response of aldosterone after ACTH stimulation than those in 12 patients with aldosterone-producing adenoma without hypercortisolism. All 8 PA/SCS patients showed unilateral uptake by adrenal scintigraphy at the ipsilateral side, whereas the laterality of aldosterone hypersecretion as determined by adrenal venous sampling varied from ipsilateral (3), contralateral (2), and bilateral side (2). 6 PA/SCS patients who underwent adrenalectomy required hydrocortisone replacement postoperatively. Histopathological analysis of the resected adrenal tumors from 5 PA/SCS patients revealed a single adenoma in 3, and double adenomas in 2, with varying degrees of positive immunoreactivities for steroidgenic enzymes 3β-hydroxysteroid dehydrogenase (HSD), P450 C17 ) by immunohistochemical study as well as CYP11B2 mRNA expression as measured by real-time radiotherapy-polymerase chain reaction (RT-PCR). In conclusion, PA/SCS consists of a variety of adrenal pathologies so that therapeutic approach differs depending on the disease subtype. (author)

Invasive fungal infections in endogenous Cushing's syndrome

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Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

2010-01-01

Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

Clinical study on postoperative steroid hormon replacement for preclinical Cushing's syndrome

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Furuta, Nozomu; Koide, Haruhisa; Sasaki, Hiroshi; Miki, Jun; Kimura, Takahiro; Egawa, Shin

2009-01-01

Diagnostic criteria for preclinical Cushing's syndrome (PCS) were reported in 1996. However, requirement of postoperative steroid hormone replacement is still controversial issue. In this study, we observed recent surgical cases retrospectively and evaluate the use of postoperative steroid hormone replacement. Eighteen patients with PCS underwent surgery from 1997 to 2007 in Jikei University Hospital. Thirteen of them received postoperative steroid hormone replacement. We investigated preoperative hormone activity by 131 I-adosterol scintigraphy and suppression of adrenocorticotropic hormone (ACTH) and evaluated the requirement of postoperative steroid hormone replacement. Preoperative serum cortisol was normal range in all patients. Serum ACTH was suppressed in 10 of them (56%). In 131 I-adosterol scintigraphy, accumulation in ipsilateral side was observed in all patients. Accumulation in contralateral side was observed in 13 patients whose serum ACTH had tendency to be suppressed. Mean period of steroid hormone replacement was 19.8 weeks. Patients with lower preoperative ACTH tended to require longer period until withdrawal of steroid hormone replacement. In addition, patients received steroid hormone replacement with higher starting dose significantly required longer period. Three of them had complications during tapering of steroid hormone. Postoperative adrenal insufficiency is important issue as postoperative management of PCS patients whose function of contralateral adrenal or pituitary gland is suppressed. 131 I-adosterol scintigraphy and preoperative serum ACTH were important factors to evaluate the requirement of postoperative steroid hormone replacement. Especially, patients with low preoperative serum ACTH tended to require long duration of postoperative steroid hormone replacement. On the other hand, patients with accumulation of contralateral side in 131 I-adosterol scintigraphy and without suppression of serum ACTH may not require steroid hormone

Daily blood pressure profile in Cushing's syndrome before and after surgery

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Kreze A.

1999-01-01

Full Text Available No significant difference has been demonstrated in the altered circadian blood pressure pattern between the pituitary-dependent and adrenal forms of Cushing's syndrome before surgery. The effect of therapy, however, proved to be different. The mesor was normalized in the pituitary-dependent Cushing's syndrome more conspicuously for systolic than for diastolic blood pressure. In Cushing's syndrome due to adrenal adenoma, systolic and diastolic blood pressure mesors have been even significantly "overnormalized" after treatment, being 11 to 27 and 2 to 13 mmHg (95% confidence lower than corresponding mesors in controls. There was no difference between forms in the effect of treatment on blood pressure amplitudes, which remained significantly lower than in controls. Finally, acrophase patterns were partly normalized after treatment of the pituitary-dependent form only for diastolic blood pressure, while both systolic and diastolic blood pressure acrophases were normalized in the treated adrenal form. In conclusion, complete normalization of the pattern of daily blood pressure profile has not been achieved in either form of the syndrome. This may be one of the reasons for the reduced long-term survival after surgical cure of hypercortisolism, than expected.

Left ventricular structural and functional characteristics in Cushing's syndrome.

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Muiesan, Maria Lorenza; Lupia, Mario; Salvetti, Massimo; Grigoletto, Consuelo; Sonino, Nicoletta; Boscaro, Marco; Rosei, Enrico Agabiti; Mantero, Franco; Fallo, Francesco

2003-06-18

This study was designed to evaluate left ventricular (LV) anatomy and function in patients with Cushing's syndrome. A high prevalence of LV hypertrophy and concentric remodeling has been reported in Cushing's syndrome, although no data have been reported on LV systolic and diastolic function. Forty-two consecutive patients with Cushing's syndrome and 42 control subjects, matched for age, gender, and blood pressure, were studied. Left ventricular mass index (LVMI) and relative wall thickness (RWT) were measured by echocardiography, endocardial and midwall fractional shortening (FS) were assessed, and diastolic filling was measured by Doppler transmitral flow. The RWT was significantly greater in Cushing patients than in controls. Left ventricular hypertrophy and concentric remodeling were observed in 10 and 26 patients with Cushing's syndrome, respectively. In Cushing patients, midwall FS was significantly reduced compared with controls (16.2 +/- 3% vs. 21 +/- 4.5%, p = 0.01). The ratio of transmitral E and A flow velocities was reduced and E deceleration time was prolonged in Cushing patients compared with controls (p = 0.03 and p < 0.001, respectively). In patients with Cushing's syndrome, cardiac structural changes are associated with reduced midwall systolic performance and with diastolic dysfunction that may contribute to the high risk of cardiovascular events observed in these patients.

Cushing?s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment

OpenAIRE

Buliman, A; Tataranu, LG; Paun, DL; Mirica, A; Dumitrache, C

2016-01-01

Cushing?s disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing?s disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations,...

Ectopic corticotroph syndrome

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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

Cushing's Syndrome

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... person cured of Cushing’s syndrome might have some memory loss and slight mental decline. But the change is ... Categories: Family Health, Infants and Toddlers, Kids and Teens, Men, Seniors, WomenTags: acth, adenomas, hormone, sickness September ...

Cardiovascular autonomic function in Cushing's syndrome.

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Fallo, F; Maffei, P; Dalla Pozza, A; Carli, M; Della Mea, P; Lupia, M; Rabbia, F; Sonino, N

2009-01-01

Cardiac autonomic dysfunction is associated with increased cardiovascular mortality. No data on sympathovagal balance are available in patients with Cushing's syndrome, in whom cardiovascular risk is high. We studied 10 patients with newly diagnosed Cushing's syndrome (1 male/9 females; age mean+/-SD, 47+/-10 yr) and 10 control subjects matched for age, sex, body mass index, and cardiovascular risk factors. In both groups there were 7 patients with arterial hypertension, 3 with diabetes mellitus, and 2 with obesity. Cardiac autonomic function was evaluated by analysis of short time heart rate variability (HRV) measures in frequency domain over 24-h, daytime, and nighttime. The 24-h ambulatory blood pressure monitoring and echocardiography were also performed. In comparison with controls, patients with Cushing's syndrome had lower 24-h (1.3+/-0.6 vs 3.7+/-1.5, mean+/-SD, p<0.01), daytime (2.0+/-1.4 vs 4.5+/-1.6, p<0.01), and night-time (1.0+/-0.4 vs 3.5+/-2.3, p<0.01) low-frequency/ high frequency (LF/HF) power ratio. In the presence of similar LF power, the difference was due to elevation in HF power in Cushing's syndrome compared to controls: 24-h, 12.7+/-6.7 vs 5.8+/-2.8, p<0.01; daytime, 10.2+/-7.3 vs 4.5+/-2.1, p<0.05; nighttime, 14.2+/-7.0 vs 7.8+/-4.7, p<0.05. Eight Cushing patients vs 4 controls had a non-dipping blood pressure profile. At echocardiography, Cushing patients had a greater left ventricular mass index and/or relative wall thickness, and impaired diastolic function, compared with controls. Compared to controls, patients with Cushing's syndrome showed a sympathovagal imbalance, characterized by a relatively increased parasympathetic activity. Whether this autonomic alteration is meant to counterbalance cortisol-induced effects on blood pressure and cardiac structure/function or has a different pathophysiological significance is still unknown.

Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

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Gloria Aranda

2017-01-01

Full Text Available Glucocorticoids (GC induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC. Aim. To investigate adhesion and activation surface cell markers (CDs of peripheral IMNC in endogenous Cushing syndrome (CS and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D, 10 ACTH-independent (ACTH-ID CS, and 16 healthy controls (C were included. Leukocytes (Leuc, monocytes (MN, lymphocytes (Lym, and neutrophils (N were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p<0.05, WC (p<0.001, WHR (p=0.003, BMI (p<0.001, and hs-CRP (p<0.001. CD14++CD16+ (p=0.047; CD14+CD16++ (p=0.053 MN; CD15+ (p=0.027; CD15+CD16+ (p=0.008 N; and NK-Lym (p=0.019 were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5% versus ACTH-D CS (4.2 ± 1.9% versus C (4.9 ± 2.3%. NK-Lym correlated with c-LDL (r = 0.433, p=0.039 and CD15+ N with hs-CRP (r = 0.446, p=0.037. In multivariate analysis, Leuc, N, and MN depended on BMI (p=0.021, WC (p=0.002, and WHR (p=0.014, while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p=0.035. Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

Internal jugular vein adrenocorticotropic hormone estimation for diagnosis of adrenocorticotropic hormone-dependent Cushing′s syndrome: Ultrasound-guided direct jugular vein sample collection

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Jaya Prakash Sahoo

2012-01-01

Full Text Available Aim of Study: To assess the utility of internal jugular vein (IJV / peripheral adrenocorticotropic hormone (ACTH gradient in determining the etiology of ACTH- dependent Cushing′s syndrome. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome, (except children less than 12 years, had IJV blood collection under ultrasound guidance using a linear 7 MHZ probe. Blood was collected with a 21 G needle at the level of mandible with the patient in supine position. Six ml of blood was collected sequentially from right and left internal jugular veins for ACTH and prolactin estimation. Peripheral blood for ACTH and prolactin was taken from a previously placed IV cannula in the antecubital vein. Results: Thirty patients (20 F, 10 M, age 14 to 50 yrs were enrolled for this study. Source of ACTH excess was pituitary in 22, ectopic ACTH in 4, and unknown in 4 cases. Using an IJV: Peripheral ACTH ratio of ≥ 1.6, 15 out of 22 Cushing′s disease patients were correctly identified. However, 1 out of 4 ectopic Cushing also had IJV: Peripheral ratio ≥ 1.6. Overall, it had sensitivity of 68% with specificity of 75% while MRI pituitary and HDDST had sensitivity of 86% and 59%, respectively, with specificity of 100% each. Conclusion: IJV: Peripheral ACTH gradient was observed in 68% of patients with Cushing′s disease. Simultaneous IJV and peripheral sample collection with CRH stimulation may improve sensitivity and specificity of this test.

Iatrogenic Cushing's syndrome caused by intranasal steroid use.

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Dursun, Fatma; Kirmizibekmez, Heves

2017-01-01

Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

Cushing's disease in the elderly patient

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Maritza Cardosa Samón

2012-05-01

Full Text Available Introduction: Cushing's disease arises from increased ACTH secretion from a pituitary tumor that stimulates the area fasciculata of the adrenal cortex and produces hypersecretion of glucocorticoids. Objectives: To explain the clinical and humoral manifestations of Cushing's disease in elderly adults. Methods: The article is a descriptive and retrospective study of a case report on a 62 year old patient that is admitted to our Center with manifestations of facial plethora and centripetal obesity. Onset was characterized by hypertension and diabetes mellitus. Definitive diagnosis was Cushing's disease from a macroadenoma with increased ACTH secretion.

Case Of Iatrogenic Cushing's Syndrome By Topical Triamcinolone.

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Zil-E-Ali, Ahsan; Janjua, Omer Hanif; Latif, Aiza; Aadil, Muhammad

2018-01-01

Cushing's syndrome is a collection of signs and symptoms due to hypercortisolism. Prolong use of topical steroid may cause this syndrome and suppression of hypothalamic and pituitary function, however such events are more common with oral and parenteral route. There are very few cases of Cushing's syndrome with a topical application amongst which triamcinolone is the rarest drug. We report a case of 11-year-old boy is presented who developed Cushing's disease by topical application. The child had body rashes for which the caregiver consulted a local quack, a topical cream of triamcinolone was prescribed. After application for three months, the patient became obese and developed a moon-like face. A thorough biochemical workup and diagnostic test for Cushing's disease was done to confirm. The following case report a dramatic example of development of the syndrome from chronic topical application of the least potent corticosteroid.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing's syndrome

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Andereggen, Lukas [Bern University Hospital, University Institute of Diagnostic and Interventional Neuroradiology, Bern (Switzerland); Bern University Hospital, Department of Neurosurgery, Bern (Switzerland); Schroth, Gerhard; Gralla, Jan; Ozdoba, Christoph [Bern University Hospital, University Institute of Diagnostic and Interventional Neuroradiology, Bern (Switzerland); Seiler, Rolf; Mariani, Luigi; Beck, Juergen; Widmer, Hans-Rudolf; Andres, Robert H. [Bern University Hospital, Department of Neurosurgery, Bern (Switzerland); Christ, Emanuel [Bern University Hospital, Division of Endocrinology, Diabetology and Clinical Nutrition, Bern (Switzerland)

2012-05-15

Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma. We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation. In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing's disease patients. BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor. (orig.)

Past and present in abdominal surgery management for Cushing's syndrome.

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Vilallonga, Ramon; Zafon, Carles; Fort, José Manuel; Mesa, Jordi; Armengol, Manel

2014-01-01

Data on specific abdominal surgery and Cushing's syndrome are infrequent and are usually included in the adrenalectomy reports. Current literature suggests the feasibility and reproducibility of the surgical adrenalectomies for patients diagnosed with non-functioning tumours and functioning adrenal tumours including pheochromocytoma, Conn's syndrome and Cushing's syndrome. Medical treatment for Cushing's syndrome is feasible but follow-up or clinical situations force the patient to undergo a surgical procedure. Laparoscopic surgery has become a gold standard nowadays in a broad spectrum of pathologies. Laparoscopic adrenalectomies are also standard procedures nowadays. However, despite the different characteristics and clinical disorders related to the laparoscopically removed adrenal tumours, the intraoperative and postoperative outcomes do not significantly differ in most cases between the different groups of patients, techniques and types of tumours. Tumour size, hormonal type and surgeon's experience could be different factors that predict intraoperative and postoperative complications. Transabdominal and retroperitoneal approaches can be considered. Outcomes for Cushing's syndrome do not differ depending on the surgical approach. Novel technologies and approaches such as single-port surgery or robotic surgery have proven to be safe and feasible. Laparoscopic adrenalectomy is a safe and feasible approach to adrenal pathology, providing the patients with all the benefits of minimally invasive surgery. Single-port access and robotic surgery can be performed but more data are required to identify their correct role between the different surgical approaches. Factors such as surgeon's experience, tumour size and optimal technique can affect the outcomes of this surgery.

High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing.

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Friedman, T C; Ghods, D E; Shahinian, H K; Zachery, L; Shayesteh, N; Seasholtz, S; Zuckerbraun, E; Lee, M L; McCutcheon, I E

2010-11-01

Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism. © Georg Thieme Verlag KG Stuttgart · New York.

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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Sarma, Asha; Shyn, Paul B.; Vivian, Mark A.; Ng, Ju-Mei; Tuncali, Kemal; Lorch, Jorchen H.; Zaheer, Sarah N.; Gordon, Michael S.; Silverman, Stuart G.

2015-01-01

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org [Brigham and Women’s Hospital, Department of Radiology (United States); Vivian, Mark A. [University of Manitoba, Department of Radiology (Canada); Ng, Ju-Mei [Brigham and Women’s Hospital, Department of Anesthesiology (United States); Tuncali, Kemal [Brigham and Women’s Hospital, Department of Radiology (United States); Lorch, Jorchen H. [Dana Farber Cancer Institute, Department of Medicine (United States); Zaheer, Sarah N.; Gordon, Michael S. [Brigham and Women’s Hospital, Department of Endocrinology (United States); Silverman, Stuart G. [Brigham and Women’s Hospital, Department of Radiology (United States)

2015-10-15

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

Acute mesenteric ischemia and hepatic infarction after treatment of ectopic Cushing's syndrome.

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Takayasu, Shinobu; Murasawa, Shingo; Yamagata, Satoshi; Kageyama, Kazunori; Nigawara, Takeshi; Watanuki, Yutaka; Kimura, Daisuke; Tsushima, Takao; Sakamoto, Yoshiyuki; Hakamada, Kenichi; Terui, Ken; Daimon, Makoto

2017-01-01

Patients with Cushing's syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing's syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing's syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing's syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing's syndrome are acutely needed. The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing's syndrome.Patients with Cushing's syndrome are at increased risk for thromboembolic events and increased morbidity and mortality.An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing's syndrome.Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

Growth hormone deficiency in treated acromegaly and active Cushing's syndrome.

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Formenti, Anna Maria; Maffezzoni, Filippo; Doga, Mauro; Mazziotti, Gherardo; Giustina, Andrea

2017-02-01

Growth hormone deficiency (GHD) in adults is characterized by reduced quality of life and physical fitness, skeletal fragility, increased weight and cardiovascular risk. It may be found in (over-) treated acromegaly as well as in active Cushing's syndrome. Hypopituitarism may develop in patients after definitive treatment of acromegaly, although the exact prevalence of GHD in this population is still uncertain because of limited awareness, and scarce and conflicting data so far available. Because GHD associated with acromegaly and Cushing's syndrome may yield adverse consequences on similar target systems, the final outcomes of some complications of both acromegaly and Cushing's syndrome may be further affected by the occurrence of GHD. It is still largely unknown, however, whether GHD in patients with post-acromegaly or active Cushing's syndrome (e.g. pharmacologic glucocorticoid treatment) may benefit from GH replacement. We review the diagnostic, clinical and therapeutic aspects of GHD in adults treated for acromegaly and in those with active Cushing's syndrome. Copyright © 2017 Elsevier Ltd. All rights reserved.

NIH Researchers Find Potential Genetic Cause of Cushing Syndrome

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... 2017 NIH researchers find potential genetic cause of Cushing syndrome Finding may lead to therapies that prevent pituitary ... mutations in the gene CABLES1 may lead to Cushing syndrome, a rare disorder in which the body overproduces ...

Cushing's syndrome: update on signs, symptoms and biochemical screening.

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Nieman, Lynnette K

2015-10-01

Endogenous pathologic hypercortisolism, or Cushing's syndrome, is associated with poor quality of life, morbidity, and increased mortality. Early diagnosis may mitigate against this natural history of the disorder. The clinical presentation of Cushing's syndrome varies, in part related to the extent and duration of cortisol excess. When hypercortisolism is severe, its signs and symptoms are unmistakable. However, most of the signs and symptoms of Cushing's syndrome are common in the general population (e.g., hypertension and weight gain) and not all are present in every patient. In addition to classical features of glucocorticoid excess, such as proximal muscle weakness and wide purple striae, patients may present with the associated comorbidities that are caused by hypercortisolism. These include cardiovascular disease, thromboembolic disease, psychiatric and cognitive deficits, and infections. As a result, internists and generalists must consider Cushing's syndrome as a cause, and endocrinologists should search for and treat these comorbidities. Recommended tests to screen for Cushing's syndrome include 1  mg dexamethasone suppression, urine free cortisol, and late night salivary cortisol. These may be slightly elevated in patients with physiologic hypercortisolism, which should be excluded, along with exogenous glucocorticoid use. Each screening test has caveats and the choice of tests should be individualized based on each patient's characteristics and lifestyle. The objective of this review is to update the readership on the clinical and biochemical features of Cushing's syndrome that are useful when evaluating patients for this diagnosis. © 2015 European Society of Endocrinology.

Nelson syndrome: historical perspectives and current concepts.

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Hornyak, Mark; Weiss, Martin H; Nelson, Don H; Couldwell, William T

2007-01-01

The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

Adrenal Surgery for Cushing's Syndrome: An Update.

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Di Dalmazi, Guido; Reincke, Martin

2018-06-01

Recent advances in the molecular pathogenesis and the natural history of Cushing's syndrome have improved the understanding of the management of this disease. The long-term efficacy of several cortisol-lowering medical treatments is currently under evaluation. However, adrenalectomy is a safe option for the treatment of patients affected by Cushing's syndrome. Unilateral adrenalectomy is the gold standard for treatment of adrenocortical adenomas associated with hypercortisolism. Bilateral adrenalectomy has been widely used in the past as definitive treatment of bilateral macronodular hyperplasia and persistent or recurrent Cushing's disease. The indication and the potential applications of this technique have been recently critically analyzed. Copyright © 2018 Elsevier Inc. All rights reserved.

Psychosomatic aspects of Cushing's syndrome.

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Sonino, Nicoletta; Fallo, Francesco; Fava, Giovanni A

2010-06-01

There has been growing interest in the psychosocial aspects of Cushing's syndrome, such as the role of life stress as a pathogenetic factor, the association with affective disorders, and the presence of residual symptoms after treatment. Interestingly, a temporal relationship between stressful life events and disease onset is relevant only to pituitary-dependent Cushing's disease, and not to the pituitary-independent forms. A number of psychiatric and psychological disturbances may be associated with the active hypercortisolemic state, regardless of its etiology. Within the high frequency of mood disorders (about 60%), major depression is the most common complication. Other psychopathological aspects include mania, anxiety disorders, psychological symptoms (demoralization, irritable mood, somatization) and cognitive impairment. Cognitive symptoms are associated with brain abnormalities (mainly loss of brain volume). Quality of life may be seriously compromised during both active and post-treatment phases. Long-standing hypercortisolism may imply a degree of irreversibility of the pathological process. Recovery, thus, may be delayed and be influenced by highly individualized affective responses. Outcomes of Cushing's syndrome treatment are not fully satisfactory. Within its great complexity, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary to improve effectiveness. It is time to translate the research evidence that has accumulated into clinical practice initiatives. To patients who show persistence or even worsening of psychological distress upon adequate endocrine treatment psychiatric/psychological interventions should be readily available. Applying interdisciplinary expertise and addressing the needs for rehabilitation would markedly improve final outcome.

[CHALLENGES IN THE DIAGNOSIS OF CUSHING'S SYNDROME IN THE MODERN ERA].

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Saiegh, Leonard; Sheikh-Ahmad, Mohammad; Reut, Maria; Jubran, Yousef; Shechner, Carmela

2015-12-01

Cushing's syndrome results from prolonged and excessive exposure to medically prescribed corticosteroids, or from excess endogenous cortisol secretion. When endogenous cortisol secretion is suspected, several screening tests are conducted in order to confirm or to rule out the diagnosis. In recent years, as the cut-off point of cortisol concentration on the 1 mg overnight dexamethasone suppression test was lowered, the prevalence of Cushing's syndrome has increased, and more cases of mild syndromes, with negative results on one or more screening tests, have increasingly been reported. In this paper, we will describe the various screening tests used for Cushing's syndrome, and will discuss their degree of sensitivity in the diagnosis of mild cases. We conclude that, in cases of mild syndromes, the sensitivity of some tests appears to be notably lower than has been reported. Until recently, the major challenge has been to distinguish between pseudo-Cushing's states and Cushing's syndrome. Today, however, the challenge has become to avoid misdiagnosis of mild cases, presenting with normal results on some screening tests. The sensitivity of urinary free cortisol seems to be lower than previously reported. Therefore, we recommend not to rely solely on this test in ruling out Cushing's syndrome.

Gallium-68 DOTA-TATE Positron Emission Tomography/Computed Tomography: Scintigraphic Changes of Adrenal Glands Following Management of Ectopic Cushing's Syndrome by Steroidogenesis Inhibitors

International Nuclear Information System (INIS)

Huang, Yu-Ting; Aziz, Shaikh Irfan; Kumar, Aravind S. Ravi

2014-01-01

In the era of emerging functional imaging techniques, an understanding of the effects of hormonal therapies on the scintigraphic appearance of endocrine organs is desirable to minimize the erroneous scan interpretation. The mechanisms by which changes in the scintigraphic appearance of endocrine organs occur however sometimes remain ambiguous. This case demonstrates the gallium-68 (Ga-68) DOTA-TATE positron emission tomography/computed tomography (CT) appearance of adrenal glands following management with steroidogenesis inhibitors. The potential mechanisms underlying this change are discussed. A 17-year-old boy with adrenocorticotropic hormone (ACTH) dependent Cushing's syndrome secondary to ectopic ACTH secretion underwent pre- and post-metyrapone and dexamethasone treatment Ga-68 DOTA-TATE scans 4 months apart. Pretreatment, both adrenals demonstrated normal symmetrical prominent Ga-68 DOTA-TATE uptake and normal CT appearance. The posttherapy scan revealed marked symmetrical suppression of Ga-68 DOTA-TATE uptake, but with bilateral adrenal hypertrophy on CT

Pituitary Apoplexy due to the Diagnostic Test in a Cushing"s Disease Patient.

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Kuzu, Fatih; Unal, Mustafa; Gul, Sanser; Bayraktaroglu, Taner

2018-01-01

Pituitary apoplexy is a medical condition that needs urgent diagnosis and treatment. It may occur spontaneously or may be precipitated by a variety of reasons including dynamic endocrine tests. Although pituitary apoplexy is usually seen in nonfunctional pituitary adenoma, it can also be seen in ACTH secreting macroadenomas. ACTH secreting adenomas present usually as microadenomas and in these patients apoplexy is rarely seen. In this paper we present a 30-year-old male patient with a history of Cushing"s disease who suffered from pituitary apoplexy after the 1 mg dexamethasone suppression test. He underwent endoscopic endonasal transsphenoidal surgery and his symptoms and signs were significantly improved.

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.

Cushing's syndrome: epidemiology and developments in disease management.

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Sharma, Susmeeta T; Nieman, Lynnette K; Feelders, Richard A

2015-01-01

Cushing's syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing's syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of Cushing's syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities.

Exophthalmos: A Forgotten Clinical Sign of Cushing's Syndrome

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Aldo Schenone Giugni

2013-01-01

Full Text Available Exophthalmos is typically associated with Graves' ophthalmopathy. Although originally described by Harvey Cushing, exophthalmos is an underappreciated sign of Cushing's syndrome. We present a case of a 38-year-old female who presented with severe bilateral proptosis and was subsequently diagnosed with Cushings disease. We discuss the possible mechanisms causing exophthalmos in patients with either endogenous or exogenous hypercortisolemia.

Two Cases of. Cushing's Syndrome tumour and bilateral hyperplasia

African Journals Online (AJOL)

Two patients, one with Cushing's syndrome and one with Cushing's disease, are presented. In the first case the syndrome was caused by a tumour of the right suprarenal gland which was treated by unilateral adrenalectomy, and the second case was diagnosed as hyperplasia of the left suprarenal gland, eventually leading ...

Current status of adrenalectomy for Cushing's disease

International Nuclear Information System (INIS)

Brunicardi, F.C.; Rosman, P.M.; Lesser, K.L.; Andersen, D.K.

1985-01-01

To evaluate the current use of adrenalectomy in the treatment of Cushing's disease, we reviewed seven consecutive patients who have undergone adrenalectomy for Cushing's disease at this medical center during 1983 to 1984. Seventy-one percent (5/7) had pituitary, or type I, Cushing's disease, while 29% (2/7) had adrenal, or type II, Cushing's disease from either an adenoma or an adrenocortical carcinoma. Presenting signs and symptoms, either initially or at the time of recurrence, were typical of Cushing's syndrome. Four of five patients with type I disease had recurrent disease after transphenoidal hypophysectomy, bilateral adrenalectomy, or unilateral adrenalectomy. In three of five patients, medical therapy of hypercortisolism was abandoned because of adverse side effects. Preoperative evaluation in all patients included cortisol and ACTH levels, dexamethasone suppression tests, and computerized tomography (both abdominal and head). In patients with a prior history of adrenalectomy, radiocholesterol scans were also performed and were useful. Angiographic procedures were not required in these patients. In patients with type I disease, posterior operative approaches were used. In patients with type II disease, an anterolateral approach was used. Posterolateral incisions are preferred over Hugh-Young incisions and provide better exposure with a reduced risk of poor wound healing. Morbidity and mortality included one death and three nonhealing wounds. In the six surviving patients, symptoms resolved with variable frequency. Findings suggestive of Nelson's syndrome (hyperpigmentation) have occurred in two patients; serial computerized tomographic scans fail to reveal evidence of pituitary tumors

Bilateral inferior petrosal sinus sampling using vasopressin

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Narendra Kotwal

2016-01-01

Full Text Available Context: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. Aims: To study the tumor localization and lateralization in difficult to localize cases of ACTH-dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. Settings and Design: Prospective observational study. Subjects and Methods: Six patients (5 females meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. Results: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. Conclusions: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS.

Gêmeas idênticas discordantes para a doença de Cushing: relato de caso Identical twins discordant for Cushing's disease: case report

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MARCELO MAIA PINHEIRO

1999-09-01

Full Text Available A doença de Cushing é rara em crianças e sua ocorrência em gêmeos é ainda mais rara. O presente estudo relata a ocorrência de gêmeas idênticas discordantes quanto à doença de Cushing. Uma das gêmeas, desenvolveu síndrome de Cushing aos 10 anos de idade. Sua investigação demonstrou cortisol urinário elevado, ACTH sérico elevado e testes de supressão com dexametasona compatíveis com doença de Cushing. A RMN mostrou macroadenoma hipofisário que foi operado por via transesfenoidal. O estudo imuno-histoquímico confirmou a presença de células produtoras de ACTH. A paciente entrou em remissão clínica e laboratorial desde a cirurgia. Após o desaparecimento dos estigmas do Cushing, a paciente reiniciou ganho estatural, mas permanece menor que sua irmã gêmea. Esta última permanece saudável 4 anos após o início da doença de sua irmã. Este é o terceiro caso do gênero relatado na literatura. Estes achados sugerem que fatores não genéticos estão envolvidos na gênese da doença de Cushing.Cushing's disease is rare in children and its ocurrence in identical twins is extremely rare. This paper reports on identical twins discordant for Cushing's disease. One of them first presented with a cushingoid phenotype by the age of 10. Her evaluation showed an increased urinary free-cortisol and serum ACTH. Her pattern in the dexametazone supression tests was compatible with Cushing's disease. MRI disclosed a pituitary macroadenoma which was removed by the transesphenoidal approach. Immunohistochemical studies of the tumor showed the presence of ACTH-producing cells. The patient went into clinical and laboratorial remission after surgery. She re-started to grow after the disappearance of the Cushing's phenotype but she is still shorter than her healthy sister. The latter remains disease-free 4 years after her sister's diagnosis. This represents the third such case reported in the literature. Our findings suggest that acquired

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

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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.

Cushing's Syndrome: Where and How to Find It.

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Debono, Miguel; Newell-Price, John D

2016-01-01

The diagnosis of Cushing's syndrome is challenging to endocrinologists as patients often present with an insidious history, together with subtle external clinical features. Moreover, complications of endogenous hypercortisolism, such as visceral obesity, diabetes, hypertension and osteoporosis, are conditions commonly found in the population, and discerning whether these are truly a consequence of hypercortisolism is not straightforward. To avoid misdiagnosis, a careful investigative approach is essential. The investigation of Cushing's syndrome is a three-step process. Firstly, after exclusion of exogenous glucocorticoid use, the decision to initiate investigations should be based on whether there is a clinical index of suspicion of the disease. Specific signs of endogenous hypercortisolism raise the a priori probability of a truly positive test. Secondly, if the probability of hypercortisolism is high, one should carry out specific tests as indicated by Endocrine Society guidelines. Populations with non-distinguishing features of Cushing's syndrome should not be screened routinely as biochemical tests have a high false-positive rate if used indiscriminately. Thirdly, once hypercortisolism is confirmed, one should move to establish the cause. This usually entails distinguishing between adrenal or pituitary-related causes and the remoter possibility of the ectopic adrenocorticotropic hormone syndrome. It is crucial that the presence of Cushing's syndrome is established before any attempt at differential diagnosis. © 2016 S. Karger AG, Basel.

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

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Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

2016-01-01

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the

Cushing's syndrome in type 2 diabetes patients with poor glycemic control.

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Gungunes, Askin; Sahin, Mustafa; Demirci, Taner; Ucan, Bekir; Cakir, Evrim; Arslan, Muyesser Sayki; Unsal, Ilknur Ozturk; Karbek, Basak; Calıskan, Mustafa; Ozbek, Mustafa; Cakal, Erman; Delibasi, Tuncay

2014-12-01

Cushing's syndrome may be more frequent in some specific patient groups such as type 2 diabetes and obesity. The aim of this study was to investigate the prevalence of Cushing's syndrome in outpatients with type 2 diabetes with poor glycemic control despite at least 3-months insulin therapy. Outpatients with type 2 diabetes whose glycemic control is poor (Hb Alc value >7 %) despite receiving at least 3-months long insulin treatment (insulin alone or insulin with oral antidiabetics) were included. Patients with classic features of Cushing's syndrome were excluded. Overnight 1 mg dexamethasone suppression test (DST) was performed as a screening test. A total of 277 patients with type 2 diabetes whose glycemic control is poor (Hb Alc value >7 %) despite insulin therapy were included. Two of the 277 patients with type 2 diabetes were diagnosed with Cushing's syndrome (0.72 %). Hypertension was statistically more frequent in the patients with cortisol levels ≥1.8 μg/dL than the patients with cortisol levels Cushing's syndrome among patients with type 2 diabetes with poor glycemic control despite insulin therapy is much higher than in the general population. The patients with type 2 diabetes with poor glycemic control despite at least three months of insulin therapy should be additionally tested for Cushing's syndrome if they have high dose insülin requirements.

Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

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van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

2018-01-01

Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

Imaging in covert ectopic ACTH secretion: a CT pictorial review

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Sookur, Paul A.; Sahdev, Anju; Rockall, Andrea G.; Reznek, Rodney H. [St Bartholomew' s Hospital, Department of Academic Radiology, Dominion House, London (United Kingdom); Isidori, Andrea M. [Sapienza University of Rome, Department of Medical Pathophysiology, Rome (Italy); Monson, John P.; Grossman, Ashley B. [St Bartholomew' s Hospital, Department of Endocrinology, London (United Kingdom)

2009-05-15

The syndrome of ectopic adrenocorticotrophin secretion (EAS) is rare and is due to excess adrenocorticotrophin (ACTH) production from a nonpituitary tumour. These tumours can be covert, where the tumours are not readily apparent, and very small making them challenging to image. It is clinically and biochemically difficult to distinguish between covert EAS and Cushing's disease. The first-line investigation in locating the source of ACTH production is computed tomography (CT). The aim of this pictorial review is to illustrate the likely covert sites and related imaging findings. We review the CT appearances of tumours resulting in covert EAS and the associated literature. The most common tumours were bronchial carcinoid tumours, which appear as small, well-defined, round or ovoid pulmonary lesions. Rarer causes included thymic carcinoids, gastrointestinal carcinoids and pancreatic neuroendocrine tumours. Awareness of the imaging characteristics will aid identification of the source of ACTH production and allow potentially curative surgical resection. (orig.)

Diagnosis of Cushing's disease in children: a challenge for the radiologist

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Kalifa, G.; Adamsbaum, C.; Carel, J.C.; Andre, C.; Bougneres, P.F.; Chaussain, J.L.

1994-01-01

Cushing's disease is the most common cause of Cushing's syndrome in children and is almost always related to over secretion of ACTH by the pituitary gland. It is important to identify a secreting adenoma prior to surgery. Seven cases studied with MRI are reviewed. In five cases the MRI findings suggested adenoma. Three secreting adenomas were confirmed at surgery. One case was in fact a cyst of the pars intermedia, and nothing could be found in the last case. Two patients presented with apparently normal findings on MRI, which was confirmed. There is a close correlation between identifying an adenoma and the success of surgery. (orig.)

Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

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Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-11-01

Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report.

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Sedhom, Ramy; Hu, Sophia; Ohri, Anupam; Infantino, Dorian; Lubitz, Sara

2016-10-12

Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone. We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease.

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Liu, Ning-Ai; Araki, Takako; Cuevas-Ramos, Daniel; Hong, Jiang; Ben-Shlomo, Anat; Tone, Yukiko; Tone, Masahide; Melmed, Shlomo

2015-07-01

Cushing disease, due to pituitary corticotroph tumor ACTH hypersecretion, drives excess adrenal cortisol production with adverse morbidity and mortality. Loss of glucocorticoid negative feedback on the hypothalamic-pituitary-adrenal axis leads to autonomous transcription of the corticotroph precursor hormone proopiomelanocortin (POMC), consequent ACTH overproduction, and adrenal hypercortisolism. We previously reported that R-roscovitine (CYC202, seliciclib), a 2,6,9-trisubstituted purine analog, suppresses cyclin-dependent-kinase 2/cyclin E and inhibits ACTH in mice and zebrafish. We hypothesized that intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription independently of cell cycle progression. The aim was to investigate whether R-roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin-dependent kinase 2/cyclin E signaling pathway. Primary cell cultures of surgically resected human corticotroph tumors were treated with or without R-roscovitine, ACTH measured by RIA and quantitative PCR, and/or Western blot analysis performed to investigate ACTH and lineage-specific transcription factors. Cyclin E and E2F transcription factor 1 (E2F1) small interfering RNA (siRNA) transfection was performed in murine corticotroph tumor AtT20 cells to elucidate mechanisms for drug action. POMC gene promoter activity in response to R-roscovitine treatment was analyzed using luciferase reporter and chromatin immunoprecipitation assays. R-roscovitine inhibits human corticotroph tumor POMC and Tpit/Tbx19 transcription with decreased ACTH expression. Cyclin E and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. R-roscovitine disrupts E2F1 binding to the POMC gene promoter and suppresses Tpit/Tbx19 and other lineage-specific POMC transcription cofactors via E2F1-dependent and -independent pathways. R-roscovitine inhibits human pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway. Pituitary cyclin E

[Psychiatric disorders in patients with Cushing's disease before and after neurosurgery].

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Gnjidiae, Zivko; Karloviae, Dalibor; Buljan, Danijel; Malencia, Masa; Kovak-Mufiae, Ana; Kostanjsak, Lidija

2011-01-01

Cushing's disease which is a consequence of ACTH-secreting pituitary adenoma leads to hypercortisolism. Cushing's disease is associated with several psychiatric disturbances. The aim of the present study was to identify which psychiatric disorders were present in patients with Cushing's disease over a 2-year period and to monitor their general psychiatric condition. Additionally, the study aimed to examine the relationship between the duration of Cushing's disease, and the severity of psychiatric conditions based on psychiatric rating scales. The study included 39 patients with Cushing's disease that underwent neurosurgery for ACTH-secreting pituitary adenomas. The transsphenoidal approach (the standard microsurgery technique) was performed in all patients. ACTH-secreting pituitary adenomas were confirmed based on immunohistochemistry in all patients. Psychiatric conditions in the patients were identified using the Clinical Global Impression Scale (CGI) and ICD 10 diagnostic criteria at 3 time points: prior to surgery, and 6 and 48 months post surgery. The Cushing's disease patients exhibited statistically significant improvement in their psychiatric condition, according to the CGI, 6 and 48 months post surgery. There wasn't any significant correlation between the duration of Cushing's disease and psychiatric status, as measured by the CGI prior to surgery, 6 months post surgery, or 48 months post surgery. Patients with Cushing's disease had a significant level psychiatric disturbance that remitted after surgery. There wasn't a significant correlation between the duration of Cushing's disease and psychiatric status.

Subclinical Cushing's syndrome: current concepts and trends.

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Zografos, George N; Perysinakis, Iraklis; Vassilatou, Evangeline

2014-01-01

Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclinical cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic-pituitary-adrenal axis due to adrenal autonomy. This disorder has been described as subclinical Cushing's syndrome, since there is no typical clinical phenotype. The diagnosis of subclinical Cushing's syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (DST) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical Cushing's syndrome. DST is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hypersecretion and these morbidities. Therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. The optimal management of patients with subclinical Cushing's syndrome is not yet defined. The conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.

Ectopic corticotropin-releasing hormone (CRH syndrome from metastatic small cell carcinoma: a case report and review of the literature

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Shahani Sadeka

2010-08-01

Full Text Available Abstract Background Cushing's Syndrome (CS which is caused by isolated Corticotropin-releasing hormone (CRH production, rather than adrenocorticotropin (ACTH production, is extremely rare. Methods We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing. Results A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml which should have been suppressed in the presence of high cortisol. Conclusions This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.

Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling.

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Martins, Raquel G; Agrawal, Reshma; Berney, Daniel M; Reznek, Rodney; Matson, Matthew; Grossman, Ashley B; Druce, Maralyn R

2012-01-01

To outline the potential role for adrenal venous sampling in the diagnosis and management of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). We present a case description and discuss the management of a 59-year-old woman with an 8-year history of weight gain, centripetal obesity, a round plethoric face, skin thinning, easy bruising, hirsutism, and progressive muscle weakness. The patient reported a prior personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia, and bilateral leg ulcers, but she denied having any personal or family history of endocrinopathy and was not taking any corticosteroid medication. Elevated midnight serum cortisol, failure to suppress cortisol levels with a low-dose dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH-independent CS. Additional investigations including dynamic tests and adrenal imaging were supported by adrenal venous sampling in order to make a diagnosis and formulate a management plan. She was ultimately noted to have bilateral functioning adrenal nodules (adenoma and adenolipoma) and underwent successful bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and mineralocorticoid replacement. Adrenal venous sampling may be an important step in the differential diagnosis of CS and localization of the source of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary bilateral adrenalectomy. It can also ensure that the correct operation is completed, if required, and thus avoid the increased morbidity and mortality associated with repeated surgical interventions.

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.)

Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study.

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Tirosh, Amit; Lodish, Maya; Lyssikatos, Charalampos; Belyavskaya, Elena; Feelders, Richard A; Stratakis, Constantine A

2017-05-01

Previous studies reported a higher prevalence of venous-thromboembolic events among patients with Cushing disease (CD) compared to those with ACTH-independent Cushing syndrome (CS) from adrenal sources. The objective of the current study was to evaluate the coagulation profile of patients with CS from different etiologies. A prospective observational study was conducted at a clinical research center. The study included adult patients admitted for evaluation of suspected CS (n=85), that were divided into 3 groups: CD (n=22), ACTH-independent CS from an adrenal tumor/hyperplasia (adrenal CS, n=21), and a control group consisting of subjects with negative screening for CS (rule-out CS, n=42). Coagulation profiles were drawn before and 8.5±4.3 months after surgery (trans-sphenoidal or adrenalectomy, n=18), and included fibrinogen, Factor VIII (FVIII), von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor-1 (PAI-1), antithrombin III (ATIII), Protein C (PC), Protein S (PS), α2-antiplasmin (α2AP), and aPTT measurements. Patients with CD had higher baseline mean cortisol levels, ATIII activity and vWF:Ag levels compared with adrenal CS. Differences in ATIII activity and vWF:Ag levels remained even after controlling for BMI, and ATIII after also controlling for 24-h urinary free cortisol collections. Our study showed for the first time the differences in coagulation profiles between various etiologies of CS. We assume that the higher cortisol burden among CD patients may explain the differences found in the coagulation profile as well as the higher risk for VTE compared with primary adrenal CS patients. © Georg Thieme Verlag KG Stuttgart · New York.

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study.

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Fardet, Laurence; Petersen, Irene; Nazareth, Irwin

2012-07-30

To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing's syndrome during treatment with glucocorticoids. Cohort study. 424 UK general practices contributing to The Health Improvement Network database. People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome (n = 547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing's syndrome (n = 3231) and those not prescribed systemic glucocorticoids (n = 3282). Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing's syndrome or after a randomly selected date, and association between iatrogenic Cushing's syndrome and risk of cardiovascular events. 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n = 177, heart failure n = 101, ischaemic stroke n = 63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing's syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing's syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with

Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome.

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Eisenhofer, Graeme; Masjkur, Jimmy; Peitzsch, Mirko; Di Dalmazi, Guido; Bidlingmaier, Martin; Grüber, Matthias; Fazel, Julia; Osswald, Andrea; Beuschlein, Felix; Reincke, Martin

2018-03-01

Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes. © 2017 American Association for Clinical Chemistry.

Impact and Timing of Bilateral Adrenalectomy for Refractory ACTH-Dependent Cushing’s Syndrome

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Morris, Lilah F.; Harris, Rachel S.; Milton, Denái R.; Waguespack, Steven G.; Habra, Mouhammed A.; Jimenez, Camilo; Vassilopoulou-Sellin, Rena; Lee, Jeffrey E.; Perrier, Nancy D.; Grubbs, Elizabeth G.

2014-01-01

Introduction In patients with refractory ACTH-dependent Cushing’s syndrome (CS), we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. Methods Clinical data from patients treated 1970-2012 were retrospectively reviewed by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). Results 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n=21,32%) or SI alone (n=44,68%). Presenting M scores and source of ACTH excess (ectopic vs. pituitary) were similar. Both groups improved metabolically after treatment. 39% of AEs in the SI+BA group occurred within 12 months of presentation. 24(55%) SI patients died (median survival 24.0 months); steroid excess contributed to 71%. Six SI+BA patients died (29%), including all 3 patients with recurrent CS after BA. Minor perioperative complications occurred in 7 patients (33%). Conclusions Post-treatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early surgical intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable CS. PMID:24383115

Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

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Ramalingam, Sundhar; Eisenberg, Adva; Foo, Wen Chi; Freedman, Jennifer; Armstrong, Andrew J; Moss, Larry G; Harrison, Michael R

2016-12-01

Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome. © 2016 The Japanese Urological Association.

Complications of Cushing's syndrome: state of the art.

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Pivonello, Rosario; Isidori, Andrea M; De Martino, Maria Cristina; Newell-Price, John; Biller, Beverly M K; Colao, Annamaria

2016-07-01

Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cushing syndrome secondary to a medullary thyroid carcinoma: report of a case and review of the literature = Síndrome de Cushing secundario a carcinoma medular de tiroides: descripción de un caso y revisión de la literatura

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Gutiérrez Restrepo, Johnayro

2014-08-01

Full Text Available We report the case of a 29-year old female who was evaluated because of a thyroid tumor. The initial pathological classification was an insular thyroid carcinoma. There was strong involvement in the neck, mediastinum and lungs. Three years after receiving specific therapy for her thyroid neoplasia, she developed a Cushing syndrome and liver lesions suggestive of metastases from the primary tumor. A review of the previous pathological material revealed a medullary thyroid carcinoma producing ACTH, instead of the insular carcinoma. Based on this case a review of the literature is presented.

A Challenging Case of an Ectopic Cushing Syndrome

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Joana Menezes Nunes

2014-01-01

Full Text Available Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by 18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

Cushing's syndrome and bone mineral density: lowest Z scores in young patients.

NARCIS (Netherlands)

Eerden, A.W.A.; Heijer, M. den; Oyen, W.J.G.; Hermus, A.R.M.M.

2007-01-01

Background: Patients with Cushing's syndrome have a high prevalence of osteoporotic fractures. Little is known about factors determining bone mineral density (BMD) in these patients. Objective: To evaluate which factors influence BMD at the time of diagnosis of Cushing's syndrome. Methods: In 77

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome.

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Pazderska, A; Crowther, S; Govender, P; Conlon, K C; Sherlock, M; Gibney, J

2016-01-01

Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normalAVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing's syndrome.

Cushing's syndrome after intralesional triamcinolone acetonide: a systematic review of the literature and multinational survey.

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Fredman, Rafi; Tenenhaus, Mayer

2013-06-01

Intralesional triamcinolone acetonide (TAC) is a well-established treatment for keloids and hypertrophic scars. The present text provides a systematic review of all previously reported cases of Cushing's syndrome resulting from intralesional TAC in an effort to discover whether an association exists between dosage or frequency of injection and the subsequent development of Cushing's syndrome. Data collected from a multinational survey of plastic surgeons is presented and discussed to understand current trends in the use of TAC. Recommendations for early recognition of Cushing's syndrome, TAC dosages in children, and follow up guidelines are presented. A systematic review of the literature from 1950 to 2012 was performed to evaluate outcomes following intralesional TAC used for the treatment of scars. A confidential survey was sent to 4125 plastic surgeons, 102 responses from 9 countries were received. A total of 18 cases of Cushing's syndrome after intralesional TAC have been reported in the English world literature. Survey data reveals that at least 30% (25/84) of plastic surgeons exceed the recommended dosage of TAC and 47% (46/97) are not aware of Cushing's syndrome as a possible complication of intralesional TAC. Cushing's syndrome resulting from intralesional TAC has been reported multiple times in the literature. Published literature suggests that TAC administered within the most recent recommendations does not appear to place adult patients at increased risk for developing Cushing's syndrome. Children appear to be most at risk for developing Cushing's syndrome and yet insufficient recommendations currently exist with regard to their safe dosage. Intralesional dosage should not exceed 30 mg per month in children while noting that at least one reported case of Cushing's syndrome resulted from a smaller dose. Diligent follow up and patient education is advised for any patient treated with TAC so that complications can be recognized and addressed promptly

Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathy.

Science.gov (United States)

Fayol, L; Masson, P; Millet, V; Simeoni, U

2004-10-01

Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur.

Drawings reflect a new dimension of the psychological impact of long-term remission of Cushing's syndrome.

Science.gov (United States)

Tiemensma, Jitske; Daskalakis, Nikolaos P; van der Veen, Else M; Ramondt, Steven; Richardson, Stephanie K; Broadbent, Elizabeth; Romijn, Johannes A; Pereira, Alberto M; Biermasz, Nienke R; Kaptein, Adrian A

2012-09-01

Drawings can be used to assess perceptions of patients about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions, quality of life (QoL), and clinical disease severity in patients after long-term remission of Cushing's syndrome. We conducted a cross-sectional study including 47 patients with long-term remission of Cushing's syndrome. Patients completed the drawing test, the Illness Perception Questionnaire-Revised, the Short-Form 36, the EuroQoL-5D, and the Cushing QoL. The Cushing's syndrome severity index was scored based on medical records. Characteristics of the drawings were strongly associated with the Cushing's syndrome severity index and severity ratings of health professionals (all P Cushing's syndrome because drawings do not share common properties with parameters of QoL or illness perceptions, but do represent the clinical severity of the disease. The assessment of drawings may enable doctors to appreciate the perceptions of patients with long-term remission of Cushing's syndrome and will lead the way in dispelling idiosyncratic beliefs.

Ambulatory blood pressure monitoring-derived short-term blood pressure variability is increased in Cushing's syndrome.

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Rebellato, Andrea; Grillo, Andrea; Dassie, Francesca; Sonino, Nicoletta; Maffei, Pietro; Martini, Chiara; Paoletta, Agostino; Fabris, Bruno; Carretta, Renzo; Fallo, Francesco

2014-11-01

Cushing's syndrome is associated with high cardiovascular morbility and mortality. Blood pressure (BP) variability within a 24-h period is increasingly recognized as an independent predictor of cardiovascular risk. The aim of our study was to investigate the short-term BP variability indices in Cushing's syndrome. Twenty-five patients with Cushing's syndrome (mean age 49 ± 13 years, 4 males; 21 Cushing's disease and 4 adrenal adenoma patients) underwent 24-h ambulatory BP monitoring (ABPM) and evaluation of cardiovascular risk factors. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 17 hypertensive (HYP-CUSH) patients and were compared with 20 normotensive (NOR-CTR) and 20 hypertensive (HYP-CTR) age-, sex-, and BMI-matched control subjects. Short-term BP variability was derived from ABPM and calculated as the following: (1) standard deviation (SD) of 24-h, daytime, and nighttime BP; (2) 24-h weighted SD of BP; and (3) average real variability (ARV), i.e., the average of the absolute differences between consecutive BP measurements over 24 h. In comparison with controls, patients with Cushing's syndrome, either normotensive or hypertensive, had higher 24-h and daytime SD of BP, as well as higher 24-h weighted SD and ARV of BP (P = 0.03 to P CUSH or between HYP-CTR and HYP-CUSH subgroups. ABPM-derived short-term BP variability is increased in Cushing's syndrome, independent of BP elevation. It may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in BP variability has to be further clarified.

Syndrome of achalasia, ACTH insensitivity and alacrima

Energy Technology Data Exchange (ETDEWEB)

Ambrosino, M.M.; Genieser, N.B.; Becker, M.H.; Bangaru, B.S.; Sklar, C.

1986-05-01

An unusual multisystem disorder characterized by the triad of selective ACTH insensitivity, achalasia and alacrima has recently been described. The following case fulfills the criteria for this syndrome which has not been previously reported in the radiographic literature.

ACTH antagonists

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Adrian John Clark

2016-08-01

Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

Ectopic adrenocorticotropic hormone syndrome presenting as hypokalemic metabolic alkalosis and hypertension

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Mansoor C Abdulla

2016-01-01

Full Text Available The ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon cause of hypercortisolism, which should be considered in patients with hypokalemic metabolic alkalosis and hypertension in the context of lung neoplasm. We report a 60-year-old male patient with severe hypertension, metabolic alkalosis, and hypokalemia as the initial manifestations of an ACTH-secreting small cell lung carcinoma. Ectopic Cushing's syndrome should always be ruled out in patients with severe hypertension and hypokalemia.

Serum albumin-adjusted glycated albumin is an adequate indicator of glycemic control in patients with Cushing's syndrome.

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Kitamura, Tetsuhiro; Otsuki, Michio; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Bando, Yukihiro; Shimomura, Iichiro; Koga, Masafumi

2014-12-01

We recently reported that glycated albumin (GA) in patients with Cushing's syndrome is low. In the present study, we examined whether serum albumin (SA)-adjusted GA (SAaGA) is an adequate indicator of glycemic control in patients with Cushing's syndrome. We studied 26 patients with Cushing's syndrome (13 patients without diabetes and 13 patients with diabetes). Twenty six non-diabetic subjects and 26 patients with type 2 diabetes mellitus matched for age, sex and BMI were used as the controls. SAaGA was calculated using the regression formula between SA and GA in non-diabetic patients with Cushing's syndrome and non-diabetic subjects. SA showed a significant correlation with GA in non-diabetic patients with Cushing's syndrome and non-diabetic subjects. GA, but not SAaGA, in non-diabetic patients with Cushing's syndrome was significantly lower than that in the non-diabetic controls. Furthermore, the GA/HbA1c ratio, but not the SAaGA/HbA1c ratio, in diabetic patients with Cushing's syndrome was significantly lower than that in the diabetic controls. The measured GA in the patients with Cushing's syndrome was significantly lower than the estimated GA, but there was no difference between SAaGA and the estimated GA. The present findings suggest that SAaGA is an adequate indicator of the glycemic control in patients with Cushing's syndrome. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Massive Thoracoabdominal Aortic Thrombosis in a Patient with Iatrogenic Cushing Syndrome

International Nuclear Information System (INIS)

Kim, Dong Hun; Choi, Dong Hyun; Lee, Young Min; Kim, Bo Bae; Ki, Young Jae; Kim, Jin Hwa; Chung, Joong Wha; Koh, Young Youp; Kang, Joon Tae; Chae, Seung Seok

2014-01-01

Massive thoracoabdominal aortic thrombosis is a rare finding in patients with iatrogenic Cushing syndrome in the absence of any coagulation abnormality. It frequently represents an urgent surgical situation. We report the case of an 82-year-old woman with massive aortic thrombosis secondary to iatrogenic Cushing syndrome. A follow-up computed tomography scan showed a decreased amount of thrombus in the aorta after anticoagulation therapy alone.

Ritonavir and Topical Ocular Corticosteroid Induced Cushing's Syndrome in an Adolescent With HIV-1 Infection.

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Rainsbury, Paul G; Sharp, Jessica; Tappin, Alison; Hussey, Martin; Lenko, Alexandra; Foster, Caroline

2017-05-01

Cushing's syndrome after topical ocular corticosteroid use is extremely rare. We describe a case of symptomatic Cushing's syndrome in an adolescent male with sight-threatening vernal keratoconjunctivitis on antiretroviral therapy for HIV-1 infection that included ritonavir, a potent cytochrome p450 CYP3A4 inhibitor. CYP3A4 inhibition reduces the metabolism of exogenous corticosteroids leading to suppression of endogenous steroid production and Cushing's syndrome.

Cushing's syndrome in children and adolescents

DEFF Research Database (Denmark)

Holst, Johanne Marie; Horváth-Puhó, Erzsebet; Jensen, Rikke Bodin Beck

2017-01-01

OBJECTIVE: Cushing's syndrome (CS) affects all age groups, but epidemiologic data in young patients are very limited. We therefore examined the incidence, prevalence and hospital morbidity of CS in children and adolescents. DESIGN: In a nationwide cohort study, we included all Danish citizens aged...

Clinical features and management of ectopic ACTH syndrome at a single institute in Japan

International Nuclear Information System (INIS)

Doi, Masaru; Sugiyama, Toru; Izumiyama, Hajime; Yoshimoto, Takanobu; Hirata, Yukio

2010-01-01

Ectopic ACTH syndrome (EAS) is a diagnostic challenge because it is often indistinguishable from Cushing's disease. We describe our series of EAS patients referred to us during 1992-2009. Among 16 cases (9 females/7 males), with mean age of 58.4±19.0 yr, the ectopic source was identified in ten (proven EAS), whereas unidentified in six (occult/unknown EAS). Their salient clinical manifestations included Cushingoid feature (88%), skin pigmentation (88%), profound hypokalemia (88%), hypertension (75%), diabetes/impaired glucose tolerance (75%), hyperlipidemia (69%), and severe infection (44%). Dynamic endocrine tests revealed markedly elevated plasma ACTH levels (211±116 pg/mL) and cortisol levels (60.9±30.1 μg/dL) which showed resistance to overnight high-dose (8 mg) dexamethasone suppression test in 15 (94%) and unresponsiveness to corticotropin releasing hormone (CRH) stimulation in 12 (75%). No ACTH gradient during inferior petrosal sampling was noted in 13 of 15 (87%). Imaging tests by CT/MRI identified the tumors in 8 of 16 (50%), in 4 of 11 (36%) and 4 of 6 (66.7%) octreotide-responders by somatostatin receptor scintigraphy, but in only one of 9 (11.1%) by [ 18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. Six cases deceased, including small cell carcinoma (2) and adenocarcinoma (1) of lung, neuroendocrine carcinoma of pancreas (1) and stomach (1), and olfactory neuroblastoma (1), whereas 4 cases survived after removal of the tumors, including bronchial carcinoid tumor (3) and thymic hyperplasia (1). Six occult/unknown EAS patients survived for 67.5 months after medical treatment with metyrapone to control hypercortisolism. Thus, various endocrine tests combined with imaging studies are required to correctly localize the tumors. Control of hypercortisolemia by metyrapone, even if tumor is unrecognized, is critical for better prognosis, and the long-term follow-up by repeated endocrine and imaging tests is mandatory. (author)

[Study on the reproducibility of ACTH concentrations in plasma of horses with and without equine Cushing syndrome].

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Gehlen, Heidrun; Bradaric, Zrinkja

2013-01-01

The evaluation of plasma ACTH and the dexamethasone suppression test are considered the methods of choice to evaluate the course of therapy of pituitary pars intermedia dysfunction (PPID). Sampling protocols as well as vacutainers for analysis differ between the laboratories. To evaluate the reproducability of plasma ACTH measurement between four different laboratories (A, B, C, D) in Germany as well as within the laboratories themselves, ten horses with previously diagnosed PPID and four healthy horses were sampled and analyzed. Each laboratory received two differently labeled samples of each horse which had been drawn at the same time (blinded samples). Sampling was performed in the morning at the same time. The sampling vacutainers (with and without addition of coagulation and proteinase inhibitors) and postage of the samples was performed according to laboratory standards. In one laboratory the influence of the time of centrifugation (immediately after taking blood versus after one hour) was determined. The samples were processed and analyzed according to laboratory protocols. Determination of ACTH levels was performed using chemiluminescence immunoassay. In total 132 blood samples were analyzed. The results of doubled blood samples of the same horse showed a standard deviation ranging from +/- 6 to +/- 27 pg/ml within the laboratories (Ø 19,29 pg/ml). The standard deviation of the repeatability of the variation coefficient was 13,48%. Blood samples of the same horse resulted in ACTH levels of 121 pg/ml in the first probe and in < 5 pg/ml in the second probe. Standard deviation of measured ACTH values between the laboratories was +/- 26,4 pg/ml (Ø 27,44 pg/ml). The standard deviation of the reproducibility of the variation coefficient was 18,36%. In a 20 year old gelding the lowest ACTH value was 60.9 pg/ml whereas the highest measured value was 108 pg/ml. Immediate centrifugation of blood samples resulted in significantly higher ACTH values at an average of

Glycated albumin is set lower in relation to plasma glucose levels in patients with Cushing's syndrome.

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Kitamura, Tetsuhiro; Otsuki, Michio; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi

2013-09-23

Glycated albumin (GA) is an indicator of glycemic control, which has some specific characters in comparison with HbA1c. Since glucocorticoids (GC) promote protein catabolism including serum albumin, GC excess state would influence GA levels. We therefore investigated GA levels in patients with Cushing's syndrome. We studied 16 patients with Cushing's syndrome (8 patients had diabetes mellitus and the remaining 8 patients were non-diabetic). Thirty-two patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI were used as controls. In the patients with Cushing's syndrome, GA was significantly correlated with HbA1c, but the regression line shifted downwards as compared with the controls. The GA/HbA1c ratio in the patients with Cushing's syndrome was also significantly lower than the controls. HbA1c in the non-diabetic patients with Cushing's syndrome was not different from the non-diabetic controls, whereas GA was significantly lower. In 7 patients with Cushing's syndrome who performed self-monitoring of blood glucose, the measured HbA1c was matched with HbA1c estimated from mean blood glucose, whereas the measured GA was significantly lower than the estimated GA. We clarified that GA is set lower in relation to plasma glucose levels in patients with Cushing's syndrome. Copyright © 2013 Elsevier B.V. All rights reserved.

Pitfalls in the diagnosis and management of Cushing's syndrome.

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Bansal, Vivek; El Asmar, Nadine; Selman, Warren R; Arafah, Baha M

2015-02-01

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone-secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e

White matter alterations in the brains of patients with active, remitted, and cured cushing syndrome: a DTI study.

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Pires, P; Santos, A; Vives-Gilabert, Y; Webb, S M; Sainz-Ruiz, A; Resmini, E; Crespo, I; de Juan-Delago, M; Gómez-Anson, B

2015-06-01

Cushing syndrome appears after chronic exposure to elevated glucocorticoid levels. Cortisol excess may alter white matter microstructure. Our purpose was to study WM changes in patients with Cushing syndrome compared with controls by using DTI and the influence of hypercortisolism. Thirty-five patients with Cushing syndrome and 35 healthy controls, matched for age, education, and sex, were analyzed through DTI (tract-based spatial statistics) for fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity (general linear model, family-wise error, and threshold-free cluster enhancement corrections, P Cushing syndrome with active hypercortisolism, 7 with Cushing syndrome with medication-remitted cortisol, 20 surgically cured, and 35 controls. Cardiovascular risk factors were used as covariates. In addition, correlations were analyzed among DTI values, concomitant 24-hour urinary free cortisol levels, and disease duration. There were widespread alterations (reduced fractional anisotropy, and increased mean diffusivity, axial diffusivity, and radial diffusivity values; P Cushing syndrome compared with controls, independent of the cardiovascular risk factors present. Both active and cured Cushing syndrome subgroups showed similar changes compared with controls. Patients with medically remitted Cushing syndrome also had reduced fractional anisotropy and increased mean diffusivity and radial diffusivity values, compared with controls. No correlations were found between DTI maps and 24-hour urinary free cortisol levels or with disease duration. Diffuse WM alterations in patients with Cushing syndrome suggest underlying loss of WM integrity and demyelination. Once present, they seem to be independent of concomitant hypercortisolism, persisting after remission/cure. © 2015 by American Journal of Neuroradiology.

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing's syndrome during pregnancy: solved and unsolved questions.

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Brue, Thierry; Amodru, Vincent; Castinetti, Frederic

2018-06-01

With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained. © 2018 European Society of Endocrinology.

Survey of 26 suprarenal scintigraphs on Cushing's syndrome patients

International Nuclear Information System (INIS)

Venot, A.; Luton, J.P.; Roucayrol, J.C.; Bricaire, H.

On the basis of the results of 26 Cushing's syndrome examinations some new scintigraphic aspects are described, suprarenal scintigraphy is compared with retroperitoneal insufflation, its value in the observation of a medical treatment of Cushing's disease is demonstrated and finally some preliminary results are given on the application in the same pathological context, of 75 Se-6-selenocholesterol which was compared with 131 I-19-iodocholesterol [fr

The Value of Perioperative Levels of ACTH, DHEA, and DHEA-S and Tumor Size in Predicting Recurrence of Cushing Disease.

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El Asmar, Nadine; Rajpal, Aman; Selman, Warren R; Arafah, Baha M

2018-02-01

Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 μg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 μg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 μg/dL vs 2.9 ± 2.2 μg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P 20 in all REC patients and disease recurrence, particularly in those with profound hypocortisolemia. Copyright © 2017 Endocrine Society

Morbidity of Cushing's Syndrome and Impact of Treatment.

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Webb, Susan M; Valassi, Elena

2018-06-01

Cortisol excess in Cushing's syndrome is associated with metabolic, cardiovascular, and cognitive alterations, only partially reversible after resolution of hypercortisolism. Elevated cardiovascular risk may persist after eucortisolism has been achieved. Fractures and low bone mineral density are also described in Cushing's syndrome in remission. Hypercortisolism may induce irreversible structural and functional changes in the brain, leading to neuropsychiatric disorders in the active phase of the disease, which persist. Sustained deterioration of the cardiovascular system, bone remodeling, and cognitive function along with neuropsychological impairment are associated with high morbidity and poor quality of life before and after remission. Copyright © 2018 Elsevier Inc. All rights reserved.

Coagulation Profile Dynamics in Pediatric Patients with Cushing Syndrome: A Prospective, Observational Comparative Study

NARCIS (Netherlands)

Birdwell, L. (Leah); M.B. Lodish (Maya Beth); Tirosh, A. (Amit); P. Chittiboina (Prashant); M. Keil (Mark); Lyssikatos, C. (Charlampos); Belyavskaya, E. (Elena); R.A. Feelders (Richard); C.A. Stratakis (Constantine)

2016-01-01

textabstractObjective To evaluate the association between Cushing syndrome and hypercoagulability in children. Study design A prospective, observational study was performed of 54 patients with Cushing syndrome, 15.1 ± 3.9 years, treated at the National Institutes of Health Clinical Center.

Cushing's syndrome with an apparently normal CT scan

International Nuclear Information System (INIS)

Vlahos, L.; Strigaris, K.; Aliferopoulos, D.; Pontifex, G.

1981-01-01

A case of Cushing's syndrome is described in which the CT scan was considered as normal. The diagnosis was established with selective venography and blood sampling and was verified surgically. (orig.)

Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

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Fatemeh Esfahanian

2010-08-01

Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome

Directory of Open Access Journals (Sweden)

Younghak Lee

2017-09-01

Full Text Available BackgroundCushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined.MethodsA retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records.ResultsEosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome.ConclusionSmaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome.

Science.gov (United States)

Lee, Younghak; Yi, Hyon Seung; Kim, Hae Ri; Joung, Kyong Hye; Kang, Yea Eun; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

2017-09-01

Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome. Copyright © 2017 Korean Endocrine Society

Reassessing the reliability of the salivary cortisol assay for the diagnosis of Cushing syndrome.

Science.gov (United States)

Zhang, Qian; Dou, Jingtao; Gu, Weijun; Yang, Guoqing; Lu, Juming

2013-10-01

The cortisol concentration in saliva is 10-fold lower than total serum cortisol and accurately reflects the serum concentration, both levels being lowest around midnight. The salivary cortisol assay measures free cortisol and is unaffected by confounding factors. This study analysed published data on the sensitivity and specificity of salivary cortisol levels in the diagnosis of Cushing syndrome. Data from studies on the use of different salivary cortisol assay techniques in the diagnosis of Cushing syndrome, published between 1998 and 2012 and retrieved using Ovid MEDLINE®, were analysed for variance and correlation. For the 11 studies analysed, mean sensitivity and specificity of the salivary cortisol assay were both >90%. Repeated measurements were easily made with this assay, enabling improved diagnostic accuracy in comparison with total serum cortisol measurements. This analysis confirms the reliability of the saliva cortisol assay as pragmatic tool for the accurate diagnosis of Cushing syndrome. With many countries reporting a rising prevalence of metabolic syndrome, diabetes and obesity--in which there is often a high circulating cortisol level--salivary cortisol measurement will help distinguish these states from Cushing syndrome.

Surgical management of Cushing Syndrome secondary to micronodular adrenal hyperplasia

Science.gov (United States)

Powell, Anathea C.; Stratakis, Constantine A.; Patronas, Nicholas J.; Steinberg, Seth M.; Batista, Dalia; Alexander, H. Richard; Pingpank, James F.; Keil, Meg; Bartlett, David L.; Libutti, Steven K.

2008-01-01

Background We reviewed our experience with micronodular adrenal hyperplasia (MAH), its pigmented variant primary pigmented nodular adrenocortical disease (PPNAD), and the association with Carney’s Complex (CNC) in order to better characterize the disorders. Methods This study is a retrospective analysis of clinical data and operative reports of 34 patients identified with MAH and/or PPNAD who underwent resection between 1969 and 2006 at the Clinical Research Center, an inpatient research hospital, at the National Institutes of Health. Symptoms and anthropometric and biochemical data were used to evaluate effect of resection. Results Fifteen patients (44%) presented as adults and 19 (56%) as children. Twenty five patients (74%) presented with non-cyclic Cushing syndrome and nine patients (26%) presented with cyclic Cushing Syndrome. Thirty one patients underwent bilateral resection; this was curative biochemically in 30 patients. Fourteen operations were performed laparoscopically (41%), and 20 were perfomed as open resections (59%). There was one post-operative complication in the laparoscopic group (7%) and 6 complications in the open group (30%) (p=0.20). Follow-up was available for 25 patients (74%). Statistically significant improvements in anthropometrics were observed for both adults and children. The most frequent manifestation of CNC requiring additional operation was cardiac myxoma which was associated strongly with an atypical (cyclic) presentation of Cushing Syndrome (p=0.009). Conclusion Cushing Syndrome due to MAH and PPNAD may be cured by bilateral adrenal resection. All patients should be screened for manifestations of CNC at the time of adrenal diagnosis with particular attention to cardiac disease. PMID:18549891

Ectopic ACTH syndrome: a clinical challenge | Tsabedze | Journal of ...

African Journals Online (AJOL)

A patient was managed in our endocrinology unit with ectopic Cushing's syndrome from an adrenocorticotropic hormoneproducing neuroendocrine carcinoma of the anal canal. There was limited response to standard therapy, which made it difficult to correct the electrolyte and metabolic derangements associated with the ...

Medical Therapy for Cushing's Syndrome in the Twenty-first Century.

Science.gov (United States)

Tritos, Nicholas A; Biller, Beverly M K

2018-06-01

Medical therapy has a useful adjunctive role in many patients with Cushing's syndrome. Patients with pituitary corticotroph adenomas who have received radiation therapy to the sella require medical therapy until the effects of radiation therapy occur. In addition, patients with Cushing's syndrome who cannot undergo surgery promptly, including those who are acutely ill and cannot safely undergo tumor resection, may benefit from medical therapy as a bridge to surgery. Other possible candidates for medical therapy are those with unresectable tumors or those whose tumor location remains unknown despite adequate diagnostic evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome.

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Moeller, Scott J; Couto, Lizette; Cohen, Vanessa; Lalazar, Yelena; Makotkine, Iouri; Williams, Nia; Yehuda, Rachel; Goldstein, Rita Z; Geer, Eliza B

2016-01-01

The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing's syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing's syndrome (13 with active disease; 10 with disease in remission) and 15 controls with a comparably high body mass index (BMI) completed two simulated food-choice tasks (one with "explicit" task contingencies and one with "probabilistic" task contingencies), during which they indicated their objective preference for viewing high calorie food images vs. standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-h urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task), participants with active Cushing's syndrome made fewer food-related choices than participants with Cushing's syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing's patients. Taken together, relative to overweight controls, Cushing's patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing's, these results may have relevance for elucidating

Genetics Home Reference: primary macronodular adrenal hyperplasia

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... Support and Research Foundation: Genetic Changes Found in Cushing's Disease, Adrenal Tumors, and Adrenal Hyperplasia MalaCards: acth-independent ... macronodular adrenal hyperplasia 2 Merck Manual (Home Edition): Cushing ... Adrenal Diseases Foundation: Cushing's Syndrome Orphanet: Cushing syndrome due to ...

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score.

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Vinolas, Helene; Grouthier, Virginie; Mehsen-Cetre, Nadia; Boisson, Amandine; Winzenrieth, Renaud; Schaeverbeke, Thierry; Mesguich, Charles; Bordenave, Laurence; Tabarin, Antoine

2018-05-21

Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. University Hospital. Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P < .03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P < .04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P = .07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P < .01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P < .02). Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice. © 2018 John Wiley & Sons Ltd.

[Management of hypercortisolism].

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Rosales, C; Fierrard, H; Bertagna, X; Raffin-Sanson, M-L

2008-04-01

Cushing's syndrome is a rare but frequently considered disease. Its diagnosis can lead to some difficulties, including confirming the effective endogenous hypercortisolism and determining its cause. The severity of this disease, the diversity of its complications and the multiple therapeutic options make its management challenging. The aim of this review is to present the most recent data about management of Cushing's syndrome, especially diagnostic approaches and therapeutic options. Our references were obtained by screening MEDLINE database from 1996 to 2006. We also included some anterior reviews and consensus statements. We retained the following points: midnight salivary cortisol is a useful tool in the diagnosis of Cushing's syndrome; the desmopressin test can help to distinguish between Cushing's syndrome and "pseudoCushing's" due to alcohol consumption or psychiatric disorders; cavernous sinus and inferior petrosal sinus sampling is indicated in the evaluation of ACTH-dependent Cushing's syndromes when pituitary imaging is normal or equivocal or when dynamic tests are contradictory; multislice computed-tomography of the chest and the abdomen and somatostatin analogue scintigraphy, eventually combined, are the best imaging procedures in occult ectopic ACTH syndromes; patients with Cushing's disease should be referred to a neurosurgeon experienced in corticotroph adenomas surgery; metabolic consequences of Cushing's syndrome, such as cardiovascular risk factors and osteoporosis need an aggressive treatment. The incidence of Cushing's syndrome is only 1/100000 per year. However, hypercortisolism is diagnosed by systematic evaluation in 2 to 5% of patients with poorly controlled type 2 diabetes and adrenal incidentalomas. Endocrinological management of the disease improves metabolic disorders in these patients. If these results are confirmed, screening for Cushing's syndrome should be systematically performed in these populations.

Evidence for orphan nuclear receptor TR4 in the etiology of Cushing disease

NARCIS (Netherlands)

Du, Li; Bergsneider, Marvin; Mirsadraei, Leili; Young, Steven H.; Jonker, Johan W.; Downes, Michael; Yong, William H.; Evans, Ronald M.; Heaney, Anthony P.

2013-01-01

Cushing disease (CD) is a life-threatening disorder attributed to excess pituitary tumor-derived adrenocorticotrophic hormone (ACTH) and adrenal steroid secretion caused by pituitary tumors. Whereas CD was first described in 1932, the underlying genetic basis driving tumor growth and ACTH secretion

DHEA(S)--a novel marker in Cushing's disease.

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Burkhardt, T; Schmidt, N O; Vettorazzi, E; Aberle, J; Mengel, M; Flitsch, J

2013-03-01

Dehydroepiandrosterone sulfate (DHEA(S)) is a multi-functional steroid implicated in a broad range of biological effects, including obesity, diabetes, bone metabolism, neuroprotection, and anti-tumorigenesis. It has not yet undergone wider research in the context of Cushing's disease. The objective of this study was to determine if perioperative blood levels of DHEA(S) correlate with levels of ACTH and cortisol, and therefore may be useful as a new, additional marker for the early definition of cure in patients suffering from Cushing's disease. Forty-two consecutive patients undergoing transsphenoidal surgery for Cushing's disease from September 2009 to September 2010 were perioperatively monitored for ACTH, cortisol, and DHEA(S). Pre-operative blood samples revealed ACTH levels of median 65 ng/l (range 11-1,183 ng/l, standard deviation 183.76), cortisol of median 257 μg/l (range 93-803 μg/l, standard deviation 140.88), and DHEA(S) of median 2.22 mg/l (range 0.44-7.79 mg/l, standard deviation 1.82) according to the pathology of Cushing's disease. Postoperative blood samples drawn over a 7-day time span showed a drop in median ACTH to just 14.5 % (median: 9 ng/l, range 2-44, standard deviation 12.75) of its median preoperative figure. Median cortisol levels were reduced to 6.9 % (median: 18 μg/l, range 10-190 μg/l, standard deviation 38.04) of their preoperative values and DHEA(S) levels decreased to 17 % (median: 0.38 mg/l, range 0.05-2.29, standard deviation 0.51). In persistent disease, no patient showed a drop in DHEA(S) below 38 % of its preoperative figures. DHEA(S) shows the potential to become an additional marker in the diagnosis and follow-up of patients. However, it needs to be examined further, including whether DHEA(S) may also be a useful predictor of recovery of the HPA-axis after successful surgery.

Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

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Aktas, G E; Soyluoglu Demir, S; Sarikaya, A

2016-01-01

The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

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Isabelle Sahut-Barnola

2010-06-01

Full Text Available Carney complex (CNC is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD, a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha of the cAMP-dependent protein kinase (PKA have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO. AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.

Avascular necrosis of femoral heads post-adrenal surgery for Cushing's syndrome: a rare presentation.

LENUS (Irish Health Repository)

2012-01-31

Avascular necrosis (AVN) is a well-recognized complication of patients on high-dose steroids for a long time. Exogenous hypercortisolism is a well known cause of AVN and a number of cases have been reported. Cushing\\'s syndrome describes hypercortisolism of any cause endogenous or exogenous. A variety of traumatic and non-traumatic factors contribute to the aetiology of AVN although exogenous glucocorticoids administration and alcoholism are among the most common non-traumatic causes. AVN secondary to endogenous hypercortisolism is rare and very few case reports are available describing this complication. No literature is available on AVN presenting post-adrenal surgery. Here we present a young woman who presented with avascular necrosis of both hips 1 year after adrenalectomy for Cushing\\'s syndrome.

Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

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Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

2012-06-01

A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

Science.gov (United States)

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Hypercoagulable State in Cushing's Syndrome: A Systematic Review

NARCIS (Netherlands)

van Zaane, Bregje; Nur, Erfan; Squizzato, Alessandro; Dekkers, Olaf M.; Twickler, Marcel Th B.; Fliers, Eric; Gerdes, Victor E. A.; Büller, Harry R.; Brandjes, Dees P. M.

2009-01-01

Context: It has been debated whether an increased risk of venous thromboembolism (VTE) exists in patients with Cushing's syndrome. Objective: We aimed to summarize published literature on the effects of endogenous hypercortisolism on coagulation and fibrinolysis, as well as on the clinical outcome

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome

Energy Technology Data Exchange (ETDEWEB)

Tsigos, C.; Arai, K.; Latronico, A.C. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)]|[Temple Univ. School of Medicine, Philadelphia, PA (United States)]|[Children`s Hospital of New Jersey, Newark, NJ (United States)] [and others

1995-07-01

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 famlies with triple A syndrome. The proband with IGD was a homozygote for an A {r_arrow}G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome. 19 refs., 1 fig.

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

Directory of Open Access Journals (Sweden)

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.

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.

Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

Science.gov (United States)

Nieman, Lynnette K.; Biller, Beverly M. K.; Findling, James W.; Murad, M. Hassan; Newell-Price, John; Savage, Martin O.; Tabarin, Antoine

2015-01-01

Objective: The objective is to formulate clinical practice guidelines for treating Cushing's syndrome. Participants: Participants include an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. The European Society for Endocrinology co-sponsored the guideline. Evidence: The Task Force used the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: The Task Force achieved consensus through one group meeting, several conference calls, and numerous e-mail communications. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: Treatment of Cushing's syndrome is essential to reduce mortality and associated comorbidities. Effective treatment includes the normalization of cortisol levels or action. It also includes the normalization of comorbidities via directly treating the cause of Cushing's syndrome and by adjunctive treatments (eg, antihypertensives). Surgical resection of the causal lesion(s) is generally the first-line approach. The choice of second-line treatments, including medication, bilateral adrenalectomy, and radiation therapy (for corticotrope tumors), must be individualized to each patient. PMID:26222757

Cushing's syndrome: aftermath of the cure

OpenAIRE

Pivonello, Rosario; De Martino, Maria Cristina; De Leo, Monica; Tauchmanovà, Libuse; Faggiano, Antongiulio; Lombardi, Gaetano; Colao, Annamaria

2007-01-01

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, a...

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

Science.gov (United States)

Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

2017-06-01

Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

Pulsatile thyrotropin secretion in patients with Cushing's syndrome

NARCIS (Netherlands)

Adriaanse, R.; Brabant, G.; Endert, E.; Wiersinga, W. M.

1994-01-01

Pulsatile and circadian thyrotropin (TSH) secretion were studied in 16 healthy controls and in three patients with Cushing's syndrome who were studied twice (before and after treatment). Blood was sampled every 10 minutes over 24 hours for TSH (immunoradiometric assay [IRMA]). Mean 24-hour TSH in

Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission.

Science.gov (United States)

Giordano, Roberta; Picu, Andreea; Marinazzo, Elisa; D'Angelo, Valentina; Berardelli, Rita; Karamouzis, Ioannis; Forno, Daniela; Zinnà, Domenico; Maccario, Mauro; Ghigo, Ezio; Arvat, Emanuela

2011-09-01

Cushing's syndrome is associated with several comorbidities responsible for the increased cardiovascular risk, not only during the active phase but also after disease remission. In 29 patients with Cushing's syndrome (14 Cushing's diseases and 15 adrenal adenomas), waist circumference, fasting and 2-h glucose after oral glucose tolerance test (OGTT), lipid profile and blood pressure were evaluated during the active disease and 1 year after remission and compared with those in 29 sex-, age- and BMI-matched controls. During the active disease, waist circumference, 2-h glucose after OGTT, total and LDL cholesterol were higher in patients with Cushing's syndrome than in controls (P Cushing's disease and adrenal adenomas. The prevalence of impaired glucose tolerance (IGT), diabetes mellitus, dyslipidaemia and hypertension was higher (P Cushing's syndrome (27%, 24%, 59% and 72%) than in controls (10%, 0%, 21% and 10%), with no significant difference between Cushing's disease and adrenal adenomas. One year following hormonal remission, waist circumference persisted higher than in controls (P Cushing's disease and adrenal adenomas. Metabolic and cardiovascular abnormalities were still present in both groups, although with a lower prevalence, as well as with a more marked decrease in adrenal adenomas (P Cushing's disease after hormonal remission. Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. © 2011 Blackwell Publishing Ltd.

In what clinical settings should Cushing´s syndrome be suspected? ¿En qué situaciones clínicas debe sospecharse un síndrome de Cushing?

Directory of Open Access Journals (Sweden)

Oscar D. Bruno

2009-12-01

Full Text Available Despite its low frequency, endogenous Cushing's syndrome is not an exceptional clinical entity. A growing number of cases are currently derived to specialized centers suggesting an increasing knowledge of the clinical features of hypercortisolism by specialists of diverse branches of clinical medicine. Clinical signs derive from an exaggeration of the physiological actions of cortisol inducing protein breakdown, hyperglycemia, fat mobilization, dyslipidemia, hydrosaline retention, immunosuppression and increased susceptibility to infection. Despite its low specificity, symptoms such as unexplained development of central obesity, mood changes, fatigue, weakness, myopathy, easy bruisability, red striae, arterial hypertension, diabetes and hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of view, Cushing's syndrome is to be suspected and consequently searched for among patients with uncontrolled high blood pressure or diabetes mellitus, metabolic syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal incidentaloma. True Cushing's syndrome has to be differentiated from pseudo syndromes. Most sensitive physical signs for discriminating Cushing's syndrome from pseudo-Cushing states are the presence of supraclavicular fat pads, myopathy, thin skin and easy bruising. The recognition of the clinical manifestations of Cushing's syndrome and of the sub-populations at risk of contracting the disease should be improved through medical education at the medical school and at postgraduate levels. Clinical detection of Cushing's syndrome must be performed mainly by non-endocrinologists, yet its etiological diagnosis and therapeutic management is to be carried out in highly experienced and specialized centers, to ensure the best results in the treatment of this really challenging endocrine disturbance.El síndrome de Cushing no es una entidad clínica excepcional, pese a su baja frecuencia. El creciente número de

Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

Science.gov (United States)

Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar

2013-01-01

To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

Direct measurement of the precursors of adrenocorticotropin in human plasma by two-site immunoradiometric assay

International Nuclear Information System (INIS)

Crosby, S.R.; Stewart, M.F.; Ratcliffe, J.G.; White, A.

1988-01-01

An immunoradiometric assay (IRMA) for the direct measurement of the precursors of ACTH in unextracted human plasma has been developed and evaluated clinically in normal subjects and patients with disorders of the hypothalamic-pituitary-adrenal axis. The IRMA is based on an iodinated monoclonal antibody to ACTH and a monoclonal antibody to gamma MSH coupled to Sephacryl S300. The assay detects only peptides containing both epitopes, i.e. POMC (31K) and pro-ACTH (22K). The reference standard was partially purified POMC from culture medium of human corticotroph adenoma cells. The detection limit (greater than +2.5SD of the 0 standard) was 2.0 pmol/L and the within-assay coefficient of variation was less than 10% between 29 and 2600 pmol/L. Plasma concentrations of ACTH precursor peptides in 11 normal subjects sampled at 0930 h ranged from 5-34 pmol/L. The concentrations in the patient groups studied were: 260-2300 pmol/L in 5 patients with the ectopic ACTH syndrome associated with small cell lung cancer, less than 2.0-104 pmol/L in 10 patients with pituitary-dependent Cushing's disease, 23 pmol/L in a patient with Nelson's syndrome, and 3.0-230 pmol/L in 5 patients with Addison's disease. We conclude that this IRMA offers a simple and reliable method for measuring ACTH precursors in unextracted plasma. The proportionately greater elevation of ACTH precursors compared to ACTH in patients with the ectopic ACTH syndrome associated with small cell lung cancer but not in pituitary-dependent Cushing's syndrome, suggests that this assay may be clinically useful

Gamma Knife Radiosurgery for Cushing's Disease and Nelson's Syndrome

Czech Academy of Sciences Publication Activity Database

Marek, J.; Ježková, J.; Hána, V.; Kršek, M.; Liščák, R.; Vladyka, V.; Pecen, Ladislav

2015-01-01

Roč. 18, č. 3 (2015), s. 376-384 ISSN 1386-341X Institutional support: RVO:67985807 Keywords : Cushing's disease * Nelson's syndrome * Gamma knife surgery * Pituitary adenoma Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.407, year: 2015

Effect of Cushing's syndrome - Endogenous hypercortisolemia on cardiovascular autonomic functions.

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Jyotsna, V P; Naseer, Ali; Sreenivas, V; Gupta, Nandita; Deepak, K K

2011-02-24

Cushing's syndrome is associated with increased cardiovascular morbidity and mortality. It's also associated with other cardiac risk factors like hypertension, diabetes mellitus and obesity. Cardiovascular autonomic function impairment could predict cardiovascular morbidity and mortality. Twenty five patients with Cushing's syndrome without diabetes and twenty five age matched healthy controls underwent a battery of cardiovascular autonomic function tests including deep breath test, Valsalva test, hand grip test, cold pressor test and response to standing from lying position. The rise in diastolic blood pressure on hand grip test and diastolic BP response to cold pressor test in Cushing's patients were significantly less compared to healthy controls (9.83 ± 3.90 vs 20.64 ± 9.55, p<0.001 and 10.09 ± 4.07 vs 15.33 ± 6.26, p<0.01 respectively). The E:I ratio on deep breathing test was also less in the patients in comparison to controls (1.36 ± 0.21 vs 1.53 ± 0.19, p<0.01). Seven patients underwent the same battery of tests 6 months after a curative surgery showing a trend towards normalization with significant improvement in expiratory to inspiratory ratio and sinus arrhythmia delta heart rate. To conclude, this study showed that chronic endogenous hypercortisolism in Cushing's is associated with an impaired sympathetic cardiovascular autonomic functioning. After a curative surgery, some of the parameters tend to improve. Copyright © 2010 Elsevier B.V. All rights reserved.

Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy

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Gueorgui Dubrocq

2017-10-01

Full Text Available An 11-year-old male with perinatally acquired human immune deficiency virus (HIV infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom, didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 μg/L. This prompted further evaluation of the hypothalamic–pituitary axis (HPA by standard dose adrenocorticotropic hormone (ACTH stimulation test. A 250 μg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 μg/dL and stimulated cortisol level at 30 min was 3.8 μg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout

Medical treatment of Cushing's disease: Overview and recent findings

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Stephanie Smooke Praw

2009-10-01

Full Text Available Stephanie Smooke Praw1, Anthony P Heaney1,21Department of Medicine, 2Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Cushing's disease, due to pituitary adrenocorticotropic hormone (ACTH hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing's disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing’s disease.Keywords: Cushing's disease, treatment, pasireotide, PPAR-γ, 11 β-hydroxysteroid dehydrogenase inhibitors, dopamine agonists

Adrenal scintigraphy with 131I-19 iodocholesterol. Interest in Cushing syndrome investigation

International Nuclear Information System (INIS)

Vuidard, Claudine.

1977-01-01

A review of the physico-chemical properties of 131 I-19-iodocholesterol is followed by a study of its metabolism in both animals and man, giving for the latter the doses delivered to different organs and especially to the gonads. The exploration technique is then described. Scintigraphic examinations are performed on the 3rd day, the 8th day and sometimes the 15th day after injection. However the uptake rate at the adrenal gland depends essentially on the causes of the illness affecting the suprarenal. In Cushing's syndrome the uptake rate is relatively fast and the 1st scintigraphic examination must therefore be carried out earlier (48 hours after injection). The value of isotopic exploration in the etiological evaluation of hypercortisolism is shown to be chiefly morphological, the scintigraphic image serving as a guide to etiological diagnosis. If too adrenal glands are visible this is a sign of bilateral suprerenal hyperplasia. Only one gland clearly visible indicates an adenoma, with functional hypoplasia of the contralateral gland. On the other hand an absence of fixation in the presence of a certain Cushing syndrome would point to malignant cortical carcinoma [fr

Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

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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

Gestación y psicosis esteroidea en el curso del síndrome de Cushing Pregnancy and steroid psychosis in the course of Cushing's syndrome

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Marelys Yanes Quesada

2011-12-01

Full Text Available La gestación en el curso del síndrome de Cushing es infrecuente, así como el caso inverso; o sea, que se realice el diagnóstico de síndrome de Cushing durante la gestación. Sin embargo, es posible. Se presenta el caso clínico de una paciente femenina, de 28 años, con un adenoma cortical de suprarrenal derecha productor de cortisol, que en el curso de su enfermedad, resultó embarazada. Se decidió interrupción del embarazo debido al riesgo materno fetal. Durante la evolución del síndrome de Cushing presentó una psicosis esteroidea que requirió tratamiento medicamentoso. Después de realizada la adrenalectomía, se produjo remisión del cuadro clínico y bioquímico. Por tal razón, alertamos a la comunidad médica a insistir en el control preconcepcional de estas pacientes.Pregnancy in the course of Cushing syndrome is not frequent, as well as the contrary case, in other words, that diagnosis of Cushing's syndrome be made during pregnancy. However, it is possible. This is a clinical case of a female patient aged 28 with a cortical adenoma of the right suprarenal gland producing cortisol, which in the course of her disease became pregnant. We decide the termination of pregnancy due to mother-fetus risk. Over the course of Cushing's syndrome there was steroid psychosis requiring drug therapy. After the adrenalectomy threw was a remission of clinical and biochemical picture. Thus, it is necessary to alert the medical community to insist in preconception control of these patients.

Concordance of the late night salivary cortisol in patients with Cushing's syndrome and elevated urine-free cortisol.

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Doi, Suhail A R; Clark, Justin; Russell, Anthony W

2013-04-01

The concordance of the late night salivary cortisol (LNSC) results with the 24-h urine-free cortisol (UFC) results in the biochemical screening for Cushing's syndrome is unknown. We investigated this in a population of Cushing's syndrome subjects. We used meta-analytic methods to pool proportions of LNSC-positive subjects from diagnostic evaluations of Cushing's syndrome subjects where both tests were performed and the UFC was elevated (any level). Cushing's syndrome was confirmed in all subjects by two out of three conventional tests. LNSC was collected between 22:00 to 24:00 h and measured around the same time period as the UFC. Minimum cutoffs of ≥4 and ≥10 nmol/L were used to determine concordance with the UFC and studies were limited to those that used radioimmunoassays or electrochemiluminiscence immunoassays for LNSC. The concordance of LNSC ≥4 nmol/L was 97 % (95 % CI 95-99 %) and studies were homogeneous. With LNSC ≥10 nmol/L, there was heterogeneity and two groups were discernible with a pooled concordance of 69 % (95 % CI 60-77 %) and 95 % (95 % CI 92-97 %). Within these sub-groups, studies were homogeneous and there was no difference between them in collection methods, assays used, geographic location, year of publication, or the quality of the underlying studies. The LNSC at a very specific cutoff detects at best 95 % of cases and at worst 69 % of cases of Cushing's syndrome that are UFC positive. The two tests become equivalent at the more sensitive cutoff (>4 nmol/L). We conclude that, given its many benefits and the currently documented equivalence to the UFC, the LNSC should replace the conventional 24-h UFC as the frontline test when screening for Cushing's syndrome.

Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

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Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

2014-01-01

Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

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.

Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

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Tatsi, Christina; Stratakis, Constantine A

2018-03-01

Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia. Published by Elsevier Inc.

Adrenal Incidentalomas with Supraphysiologic Response to ACTH Stimulus: A Case Report

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Marianna Antonopoulou

2012-01-01

Full Text Available We present the diagnostic approach of a patient with adrenal incidentalomas. A 72-year-old African American male had a CT scan of the abdomen showing right and left adrenal masses measuring and , respectively. The patient had negative hormonal workup. The radiologist insisted that the CT findings are consistent with adrenal hyperplasia, and therefore he underwent ACTH stimulation to rule out late-onset congenital adrenal hyperplasia (CAH. The stimulation test revealed that 17-hydroxyprogesterone and 11-deoxycortisol increased to levels high enough to confirm CAH, but cortisol had exaggerated response as well, thus making the diagnosis of CAH unlikely where metabolism is shifted to precursors. Subsequently, the patient underwent screening for Cushing's syndrome (CS with a dexamethasone suppression test. Patient failed the suppresion test, raising the issue for subclinical CS (SCS, likely due to ACTH-independent macronodular adrenal hyperplasia. Our patient had been diagnosed with MGUS and so far there are only 3 case reports of extramedullary plasmacytoma arising from the adrenals. One was bilateral and one had functional abnormalities. Our differential diagnosis includes subclinical CS with aberrant receptors versus a functioning extramedullary plasmacytoma.

Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

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Michaud, Kathy; Forget, Helene; Cohen, Henri

2009-01-01

Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

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Bruno, Oscar D; Rossi, María A; Juárez-Allen, Lea; Serra, Héctor A; Albiero, María C

2015-01-01

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p Cushing's syndrome.

Hypertensive crisis in pregnancy due to a metamorphosing pheochromocytoma with postdelivery Cushing's syndrome.

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Langton, Katharina; Gruber, Matthias; Masjkur, Jimmy; Steenblock, Charlotte; Peitzsch, Mirko; Meinel, Jörn; Lenders, Jacques; Bornstein, Stefan; Eisenhofer, Graeme

2018-01-01

Pheochromocytomas in pregnancy are rare but potentially lethal. Even rarer is the combination of pheochromocytoma in pregnancy with subsequent development of ectopic Cushing's syndrome. We report a 36-year-old woman, previously diagnosed with essential hypertension, who developed severe hypertension in pregnancy complicated by insulin-dependent gestational diabetes. A cesarean section was performed at 32 weeks following a hypertensive crisis after routine administration of betamethasone. Postnatal persistence of signs and symptoms of catecholamine excess led to the diagnosis of a left adrenal pheochromocytoma. Between diagnosis and planned tumor removal, the patient developed signs and symptoms of Cushing's syndrome (facial edema and hirsutism, myopathy and fatigue). Biochemical testing confirmed hypercortisolism with extremely elevated levels of plasma adrenocorticotropin, urinary cortisol and multiple steroids of a plasma panel that were all normal at previous testing. The previously noradrenergic tumor also started producing epinephrine. Histopathological examination confirmed the pheochromocytoma, which was also immunohistochemically positive for adrenocorticotropin. Full post-surgical recovery was sustained with normal blood pressure and biochemical findings after one year. This report not only underlines the chameleon behavior of pheochromocytoma but also illustrates its potential for a metamorphosing presentation. Corticosteroid administration in pregnancy requires a cautious approach in patients with hypertension.

Cushing's disease due to mixed pituitary adenoma-gangliocytoma of the posterior pituitary gland presenting with Aspergillus sp. sinus infection.

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Bridenstine, Mark; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-DeMasters, Bette K

2013-01-01

Gangliocytic lesions of the pituitary gland producing Cushing's disease are extremely rare entities that may exist with or without a pituitary adenoma. The latter have been designated mixed pituitary adenoma-gangliocytomas, the majority of which produce growth hormone, not adrenocorticotropin (ACTH), and are localized to the anterior gland. We now report an immunocompetent woman with hypercortisolism who presented with an intranasal aspergilloma eroding the bony sellar floor. The fungal ball was contiguous with, and extended into, a large neurohypophyseal-centered mass. Transsphenoidal resection revealed a gangliocytic lesion of the posterior gland with small clusters of intimately admixed ACTH-immunoreactive adenoma cells as the cause of her Cushing's disease. Rare transitional sizes and shapes of cells coupled with immunohistochemical findings supported interpretation as advanced neuronal metaplasia within an ACTH adenoma. This mixed ACTH adenoma-gangliocytoma is the first example to present clinically with an opportunistic infection.

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)

Long-term follow-up on Cushing disease patient after transsphenoidal surgery.

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Jeong, Insook; Oh, Moonyeon; Kim, Ja Hye; Cho, Ja Hyang; Choi, Jin-Ho; Yoo, Han-Wook

2014-09-01

Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH) production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Hypothalamic-Pituitary-Adrenal Suppression and Iatrogenic Cushing's Syndrome as a Complication of Epidural Steroid Injections

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Joyce Leary

2013-01-01

Full Text Available Epidural steroid injections are well accepted as a treatment for radicular back pain in appropriate candidates. While overall incidence of systemic side effects has not been well established, at least five biochemically proven cases of iatrogenic Cushing's Syndrome have been reported as complications of epidural steroid treatment. We present an additional case of iatrogenic Cushing's Syndrome and adrenal suppression in a middle-aged woman who received three epidural steroid injections over a four-month period. We review this case in the context of previous cases and discuss diagnostic and management issues.

Sustained weight loss in patients treated with mifepristone for Cushing?s syndrome: a follow-up analysis of the SEISMIC study and long-term extension

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Fein, Henry G.; Vaughan, T. Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

2015-01-01

Background Overweight and obesity are common among patients with Cushing?s syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N?=?50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had fai...

Cushing's syndrome: Stepwise approach to diagnosis

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Lila, Anurag R.; Sarathi, Vijaya; Jagtap, Varsha S.; Bandgar, Tushar; Menon, Padmavathy; Shah, Nalini S.

2011-01-01

The projected prevalence of Cushing's syndrome (CS) inclusive of subclinical cases in the adult population ranges from 0.2–2% and it may no longer be considered as an orphan disease (2–3 cases/million/year). The recognition of CS by physicians is important for early diagnosis and treatment. Late-night salivary cortisol, dexamethasone suppressiontesti, or 24-h urine free cortisol are good screening tests. Positively screened cases need stepwise evaluation by an endocrinologist. This paper discusses the importance of screening for CS and suggests a stepwise diagnostic approach to a case of suspected hypercortisolism. PMID:22145134

Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration.

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Starkman, Monica N

2013-09-01

This article reviews the neuropsychiatric presentations elicited by spontaneous hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with Cushing disease and syndrome develop a depressive syndrome: irritable and depressed mood, decreased libido, disrupted sleep and cognitive decrements. Exogenous short-term glucocorticoid administration may elicit a hypomanic syndrome with mood, sleep and cognitive disruptions. Treatment options are discussed. Brain imaging and neuropsychological studies indicate elevated cortisol and other glucocorticoids are especially deleterious to hippocampus and frontal lobe. The research findings also shed light on neuropsychiatric abnormalities in conditions that have substantial subgroups exhibiting elevated and dysregulated cortisol: aging, major depressive disorder and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.

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Broersen, Leonie H A; Jha, Meghna; Biermasz, Nienke R; Pereira, Alberto M; Dekkers, Olaf M

2018-05-31

To systematically review the effectiveness of medical treatment for Cushing's syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies. Eight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing's syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals. We included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing's disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing's disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data. This meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing's disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.

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

Bilateral adrenalectomy for Cushing's syndrome: Pros and cons

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O P Prajapati

2015-01-01

Full Text Available Aim: To assess the outcome of patients undergoing bilateral adrenalectomy for Cushing's syndrome (CS. Methods: All patients who underwent bilateral adrenalectomy for CS at the Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences hospital between 1991 and 2013 were included. Medical records were reviewed to obtain patient characteristics and follow-up data. Results: Twenty-seven patients were studied. Mean age was 28.74 ± 12.95 years (range 9–60, male:female ratio was 1.7:1. About half that is, 48.19% were of Cushing's disease (failed trans-sphenoidal surgery [TSS], 37.04% were of ectopic CS (ECS, and 14.81% were of CS due to bilateral adrenal pathology. Median follow-up period was 80.5 months. Before surgery, 74.1% patients had body mass index > which after surgery declined to <25 in 75% of them. Hypertension was present in 85.2% and after surgery resolved in 40%. Diabetes mellitus was present in 44.4% and after surgery resolved in 33% of them. Hirsutism and proximal muscle weakness were present in 55.6% and 70.4% patients, respectively, and after surgery improved markedly in all patients. Adrenal crisis developed in 36.3% and Nelson's syndrome in 41.7% patients during follow-up. Three patients died in perioperative period while three succumbed to the disease during follow-up. Two patients developed recurrence of endogenous cortisol production during the follow-up period. Conclusions: Bilateral adrenalectomy is a valid treatment option for palliating severe symptoms in Pituitary Cushing's with failed TSS and unlocalized ECS but the procedure is curative for CS due to bilateral adrenal disease. Overall morbidity and mortality is higher than other endocrine operations. Co-morbidities tend to be more severe and are a risk factor for mortality during the time patient survives.

Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

Science.gov (United States)

Buliman, A; Tataranu, L G; Paun, D L; Mirica, A; Dumitrache, C

2016-01-01

Cushing's disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing's disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing's disease using the most recent available guidelines.

A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease.

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Riebold, Mathias; Kozany, Christian; Freiburger, Lee; Sattler, Michael; Buchfelder, Michael; Hausch, Felix; Stalla, Günter K; Paez-Pereda, Marcelo

2015-03-01

One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotroph adenomas that excessively secrete ACTH, which leads to hypercortisolism. Mutations that impair GR function explain glucocorticoid resistance only in sporadic cases. However, the proper folding of GR depends on direct interactions with the chaperone heat shock protein 90 (HSP90, refs. 7,8). We show here that corticotroph adenomas overexpress HSP90 compared to the normal pituitary. N- and C-terminal HSP90 inhibitors act at different steps of the HSP90 catalytic cycle to regulate corticotroph cell proliferation and GR transcriptional activity. C-terminal inhibitors cause the release of mature GR from HSP90, which promotes its exit from the chaperone cycle and potentiates its transcriptional activity in a corticotroph cell line and in primary cultures of human corticotroph adenomas. In an allograft mouse model, the C-terminal HSP90 inhibitor silibinin showed anti-tumorigenic effects, partially reverted hormonal alterations, and alleviated symptoms of Cushing disease. These results suggest that the pathogenesis of Cushing disease caused by overexpression of heat shock proteins and consequently misregulated GR sensitivity may be overcome pharmacologically with an appropriate HSP90 inhibitor.

Long-term follow-up on Cushing disease patient after transsphenoidal surgery

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Insook Jeong

2014-09-01

Full Text Available Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.

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London, E; Lodish, M; Keil, M; Lyssikatos, C; de la Luz Sierra, M; Nesterova, M; Stratakis, C A

2014-11-01

The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS. © Georg Thieme Verlag KG Stuttgart · New York.

Reduced DNA methylation of FKBP5 in Cushing's syndrome.

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Resmini, Eugenia; Santos, Alicia; Aulinas, Anna; Webb, Susan M; Vives-Gilabert, Yolanda; Cox, Olivia; Wand, Gary; Lee, Richard S

2016-12-01

FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.

Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease.

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Hackman, Kathryn L; Davis, Anna L; Curnow, Paul A; Serpell, Jonathan W; McLean, Catriona A; Topliss, Duncan J

2010-01-01

To report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman. We describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease. A 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercortisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene. Primary pigmented nodular adrenal disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations.

Pasireotid: Eine neue Therapieoption bei Morbus Cushing

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Luger A

2012-01-01

Full Text Available Im Behandlungsalgorithmus des Morbus Cushing war bisher keine zugelassene pharmakologische Behandlungsmöglichkeit verfügbar. Mit dem Multirezeptor-Somatostatinanalogon Pasireotid steht nun mit der im April 2012 erfolgten Zulassung die erste, spezifisch für die Therapie dieses Krankheitsbildes entwickelte Substanz zur Verfügung. Die Studienevidenz belegt eine schnelle und nachhaltige Reduktion der ACTH- und Kortisolproduktion mit klinischer Besserung bei einem Großteil der Patienten.

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.

A perforated diverticulum in Cushing's disease

OpenAIRE

de Havenon, Adam; Ehrenkranz, Joel

2011-01-01

We report a case of perforated colonic diverticulum in Cushing's disease. Although perforated diverticuli have been described in patients with Cushing's syndrome secondary to exogenous glucocorticoids, this complication has not been described in patients with Cushing's disease. Patients with hypercortisolism, from either exogenous or endogenous sources, should be monitored for diverticular perforation.

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

Diurnal Blood Pressure Variation in Pheochromocytoma, Primary Aldosteronism and Cushing's Syndrome

Czech Academy of Sciences Publication Activity Database

Zelinka, T.; Štrauch, B.; Pecen, Ladislav; Widimský jr., J.

Roc. 18, c. 1 (2004), s. 107-111 ISSN 0950-9240 R&D Projects: GA MŠk LN00B107 Institutional research plan: CEZ:AV0Z1030915 Keywords : primary aldosteronism * pheochromocytoma * Cushing's syndrome * cirardian blood pressure rhythm Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.930, year: 2004

Nelson syndrome: definition and management.

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Barber, T M; Adams, E; Wass, J A H

2014-01-01

Nelson syndrome is an important complication of treatment with total bilateral adrenalectomy (TBA) for patients with refractory Cushing's disease. Although early cases of Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary radiotherapy post-TBA surgery may predict future development of Nelson syndrome, other predictive factors remain controversial. Therefore, Nelson syndrome should be screened for closely and long-term in all patients with a history of Cushing's disease and TBA. The diagnosis of Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of cortisol following TBA), and the "aggressive corticotropinoma" mechanism (Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of Nelson syndrome with pituitary surgery and radiotherapy is often a challenge. Other therapies (such as Gamma Knife surgery and temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of Nelson syndrome. © 2014 Elsevier B.V. All rights reserved.

Cushing's Syndrome and Steroid Dementia.

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Bernini, Giampaolo; Tricò, Domenico

2016-01-01

Cushing's Syndrome (CS) is associated with a specific spectrum of dementia-like symptoms, including psychiatric disorders, such as major depression, anxiety and mania, and neurocognitive alterations, like impairment of memory and concentration. This pattern of clinical complications, which significantly impair the health-related quality of life of CS patients, is sometimes referred to as "steroid dementia syndrome" (SDS). The SDS is the result of anatomical and functional anomalies in brain areas involved in the processing of emotion and cognition, which are only partially restored after the biochemical remission of the disease. Therefore, periodical neuropsychiatric evaluations are recommended in all CS patients, and a long-term follow-up is required after normalization of hypercortisolism. Recent evidences demonstrate that three classes of drugs (glucocorticoid receptor antagonists, steroidogenesis inhibitors, and pituitary tumor-targeted drugs), which are used for medical treatment of CS, can rapidly relief neuropsychiatric symptoms of SDS. Furthermore, several psychoactive medications have demonstrated effectiveness in the treatment of symptoms induced by the acute or chronic glucocosteroid administration. In this paper, a review of the current and future patents for the treatment and prevention of CS and SDS will be presented.

Cushing's syndrome: aftermath of the cure.

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Pivonello, Rosario; De Martino, Maria Cristina; De Leo, Monica; Tauchmanovà, Libuse; Faggiano, Antongiulio; Lombardi, Gaetano; Colao, Annamaria

2007-11-01

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

Macroadenomas Causing Cushing’s Disease

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Aydin K

2014-01-01

Full Text Available Kortikotrope Hypophysen-Makroadenome vs. Mikroadenome als Ursache des Morbus Cushing. Ziel: Kortikotrope Hypophysen- Makroadenome werden für eine geringe Zahl von Fällen des Cushing-Syndroms verantwortlich gemacht, man geht jedoch davon aus, dass ihre genaue Prävalenz unterschätzt wird. Des Weiteren fallen die klinischen und biochemischen Manifestationen kortikotroper Makro- und Mikroadenome sehr unterschiedlich aus und in bisherigen Studien wurde nur eine geringe Anzahl von Patienten eingeschlossen. In dieser Arbeit analysieren und vergleichen wir die klinischen Charakteristika und biochemischen Eigenschaften von Patienten mit kortikotropen Makro- und Mikroadenomen, die Morbus Cushing verursachen. Methoden: Wir schlossen 107 Patienten mit M. Cushing ein (67 Mikroadenome, 40 Makroadenome. Klinische Charakteristika, biochemische Analysen des Hyperkortisolismus, Ergebnisse des Hypophysen-Imaging, Behandlungsmodalitäten sowie Raten für Remission und Wiederauftreten wurden erfasst. Ergebnisse: Das Durchschnittsalter der Patienten lag bei 46,5 ± 11,4 Jahren für Makroadenome und 37,3 ± 12,1 Jahre für Mikroadenome (p 0,001. Die Geschlechterverteilung war bei den Makroadenompatienten gleich, während bei den Mikroadenompatienten ein Vorherrschen der Frauen offensichtlich war (p = 0,001. Verglichen mit den Makro- war die klinische Evidenz des Hyperkortisolismus bei den Mikroadenomen stärker ausgeprägt. Obwohl die Präsentation der klinischen Manifestationen unterschiedlich war, waren die biochemische Analyse des Hyperkortisolismus (inklusive Basalkortisol, ACTH, 24-Stunden-Harnkortisol-Levels und Ansprechen auf eine niedrig dosierte Dexamethason-Suppression zwischen den Gruppen ähnlich. Die Unterdrückbarkeit des Serumkortisols nach Gabe von hochdosiertem Dexamethason war für Makroadenome niedriger, erreichte aber keine Signifikanz (p = 0,074. Die Remissionsraten nach dem ersten hypophysenchirurgischen Eingriff (67,5 vs. 82,8 % sowie die

Le syndrome de cushing chez l'adolescent: à propos de 18 patients ...

African Journals Online (AJOL)

adolescent. Elle diffère de la pathologie adulte par le mode de présentation et la prise en charge. Il s'agit d'une étude rétrospective des dossiers de patients suivis pour syndrome de Cushing au service d'endocrinologie de Casablanca entre ...

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.

Unusual cause for recurrent Cushing syndrome and its diagnosis by computed tomography and NP-59 radiocholesterol scanning

International Nuclear Information System (INIS)

Harris, R.D.; Herwig, K.R.

1990-01-01

Cushing syndrome can recur following an adrenalectomy. One of the primary causes is recurrence of adrenal carcinoma either locally or from metastases. Hyperplasia and hyperfunction of adrenal remnants may also occur if there is pituitary stimulation. We have a patient in whom recurrent Cushing syndrome developed from small nonmalignant deposits of adrenal tissue in the perirenal adipose tissue following adrenalectomy of a benign adenoma. These deposits were identifiable by computed tomography. A false-negative NP-59 iodocholesterol scan was instructive in pointing out some problems in the interpretation of this type of scan for adrenal tissue

The role of intrа- and postoperative ACTH and cortisol levels measurement in patients with Cushing’s disease as an early predictors of remission

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Elena Y. Nadezhdina

2017-07-01

Full Text Available Objectives. The aim of this research was to study the dynamic changes of intra- and early postoperative hormonal parameters (ACTH and cortisol as predictors of hypercorticism remission. Material and methods. 50 patients with confirmed Cushing`s disease (CD were sampled for this research. The patients were divided into 3 groups depending on the outcome of the operation. The first group – patients with secondary adrenal insufficiency confirmed by clinical picture and the level of cortisol less than 50 nmol/l; the second group – with normalization of levels of ACTH and cortisol; the third – with the persistence of the CD. The results of intraoperative studies during the transnasal adenomectomy were then studied. The group sample consisted of 38 women and 12 men, aged 15–66 years. To assess the levels of ACTH and cortisol blood sampling was performed from a peripheral vein. The first sample was taken during the incision of the Dura mater, the second – immediately after removal of the tumor and the last – 20 minutes after the removal of the adenoma. Then, 1 day after the surgery the hormones mentioned above were studied in all patients. The levels of ACTH and cortisol were measured by immunochemiluminescent analysis on the automated system Cobas 6000 (Roche, France. Reference intervals ACTH 0–30 ng/ml, cortisol123–626 nmol/l. Results. The analysis of the obtained data did not suggest a relationship between the changes of intraoperative indicators of hormonal status and the likelihood of disease remission (p > 0.125. In the postoperative period, of the 50 patients, 41 (82% developed adrenal insufficiency, 5 (10% showed normalization and in 4 patients (8% adrenal insufficiency was not observed. The results of the hormonal research after 1 day had a correlation with the frequency of postoperative remission (p < 0.125. Conclusion. Intraoperative measurement of levels of ACTH and cortisol is not appropriate and cannot serve as guidance for

Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing's syndrome.

Science.gov (United States)

Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Rodella, Luigi F; Paiardi, Silvia; Rizzardi, Nicola; Platto, Caterina; Boari, Gianluca E M; Pilu, Annamaria; Tiberio, Guido A M; Giulini, Stefano M; Favero, Gaia; Rezzani, Rita; Rosei, Claudia Agabiti; Bulgari, Giuseppe; Avanzi, Daniele; Rosei, Enrico Agabiti

2009-12-01

Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome. We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress. Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels. Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

A comparison of the use of urinary cortisol to creatinine ratios and nocturnal salivary cortisol in the evaluation of cyclicity in patients with Cushing's syndrome.

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Graham, U M; Hunter, S J; McDonnell, M; Mullan, K R; Atkinson, A B

2013-01-01

Cyclical Cushing's syndrome is detected in our center by collecting sequential early morning urine (EMU) samples for cortisol to creatinine ratio over 28 d. The Endocrine Society suggests that nocturnal salivary cortisol (NSC) may be used to assess patients for cyclical Cushing's. However, there is only very limited evidence that it correlates with EMU testing or that it demonstrates cycling over 28 d. We sought to correlate NSC with EMU results collected the following morning and to determine whether NSC could be used to detect cyclical Cushing's. An observation study of 28-d collections for NSC and EMU was performed in a tertiary referral center over 1 yr. A 28-d collection of NSC and EMU was performed in 10 patients with confirmed or suspected Cushing's syndrome. The main outcome of the study was the correlation of salivary and urinary cortisol with graphical assessment of results for cycling. Eleven collections were performed. One patient with cyclical Cushing's completed the collection before and after cabergoline therapy. Two hundred seventy matched salivary and urinary results were correlated (r = 0.79; P Cushing's, EMU and NSC followed a similar cyclical pattern. In one patient with recurrent cyclical Cushing's, cortisol was elevated in both saliva and urine but with more prominent cycles in saliva. NSC correlated well with EMU. NSC detected all cases of cyclical Cushing's. Therefore, NSC may prove to be an additional option or replacement for EMU in detecting cyclical Cushing's syndrome.

Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

LENUS (Irish Health Repository)

Noctor, E

2015-06-01

Cushing\\'s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing\\'s syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing\\'s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.

Neuropsychiatric disorders in Cushing's syndrome

Science.gov (United States)

Pivonello, Rosario; Simeoli, Chiara; De Martino, Maria Cristina; Cozzolino, Alessia; De Leo, Monica; Iacuaniello, Davide; Pivonello, Claudia; Negri, Mariarosaria; Pellecchia, Maria Teresa; Iasevoli, Felice; Colao, Annamaria

2015-01-01

Endogenous Cushing's syndrome (CS), a rare endocrine disorder characterized by cortisol hypersecretion, is associated with psychiatric and neurocognitive disorders. Major depression, mania, anxiety, and neurocognitive impairment are the most important clinical abnormalities. Moreover, patients most often complain of impairment in quality of life, interference with family life, social, and work performance. Surprisingly, after hypercortisolism resolution, despite the improvement of the overall prevalence of psychiatric and neurocognitive disorders, the brain volume loss at least partially persists and it should be noted that some patients may still display depression, anxiety, panic disorders, and neurocognitive impairment. This brief review aimed at describing the prevalence of psychiatric and neurocognitive disorders and their characterization both during the active and remission phases of CS. The last section of this review is dedicated to quality of life, impaired during active CS and only partially resolved after resolution of hypercortisolism. PMID:25941467

The hypertension of Cushing's syndrome: controversies in the pathophysiology and focus on cardiovascular complications

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Isidori, Andrea M.; Graziadio, Chiara; Paragliola, Rosa Maria; Cozzolino, Alessia; Ambrogio, Alberto G.; Colao, Annamaria; Corsello, Salvatore M.; Pivonello, Rosario

2015-01-01

Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of in-vivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first ‘Altogether to Beat Cushing's syndrome’ workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome. PMID:25415766

Multiple osteoblastomas in a child with Cushing syndrome due to bilateral adrenal micronodular hyperplasias

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Hyeoh Won Yu

2016-03-01

Full Text Available Adrenocorticotropin-independent adrenal hyperplasias are rare diseases, which are classified into macronodular (>1 cm and micronodular (≤1 cm hyperplasia. Micronodular adrenal hyperplasia is subdivided into primary pigmented adrenocortical disease and a limited or nonpigmented form 'micronodular adrenocortical disease (MAD', although considerable morphological and genetic overlap is observed between the 2 groups. We present an unusual case of a 44-month-old girl who was diagnosed with Cushing syndrome due to MAD. She had presented with spotty pigmentation on her oral mucosa, lips and conjunctivae and was diagnosed with multiple bone tumors in her femur, pelvis and skull base at the age of 8 years. Her bone tumor biopsies were compatible with osteoblastoma. This case highlights the importance of verifying the clinicopathologic correlation in Cushing syndrome and careful follow-up and screening for associated diseases.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

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Roerink, Sean H P P; Wagenmakers, Margreet A E M; Langenhuijsen, Johan F; Ballak, Dov B; Rooijackers, Hanne M M; d'Ancona, Frank C; van Dielen, François M; Smit, Jan W A; Plantinga, Theo S; Netea-Maier, Romana T; Hermus, Ad R M M

2017-08-01

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile. © 2017 The Obesity Society.

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

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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.

Otolaryngic manifestations of Cushing disease.

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Kuan, Edward C; Peng, Kevin A; Suh, Jeffrey D; Bergsneider, Marvin; Wang, Marilene B

2017-08-01

Cushing disease is a relatively rare cause of Cushing syndrome secondary to a hyperfunctioning pituitary adenoma. In addition to signs and symptoms of hypercortisolism, Cushing disease may present with diverse otolaryngic manifestations, which may guide diagnosis and management. We performed a retrospective chart review of patients who were found to have Cushing disease and who underwent transnasal transsphenoidal surgery for pituitary adenomas between January 1, 2007, and July 1, 2014, at a tertiary academic medical center. There were 37 consecutive patients in this series with Cushing disease caused by a pituitary adenoma. Fifteen (41%) patients complained of visual changes. Five (14%) patients suffered from obstructive sleep apnea. Four (11%) patients had thyroid disease. Other symptoms included hearing loss, vertigo, tinnitus, epistaxis, dysphagia, and salivary gland swelling. Although Cushing disease traditionally presents with classic "Cushingoid" systemic features, it also may present with various otolaryngic manifestations. A thorough workup by otolaryngologists is critical in the comprehensive management of these patients.

Metabolomic Biomarkers in Urine of Cushing's Syndrome Patients.

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Kotłowska, Alicja; Puzyn, Tomasz; Sworczak, Krzysztof; Stepnowski, Piotr; Szefer, Piotr

2017-01-29

Cushing's syndrome (CS) is a disease which results from excessive levels of cortisol in the human body. The disorder is associated with various signs and symptoms which are also common for the general population not suffering from compound hypersecretion. Thus, more sensitive and selective methods are required for the diagnosis of CS. This follow-up study was conducted to determine which steroid metabolites could serve as potential indicators of CS and possible subclinical hypercortisolism in patients diagnosed with so called non-functioning adrenal incidentalomas (AIs). Urine samples from negative controls ( n = 37), patients with CS characterized by hypercortisolism and excluding iatrogenic CS ( n = 16), and patients with non-functioning AIs with possible subclinical Cushing's syndrome ( n = 25) were analyzed using gas chromatography-mass spectrometry (GC/MS) and gas chromatograph equipped with flame ionization detector (GC/FID). Statistical and multivariate methods were applied to investigate the profile differences between examined individuals. The analyses revealed hormonal differences between patients with CS and the rest of examined individuals. The concentrations of selected metabolites of cortisol, androgens, and pregnenetriol were elevated whereas the levels of tetrahydrocortisone were decreased for CS when opposed to the rest of the study population. Moreover, after analysis of potential confounding factors, it was also possible to distinguish six steroid hormones which discriminated CS patients from other study subjects. The obtained discriminant functions enabled classification of CS patients and AI group characterized by mild hypersecretion of cortisol metabolites. It can be concluded that steroid hormones selected by applying urinary profiling may serve the role of potential biomarkers of CS and can aid in its early diagnosis.

Neuroendocrine Tumor, diagnostic difficulties

Directory of Open Access Journals (Sweden)

Pedro Oliveira

2017-06-01

Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

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

Directory of Open Access Journals (Sweden)

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.

Currently used and investigational drugs for Cushing´s disease.

Science.gov (United States)

Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K

2017-01-01

Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.

Clinical Characteristics and Metabolic Features of Patients with Adrenal Incidentalomas with or without Subclinical Cushing's Syndrome

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Bo-Yeon Kim

2014-12-01

Full Text Available BackgroundThe aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT and to investigate metabolic features of subclinical Cushing's syndrome (SCS in patients with adrenal incidentalomas in a tertiary hospital in Korea.MethodsThis retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed.ResultsMost (n=218, 81.3% cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%, 19 (7.1% were diagnosed with SCS, nine (3.4% with overt Cushing's syndrome, 12 (4.5% with primary aldosteronism, and 10 (3.7% with pheochromocytoma. Malignant tumors (both primary and metastatic were rare (n=2, 0.7%. Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors.ConclusionFunctioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis

NARCIS (Netherlands)

Wulffraat, N. M.; Drexhage, H. A.; Wiersinga, W. M.; van der Gaag, R. D.; Jeucken, P.; Mol, J. A.

1988-01-01

The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical

An update on Cushing syndrome in pediatrics.

Science.gov (United States)

Stratakis, Constantine A

2018-04-09

Cushing syndrome (CS) in childhood results mostly from the exogenous administration of glucocorticoids; endogenous CS is a rare disease. The latter is the main reason pediatric patients with CS escape diagnosis for too long. Other barriers to optimal care of a pediatric patient with CS include improper following of the proper sequence of testing for diagnosing CS, which stems from lack of understanding of pathophysiology of the hypothalamic-pituitary-adrenal axis; lack of access to proper (i.e., experienced, state-of-the-art) surgical treatment; and unavailability of well-tolerated and effective medications to control hypercortisolemia. This report reviews the state-of-the-art in diagnosing CS and provides an update on the most recent discoveries in its genetics and treatment. Copyright © 2018. Published by Elsevier Masson SAS.

Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.

Science.gov (United States)

Di Dalmazi, Guido; Kisker, Caroline; Calebiro, Davide; Mannelli, Massimo; Canu, Letizia; Arnaldi, Giorgio; Quinkler, Marcus; Rayes, Nada; Tabarin, Antoine; Laure Jullié, Marie; Mantero, Franco; Rubin, Beatrice; Waldmann, Jens; Bartsch, Detlef K; Pasquali, Renato; Lohse, Martin; Allolio, Bruno; Fassnacht, Martin; Beuschlein, Felix; Reincke, Martin

2014-10-01

Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses. Samples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed. PRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects. These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome.

Phosphorylated form of adrenocorticotropin and corticotropin-like intermediary lobe peptide in human tumors

International Nuclear Information System (INIS)

Massias, J.F.; Hardouin, S.; Vieau, D.; Lenne, F.; Bertagna, X.

1994-01-01

Many peptides contribute to the heterogeneity of immunoreactive adrenocorticotropin (ACTH) in man. The use of a radioimmunoassay (RIA) specifically directed against the C-terminal end of ACTH allowed the precise study of the following four peptides: ACTH itself, corticotropin-like intermediary lobe peptide (CLIP) or ACTH and their phosphorylated forms on SeR 31 . The authors have set up a high-performance liquid chromatography system that separates these four molecules in a single run, to establish their relative distributions in tumors responsible for Cushing's disease or for the ectopic ACTH syndrome, and to evaluate the possible interference of phospho-Ser 31 on various RIA or immuno-radiometric assay (IRMA) recognition systems for ACTH. In this system, alkaline phosphatase treatment shifted the retention time of the phosphorylated peptides to that of their non-phosphorylated counterparts. In three tumors responsible for the ectopic ACTH syndrome, CLIP peptides were predominant in two and phosphorylated molecules represented between 22% and 50% of immuno-reactive materials. In five pituitary tumors responsible for Cushing's disease, ACTH peptides were predominant and the phosphorylated molecules varied between 35% and 75% in four of them. In the same tumor the ratios of phosphorylated to non-phosphorylated CLIP or ACTH were identical. The presence of phospho-Ser 31 did not affect the recognition ability of two mid-ACTH and two C-terminal ACTH RIA's, nor of the ACTH IRMA. 15 refs., 5 figs., 2 tabs

A Case Report of Cushing's Disease Presenting as Hair Loss.

Science.gov (United States)

Lefkowitz, Emily G; Cossman, Jack P; Fournier, John B

2017-01-01

Cushing's syndrome is a rare endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids. Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing's disease. Most of the signs and symptoms are nonspecific and common in the general population, making a diagnosis often challenging. However, several dermatological manifestations, such as fragile skin, easy bruising, and reddish purple striae, are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology is associated with substantial morbidity, including increased cardiovascular disease and mortality, it is important to make an early diagnosis. Unfortunately, median delays of 2 years to diagnosis have been reported. We report a case of a woman who had multiple dermatological findings, including facial plethora, easy bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting androgen excess. Of interest, our patient presented with a chief complaint of hair loss, a common complaint in the general population that occurs with a greater frequency in patients with Cushing's disease and is attributed to androgenetic alopecia, but it is rarely the presenting symptom.

Markers of atherosclerosis in patients with Cushing's syndrome: a meta-analysis of literature studies.

Science.gov (United States)

Lupoli, Roberta; Ambrosino, Pasquale; Tortora, Anna; Barba, Livia; Lupoli, Gelsy Arianna; Di Minno, Matteo Nicola Dario

2017-05-01

Several studies reported an increased cardiovascular (CV) risk in Cushing's syndrome (CS). We performed a meta-analysis on the impact of CS on major markers of atherosclerosis. Studies on intima-media thickness (IMT), carotid plaques prevalence, and flow-mediated dilation (FMD) in CS patients and controls were searched in the PubMed, Web of Science, Scopus, and EMBASE. Differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95%CI) for continuous variables, and as Odds Ratio (OR) with 95%CI for dichotomous variables. Fourteen studies (332 CS, 462 controls) were included. Compared with controls, CS patients showed higher IMT (MD: 0.20 mm; 95% CI: 0.12, 0.28; p Cushing's syndrome (CS). In the present meta-analysis we demonstrated that CS is associated with an increased intima-media thickness, higher prevalence of carotid plaques, and lower flow-mediated dilation as compared with controls. These data consistently suggest the need for a strict monitoring of early signs of subclinical atherosclerosis in CS patients.

Recent developments in canine Cushing’s syndrome

NARCIS (Netherlands)

Galac, S.

Cushing’s syndrome or hypercortisolism is in most of the cases ACTH-dependent due to ACTH hypersecretion by a pituitary corticotroph adenoma, however, the ectopic ACTH secretion has been now described in a dog as well. In the remaining cases, hypercortisolism is ACTH-independent and results from

Analysis of adrenocortical hyperplasia by computed tomography in patients with Cushing's disease, idiopathic hyperaldosteronism and adrenogenital syndrome

International Nuclear Information System (INIS)

Komiya, Ichiro; Ohara, Noriko; Nagasawa, Yoshitaka; Asawa, Takayuki; Hashizume, Kiyoshi; Takasu, Nobuyuki; Yamada, Takashi.

1994-01-01

We assessed the usefulness and reliability of computed tomography (CT scan) in evaluating adrenal hyperplasia in 38 patients, including 14 with Cushing's disease, 17 with idiopathic hyperaldosteronism (IHA), and 7 with the adrenogenital syndrome (AGS). Eighty-two normal subjects were also examined. We analyzed the shape of the adrenal gland and quantitated its thickness, width and length. Visual inspection revealed V-shaped right adrenal glands in 100% of patients with Cushing's disease, 94% of patients with IHA, 100% of patients with AGS and in 41% of the normal subjects. Triangular left adrenal glands were observed in 100% of patients with Cushing's disease, 82% of patients with IHA, 67% of patients with AGS and in 12% of the normal subjects. Quantitative analysis showed that the right adrenal gland was significantly thicker and longer in patients with Cushing's disease, IHA and in those with AGS than in normal subjects. The right adrenal gland was significantly wider in the patients with Cushing's disease and AGS than in control subjects. The left adrenal gland was significantly wider and longer in patients with Cushing's disease and AGS than in the normal controls. Analysis of individual data indicated that the upper limit of normal for thickness of the right adrenal was 7 mm. Therefore, adrenal hyperplasia was strongly suggested when the right adrenal gland was more than 7 mm thick. Our findings suggest that the CT scan is useful and reliable in diagnosing adrenal hyperplasia. (author)

The recovery of the hypothalamo-pituitary-adrenal axis after transsphenoidal operation in three patients with Cushing's disease

International Nuclear Information System (INIS)

Lamberts, S.W.J.; Klijn, J.G.M.; Jong, F.H. de; Birkenhager, J.C.

1981-01-01

The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation. (author)

Management of Cushing disease.

Science.gov (United States)

Tritos, Nicholas A; Biller, Beverly M K; Swearingen, Brooke

2011-05-01

Cushing disease is caused by a corticotroph tumor of the pituitary gland. Patients with Cushing disease are usually treated with transsphenoidal surgery, as this approach leads to remission in 70-90% of cases and is associated with low morbidity when performed by experienced pituitary gland surgeons. Nonetheless, among patients in postoperative remission, the risk of recurrence of Cushing disease could reach 20-25% at 10 years after surgery. Patients with persistent or recurrent Cushing disease might, therefore, benefit from a second pituitary operation (which leads to remission in 50-70% of cases), radiation therapy to the pituitary gland or bilateral adrenalectomy. Remission after radiation therapy occurs in ∼85% of patients with Cushing disease after a considerable latency period. Interim medical therapy is generally advisable after patients receive radiation therapy because of the long latency period. Bilateral adrenalectomy might be considered in patients who do not improve following transsphenoidal surgery, particularly patients who are very ill and require rapid control of hypercortisolism, or those wishing to avoid the risk of hypopituitarism associated with radiation therapy. Adrenalectomized patients require lifelong adrenal hormone replacement and are at risk of Nelson syndrome. The development of medical therapies with improved efficacy might influence the management of this challenging condition.

Nelson`s syndrome associated with a somatic frame shift mutation in the glucocorticoid recepter gene

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Karl, M.; Stratakis, C.A.; Chrousos, G.P.; Katz, D.A.; Ali, I.U.; Oldfield, E.H. [National Inst. of Neurological Disorders and Stroke, Bethesda, MD (United States)] [and others

1996-01-01

Nelson`s syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing`s disease. Extremely high plasma ACTH levels and aggressive neoplastic growth might be explained by the lack of appropriate glucocorticoid negative feedback due to defective glucocorticoid signal transduction. To study the glucocorticoid receptor (GR) gene in Nelson`s syndrome, DNA was extracted from pituitary adenomas and leukocytes of four patients with this condition and amplified by PCR for direct sequence analysis. In one of the tumors, a heterozygous mutation, consisting of an insertion of a thymine between complementary DNA nucleotides 1188 and 1189, was found in exon 2. This frame-shift mutation led to premature termination at amino acid residue 366 of the world-type coding sequence, excluding the expression of a functioning receptor protein from the defective allele. The mutation was not detected in the sequence of the GR gene in the patient`s leukocyte DNA, indicating a somatic origin. By lowering the receptor number in tumorous cells, this defect might have caused local resistance to negative glucocorticoid feedback similar to that caused by the presence of a null allele in a kindred with the generalized glucocorticoid resistance syndrome. P53 protein accumulation, previously reported in 60% of corticotropinomas, could not be detected in any of the four pituitary tumors examined by immunohistochemistry. We suggest that a somatic GR defect might have played a pathophysiological role in the tumorigenesis of the corticotropinoma bearing this mutation. 35 refs., 3 figs., 1 tab.

Use of quantitative ultrasound of the hand phalanges in the diagnosis of two different osteoporotic syndromes: Cushing's syndrome and postmenopausal osteoporosis.

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Camozzi, V; Carraro, V; Zangari, M; Fallo, F; Mantero, F; Luisetto, G

2004-06-01

The aim of this study was to assess the ability of the quantitative ultrasound of the hand phalanges to detect different types of osteoporosis resulting from different pathogenetic mechanisms. For this purpose, postmenopausal and glucocorticoid-induced osteoporosis was studied. Thirteen female patients with Cushing's syndrome (CS) resulting from pituitary-dependent bilateral adrenal hyperplasia (10 patients) and from adrenal adenoma (3 patients), and 32 postmenopausal osteoporotic (OP) women, were examined. The two groups of patients were comparable for body mass index (BMI), but CS patients were significantly younger than OP ones (CS 44.5+/-11.6; OP: 73.9+/-3.6). All the patients had femoral neck bone mineral density (BMD) T-score less than -2.0. Cushing patients had a femoral neck BMD similar to that of OP patients (CS: 603+/-66 mg/cm2; OP: 628+/-69 mg/cm2; p=0.19). In contrast, amplitude-dependent speed of sound (AD-SoS) was significantly higher in CS patients than in OP patients (CS: 1997+/-91 m/s; OP: 1707+/-114 m/s; p<0.0001). By adjusting DXA and ultrasound parameters according to age, femoral neck BMD was significantly lower in CS patients and AD-SoS remained significantly higher than in OP patients. These findings indicate that these two different kinds of osteoporosis can be distinguished by ultrasonography and that ultrasound parameters alone cannot be used for evaluating skeletal status in CS patients.

Metabolic complications of endogenous Cushing: patient selection for screening

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Zh E Belaya

2013-03-01

Full Text Available Aims: this study evaluates the most common associations of symptoms and complications in patients with Cushing’s syndrome (CS in order to choose a potential population to be screened for CS and estimates the diagnostic accuracy of first line screening tests (cortisol, ACTH to differentiate ACTH-ectopic CS from Cushing’s disease. Materials and Methods: The clinical data of 259 patients with proven CS during 2001–2011 was analyzed. The clinical presentations of 197 patients (159 Cushing’s disease, 28 ACTH-ectopic CS and 10 cases of benign cortisol-secreting adrenal adenoma were compared according to the cause of hypercortisolism. ROC-analysis was performed to estimate the diagnostic accuracy of the first line tests (cortisol, ACTH to suggest ACTH-ectopic CS. A threshold for the test with the highest area under the curves was chosen based on the maximum sum of the sensitivity and specificity. Results: The most frequent complaints were related to fatigue, muscle weakness, weight gain and changes in appearance (facial plethora and fullness, striae. Among the complications of CS the most frequent were being overweight or obese (71%, hypertension (63%, dislipoproteinemia (41%, low traumatic fractures (43% and steroid-induced diabetes (31%. In women, 16% were older than 50, in those who were younger amenorrhea was registered in 43%. The patients with ACTH-ectopic CS had higher rate of low traumatic fractures (p=0.04, increased serum late-night cortisol, 24 hours urinary free cortisol, morning and evening ACTH and lower levels of potassium (p<0.01 for all parameters. Plasma late-night ACTH measurements showed the highest AUC (0,811 (95% CI 0,712–0,909 to differentiate ACTH-ectopic CS from Cushing’s disease. A cut off value of 108.9 pg/ml for late-night ACTH yielded a sensitivity of 60,7% and a specificity of 79%. Conclusions: patients with a coexistence of obesity, muscle weakness, fatigue, some components of metabolic syndrome and especially

Cushing's Support and Research Foundation

Science.gov (United States)

... high blood pressure, type II diabetes, polycystic ovarian syndrome, endometriosis, obesity, adult acne, metabolic disease, and panic attacks, but not Cushing's. After diagnosis and treatment, my weight is back to normal, and I ...

Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

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Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

2009-01-01

Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

Perioperative Endocrine Therapy for Patients with Cushing's Syndrome Undergoing Retroperitoneal Laparoscopic Adrenalectomy

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Xiaobo Cui

2012-01-01

Full Text Available Objectives. To investigate the efficacy and safety of perioperative endocrine therapy (PET for patients with Cushing’s syndrome (CS undergoing retroperitoneal laparoscopic adrenalectomy (RLA. Methods. The novel, simplified PET modality of 82 patients who underwent RLA procedures for CS were studied. Clinical manifestations were observed for all patients on days 1 and 5 postoperatively, and clinical data, such as blood pressure (BP, levels of serum cortisol, adrenocorticotropin (ACTH, blood glucose, and electrolytes, were acquired and analyzed. Results. Supraphysiological doses of glucocorticoid were administered during the perioperative period, and the dosage was reduced gradually. In all 82 cases, the RLAs were performed successfully without any perioperative complication, such as steroid withdrawal symptoms. The patient’s symptoms and signs were improved quickly and safely during the hospital days. The serum cortisol and potassium levels were rather stable on days 1 and 5 postoperatively, and most were within the normal range. The clinical manifestations, serum levels of cortisol, ACTH, and potassium in most patients restored to normal gradually after several months (mean, 6.7 ± 1.2 months, except for one patient undergoing bilateral adrenalectomy. Conclusions. This perioperative endocrine therapy for patients with Cushing’s syndrome (mainly for adrenocortical adenoma undergoing retro-laparoscopic adrenalectomy is both effective and safe.

Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

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Naik, Chinna; Basu, Sandip

2017-01-01

Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was

Pituitary tumors containing cholecystokinin

DEFF Research Database (Denmark)

Rehfeld, J F; Lindholm, J; Andersen, B N

1987-01-01

We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

Cushing syndrome: maybe not so uncommon of an endocrine disease.

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Guaraldi, Federica; Salvatori, Roberto

2012-01-01

Cushing syndrome (CS) is the result of extended exposure to excessive glucocorticoids from endogenous or exogenous sources. Traditionally, the most common cause of endogenous CS is a pituitary adenoma (Cushing disease). Less common causes are adrenocortical tumors and extrapituitary adrenocorticotropin-producing neoplasias. This review provides updated information regarding the potential for increased prevalence of CS in specific patient populations. Here the authors provide to family physicians clinical guidance for recognition of CS by presenting a case, discussing the advantages/disadvantages of the diagnostic tests, and discussing information about the treatment options. CS is expected to have an incidence of 10 to 15 people per million; however, studies of patients with diabetes, obesity, hypertension, and osteoporosis found a high prevalence of CS among these populations. The clinical manifestations of CS range from the distinctive clinical features (purple striae, facial plethora, proximal myopathy) to common conditions such as hypertension, obesity, and diabetes. Clinical practice guidelines recommend biochemical tests to screen patients for CS; however, the sensitivity and specificity of these tests vary, so a careful analysis must be performed to avoid misdiagnosis. CS is challenging to diagnose. Nevertheless, with a systematic approach to testing patients and an increased awareness of the high-risk patient populations, the disease can be identified in a timely manner.

Postoperative plasma cortisol levels predict long-term outcome in patients with Cushing's disease and determine which patients should be treated with pituitary irradiation after surgery

International Nuclear Information System (INIS)

Imaki, Toshihiro; Tsushima, Toshio; Hizuka, Naomi; Odagiri, Emi; Murata, Yoji; Takano, Kazue; Suda, Toshihiro

2001-01-01

Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 μg/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 μg/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 μg/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 μg/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that additional therapy should be avoided in patients with a postoperative plasma cortisol less than 2 μg/dl because relapse is

Pituitary function following megavoltage therapy for Cushings' disease; long term follow up

International Nuclear Information System (INIS)

Sharpe, G.F.; Kendall-Taylor, P.; Prescott, R.W.G.; Ross, W.M.; Davison, C.; Watson, M.J.; Cook, D.B.

1985-01-01

Eight patients who had received megavoltage therapy for Cushings' disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushings' disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow megavoltage therapy and these may progress to overt hypopituitarism. (author)

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

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Renzhi Wang

2016-09-01

Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

International Nuclear Information System (INIS)

Tamai, Isamu; Takei, Tadao; Oota, Hideomi; Maekawa, Kihei.

1981-01-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in intants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therepy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by hight doses of ACTH and in cases where brain atrophy had already been obserbed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time. (author)

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

Energy Technology Data Exchange (ETDEWEB)

Tamai, I.; Takei, T. (National Sagamihara Hospital, Kanagawa (Japan)); Oota, H.; Maekawa, K.

1981-07-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in infants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therapy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by high doses of ACTH and in cases where brain atrophy had already been observed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time.

Diagnosis of Icenko-Cushing's disease and syndrome by angiography and the determination of the content of hormones in blood samples from the adrenal vein and vena cava inferior

International Nuclear Information System (INIS)

Yugrinov, O.G.; Slavnov, V.N.; Rybakov, S.I.; Yakovlev, A.A.

1983-01-01

The paper is concerned with the procedure of a comprehensive examination of patients with hypercorticoidism including angiography of the adrenals and the determination of the hydrocortisone level in the blood. The results of the studies on 32 patients with Icenko-Cushing's syndrome and 95 patients with Icenko-Cushing's disease are presented. X-ray appearance of the focal and diffuse adrenal disorders is described. The authors provide some data on the concentration of hydrocortisone in blood samples and on the content of corticotropin The importance of these data for diagnosis and differential diagnosis of Icenko-Cushing's disease and syndrome is shown. In the authors' opinion, the chief method in this diagnostic complex should be selective adrenal venography

In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay. ACTH releasing activities by various drugs

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Hashimoto, K; Takahara, J; Hosogi, H; Ofuji, N; Yasuhara, T [Okayama Univ. (Japan). School of Medicine

1976-02-01

This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Half of a rat pituitary was preincubated in 2ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25% BSA (KRBG-BSA) for 1.5 hr (45 min x 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with that in the 1st 30 min incubation, and the result was expressed as a percentage. In the ACTH radioimmunoassay, anti-ACTH serum was diluted to 1:1,500-3,000. The /sup 125/I-..cap alpha../sup 1 -24/ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH or prolactin. Human /sup 1 -39/ACTH was used as the ACTH standard. The dilution curve of the incubation medium was parallel to the standard curve. Reproducibility of immunoassayable ACTH within-assay was 174 +- 5.0 pg/tube (CV=2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it was found that LVP, AVP, norepinephrine (100 ng/ml--200 ng/ml) and 5-hydroxytryptophane (1 ..mu..g/ml) had ACTH releasing activities, but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E/sub 1/ and indomethacin did not affect the release of ACTH.

Hipertensión secundaria a Síndrome de Cushing

OpenAIRE

Rodríguez del Río, Francisco Javier; Bravo Morales, Macarena; Portillo Sánchez, José; Martín Dávila, Francisco

2008-01-01

En un pequeño grupo de hipertensos puede identificarse una causa, responsable del aumento de las cifras de presión arterial, como el Síndrome de Cushing, que supone el 0,2-0,6% de los casos. Presentamos el caso de un paciente diagnosticado de hipertensión secundaria a Síndrome de Cushing. In a small group of hypertensive patients a cause of elevated blood pressure levels can be identified, such as Cushing syndrome, which corresponds to 0.2-0.6% of cases. We present the case of a patient di...

Postoperative plasma cortisol levels predict long-term outcome in patients with Cushing's disease and determine which patients should be treated with pituitary irradiation after surgery

Energy Technology Data Exchange (ETDEWEB)

Imaki, Toshihiro; Tsushima, Toshio; Hizuka, Naomi; Odagiri, Emi; Murata, Yoji; Takano, Kazue [Tokyo Women' s Medical Univ. (Japan). Inst. of Clinical Endocrinology; Suda, Toshihiro

2001-02-01

Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 {mu}g/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 {mu}g/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 {mu}g/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 {mu}g/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that additional therapy should be avoided in patients with a postoperative plasma cortisol less

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

International Nuclear Information System (INIS)

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

1986-01-01

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

Energy Technology Data Exchange (ETDEWEB)

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

1986-01-01

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.

Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study.

Science.gov (United States)

Di Dalmazi, Guido; Vicennati, Valentina; Garelli, Silvia; Casadio, Elena; Rinaldi, Eleonora; Giampalma, Emanuela; Mosconi, Cristina; Golfieri, Rita; Paccapelo, Alexandro; Pagotto, Uberto; Pasquali, Renato

2014-05-01

Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome. From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18-30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50-138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline. 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were

Fibromyalgia in a Patient with Cushing's Disease Accompanied by Central Hypothyroidism.

Science.gov (United States)

Ohara, Nobumasa; Katada, Shinichi; Yamada, Takaho; Mezaki, Naomi; Suzuki, Hiroshi; Suzuki, Akiko; Hanyu, Osamu; Yoneoka, Yuichiro; Kawachi, Izumi; Shimohata, Takayoshi; Kakita, Akiyoshi; Nishizawa, Masatoyo; Sone, Hirohito

A 39-year-old woman with a 3-year history of a rounded face developed widespread myalgia. Detailed examinations revealed no disorders that could explain the pain other than concomitant Cushing's disease and central hypothyroidism. Both the hypercortisolemia and hypothyroidism completely resolved after the patient underwent surgery to treat Cushing's disease, but she continued to experience unresolved myalgia and met the diagnostic criteria for fibromyalgia. Few studies have so far investigated patients with fibromyalgia associated with Cushing's syndrome. In our case, the hypothyroidism caused by Cushing's disease probably played an important role in triggering and exacerbating fibromyalgia. This highlights the need to examine the endocrine function in patients with muscle pain.

Harvey Cushing Treated the First Known Patient With Carney Complex.

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Tsay, Cynthia J; Stratakis, Constantine A; Faucz, Fabio Rueda; London, Edra; Stathopoulou, Chaido; Allgauer, Michael; Quezado, Martha; Dagradi, Terry; Spencer, Dennis D; Lodish, Maya

2017-10-01

Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features of Cushing syndrome and acromegaly due to functional adrenal and pituitary gland tumors. CNC has been linked to mutations in the regulatory subunit of protein kinase A type I-alpha ( PRKAR1A ) gene. Tissue samples were taken from the hypothalamus or thalamus or tumors of patients with pituitary adenomas seen and operated on by neurosurgeon Harvey Cushing between 1913 and 1932. Following DNA extraction, sequencing for genes of interest was attempted, including PRKAR1A , AIP , USP8 , GNAS1 , and GPR101 , to explore the possibility that these mutations associated with acromegaly, CNC, and Cushing syndrome have been conserved over time. We report a patient described by Dr. Cushing in 1914 with a clinical presentation and postmortem findings suggestive of CNC. Genetic sequencing of the hypothalamus and pituitary adenoma revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene, a codon previously described as mutated in CNC, but with a novel amino acid change. This patient is, to our knowledge, the first molecularly confirmed individual with CNC. This case demonstrates the power of modern genetics in studying archived tissues and the importance of recording detailed clinical notes in the diagnosis of disease.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

Science.gov (United States)

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal

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

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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.

PATIENTS' PERCEPTION ON CLINICAL OUTCOME AND QUALITY OF LIFE AFTER A DIAGNOSIS OF CUSHING SYNDROME.

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Papoian, Vardan; Biller, Beverly M K; Webb, Susan M; Campbell, Karen K; Hodin, Richard A; Phitayakorn, Roy

2016-01-01

Excess cortisol production (Cushing syndrome, CS) is a chronic disease affecting many organ systems and impacting quality of life (QoL). This study analyzed factors associated with self-reported QoL, including aspects related to the diagnosis and treatment modalities of CS. In collaboration with the Cushing's Support and Research Foundation (CSRF), surveys using a validated QoL instrument were sent to CSRF members. Data were analyzed for associations between QoL and demographic, treatment, and disease factors. A total of 269 patients completed the survey. Respondents were 89.9% female, and the mean age was 48 years (SD 12, range 16-76). Respondents visited a median of 4 physicians (range 1-40) prior to the diagnosis of CS, with a median of 5 years (mean 7, SD 5, range 1-30) to obtain a diagnosis, showing a statistically significant negative correlation (Pdisease, highlighting the need for awareness about the disorder. Patients in remission had better QoL, emphasizing the importance of disease control.

Sphenoid sinus carcinoid tumour causing ectopic ACTH syndrome.

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Perera, Sanjaya; Taha, Ahmad

2017-05-01

A thirty-eight year old patient presented with a gradual increase in weight and Cushingoid facies of two years duration. He also had orbital congestion, with puffy eyelids and corkscrew conjunctival vessels, associated with painful eye movements. An endocrine evaluation revealed raised cortisol and ACTH. Head imaging was performed which showed an enhancing tumour arising from the sphenoid sinus, with osseous erosion of the sphenoid sinus, extending to the nasopharynx, sellar and a small amount extending intracranially. He underwent an endoscopic endonasal resection of the tumour and histology revealed a low-grade carcinoid tumour with ACTH staining. The patient also underwent radiotherapy for the intracranial extension. He is currently in his fourth year of follow-up and imaging has showed a small, stable intracranial remnant. His anterior pituitary hormonal profile remains normal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of hypercortisolism control on high blood pressure in Cushing's syndrome Efecto del control del hipercortisolismo sobre la hipertensión arterial en el síndrome de Cushing

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Reynaldo M. Gómez

2007-10-01

Full Text Available Many hypertensive patients affected by endogenous Cushing's syndrome (CS persist with high blood pressure (HBP despite good control of cortisol excess. We assessed the effect of preoperative ketoconazole administration and of definitive treatment of CS on arterial hypertension and analysed the factors involved in the persistence of hypertension. We assessed retrospectively 71 patients with CS and HBP (60 women, 11 men; 50 pituitary, 21 adrenal successfully treated by surgery and/or radiotherapy; 19 of them received ketoconazole (KNZ before surgery. After treatment, patients were divided into those with persistent high blood pressure (PHBP and those with normal blood pressure (NBP. As possible predictive factors for PHBP we analysed age, duration and family history of HBP, pre-treatment 24 hour urinary free cortisol (24h-UFC and body mass index (BMI. HBP normalized in 53 out of 71 patients (74.6%, regardless of the origin of Cushing's syndrome. PHBP patients were older (p=0.003, had longer duration (p=0.007 and higher systolic blood pressure before treatment (p=0.046 than NBP patients. Thirteen out of 19 patients (68.4% treated with ketoconazole, normalized their hypertension and remained normotensive after successful surgery. Five patients became normotensive only after surgery. In conclusion: a blood pressure levels normalized in most patients after remission of CS; b ketoconazole was effective for the control of HBP, and seems to be a good indicator of post-surgical outcome, and c higher age at presentation, longer duration of hypertension and higher systolic blood pressure figures before treatment negatively influence normalization of blood pressure after resolution of Cushing's syndrome.Muchos pacientes con síndrome de Cushing (SC permanecen hipertensos a pesar del control del exceso glucocorticoideo. Investigamos el efecto de la administración de ketoconazol (KNZ y del tratamiento definitivo del SC sobre la hipertensión arterial (HTA

Megavoltage pituitary irradiation in the management of Cushing's disease and Nelson's syndrome: long-term follow-up

International Nuclear Information System (INIS)

Howlett, T.A.; Plowman, P.N.; Wass, J.A.H.; Rees, L.H.; Jones, A.E.; Besser, G.M.

1989-01-01

The authors report the long-term follow-up (up to 17.3 years) of the clinical and biochemical effects of megavoltage pituitary irradiation (radiotherapy;RT), administered as primary or secondary therapy, for pituitary Cushing's disease and Nelson's syndrome in 52 patients. Irradiation was administered, from a 4-15 MeV linear accelerator, via a three-field technique, to a total dose of 4500 cGy (rad) in 25 fractions over 35 days. (author)

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 ...

Effects of Qiangji Jianli Yin on the hypothalamus CRH contents and plasma ACTH, cortisol levels in rat models of kidney-yang deficiency syndrome

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Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou

2007-01-01

Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)

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.

Intraocular pressure and its correlation with midnight plasma cortisol level in Cushing's disease and other endogenous Cushing's syndrome

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Priyadarshini Mishra

2017-01-01

Full Text Available Purpose: The purpose of this study is to measure intraocular pressure (IOP and evaluate the correlation between IOP and midnight plasma cortisol (MPC level in patients with Cushing's disease (CD and other endogenous Cushing's syndrome (ECS. Methods: This is a cross-sectional study from a single center including newly diagnosed patients with CD or ECS. All patients underwent detailed ophthalmological evaluation. IOP was measured by Goldmann applanation tonometry in the morning and evening on two consecutive days. MPC value was obtained for each patient. The data were compared using paired and unpaired t-test, Mann–Whitney U-test, and Spearman's rank correlation coefficient. Results: Among 32 patients, 22 were CD (68.75% and 10 patients were other ECS (31.25%. A total of 25 patients (78.12% in our study group had normal IOP (<22 mmHg, and seven patients (21.88% had increased IOP (≥22 mmHg. The percentage of patients with normal IOP was found to be significantly higher compared to percentage of patients with high IOP (P = 0.001 using one-sample Chi-square test. Mean MPC value was 468.6 ± 388.3 nmol/L in patients having IOP ≥22 mmHg and 658.5 ± 584 nmol/L in those with IOP <22 mmHg from both CD and ECS groups, but the difference was not statistically significant. No correlation was found between IOP and MPC (Spearman's rank correlation rho = −0.16 [P = 0.38]. Conclusion: In CD and ECS patients, IOP elevation is an uncommon feature, and high IOP in either group does not correlate with MPC level.

Adrenal scintigraphy using 131I-19-iodocholesterol in the exploration of Cushing's syndrome

International Nuclear Information System (INIS)

Charbonnel, B.; Chupin, M.; Guillon, J.; Chatal, J.F.

1976-01-01

On the basis of 7 cases representing the essential types of aetiology of Cushing's syndrome, it is possible to define the value, limitations and role of adrenal scintigraphy using 131 I-19-iodocholesterol in the diagnostic investigation of hypercortisolism. The essential value of the investigation is morphological rather than functional. Adrenal scintigraphy has the same role in diagnostic investigation as various radiological procedures such as pneumoperitoneum and angiography. The latter, however, are technically difficult and fraught with risk, in contrast to the isotopic examination. The principle limitations of the method are not dosimetric but lie in the relative difficulty of interpretation of the documents obtained [fr

Strongyloides stercoralis Hyperinfection Syndrome Presenting as Severe, Recurrent Gastrointestinal Bleeding, Leading to a Diagnosis of Cushing Disease

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Yee, Brittany; Chi, Nai-Wen; Hansen, Lawrence A.; Lee, Roland R.; U, Hoi-Sang; Savides, Thomas J.; Vinetz, Joseph M.

2015-01-01

A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection. PMID:26195463

A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

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Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

2016-06-01

A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

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Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

2016-01-01

Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

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