scholarly journals Cyclic Cushing’s syndrome: a clinical challenge

2007 ◽  
Vol 157 (3) ◽  
pp. 245-254 ◽  
Author(s):  
J R Meinardi ◽  
B H R Wolffenbuttel ◽  
R P F Dullaart
Keyword(s):  
Cushing’S Syndrome ◽  
Screening Tool ◽  
Neuroendocrine Tumours ◽  
Clinical Signs ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
Biochemical Testing ◽  
Spurious Results

Cyclic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years. To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown. The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa. Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.

scholarly journals Cyclic Cushing's syndrome

2010 ◽  
Vol 56 (4) ◽  
pp. 44-51
Author(s):  
E I Marova ◽  
I A Voronkova
Keyword(s):  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Plasma Cortisol Level ◽  
Average Life Expectancy ◽  
Ectopic Acth ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Cortisol Levels

The cyclic Cushing's syndrome is a rare disease characterized by multiple episodes of elevated cortisol levels alternating with periods of its normal secretion. The so-called hypercorticism cycles may be either regular or episodic with intercycle intervals as long as a few days to several years. Most researchers agree that the reliable diagnosis of cyclic Cushing's syndrome should be based on laboratory detection of 3 peaks and 2 falls of plasma cortisol level. Cyclic Cushing's syndrome may be either ACTH dependent or independent. A review of 65 verified cases indicates that this condition may be caused by pituitary corticotropinoma (54%), ectopic ACTH-producing tumour (26%), and adrenal tumour (roughly 11%). The cause of the disease remains uncertain in 9% of the patients. Pathophysiological mechanisms of cyclic Cushing's syndrome are poorly known. In certain cases of bilateral macronodular adrenal hyperplasia or adrenal corticosteroma, it may be associated with the presence of ectopic receptors or anomalous expression of normally located receptors. The majority of the patients presenting with cyclic Cushing's syndrome exhibit symptoms of classical hypercorticism that manifest themselves either on a permanent or cyclic basis. In a small number of patients, clinical signs of cyclic Cushing's syndrome are virtually absent. Variations of the clinical picture and conflicting results of hormonal assays taken together make cyclic Cushing's syndrome difficult to diagnose. Therefore, physicians must be aware of this condition and actively search for it in all patients believed to have an enhanced cortisol production despite normal results of laboratory analysis. Frequent changes of urinary or salivary free cortisol levels are reliable and convenient criteria for cyclic Cushing's syndrome in patients suspected to have this condition. Results of cortisol stimulation or suppression tests are likely to lead to a false conclusion due to spontaneous falls and rises in serum cortisol levels at the time of analysis. Given laboratory confirmation of cyclic Cushing's syndrome, subsequent studies should be focused on the elucidation of its cause. The average life expectancy of patients with cyclic Cushing's syndrome remains to be determined.

scholarly journals Cushing's syndrome due to ectopic ACTH production by a nasal paraganglioma

2013 ◽  
Vol 2013 ◽  
Author(s):  
F Serra ◽  
S Duarte ◽  
S Abreu ◽  
C Marques ◽  
J Cassis ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Microscopic Analysis ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
List Type ◽  
Rare Tumour ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
The Right

Summary Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature. Learning points Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies. Most paraganglioma of the head and neck are not hormonally active. Nasal paraganglioma, especially ACTH producing, is a very rare tumour.

scholarly journals A rare case of duodenal carcinoid presenting as ectopic Cushing’s syndrome

2019 ◽  
Vol 6 (3) ◽  
pp. 959
Author(s):  
Siddharth Pugalendhi ◽  
Tarun Kumar Dutta ◽  
Dhivya . ◽  
Kiran Yadav
Keyword(s):  
Neuroendocrine Tumors ◽  
Cushing’S Syndrome ◽  
Cushing Syndrome ◽  
Somatostatin Analogues ◽  
Cushing's Syndrome ◽  
High Dose ◽  
Ectopic Acth ◽  
High Dose Dexamethasone ◽  
Ectopic Acth Production ◽  
Duodenal Carcinoid

ACTH-dependent Cushing syndrome (CS) due to an ectopic source is responsible for approximately 10-15% cases of Cushing’s syndrome. It is associated with various tumors such as small cell lung cancer and well-differentiated bronchial or gastrointestinal neuroendocrine tumors. Many a times ectopic ACTH production is difficult to manage, and identification of the source may take many years.  Hormonal diagnostics include assessments in basic conditions as well as dynamic tests, such as the high-dose dexamethasone suppression test and corticotrophin releasing hormone (CRH) stimulation test. Treatment selection depends on the type of tumor and its extent. In the case of neuroendocrine tumors, the main treatments are surgery and administration of somatostatin analogues or bilateral adrenalectomy in refractory cases and if the source remains unidentified. Here, we report a case who presented with features of Cushing’s syndrome which eventually through workup led us to a diagnosis of duodenal carcinoid producing ectopic ACTH which is extremely rare and was successfully treated.

Serum chromogranin A in the differential diagnosis of Cushing's syndrome

1994 ◽  
Vol 131 (6) ◽  
pp. 589-593 ◽  
Author(s):  
Frank RE Nobels ◽  
Wouter W de Herder ◽  
Dik J Kwekkeboom ◽  
Willy Coopmans ◽  
Andries Mulder ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cushing’S Syndrome ◽  
Immunohistochemical Staining ◽  
Chromogranin A ◽  
Neuroendocrine Tumours ◽  
Elevated Serum ◽  
Serum Levels ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Adrenocortical Tumour

Nobels FRE, de Herder WW, Kwekkeboom DJ, Coopmans W, Mulder A, Bouillon R, Lamberts SWJ. Serum chromogranin A in the differential diagnosis of Cushing's syndrome. Eur J Endocrinol 1994:131:589–93. ISSN 0804–4643 We evaluated whether measuring serum levels of chromogranin A, a marker of neuroendocrine tumours, could be useful in the differential diagnosis between pituitary, adrenal and ectopic causes of Cushing's syndrome. Thirty patients with Cushing's syndrome were studied. The localization of the tumours responsible was pituitary in 15, adrenal in 5 and ectopic in 10 patients. Serum concentrations of chromogranin A were measured in all patients. Petrosal sinus sampling for chromogranin A was performed in the cases with pituitary-dependent Cushing's syndrome. Immunohistochemical staining for chromogranin A was carried out on part of the tumour specimens. Slightly elevated serum levels of chromogranin A (range 223–262 μg/1) were detected in inferior petrosal sinus and peripheral venous samples from three patients with pituitary-dependent Cushing's syndrome. Serum chromogranin A showed no significant pituitary to peripheral gradient in these patients. Chromogranin A levels were not elevated in cases of adrenal Cushing's syndrome. Markedly elevated concentrations (range 270–13900 μg/1) were shown in seven of 10 patients with neuroendocrine tumours with ectopic adrenocorticotrophin (ACTH) and/or corticotrophin-releasing hormone (CRH) production. Widespread metastasis was present in all these cases. Subjects with "occult" carcinoid tumours, with limited spread, had normal chromogranin A levels Immunohistochemical staining for chromogranin A was positive in three out of five pituitary adenomas and in all neuroendocrine tumours with ectopic ACTH and/or CRH production, while it was negative in all adrenocortical tumour specimens. It is concluded that elevated serum levels of chromogranin A can serve as markers of neuroendocrine tumours with ectopic ACTH and/or CRH production. The circulating levels are dependent mainly on the size of the tumours. Serum chromogranin A is not useful in the diagnosis of so-called occult Cushing's syndrome, caused by ectopic ACTH and/or CRH secretion by small neuroendocrine tumours. F Nobels, Department of Endocrinology, Onze Lieve Vrouw Hospital, 164 Moorselbaan, 9300 Aalst, Belgium

scholarly journals Merits and pitfalls of mifepristone in Cushing's syndrome

2009 ◽  
Vol 160 (6) ◽  
pp. 1003-1010 ◽  
Author(s):  
F Castinetti ◽  
M Fassnacht ◽  
S Johanssen ◽  
M Terzolo ◽  
P Bouchard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adrenal Insufficiency ◽  
Cushing’S Syndrome ◽  
Psychiatric Symptoms ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Close Monitoring ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Glucose Levels

ObjectiveMifepristone is the only available glucocorticoid receptor antagonist. Only few adult patients with hypercortisolism were treated to date by this drug. Our objective was to determine effectiveness and tolerability of mifepristone in Cushing's syndrome (CS).DesignRetrospective study of patients treated in seven European centers.MethodsTwenty patients with malignant (n=15, 12 with adrenocortical carcinoma, three with ectopic ACTH secretion) or benign (n=5, four with Cushing's disease, one with bilateral adrenal hyperplasia) CS were treated with mifepristone. Mifepristone was initiated with a median starting dose of 400 mg/day (200–1000). Median treatment duration was 2 months (0.25–21) for malignant CS, and 6 months (0.5–24) for benign CS. Clinical (signs of hypercortisolism, blood pressure, signs of adrenal insufficiency), and biochemical parameters (serum potassium and glucose) were evaluated.ResultsTreatment was stopped in one patient after 1 week due to severe uncontrolled hypokalemia. Improvement of clinical signs was observed in 11/15 patients with malignant CS (73%), and 4/5 patients with benign CS (80%). Psychiatric symptoms improved in 4/5 patients within the first week. Blood glucose levels improved in 4/7 patients. Signs of adrenal insufficiency were observed in 3/20 patients. Moderate to severe hypokalemia was observed in 11/20 patients and increased blood pressure levels in 3/20 patients.ConclusionMifepristone is a rapidly effective treatment of hypercortisolism, but requires close monitoring of potentially severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency. Mifepristone provides a valuable treatment option in patients with severe CS when surgery is unsuccessful or impossible.

Cushing’s syndrome due to ectopic ACTH production by (neuroendocrine) prostate carcinoma

Pituitary ◽  
2008 ◽  
Vol 12 (3) ◽  
pp. 280-283 ◽  
Author(s):  
R. A. Alwani ◽  
S. J. C. M. M. Neggers ◽  
M. van der Klift ◽  
M. G. A. Baggen ◽  
G. J. L. H. van Leenders ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Prostate Carcinoma ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Production

Cushing’s syndrome with intermittent ectopic ACTH production

1990 ◽  
Vol 13 (4) ◽  
pp. 317-326 ◽  
Author(s):  
A. van Coevorden ◽  
E. Laurent ◽  
F. Rickaert ◽  
O. van Reeth ◽  
E. Van Cauter ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Production

scholarly journals Ectopic Cushing’s From Metastatic Prostate Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A757-A757
Author(s):  
Zachary Bloomer ◽  
Jennifer Teague ◽  
Nicole Vietor
Keyword(s):  
Prostate Cancer ◽  
Cushing’S Syndrome ◽  
Metastatic Prostate Cancer ◽  
Systemic Chemotherapy ◽  
Bronchial Carcinoma ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
Urine Cortisol ◽  
Castrate Resistant

Abstract Objective: Ectopic ACTH production from malignancy is a rare etiology of Cushing’s syndrome. The most common tumors associated with this syndrome include small cell lung cancer, pancreatic neuroendocrine tumors, pheochromoctoma, thymic carcinoma, and bronchial carcinoma. Metastatic prostate cancer does not commonly produce ACTH. Here, we present a rare case of Cushing’s syndrome due to metastatic prostate cancer. Case Report: Patient is a 64 year old man with a 2 year history of castrate-resistant prostate cancer who was admitted for the 2nd time in 1 month for profound weakness and new onset hypokalemia. Initial analysis revealed hypertension with systolic blood pressure in the 150s, potassium in the mid 2s, an ACTH level of >1000pg/mL, and a 24-hr urine cortisol of almost 10,000mcg/24hrs. This was confirmed on repeat analysis. Metyrapone was initiated for treatment of hypercortisolemia and systemic chemotherapy with Cisplatin/Irinotecan was started to treat metastatic prostate cancer. ACTH and 24-hr urine cortisol levels returned to normal within a few weeks of therapy. The patient was able to discontinue Metyrapone following systemic chemotherapy treatment. Subsequent labs following discontinuation of metyrapone confirmed ongoing resolution of hypercortisolemia. Conclusion: This case represents an extremely rare cause of Cushing’s syndrome. Metastatic prostate cancer can rarely produce ACTH and cause clinical Cushing’s syndrome. Ectopic Cushing’s syndrome is often due to very aggressive tumors and is associated with a poor prognosis. Rapid recognition and treatment of this condition can be lifesaving.

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