scholarly journals ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

2015 ◽  
Vol 173 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Katrin Ritzel ◽  
Felix Beuschlein ◽  
Christina Berr ◽  
Andrea Osswald ◽  
Nicole Reisch ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Predictive Value ◽  
Positive Likelihood Ratio ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
High Dose ◽  
Ectopic Cushing’S Syndrome ◽  
Cortisol Suppression ◽  
Dexamethasone Suppression

ObjectiveThe aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome.Subjects and methodsWe retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B) after 8 mg of dexamethasone was evaluated as a supplementary criterion.ResultsAn increase in ACTH of ≥43%B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases.ConclusionThe present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive.

scholarly journals Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

2014 ◽  
Vol 170 (4) ◽  
pp. 477-486 ◽  
Author(s):  
R A Alwani ◽  
L W Schmit Jongbloed ◽  
F H de Jong ◽  
A J van der Lely ◽  
W W de Herder ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Predictive Value ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Dexamethasone Suppression

ObjectiveTo evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS).MethodsIn this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone–CRH (Dex–CRH) test was performed in 54 patients.ResultsFifty-three patients were diagnosed with CD and subsequently treated. Twenty patients were classified as having PSC. Serum cortisol circadian rhythm: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of >0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration >243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level >9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex–CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level >87 nmol/l (T=15 min) resulted in a PPV of 100% and an NPV of 90%.ConclusionThe Dex–CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

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

2017 ◽  
Vol 2017 ◽  
Author(s):  
Regina Streuli ◽  
Ina Krull ◽  
Michael Brändle ◽  
Walter Kolb ◽  
Günter Stalla ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Rapid Development ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
High Dose ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Cushing’S Syndrome

Summary 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. Learning points: The discrimination between a Cushing’s disease and ectopic Cushing’s syndrome is challenging and has many caveats. Ectopic ACTH/CRH co-secreting tumors are very rare. Dynamic tests as well as BIPSS may be compatible with Cushing’s disease in ectopic CRH-secretion. High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH. Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing’s syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing’s syndrome and lead to further investigations.

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: A comparison with the lysine-vasopressin test

1990 ◽  
Vol 123 (3) ◽  
pp. 331-338 ◽  
Author(s):  
A. Tabarin ◽  
F. San Galli ◽  
S. Dezou ◽  
F. Leprat ◽  
J.-B. Corcuff ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
High Dose ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Etiological Diagnosis ◽  
High Dose Dexamethasone

Abstract. The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

scholarly journals Successful Long-Term Treatment of Refractory Cushing’s Disease with High-Dose Mifepristone (RU 486)

2001 ◽  
Vol 86 (8) ◽  
pp. 3568-3573 ◽  
Author(s):  
James W. Chu ◽  
Dwight F. Matthias ◽  
Joseph Belanoff ◽  
Alan Schatzberg ◽  
Andrew R. Hoffman ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Mineralocorticoid Receptor ◽  
Cushing's Syndrome ◽  
Term Treatment ◽  
Cushing's Disease ◽  
High Dose ◽  
Metabolic Disturbances ◽  
Long Term Treatment

An extremely ill patient, with Cushing’s syndrome caused by an ACTH-secreting pituitary macroadenoma, experienced complications of end-stage cardiomyopathy, profound psychosis, and multiple metabolic disturbances. Initially treated unsuccessfully by a combination of conventional surgical, medical, and radiotherapeutic approaches, he responded dramatically to high-dose long-term mifepristone therapy (up to 25 mg/kg·d). Treatment efficacy was confirmed by the normalization of all biochemical glucocorticoid-sensitive measurements, as well as by the significant reversal of the patient’s heart failure, the resolution of his psychotic depression, and the eventual unusual return of his adrenal axis to normal. His 18-month-long mifepristone treatment course was notable for development of severe hypokalemia that was attributed to excessive cortisol activation of the mineralocorticoid receptor, which responded to spironolactone administration. This case illustrates the efficacy of high-dose long-term treatment with mifepristone in refractory Cushing’s syndrome. The case also demonstrates the potential need for concomitant mineralocorticoid receptor blockade in mifepristone-treated Cushing’s disease, because cortisol levels may rise markedly, reflecting corticotroph disinhibition, to cause manifestations of mineralocorticoid excess.

BIOSYNTHESIS OF CORTICOIDS AND ANDROGENS IN AN ADENOMA FROM A CUSHING'S SYNDROME PATIENT

1963 ◽  
Vol 42 (2) ◽  
pp. 187-194
Author(s):  
Menek Goldstein ◽  
Marcel Gut ◽  
Ralph I. Dorfman ◽  
Louis J. Soffer ◽  
J. Lester Gabrilove
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Syndrome Patient ◽  
Adrenal Tissue

ABSTRACT Incubation of cholesterol-4-14C and pregnenolone-7-3H with a homogenate of adenomatous adrenal tissue from a patient with Cushing's disease yielded 14C and 3H labelled, cortisol, cortisone, 11-deoxycortisol, deoxycorticosterone, dehydroepiandrosterone, and 11β-hydroxy-androst-4-3,17-dione.

Pitfalls in the diagnosis and management of Cushing's syndrome

2015 ◽  
Vol 38 (2) ◽  
pp. E4 ◽  
Author(s):  
Vivek Bansal ◽  
Nadine El Asmar ◽  
Warren R. Selman ◽  
Baha M. Arafah
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Salivary Cortisol ◽  
Clinical Symptoms ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Biochemical Tests ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol

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.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

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