scholarly journals SUN-LB34 A Case of BMAH With Aberrant Vasopressin Adrenal Receptors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Faheem Seedat ◽  
Nazeer Ahmed Mohamed ◽  
Nereshni Lutchman
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Incidental Finding ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Screening Tests ◽  
Pathological Examination ◽  
Unilateral Adrenalectomy ◽  
Urine Free Cortisol ◽  
Free Cortisol

Abstract We report on a 42 - year old woman was referred following an incidental finding of bilateral macronodular (nodules > 1cm) adrenal glands after a computed tomography scan for investigation of an unrelated urological problem. Clear features of Cushing’s syndrome were elicited on initial clincal evaluation and screening tests confirmed the diagnosis biochemically: midnight salivary cortisol 15.4nmol/L (0.2 - 3nmol/L), 24 hour urine free cortisol > 662.4nmol/L (8.3 - 118.7nmol/L per 24 hours) and an 8am serum cortisol measured 951nmol/L following 1mg dexamethasone suppression test (< 50nm/L). A serum adrenocorticotropic hormone (ACTH) measured 0.3pmol/L (1.6 - 13.9pmol/L) suggesting, in light of the CT findings, an adrenal source of the elevated cortisol. Screening for aberrant adrenal receptors to catecholamines, Gastric inhibitory peptide, ACTH, vasopressin and Gonadotropin releasing hormone was performed. A positive biochemical response to ACTH and vasopressin was noted as measured serum cortisol increased to 1600pmol/L (upper limit of the assay). Following a unilateral adrenalectomy, were pathological examination of the respected adrenal gland confirmed adrenal hyperplasia, the patient had both clinical and biochemical resolution of hypercortisolemia. 2 weeks following surgery her midnight salivary cortisol measured 2.1nmol/L (0.2 - 3nmol/L) and 24 hour urine free cortisol 218nmol/L (8.3 - 118.7nmol/L per 24 hours). Her 8am ACTH also increased to 2.9pmol/L (1.6 - 13.9pmol/L). Biochemical screening of her sister showed no evidence of Cushing’s syndrome. Bilateral macronodualr hyperplasia (BMAH) represents a rare cause of Cushing’s syndrome may be diagnosed incidentally and is often associated with an insidious onset. We use this case to highlight the complexities of provocative testing for aberrant adrenal receptors which occur with BMAH and the utilization of unilateral adrenalectomy to achieve clinical and biochemical remission of Cushing’s syndrome thus, removing the need for post - operative steroid replacement following bilateral adrenalectomy.

scholarly journals Midnight Salivary Cortisol Versus Urinary Free and Midnight Serum Cortisol as Screening Tests for Cushing’s Syndrome

2003 ◽  
Vol 88 (9) ◽  
pp. 4153-4157 ◽  
Author(s):  
Pietro Putignano ◽  
Paola Toja ◽  
Antonella Dubini ◽  
Francesca Pecori Giraldi ◽  
Salvatore Maria Corsello ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Diagnostic Performance ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Screening Tests ◽  
Late Night ◽  
Free Cortisol ◽  
Simple Obesity

The diagnosis of Cushing’s syndrome (CS) is often a challenge. Recently, the determination of late night salivary cortisol levels has been reported to be a sensitive and convenient screening test for CS. However, no studies have included a comparison with other screening tests in a setting more closely resembling clinical practice, i.e. few patients with CS to be distinguished from patients with pseudo-Cushing states (PC), including the large population of obese patients. The aim of this study was to compare the diagnostic performance of midnight salivary cortisol (MSC) measurement with that of midnight serum cortisol (MNC) and urinary free cortisol (UFC) in differentiating 41 patients with CS from 33 with PC, 199 with simple obesity, and 27 healthy normal weight volunteers. Three patients with CS had MSC levels lower than the cut-off point derived from receiver operator characteristic analysis (9.7 nmol/liter), yielding a sensitivity for this parameter of 92.7%. In the whole study population, no statistically significant differences in terms of sensitivity, specificity, diagnostic accuracy, and predictive values were observed among tests. In particular, the overall diagnostic accuracy for MSC (93%; 95% confidence interval, 90.1–95.9%) was similar to those of UFC (95.3%; 94.1–96.5%) and MNC (95.7%; 93.4–98%; both P = NS). The diagnostic performance of MSC was superimposable to that of MNC also within the area of overlap in UFC values (≤569 nmol/24 h) between CS and PC. In conclusion, MSC measurement can be recommended as a first-line test for CS in both low risk (simple obesity) and high-risk (i.e. PC) patients. Given its convenience, this procedure can be added to tests traditionally used for this purpose, such as UFC and MNC.

scholarly journals Neutrophil-Lymphocyte Ratio as an Initial Screening Biomarker for Differential Diagnosis of Cushing’s Syndrome from Nonfunctional Adenoma in Patients with an Adrenal Mass

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Wei Wang ◽  
Jianing Wang ◽  
Cheng Shen ◽  
Sainan Zhu ◽  
Ying Gao ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Mass ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Initial Screening ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Late Night ◽  
Urine Free Cortisol ◽  
Free Cortisol

Objective. Assessing excess adrenal hormones is important in patients with adrenal mass. Current screening tests for excess cortisol hormones are complex, so it cannot be done sometimes due to the limited medical resources. The aim of the study was to evaluate whether the neutrophil-lymphocyte ratio (NLR) can be used as an initial screening biomarker for Cushing’s syndrome (CS) in patients with an adrenal mass. Methods. This retrospective study included a total of 185 patients with CS and 185 patients with nonfunctional adrenal adenoma (matched 1 : 1 by sex, body mass index, and discharge date). The NLR was compared between the two groups. The association between NLR and serum and urinary cortisol concentrations was analyzed, and an NLR cut-off value for CS screening was calculated. Results. NLR (3.38 (2.33, 5.45) vs. 2.13 (1.74, 3.00), P < 0.001 ) was significantly higher in the CS group than in the nonfunctional adenoma group. In CS patients, the NLR was positively associated with serum cortisol concentrations at 8 am, with 24-hour urine free cortisol and with serum cortisol after a 1 mg dexamethasone suppression test ( P < 0.001 each). An NLR cut-off of 2.2 had a sensitivity of 80.0% and a specificity of 54.05%. The weighted Youden index for the NLR was similar to that of the 24-hour urine free cortisol and late-night serum cortisol tests, which are recommended initial tests for CS diagnosis. Conclusion. The NLR may be useful for initial screening for CS among patients with an adrenal mass as an easy and convenient marker.

scholarly journals A commentary on Diagnosing Cushing’s disease in the context of renal failure

2019 ◽  
Vol 181 (4) ◽  
pp. C9-C11
Author(s):  
Hershel Raff ◽  
Eric P Cohen ◽  
James W Findling
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Urine Free Cortisol ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol ◽  
Pituitary Adrenal Axis

The diagnosis of endogenous hypercortisolism (Cushing's syndrome) is extremely challenging. Chronic kidney disease (CKD) increases the activity of the hypothalamic-pituitary-adrenal axis making the diagnosis of Cushing's syndrome even more challenging. This is particularly so since urine free cortisol (UFC) testing is not useful in CKD. The case report by Stroud et al. in this issue of the European Journal of Endocrinology highlights this problem by finding normal UFC in a patient with pituitary ACTH-dependent Cushing's syndrome. Elevated late-night salivary cortisol (LNSC) testing was diagnostic and pituitary adenomectomy was curative. LNSC measurement is the diagnostic test of choice in patients with suspected Cushing's syndrome, particularly in the presence of CKD..

scholarly journals Is There Value in Routine Screening for Cushing’s Syndrome in Patients with Diabetes?

2010 ◽  
Vol 95 (5) ◽  
pp. 2262-2265 ◽  
Author(s):  
K. Mullan ◽  
N. Black ◽  
A. Thiraviaraj ◽  
P. M. Bell ◽  
C. Burgess ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Diabetic Patients ◽  
Diabetes Clinic ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
Dexamethasone Test

Abstract Context: Subclinical Cushing’s syndrome has been described among diabetic populations in recent years, but no consensus has emerged about the value of screening. Methods: We enrolled 201 consecutive patients attending our diabetes clinic and 79 controls. Patients with at least two of the following three criteria were offered screening using a 2300 h salivary cortisol test: glycosylated hemoglobin of at least 7%, body mass index of at least 25 kg/m2, and a history of hypertension or blood pressure of at least 140/90 mm Hg. Results are expressed as mean ± sem. Results: Mean nighttime salivary cortisol levels were similar in the two groups (8.5 ± 1.0 nmol/liter for diabetic patients vs. 5.8 ± 1.0 nmol/liter for controls). Forty-seven patients (23%) had a value of at least 10 nmol/liter, which was set as a conservative threshold above which further investigation would be performed. Thirty-five (75%) agreed to further testing with a 1-mg overnight dexamethasone test. Of the remaining 12 patients, 10 were followed up clinically for at least 1 yr, and no evidence was found of the syndrome evolving. In 28 patients, serum cortisol suppressed to 60 nmol/liter or less. Of the seven patients who failed this test, four agreed to a 2 mg/d 48-h dexamethasone test, with serum cortisol suppressing to 60 nmol/liter or less in all four. Three declined this test but had normal 24-h urinary free cortisol levels. No patient had clinical features of hypercortisolism. Conclusions: The 1–3% detection rates of three recently published series have not been realized at our center where we studied a group using criteria making patients more likely to have hypercortisolism. Our results do not support the validity of screening patients without clinical features of Cushing’s syndrome in the diabetes clinic.

scholarly journals Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome

2007 ◽  
Vol 157 (6) ◽  
pp. 725-731 ◽  
Author(s):  
Srividya Kidambi ◽  
Hershel Raff ◽  
James W Findling
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Adrenal Adenoma ◽  
High Sensitivity ◽  
Cushing's Syndrome ◽  
Urine Free Cortisol ◽  
Free Cortisol ◽  
Computer Tomography Scan ◽  
Magnetic Resonance Imaging Mri ◽  
Acth Secreting

ObjectiveCushing's syndrome (CS) is difficult to diagnose due to its nonspecific presentation. Diagnostic tests like 24-h urine free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient sensitivity and specificity. Measurement of nocturnal salivary cortisol (NSC) is an accurate and reproducible test with a high sensitivity for CS. However, its performance in mild CS has not been reported. We present 11 cases of CS with normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis.Design and methodsAll patients had at least one collection of 24-h UFC and NSC and eight had an overnight 1 mg DST. The number of NSC measurements per patient was determined by the clinical index of suspicion and the results of initial testing. Imaging studies included magnetic resonance imaging (MRI) of pituitary or computer tomography scan of abdomen.ResultsOnly four out of eleven patients had elevations in UFC and none were >2 times the upper limit of normal. Seven out of eight had an abnormal DST. All patients had some elevated NSCs (14–100%). Out of eleven patients, six had an abnormality in the pituitary gland found by MRI and two out of eleven had adrenal masses. The remaining three had normal pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's disease. All patients had appropriate surgery, and histopathology of all except one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH-secreting pituitary adenoma.ConclusionNeither a normal UFC nor a normal NSC excludes mild CS. Multiple samples (urine/saliva) and DST are needed to make the diagnosis of mild CS.

scholarly journals Scalp hair cortisol for diagnosis of Cushing’s syndrome

2017 ◽  
Vol 176 (6) ◽  
pp. 695-703 ◽  
Author(s):  
Vincent L Wester ◽  
Martin Reincke ◽  
Jan W Koper ◽  
Erica L T van den Akker ◽  
Laura Manenschijn ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Scalp Hair ◽  
Geometric Mean ◽  
Disease Onset ◽  
Cushing's Syndrome ◽  
Screening Tests ◽  
Healthy Controls ◽  
Hair Cortisol ◽  
First Line ◽  
Free Cortisol

Objective Current first-line screening tests for Cushing’s syndrome (CS) only measure time-point or short-term cortisol. Hair cortisol content (HCC) offers a non-invasive way to measure long-term cortisol exposure over several months of time. We aimed to evaluate HCC as a screening tool for CS. Design Case-control study in two academic referral centers for CS. Methods Between 2009 and 2016, we collected scalp hair from patients suspected of CS and healthy controls. HCC was measured using ELISA. HCC was available in 43 confirmed CS patients, 35 patients in whom the diagnosis CS was rejected during diagnostic work-up and follow-up (patient controls), and 174 healthy controls. Additionally, we created HCC timelines in two patients with ectopic CS. Results CS patients had higher HCC than patient controls and healthy controls (geometric mean 106.9 vs 12.7 and 8.4 pg/mg respectively, P < 0.001). At a cut-off of 31.1 pg/mg, HCC could differentiate between CS patients and healthy controls with a sensitivity of 93% and a specificity of 90%. With patient controls as a reference, specificity remained the same (91%). Within CS patients, HCC correlated significantly with urinary free cortisol (r = 0.691, P < 0.001). In two ectopic CS patients, HCC timelines indicated that cortisol was increased 3 and 6 months before CS became clinically apparent. Conclusions Analysis of cortisol in a single scalp hair sample offers diagnostic accuracy for CS similar to currently used first-line tests, and can be used to investigate cortisol exposure in CS patients months to years back in time, enabling the estimation of disease onset.

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.

scholarly journals Screening and diagnosis of Cushing's syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1191-1198 ◽  
Author(s):  
Margaret de Castro ◽  
Ayrton C. Moreira
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Linear Growth ◽  
Fat Distribution ◽  
Cushing's Syndrome ◽  
First Line ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol ◽  
Pituitary Adrenal Axis

Cushing's syndrome (CS) results from sustained pathologic hypercortisolism. The clinical features are variable and the most specific features for CS include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Clinical presentation of CS can be florid and in this case the diagnosis is usually straightforward. However, the diagnosis can be difficult particularly in states of mild or cyclical or periodical hypercortisolism. Several tests based on the understanding of the physiologic characteristics of the hypothalamic-pituitary-adrenal axis have been used extensively to confirm the diagnosis of Cushing's syndrome, but none has proven fully capable of distinguishing all cases of CS from normal and/or pseudo-Cushing individuals. Three first-line diagnostic tests are currently used to screen for CS: measurement of free cortisol in 24-hour urine (UFC), cortisol suppressibility by low doses of dexamethasone (DST), and assessment of cortisol circadian rhythm using late-night serum and/or salivary cortisol. This paper discusses the effectiveness regarding best cut-off values, the sensitivity and the specificity of these tests to screen for CS. Late-night salivary cortisol appears to be the most useful screening test. UFC and DST should be performed to provide further confirmation of the diagnosis.

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