scholarly journals Diagnostic performance of first line biochemical tests to differentiate ACTH-ectopic syndrome among ACTH dependent Cushing's syndrome

2013 ◽  
Author(s):  
Zhanna Belaya ◽  
Liudmila Rozhinskaya ◽  
Natalia Dragunova ◽  
Larisa Dzeranova ◽  
Svetlana Arapova ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Diagnostic Performance ◽  
Cushing's Syndrome ◽  
First Line ◽  
Biochemical Tests

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 Efficacy of pasireotide in controlling severe hypercortisolism until cardiac transplantation

2017 ◽  
Vol 2017 ◽  
Author(s):  
Roberto Attanasio ◽  
Liana Cortesi ◽  
Daniela Gianola ◽  
Claudia Vettori ◽  
Fulvio Sileo ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Cushing’S Syndrome ◽  
Cardiac Transplantation ◽  
Serum Cortisol ◽  
Primary Treatment ◽  
Cushing's Syndrome ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment ◽  
Undergo Heart Transplantation

Summary Cushing’s syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 µg/dL in the morning and 20.3 µg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC) was 258 µg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 µg bid was administered and uptitrated to 600 µg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 µg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy), morning serum cortisol and ACTH were 15.6 µg/dL and 54 pg/mL respectively, UFC was 37 µg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation. Learning points: Untreated Cushing’s syndrome is associated with ominous prognosis. First-line treatment is surgery (at pituitary or adrenal, according to disease localization). A few drugs are available to treat hypercortisolism. Pasireotide is a multi-ligand somatostatin analog approved for treatment of hypercortisolism. Primary treatment with pasireotide was effective in a patient with severe Cushing’s syndrome, allowing him to undergo heart transplantation.

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.

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 Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling

2008 ◽  
Vol 159 (4) ◽  
pp. 483-488 ◽  
Author(s):  
Pia Burman ◽  
ÅsaLinda Lethagen ◽  
Krasnodar Ivancev ◽  
Leif Johansson ◽  
Anders Sundin
Keyword(s):  
Cushing’S Syndrome ◽  
False Positive ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Inferior Petrosal Sinus ◽  
Biochemical Tests ◽  
Inferior Petrosal Sinus Sampling ◽  
Bronchial Carcinoids ◽  
Work Up ◽  
Dexamethasone Suppression

ContextEstablishing the cause of Cushing's syndrome (CS) can be a considerable challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome, and often requires a combination of biochemical tests and imaging procedures.SubjectA 27-year-old man presented with signs of CS. P-ACTH levels were three times above the upper limit of normal (ULN) and free urinary cortisol around 2000 nmol/24 h. The work-up showed remarkable results.ResultsA 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs showed two oval-shaped masses, 1.3×1.8 and 1.3×2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, 11C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery.ConclusionThis unique case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH production in response to dexamethasone, or steroid-induced tumor necrosis, explains the paradoxical outcome at dexamethasone suppression, and the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient. The work-up illustrates the great value of 11C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results.

scholarly journals Specificity of First-Line Tests for the Diagnosis of Cushing’s Syndrome: Assessment in a Large Series

2007 ◽  
Vol 92 (11) ◽  
pp. 4123-4129 ◽  
Author(s):  
Francesca Pecori Giraldi ◽  
Alberto G. Ambrogio ◽  
Martina De Martin ◽  
Letizia M. Fatti ◽  
Massimo Scacchi ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Large Series ◽  
First Line

Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing’s syndrome: results of a single-center 7-year experience

2018 ◽  
Vol 67 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Nusret Yilmaz ◽  
Gokhan Tazegul ◽  
Humeyra Bozoglan ◽  
Ramazan Sari ◽  
Sebahat Ozdem ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Diagnostic Performance ◽  
Cushing's Syndrome ◽  
Lower Sensitivity ◽  
Subclinical Cushing’S Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing’s syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing’s syndrome (CCS) and subclinical Cushing’s syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing’s syndrome (NoCS). The cause of the Cushing’s syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107–33) µg/dL in CCS group, 0.398 (0.16–1.02) µg/dL in SCS group, and 0.18 (0.043–0.481) µg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 µg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 µg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing’s syndrome.

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