scholarly journals The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC–MS/MS method in routine clinical practice

2014 ◽  
Vol 171 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Filippo Ceccato ◽  
Giorgia Antonelli ◽  
Mattia Barbot ◽  
Marialuisa Zilio ◽  
Linda Mazzai ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Diagnostic Performance ◽  
De Novo ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Healthy Controls ◽  
Endocrine Society ◽  
Free Cortisol

ObjectiveThe Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method.Subjects and methodsThe LC–MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16de novoand ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission.ResultsUFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity forde novoCS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy.ConclusionsOur data suggest high diagnostic performance of UFF excretion measured using LC–MS/MS, in detectingde novoCS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS.

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.

How useful is 24 hour Urinary Free Cortisol as a screening tool for Cushing's syndrome?

2018 ◽  
Author(s):  
Ahmed Hanafy ◽  
Chinnadorai Rajeswaran ◽  
Saad Saddiq ◽  
Warren Gillibrand ◽  
John Stephenson
Keyword(s):  
Cushing’S Syndrome ◽  
Screening Tool ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Free Cortisol

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.

scholarly journals Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia

2014 ◽  
Vol 2014 ◽  
Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez
Keyword(s):  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
List Type ◽  
Adrenal Hyperplasia ◽  
Benign Condition ◽  
Steroid Secretion ◽  
Free Cortisol

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.

scholarly journals Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Ariadne Bosman ◽  
Annewieke W. van den Beld ◽  
Richard A. Feelders ◽  
M. Carola Zillikens
Keyword(s):  
Linear Regression ◽  
Cushing’S Syndrome ◽  
Urinary Free Cortisol ◽  
Population Based ◽  
Cushing's Syndrome ◽  
Serum Phosphate ◽  
Rotterdam Study ◽  
Phosphate Homeostasis ◽  
Free Cortisol ◽  
Underlying Mechanisms

ObjectivesThe influence of hypercortisolism on phosphate homeostasis is relatively unknown. A few previous studies have reported on patients with Cushing’s syndrome (CS) with hypophosphatemia in whom serum phosphate normalized after initiation of treatment for CS. We aimed to investigate the prevalence of hypophosphatemia in CS, the association between the degree of hypercortisolism and serum phosphate and the change in serum phosphate after remission of CS. We compared the prevalence of hypophosphatemia in CS with the prevalence in the population-based Rotterdam Study (RS).MethodsPatients diagnosed with CS and treated at the Department of Endocrinology of Erasmus MC in the period of 2002-2020 were included and data was collected on age at diagnosis, sex, serum phosphate, calcium and potassium levels, kidney function and BMI. Using multivariate linear regression, we analyzed the association between 24h urinary free cortisol excretion (UFC) and serum phosphate. Changes in serum phosphate and covariates were tested with a repeated measurement ANOVA, using mean levels of laboratory values for the periods before remission, and 0-14 days and 15-180 days after remission.ResultsHypophosphatemia before treatment was present in 16% of the 99 CS patients with data on serum phosphate, 24h UFC and covariates. In comparison, the prevalence of hypophosphatemia in RS was 2.0-4.2%. Linear regression showed a negative association between the level of UFC and serum phosphate at diagnosis, which remained significant after adjusting for covariates [β -0.002 (95%CI -0.004; -0.0004), p=0.021]. A subset of 24 patients had additional phosphate measurements at 0-14 days and 15-180 days after remission. In this subgroup, serum phosphate significantly increased from 1.03 ± 0.17 mmol/L prior to remission to 1.22 ± 0.25 mmol/L 15-180 days after remission (p = 0.008). BMI decreased after remission [-1.1 kg/m2, (95%CI -2.09 to -0.07), p=0.037]. Other covariates did not show an equivalent change over time.ConclusionIn this retrospective study, we found that 16% of patients with CS had hypophosphatemia. Moreover, serum phosphate was related to the level of cortisoluria and increased after remission of CS. Potential underlying mechanisms related to urinary phosphate excretion and possibly involving FGF23, BMI and parathyroid hormone levels should be further explored.

scholarly journals Reversible alterations in cardiac morphology and functions in a patient with Cushing's syndrome

2014 ◽  
Vol 2014 ◽  
Author(s):  
Hiroaki Iwasaki
Keyword(s):  
Cushing’S Syndrome ◽  
Interventricular Septum ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Left Ventricular ◽  
Multidetector Row Computed Tomography ◽  
List Type ◽  
Adrenocortical Adenoma ◽  
Cardiac Morphology ◽  
Free Cortisol

Summary A 45-year-old female was referred for endocrine evaluation of an incidental mass (31×24 mm in diameter) on the right adrenal gland. The patient was normotensive and nondiabetic, and had no history of generalised obesity (body weight, 46 kg at 20 years of age and 51.2 kg on admission); however, her waist-to-hip ratio was 0.97. Elevated urinary free cortisol levels (112–118 μg/day) and other findings indicated adrenocorticotrophic hormone-independent Cushing's syndrome due to right adrenocortical adenoma. Echocardiography before adrenalectomy revealed concentric left ventricular (LV) hypertrophy with a particular increase in interventricular septum thickness leading to impaired systolic and diastolic functions. Upon surgical remission of hypercortisolism, the asymmetric hypertrophy disappeared and the cardiac dysfunctions were considerably ameliorated. Although the mechanism(s) by which excessive cortisol contributes to LV wall thickness remain(s) unclear, serial echocardiography and cardiac multidetector-row computed tomography may support the notion that abnormal fat deposition in the myocardium owing to hypercortisolism appears to be an important factor for the reversible change in the cardiac morphology. Learning points Patients with Cushing's syndrome occasionally exhibit severe LV hypertrophy related to systolic and diastolic dysfunctions although they have neither hypertension nor diabetes mellitus. Biological remission of hypercortisolism can normalise structural and functional cardiac parameters and help in differentiating the cardiac alterations induced by excessive cortisol from those induced by other diseases. Excessive lipid accumulation within the heart before myocardial fibrosis may be implicated in reversible alterations in the cardiac morphology by Cushing's syndrome. Early diagnosis and treatment of Cushing's syndrome appear to be pivotal in preventing irreversible cardiac dysfunctions subsequent to cardiovascular events and heart failure.

Values for Urinary Free Cortisol during Treatment with Amino-Glutethimide for Cushing’s Syndrome

1973 ◽  
Vol 19 (9) ◽  
pp. 1067-1068 ◽  
Author(s):  
Karl W Schmitt ◽  
Roger Juselius ◽  
James Hanlon ◽  
David Steed
Keyword(s):  
Cushing’S Syndrome ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Sensitive Indicator ◽  
Cortisol Secretion ◽  
Clinical Correlation ◽  
Free Cortisol ◽  
Amino Glutethimide

Abstract Of the chemical tests used, we found that values for urinary free cortisol had the best clinical correlation and were the most sensitive indicator of cortisol secretion in a patient with Cushing’s syndrome who was treated with amino-glutethimide.

scholarly journals Clinical Characteristics and Treatment Outcomes in Endogenous Cushing’s Syndrome: A 15-Year Experience from Thailand

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wasita Warachit Parksook ◽  
Nitchakarn Laichuthai ◽  
Sarat Sunthornyothin
Keyword(s):  
Treatment Outcomes ◽  
Cushing’S Syndrome ◽  
Clinical Characteristics ◽  
Remission Rate ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Normal Body Mass Index ◽  
Ectopic Acth ◽  
Free Cortisol

The most common subtype of endogenous Cushing’s syndrome (CS) is Cushing’s disease (CD), with higher proportions of adrenal CS reported from Asia, compared to other continents. However, little was known about CS in this territory. This study was to investigate the distribution, clinical characteristics, and treatment outcomes of CS in a single tertiary hospital in Thailand. We performed a retrospective evaluation of 82 patients with endogenous CS during 2001–2015. The most common subtype was CD, followed by adrenal CS and ectopic ACTH syndrome (EAS), respectively. Weight gain was the most common presentation. Normal body mass index (BMI), Asian cutoff, was observed in 33% of patients. Specific features of CS (plethora, muscle weakness, bruising, and/or wide purplish striae) were documented in less than half of patients. The median age, adrenocorticotropic hormone (ACTH), and urinary free cortisol (UFC) concentrations were significantly different among 3 subtypes of CS and were highest among patients with EAS. An initial remission rate after transsphenoidal surgeries in CD was 62%, with higher rates in pituitary microadenomas compared to macroadenomas. All patients with unilateral adrenal disease achieved CS remission after adrenal surgeries. Patients with EAS achieved CS remission mostly from bilateral adrenalectomy. The highest mortality rate was observed in the EAS group. These findings were consistent with previous studies in Asia, with more proportions ACTH-independent CS.

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