scholarly journals OR03-05 Novel Lipidome Signature in Active Cushing Syndrome Revealed by UHPLC-MS Metabolomics

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arturo Vega-Beyhart ◽  
Marta Iruarrizaga ◽  
Guillermo Garcia-Eguren ◽  
Adriana Pane ◽  
Oriol Giró ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Glutamate Metabolism ◽  
Serum Samples ◽  
Topological Network ◽  
Free Cortisol ◽  
Canonical Pathways ◽  
Omega 6 ◽  
Lipid Metabolites

Abstract Background: Alterations in circulating amino acids, polyamines and acylcarnitines have been reported in patients with endogenous chronic hypercortisolism. However, lipid metabolites profiling and its interplay with the serum metabolome and degree of hypercortisolism in patients with active Cushing syndrome (CS) has not been previously assessed. Objective: To identify new metabolomic biomarkers associated with active CS. Methodology: Multiple UHPLC-MS platforms were used to analyze the metabolome of serum samples obtained from 25 patients with active endogenous CS and 25 controls subjects matched by propensity score (sex, BMI, T2D, DLP, HBP). Results: Metabolome of CS patients was deeply disrupted with 122 (27%) of the assessed metabolites significantly altered (p adj. <0.05) out of which 5 bile acids resulted with the highest perturbation (> 2-fold decrease). From the altered metabolites, 3 amino acids (AA), 2 acylcarnitines (ACs), 2 ceramides (CER) and 5 glycerophospholipids showed direction of effect independently associated with 24-h urinary free cortisol (MS) levels. A highly discriminant (AUC 96%) metabolome signature (n=59) characterized by lower levels of AA, ACs, polyunsaturated fatty acids (PUFA) and monoglycerophosphocolines (MGPC) together with increased levels of triacyclglycerols (TG), CER, diacylglycerophosphocholines (DGPC) and cholesteryl esters was identified and cross-validated (R2Y= 0.92, Q2Y= 0.68) using PLS-DA VIP scores >1.5. PUFA omega-6, and alanine, aspartate and glutamate metabolism resulted the most impacted canonical pathways (q-stat 19.7, 10.8 (p<0.001). Finally, topological network analysis detected 158 pairwise differential correlations (p <0.005, 10,000-fold permutation) between 141 metabolites due to CS where the acylPC (P-18:1/0:0) resulted a key metabolite in the network (betweenness =0.117 & closeness centrality =0.467). Conclusion: Active Cushing syndrome leads to a global proatherogenic shift in the circulating ceramides, glycerophospholipids and sphingolipids metabolites which are independently associated to the levels of urinary free cortisol being potential biomarkers of patients’ cardiovascular risk.

scholarly journals Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study

2016 ◽  
Vol 71 (3) ◽  
Author(s):  
T. T. Tsoriev ◽  
Z. E. Belaya ◽  
L. Y. Rozhinskaya ◽  
G. A. Melnitchenko ◽  
T. A. Grebennikova ◽  
...  
Keyword(s):  
Young Adults ◽  
Grip Strength ◽  
Cushing Syndrome ◽  
Serum Levels ◽  
Serum Samples ◽  
Cross Sectional ◽  
Hand Grip ◽  
Free Cortisol ◽  
The Difference ◽  
Control Study

Background: Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. Aims: To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. Materials and methods: Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. Results: We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1.Conclusions: Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

scholarly journals Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Maria Gabriela Suarez ◽  
Madeleine Stack ◽  
Jose Miguel Hinojosa-Amaya ◽  
Michael D Mitchell ◽  
Elena V Varlamov ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Cushing Syndrome ◽  
Thrombotic Event ◽  
Urinary Free Cortisol ◽  
Bilateral Adrenalectomy ◽  
Bleeding Complications ◽  
Single Center ◽  
Free Cortisol ◽  
Prophylactic Anticoagulation

Abstract Background The risk of Cushing syndrome (CS) patients experiencing a thrombotic event (TE) is significantly higher (odds ratio; OR 18%) than that of the general population. However, there are currently no anticoagulation guidelines. Methods A retrospective, single-center, longitudinal study of patients undergoing all types of treatment—surgical (pituitary, unilateral, and bilateral adrenalectomy) and medical treatment—was undertaken. TEs were recorded at any point up until last patient follow-up; myocardial infarction (MI), deep venous thrombosis (DVT), and pulmonary embolism (PE) or stroke. Patients’ doses and complications of anticoagulation were recorded. Results Included were 208 patients; a total of 165 (79.3%) were women, and mean age at presentation was 44 ± 14.7 years. Thirty-nine (18.2%) patients had a TE; extremity DVT (38%), cerebrovascular accident (27%), MI (21%), and PE (14%). Of 56 TEs, 27 (48%) were arterial and 29 (52%) were venous. Patients who underwent bilateral adrenalectomy (BLA) had an odds ratio of 3.74 (95% CI 1.69-8.27) of developing a TE. Of patients with TEs, 40.5% experienced the event within the first 60 days after surgery. Baseline 24-hour urinary free cortisol levels did not differ in patients with or without TE after BLA. Of 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery, with 2% having bleeding complications. Conclusions The risk of TEs in patients with CS was approximately 20%. Many patients had more than 1 event, with higher risk 30 to 60 days postoperatively. The optimal prophylactic anticoagulation duration is unknown, but most likely needs to continue up to 60 days postoperatively, particularly after BLA.

scholarly journals Pseudo-Cushing Syndrome Caused by Fenofibrate Interference with Urinary Cortisol Assayed by High-Performance Liquid Chromatography

2003 ◽  
Vol 88 (8) ◽  
pp. 3521-3524 ◽  
Author(s):  
A. Wayne Meikle ◽  
James Findling ◽  
Mark M. Kushnir ◽  
Alan L. Rockwood ◽  
Gordon J. Nelson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Urinary Cortisol ◽  
Free Cortisol ◽  
Hplc Peak ◽  
Major Transition ◽  
Single Transition ◽  
Mass Spectrometry Mass Spectrometry

Urinary free cortisol (UFC) excretion over 24 h reflects the production rate of cortisol and is used commonly in the diagnosis of Cushing syndrome. We report on two patients evaluated for Cushing syndrome who had elevated UFC when analyzed by HPLC but normal values for the analysis performed by RIA and HPLC-mass spectrometry/mass spectrometry (HPLC-MS/MS). Other laboratory testing was inconsistent with the diagnosis of Cushing syndrome and raised doubts about the diagnosis. We identified a probable cause of analytical interference as coming from fenofibrate (Tricor), medication taken by the patients. Fenofibrate peak overlapped with the HPLC peak of cortisol and produced an MS/MS transition overlapping the major transition of cortisol. A second MS/MS transition was free from interference. In summary, fenofibrate administration may cause false elevation of UFC values determined by HPLC or HPLC-MS/MS in patients evaluated for Cushing syndrome. An HPLC-MS/MS method using multiple mass transitions, rather than a single transition, allows accurate quantitation of urinary cortisol in patients taking fenofibrate.

scholarly journals A Challenging Case of an Ectopic Cushing Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Joana Menezes Nunes ◽  
Elika Pinho ◽  
Isabel Camões ◽  
João Maciel ◽  
Pedro Cabral Bastos ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Lung Resection ◽  
Signs And Symptoms ◽  
Urinary Free Cortisol ◽  
Community Acquired Pneumonia ◽  
Interesting Case ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Fdg Pet Scan

Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

scholarly journals Ectopic ACTH-Producing Pheochromocytoma as a Rare Cause for Rapid Progressing Cushing Syndrome: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A128-A128
Author(s):  
Daniela Salazar ◽  
Cláudia Fernandes Costa ◽  
Joana Oliveira ◽  
Liliana Violante ◽  
Ana Luísa Cunha ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cushing Syndrome ◽  
Somatostatin Receptors ◽  
Osteoporotic Fractures ◽  
Urinary Free Cortisol ◽  
Hand Tremor ◽  
Ectopic Acth ◽  
Late Night ◽  
Free Cortisol ◽  
The Right

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N < 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N < 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol < 0,0544 µg/dL (N < 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.

scholarly journals Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome

2018 ◽  
Vol 64 (3) ◽  
pp. 586-596 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jimmy Masjkur ◽  
Mirko Peitzsch ◽  
Guido Di Dalmazi ◽  
Martin Bidlingmaier ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Multistep Process ◽  
Steroid Profiles ◽  
Plasma Steroids ◽  
Metabolome Profiling ◽  
Adrenal Disease

Abstract BACKGROUND Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. METHODS In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. RESULTS Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). CONCLUSIONS Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome

2020 ◽  
Vol 105 (6) ◽  
pp. 2081-2094 ◽  
Author(s):  
Brandon P Galm ◽  
Nidan Qiao ◽  
Anne Klibanski ◽  
Beverly M K Biller ◽  
Nicholas A Tritos
Keyword(s):  
Likelihood Ratio ◽  
Diagnostic Tests ◽  
Cushing Syndrome ◽  
Data Extraction ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Late Night ◽  
Free Cortisol

Abstract Context The diagnosis of Cushing syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate. Objective To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models). Data Sources PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systemic Reviews (inception until August 3, 2018). Study Selection Studies performed in adults that determined the accuracy of one or more diagnostic tests: overnight 1-mg dexamethasone suppression test (DST), 2-day low-dose DST (2d DST), 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), midnight serum cortisol (MSC), and the dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests. Data Extraction Two authors independently extracted data and performed methodological assessments. Data Synthesis One hundred thirty-nine studies (14 140 participants) were included in the analysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (95% confidence interval [CI]) estimates include the following: DST 98.6% (96.9%-99.4%), 90.6% (86.4%-93.6%), 10.5 (7.2-15.3), and 0.016 (0.007-0.035); 2d DST 95.3% (91.3%-97.5%), 92.8% (85.7%-96.5%), 13.2 (6.47-27.1), and 0.051 (0.027-0.095); UFC 94.0% (91.6%-95.7%), 93.0% (89.0%-95.5%), 13.3 (8.47-21.0), and 0.065 (0.046-0.092); LNSC 95.8% (93.%-97.2%), 93.4% (90.7%-95.4%), 14.6 (10.3-20.7), and 0.045 (0.030-0.066); MSC 96.1% (93.5%-97.6%), 93.2% (88.1%-96.3%), 14.2 (7.96-25.2), and 0.042 (0.026-0.069); and dex-CRH 98.6% (90.4%-99.8%), 85.9% (67.6%-94.7%), 7.0 (2.80-17.6), and 0.016 (0.002-0.118). A single study evaluated dex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST is the most sensitive while UFC is the least sensitive. Conclusions All of the included diagnostic tests for CS are highly sensitive and specific. It appears that the DST is the most sensitive while the UFC is less sensitive. The specificity of all first-line tests appears comparable.

scholarly journals MON-055 A Rare Case of a Macroadenoma Causing Cushing Syndrome in a Pediatric Patient

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Erica Patel ◽  
Marc Weigensberg
Keyword(s):  
Pediatric Patient ◽  
Cushing Syndrome ◽  
Pubertal Development ◽  
Urinary Free Cortisol ◽  
High Dose ◽  
Pituitary Macroadenoma ◽  
Central Adiposity ◽  
Rapid Weight Gain ◽  
Presenting Symptoms ◽  
Free Cortisol

Abstract Background: Pediatric Cushing Syndrome, a rare diagnosis, is almost always caused by pituitary microadenomas less than 5 mm in children older than 6 years old. We report on a 9-year-old girl with a 2.3 cm pituitary macroadenoma, whose ACTH and urinary 24-hour free cortisol were the highest recorded at our institution. Clinical Case: A 9-year-old pre-pubertal female presented with six months of frontal headaches, rapid weight gain, and hirsutism. Two months prior she developed fatigue and proximal muscle weakness and pain. On physical exam, she had plethoric round facies with acne and hirsutism, dorsal fat pad, central adiposity, and violet colored abdominal striae. Her pubertal development was tanner stage 3 for breast and 2 for pubic hair. BMI was 95th percentile and height was 40th percentile, previously 75th and 50th percentile respectively one year prior. 24 hour urinary free cortisol was 40,650 mcg/day [normal:100 mcg/day]. A 48 hour high dose dexamethasone suppression test was done as it is the most accurate in pediatric patients over 40 kg, morning cortisol was 100 mcg/dL [normal: 5-20 mcg/dL], ACTH 868 pg/ml [normal: 9-57 pg/ml], 24 Urinary Free Cortisol was 15,878 mcg/day [normal: 100 mcg/day]. A MRI Pituitary/Sella revealed a 2.3 cm pituitary macroadenoma superiorly displacing and flattening the optic chiasm, invading into the right cavernous sinus. She was referred to Neurosurgery, who did a partial transphenoidal resection, pathology consistent with ACTH producing tumor. Post-operatively she developed central diabetes insipidus and adrenal insufficiency for which she received desmopressin and oral hydrocortisone respectively. Her laboratory values eight months since surgery show normalization of ACTH and cortisol levels. The patient’s general health has improved, headaches have resolved, strength has returned, and her hirsutism is reduced. Her BMI remains elevated at 88% but is declining and growth velocity is increasing back to her pre-disease level. Conclusion: Cushing Syndrome is exceedingly rare in pediatric aged patients and pituitary macroadenomas are atypical in this population.This is a unique case of an ACTH producing macroadenoma in a Pediatric patient, which has seldom been reported in the literature, and should be considered in patients with similar presenting symptoms.

LC-MSMS assays of urinary cortisol, a comparison between four in-house assays

2018 ◽  
Vol 56 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Julie Brossaud ◽  
Monique Leban ◽  
Jean-Benoit Corcuff ◽  
Florence Boux de Casson ◽  
Anne-Gaëlle Leloupp ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Normal Ranges ◽  
Free Cortisol ◽  
Solid Liquid

Abstract Background: Twenty-four hour urinary free cortisol (UFC) determination can be used for screening and follow-up of Cushing syndrome (CS). As immunoassay methods lack specificity for UFC measurement, the use of high-performance liquid chromatography coupled to mass spectrometer (LC-MSMS) is recommended. The aim of our study was to compare UFC results using four LC-MSMS methods performed in four independent laboratories in order to evaluate interlaboratory agreement. Methods: Frozen aliquots of 24-h urine samples (78 healthy volunteers and 20 patients with CS) were sent to four different laboratories for analysis. Following liquid-liquid or solid-liquid extraction, UFC were determined using four different LC-MSMS assay. Results: UFC intra- and interassays variation coefficients were lower than 10% for each centre. External quality control results were not significantly different. UFC normal ranges (established from healthy volunteers) were 17–126, 15–134, 12–118 and 27–157 nmol/day, respectively. Classification of UFC from healthy volunteers and patients with CS using a 95th percentile threshold was similar. However, for extreme UFC values (<50 or >270 nmol/day), negative or positive bias was noted. Conclusions: Even for highly specific methods such as LC-MSMS, variations of results can be found depending on analytical process. Validation of LC-MSMS methods including determination of the reference range is essential.

scholarly journals Nonsuppressible Oral Dexamethasone Suppression Tests but Not Cushing Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Abilash Nair ◽  
Atul Dhingra ◽  
Anjana Gopi ◽  
Viveka P. Jyotsna
Keyword(s):  
Cushing Syndrome ◽  
Pituitary Surgery ◽  
Urinary Free Cortisol ◽  
Young Female ◽  
Oral Dexamethasone ◽  
Free Cortisol ◽  
Fat Malabsorption ◽  
Suppression Test ◽  
Pituitary Lesion ◽  
Dexamethasone Suppression

In spite of the presence of definitive diagnostic criteria to diagnose Cushing syndrome diagnosis may become challenging. We report a young female with mild clinical features of Cushing syndrome, who had nonsuppressible oral dexamethasone suppression tests; also she had a suspicious pituitary lesion. She underwent pituitary surgery and a pituitary microadenoma (non-ACTH staining) was removed. Now she had come to us with similar complaints to those before. Again she had nonsuppressible oral dexamethasone suppression tests. As the diurnal variation of serum and salivary cortisol was maintained and urinary free cortisol was normal, further evaluation with IV dexamethasone suppression test was performed which clearly ruled out Cushing syndrome. The patient was not on any medicines known to alter dexamethasone metabolism. Fat malabsorption was also ruled out using appropriate tests. The reason for this discrepancy is thought to be altered (increased) metabolism of dexamethasone in this patient as it is widely variable in the general population.

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