Category: Adrenal Disorders
Dexamethasone suppression test (DST) is a standard of care test in patients with adrenal incidentaloma and suspected Cushing Syndrome (CS). False positive results are thought to be due poor absorption, rapid metabolism of dexamethasone, or estrogen use. We aimed to establish a normal range of post-DST free cortisol (FC) in healthy volunteers, determine the utility of measuring concomitant dexamethasone concentrations (DEXA) and compare the diagnostic accuracy of post-DST total cortisol (TC) versus FC.
Single center prospective study of patients and healthy controls undergoing assessment with DST between 2016 and 2018. Measurement of FC and DEXA was performed by tandem mass spectrometry and TC by the immunoassay at 8AM following an overnight administration of 1 mg dexamethasone.
DST was performed in 191 patients (median age 56 years (range 19-82), 68% women) and 108 healthy volunteers (median age of 31 years (range 18-74), 71% women).
In healthy volunteers, the median DEXA was 0.34 (0.09-1.12) mcg/dl, median FC was 23 (10-714) ng/ml and median TC was 0.76 (0.3-15.7) mcg/dl. Of 14 subjects with DEXA <0.2 mcg/dl, 3 (20%) subjects demonstrated FC and TC ≥ 97.5%. Of healthy women, 18 (23%) were taking oral contraceptive therapy (OCT) (median daily ethinyl estradiol dose of 30 (20-35) mcg). After excluding subjects with FC and TC in the top 2.5%, we found that women not on OCT (n=57) had lower TC (median 0.7 (0.4-1.9) vs 1.2 (0.3-4) mcg/dl, p <0.0001) as well as lower FC (median 22 (20-70) vs 29 (20-104) ng/ml, p=0.03) when compared to women on OCT (n=18). Healthy men (n=30) demonstrated median TC of 0.7 (0.4-2) mcg/dl and median FC of 21 (20-44) ng/ml.
Of 191 patients undergoing DST, undetectable DEXA (≤0.05 mcg/dl) was observed in 2 (1%) patients, excluded from analysis. Of remaining 189 patients diagnosed with overt CS (n=20), adenoma with mild autonomous cortisol secretion (MACS) (n=46) and absence of CS (n=123) based on TC after DST, when FC cutoff was applied, the rate of false positive results was 21/66 (32%) and false negative results was 9/123 (7%). Specifically, none of patients with overt CS were misdiagnosed, however, 21/46 patients with MACS (19 women on OCT) were misdiagnosed based on TC and had normal FC concentrations.
Measurement of FC improves diagnostic accuracy of DST, especially in women treated with exogenous estrogen. Simultaneous measurement of serum DEXA is helpful in a minority of patients undergoing DST. As 20% of healthy controls had abnormal FC and TC results when DEXA <0.2 mcg/dl, repeating DST with a higher dose of dexamethasoen may be considered when results are abnormal.
Ravinder Jeet Kaur– Research Fellow, Division of Endocrinology, Mayo Clinic, Rochester MN
Shobana Athimulam– Clinical Fellow, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Rochester, Minnesota
Molly Van Norman– Technical Specialist II-DLMP, Clinical Mass Spectrometry Lab, Mayo clinic
Melinda Thomas– Clinical Research Coordinator, Department of Endocrinology, Mayo Clinic, Rochester MN
Stefan K Grebe– Professor of Laboratory Medicine and Pathology, Mayo College of Medicine, Mayo Clinic, Rochester,MN
Ravinder J Singh– Professor of Laboratory Medicine and Pathology, Mayo College of Medicine, Mayo Clinic, Rochester,MN
Irina Bancos– Consultant, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Minnesota
Division of Endocrinology, Mayo Clinic, Rochester MN
Dr. Ravinder Jeet Kaur is a research Fellow in Endocrinology division at Mayo clinic, Rochester. Dr. Kaur received her Bachelors (M.B.B.S) degree from the Krishna Institute of Medical Sciences, Karad, India. Dr. Kaur served both in public and private sectors for more than four years before coming to United States. She worked as Research Trainee in Gastroenterology and Hepatology department at Mayo Clinic in 2017, followed by her current position in Division of Endocrinology. Her research interests include adrenal tumors, Cushing syndrome and steroid profiling. Dr. Kaur is currently working on several large research projects studying clinical presentation and outcomes of patients with adrenal tumors and Cushing syndrome and investigating diagnostic biomarkers in adrenal diseases.
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN
Dr Shobana Athimulam is an Instructor of Medicine and clinical fellow in the division of Endocrinology at Mayo Clinic, Rochester. She received her M.B.B.S from University College London Medical School in London, United Kingdom. She completed her core medical training in the London Deanery and obtained her Membership to the Royal College of Physicians, London (MRCP). She was a research fellow within the Neuroendocrine Tumor Unit in Royal Free Hospital, London, UK. She moved to USA in 2013 and completed her Internal Medicine Residency in Providence Hospital, Michigan State University, MI, prior to joining the Endocrinology Division in Mayo as a clinical fellow.
She is currently in her second (research) year of fellowship which includes both a lab-based component (under mentorship of Dr. Michael Jensen) as well as a clinical research component (under mentorship of Dr Irina Bancos) in her area of interest which involves adrenal tumors. Her current research projects focus on the impact of abnormal cortisol secretion and on bone metabolism and diagnostic biomarkers in patients with adrenal disorders. Dr Athimulam has delivered international and national presentations and published in academic peer-reviewed journals. With her work, Dr. Athimulam aims to answer clinically relevant questions which are applicable to patient care.
Technical Specialist II-DLMP
Clinical Mass Spectrometry Lab, Mayo clinic
Molly Van Norman is a Technical Specialist II in the Clinical Mass Spectrometry Lab at Mayo Clinic in Rochester where she has been employed for 32 years. She has a BA in Biology from St. Cloud State University in MN and has been working with mass spectrometers since their inception in the Endocrine Laboratory in the early 2000’s. She has several assays from development to the clinical laboratory setting, including free cortisol.
Clinical Research Coordinator
Department of Endocrinology, Mayo Clinic, Rochester MN
Melinda Thomas is a Clinical Research Coordinator in the Department of Endocrinology at Mayo Clinic, Rochester. She received a Bachelor of Science Degree in Sociology from Winona State University. Melinda has worked in research in the Department of Endocrinology between 2016 and 2018. The focus of her research has been diseases of the adrenal and pituitary glands. Prior to her time in Endocrinology, Melinda did research in Cardiology between 2015 and 2016. She was also in the Transplant Department where her focus was on liver diseases between 2012 and 2015.
Professor of Laboratory Medicine and Pathology
Mayo College of Medicine, Mayo Clinic, Rochester,MN
Stefan K. G. Grebe, MD/PhD
Fellow of the Royal Australasian College of Physicians, Diplomat of the American Board of Clinical Chemistry
Professor of Laboratory Medicine & Pathology, Mayo College of Medicine
Interests: Clinical applications of mass spectrometry, endocrine malignancies, tumor markers
Bibliography: 148 publications
Professor of Laboratory Medicine and Pathology
Mayo College of Medicine, Mayo Clinic, Rochester,MN
Ravinder J. Singh, Ph.D., is a Professor of Laboratory Medicine And Pathology and the director of the Mayo Clinic Endocrine Laboratory. He obtained his Bachelor, Masters and Ph.D from Guru Nanak Dev University, India. Following this, he pursued a post-doctoral fellowship in the Medical College of Wisconsin and joined Mayo Clinic in 2000. Dr. Singh studies the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to clinical laboratory analysis. Many of the methods that Dr. Singh developed are now considered reference methods. They have subsequently been utilized for method standardization efforts as well as to establish clinical disease correlates, which he has published with his collaborators. His professional highlights include :
•Co-primary investigator, one industry-funded and two NIH-funded grants
•Co-director, Immunochemical Core Laboratory, Mayo Clinic
•Clinical and Translational Science Award for novel methodology, National Center for Advancing Translational Sciences, National Institutes of Health
•Former chair, Midwest section, American Association for Clinical Chemistry (AACC)
•Treasurer, proteomics division, AACC
•Former director, Clinical Chemistry Postdoctoral Fellowship, Mayo Clinic
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Minnesota
Dr. Irina Bancos is an Assistant Professor of Medicine and works in the Pituitary-Adrenal-Gonadal subdivision of Endocrinology division at Mayo Clinic, Rochester. She also serves as Director of the Endocrine testing center. Dr. Bancos received her M.D. from the Iuliu Hatiegany Medical University in Cluj-Napoca, Romania. She has completed her Internal Medicine Residency at Danbury Hospital in CT and Endocrinology Fellowship at Mayo Clinic, Rochester. In addition, Dr. Bancos completed a two year research fellowship (Mayo Foundation Scholarship) at the University of Birmingham, United Kingdom where she received training in steroid profiling and adrenal disorders. In 2015 she returned to Mayo Clinic, where her clinical and research interests include adrenal and pituitary tumors, adrenal insufficiency, congenital adrenal hyperplasia, Cushing syndrome, and mechanisms of steroid regulation of bone metabolism. Between 2016 and 2018, Dr. Bancos was the principal investigator and leader of the Transform the Adrenal Practice team at Mayo Clinic and currently holds several grants in the field of steroid regulation of aging, metabolism and body composition.