Category: Adrenal Disorders

CLINICAL APPLICABILITY OF SERUM STEROID PRECURSORS IN THE DIAGNOSIS OF ADRENAL TUMORS AND CUSHING'S SYNDROME

Friday, Apr 26
12:45 PM – 1:00 PM

Objective : Clinical applicability of serum steroid precursors measured by current available assays has not been systematically studied. We aimed to evaluate the diagnostic value and clinical utility of serum steroid precursors in a prospective cohort of patients with adrenal tumors and Cushing syndrome (CS).


Methods :

Patients were prospectively enrolled over 3 years. Inclusion criteria were adults with any type of CS or adrenal mass and available biomaterial. Patients on exogenous steroids were excluded. 11-deoxycortisol (DCORT), 17-Hydroxypregnenolone (17OHPreg), 17-hydroxyprogesterone (17OHProg), Pregnenolone (PREG), and Androstenedione (ANDRO) were measured by LC-MS/MS. Dehydroepiandrostenedione sulfate (DHEAS) and cortisol were measured by automated chemiluminescent competitive immunoassay. For data analysis, steroids were converted into % of upper age- and sex-adjusted normal range.


Results :

A total of 370 patients (230, 62% women), median age of 59(20-95) years were diagnosed with: adrenocortical carcinoma, ACC (n=19),  adrenocortical adenoma (adrenal CS (n-21), mild autonomous cortisol secretion, MACS (n=63), non-functioning adrenal tumors, NFAT(n=128), aldosteronoma (n=34)), pheochromocytoma (n=26), other adrenal malignancies (n=17), other benign adrenal masses (n=22), pituitary CS (n=33), and ectopic CS (n=7). 
Patients with ACC demonstrated between 2.5 and 12 times higher 17OHPreg, 17OHProg, DHEAS, PREG, ANDRO and DCORT concentrations (p<0.0001 for all), when compared to patients with other adrenal tumors. A multivariable model of 17OHPreg, 17OHProg and DCORT accurately predicted ACC (ROC AUC of 0.99, p<0.0001). In patients with CS, MACS and NFAT, 17OHPreg (p=0.03) and DHEAS (p=0.0003) were lowest and DCORT (p<0.0001) was highest in patients with CS when compared with patients with MACS and NFAT. In patients with MACS vs NFAT only, 17OHPreg was a significant predictor of MACS in a multivariable model of age, sex, DHEAS, DCORT and 17OHPreg (P=0.04).Patients with ACTH-independent CS demonstrated lower 17OHPreg and DHEAS (p<0.0001 for both) but no differences in DCORT or 17OHProg when compared to patients with ACTH-dependent CS. In patients with ACTH-dependent CS, patient with ectopic CS had higher DCORT (p=0.005) and 17OHProg (p=0.04), with DCORT being significant predictor of ectopic CS even after correcting for cortisol concentrations (p=0.02).


 


Discussion : Patients with ACC, adrenal adenomas, and different subtypes of CS present with distinctive serum steroid profiles.


Conclusion :

Serum steroid precursors can serve to supplement diagnostic work up of adrenal tumors and CS, especially after validation in larger cohorts of patients.

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Shobana Athimulam

Clinical Fellow
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN
Rochester, Minnesota

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.

Ravinder Jeet Kaur

Research Fellow
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.

Jolaine Hines

Development Technologist - Immunochemical Core Laboratory
Mayo Clinic, Rochester, MN

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Stefan K Grebe

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

Ravinder J Singh

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

Irina Bancos

Consultant
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.