Category: Adrenal Disorders
Several studies report a high prevalence of bone disease (osteoporosis/osteopenia) in patients with primary aldosteronism (PA) discordant to the degree of bone density deterioration. Urine steroid metabolome analysis in PA revealed increased glucocorticoid output similar to mild autonomous cortisol secretion (MACS, also known as subclinical Cushing’s)(Arlt et al). Glucocorticoid ouput may play a role in development of bone disease in PA, a theory supported by failure of spironolactone to reverse increased risk of fractures in patients with PA(Wu et al). Bone turnover marker (BTM) analysis may elucidate the underlying mechanism in PA-related bone disease.
We conducted a pilot study to assess BTMs in male patients with PA,MACS and non-functional adrenal tumors(NFAT).
Patients were prospectively enrolled from adrenal clinics over 3 years. Inclusion criteria were men with adrenal adenomas and available biomaterial, diagnosed with NFAT, MACS (cortisol after 1 mg dexamethasone suppression, DST>1.8 mcg/dl) or PA. Patients were matched based on age and BMI. Exclusion criteria were malignancy, exogenous steroid use, other causes of osteoporosis or on therapy for osteoporosis. Osteocalcin, Procollagen I Intact N-Terminal (PINP), C-terminal telopeptide (CTX), and Sclerostin were measured blinded to diagnosis.
Of 69 patients enrolled (23 PA, 23 MACS, 23 NFAT), median age was 57(33-68) years and median BMI was 31.2(22.1-53.1) kg/m2, without differences between subgroups. Prevalence of hypertension (100% vs 82.7% vs 65.2% [p=0.002]), Type 2 Diabetes (30.4% vs 56.5% vs 43.5% [p=0.2]) and bone disease (4.35% vs 39.1% vs 17.39 % [p=0.01]) in PA vs MACS vs NFAT respectively. DST cortisol was (median 1.0[0.7-2.0]) vs median 3.8[2.1-15] vs median 1.0[1-1.8] mcg/dL) in PA vs MACS vs NFAT respectively.
Low osteocalcin concentrations were demonstrated in patients with MACS(median 16.6 [5.8-53.5] ng/mL), but not in patients with PA (median 21.2 [10-37.5] ng/mL) or patients with NFAT (median 18.6 [10 – 78.8] ng/mL)(P= 0.03). No significant differences were found in PINP, CTX and Sclerostin levels between the subgroups<./p>
Lower osteocalcin concentration in MACS patients indicate reduced bone formation from abnormal cortisol secretion. Patients with PA had osteocalcin concentrations similar to NFAT. No other abnormalities of bone metabolism were found in our small pilot study .
Higher prevalence of bone disease in PA possibly occurs through mechanism other than increased glucocorticoid output previously described. The study should be extended to include a group of healthy controls, and women with PA, to determine whether the findings are similar to men.
Shobana Athimulam– Clinical Fellow, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Rochester, Minnesota
Melinda Thomas– Clinical Research Coordinator, Department of Endocrinology, Mayo Clinic, Rochester MN
Sundeep Khosla– Consultant, Division of Endocrinology, Mayo Clinic, Rochester MN
Matthew Drake– Consultant, Division of Endocrinology, Mayo Clinic, Rochester MN
Irina Bancos– Consultant, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Minnesota
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.
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.
Division of Endocrinology, Mayo Clinic, Rochester MN
Dr. Sundeep Khosla is the Dr. Francis Chucker and Nathan Landow Research Professor of Medicine and Physiology and a Mayo Foundation Distinguished Investigator. He also serves as Director of the Center for Clinical and Translational Science and Dean for Clinical and Translational Science at Mayo Clinic. Dr. Khosla received his A.B. degree from Harvard College and his M.D. from Harvard Medical School. He was subsequently a resident in Internal Medicine and a fellow in Endocrinology at the Massachusetts General Hospital. In 1988 he moved to Mayo Clinic, where his research interests include mechanisms of age-related bone loss and sex steroid regulation of bone metabolism. Dr. Khosla has served as Chair of the NIH SBDD Study Section, on the Council of the National Institute on Aging, and as President of the American Society for Bone and Mineral Research (ASBMR). He is currently serving on the Council of NIAMS. Dr. Khosla has received numerous awards and honors for his work, including the Frederic C. Bartter Award for Clinical Investigation and the William F. Neuman Award for Outstanding Scientific Contributions from the ASBMR, the presentation of the Louis V. Avioli Plenary Lecture at the ASBMR annual meeting, the Outstanding Clinical Investigator Award and Plenary Lecture from the Endocrine Society, the Frontiers in Science Award from the American Association of Clinical Endocrinologists, the Jacobaeus Prize for outstanding research in Endocrinology, and election to the ASCI and AAP. Dr. Khosla currently serves as the Editor-in-Chief of Bone, has served as Associate Editor of the Journal of Bone and Mineral Research and as a member of the editorial boards for the Journal of Clinical Investigation, Journal of Bone and Mineral Research, Journal of Clinical Endocrinology and Metabolism, Bone, and Endocrine Reviews.
Division of Endocrinology, Mayo Clinic, Rochester MN
Dr. Drake is a consultant in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine at the Mayo Clinic in Rochester, Minnesota, where he is an Associate Professor of Medicine. He also holds a joint appointment as a consultant in the Division of Hematology, Department of Internal Medicine. He is board certified in Endocrinology, Diabetes, and Metabolism, with initial certification in 2007.
Dr. Drake currently serves as a member of the Endocrine Society Annual Meeting Steering Committee, the American Board of Internal Medicine Endocrinology, Diabetes and Metabolism Self-Assessment Committee, and the Bone, Reproductive, and Urologic Drugs Advisory Committee for the United States Food and Drug Administration. Dr. Drake also serves on the scientific advisory boards of the Rare Bone Disease Alliance and the Soft Bones Foundation. He has previously served on the Endocrine Society Facts and Figures Bone Working Group, and is a past member of the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee, where he now serves as a member of the ASBMR Ethics Advisory Committee.
Dr. Drake has received numerous awards, including the ASBMR Young Investigator Award and the Mayo Clinic Department of Medicine New Investigator Award. He serves or has served on the editorial boards of the Journal of Clinical Endocrinology and Metabolism, Bone, the Journal of Bone and Mineral Research, and Mayo Clinic Proceedings, and also serves as chair of the Mayo Clinic Endocrinology Bone Core Group.
Dr. Drake received his AB degree from Harvard College and his MD and PhD degrees from Washington University in St. Louis. His clinical training in Internal Medicine was performed at Duke University Medical Center in Durham, North Carolina, and he completed his Endocrinology fellowship training at the Mayo Clinic in Rochester, Minnesota.
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.