Non-classical cardiometabolic determinants of parathyroid hormone

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 DESCRIPTION (provided by applicant): The project proposed aims to investigate non-classical, cardiometabolic determinants of parathyroid hormone, with two specific aims: 1) to test the effect of acute and sustained use of ACE inhibition on parathyroid hormones (PTH) levels in healthy subjects and subjects with primary hyperparathyroidism, and 2) to investigate whether the association of PTH with adiposity is depot specific (i.e. driven by visceral adiposity) The context of these two aims arises from growing evidence supporting an interaction between PTH, a critical calcium-regulatory hormone, and the renin-angiotensin-aldosterone system (RAAS), which is a key regulator of blood pressure and volume status. In Aim 1, I will utilize knowledge of this interaction to test whether suppression of the RAAS by ACE inhibition causes a decrease in PTH in normal and primary hyperparathyroidism subjects. For this purpose, 20 normal subjects and 20 subjects with primary hyperparathyroidism will be recruited to perform an interventional study, testing calcium-regulatory markers, including PTH and calcium, and RAAS hormones levels before and after 1 hour and 1 week of treatment with commonly used ACE inhibitors, captopril and lisinopril, respectively. For Aim 2, a cross-sectional analysis will e performed using data from the Multi-Ethnic Study of Atherosclerosis (MESA), an ethnically diverse NIH- prospective cohort study of middle-aged men and women. Using demographic data, biochemical markers, and abdominal CT data, the association of PTH level with various abdominal adipose depots will be analyzed, adjusting for numerous confounders of PTH, to test for an independent association. In order to successfully achieve these goals, my research training plan includes training by my mentoring team (Dr. Gail Adler, Dr. Anand Vaidya, and Dr. Ian De Boer), and formal training in clinical investigation through the Harvard Catalyst Program for Clinical and Translational Science. In addition, my research environment at Brigham and Women's Hospital and the Harvard Catalyst is well-suited to allow successful completion of these aims.