OR40-3 Human interventions to assess the physiologic relationship between the renin-angiotensin-aldosterone system and parathyroid hormone

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR40-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:45 AM
Room 135 (Moscone Center)
Jenifer M Brown*1, Jonathan S Williams2, Luminita Pojoga2, Gordon H Williams3, Rajesh Kumar Garg4, Gail Kurr Adler5 and Anand Vaidya6
1Brigham & Women's Hospital, Harvard Medical School, Boston, MA, 2Brigham & Women's Hosp, Boston, MA, 3Brigham and Women's Hosp, Boston, MA, 4Harvard Medical School, Boston, MA, 5Brigham & Women's Hosp/Harvard Medical School, Boston, MA, 6Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Context: Endocrine relationships between calcium-regulatory hormones and the renin-angiotensin-aldosterone system (RAAS) are increasingly being recognized. Observational studies suggest a positive relationship between aldosterone and parathyroid hormone (PTH) in primary hyperaldosteronism (PA). However, the normal physiologic relationship between PTH and the RAAS needs clarification.

Methods: In order to evaluate the physiologic relationship between the RAAS and PTH, we performed secondary analyses of interventional studies that modulated both RAAS activity and calcium-regulatory hormones. Healthy subjects without PA were studied in a clinical research center under strict control of medications, diet, and posture. Acute changes in PTH levels were assessed in response to RAAS stimulation with angiotensin II (AngII) infusion and RAAS inhibition with captopril, in both vitamin D-deficient and vitamin D-replete states. PTH-responses to chronic aldosterone inhibition were evaluated via 6 weeks of blinded randomization to spironolactone or placebo.

Results: In a vitamin D deficient state, AngII infusion acutely increased PTH (+10.3%), while captopril acutely decreased PTH (-9.7%) and enhanced the PTH-response to a subsequent AngII infusion (+16.0% from baseline) (P<0.01). Following vitamin D3therapy, the acute PTH-response to AngII was further increased (+26.4%) while the PTH-response to captopril decreased (-6.8%). Chronic spironolactone therapy did not influence PTH, calcium, vitamin D, or markers of metabolic bone activity. 

Conclusions: The results of our human intervention studies extend the current understanding of endocrine relationships between calcium-regulatory hormones and the RAAS. We observed a physiologic relationship between the RAAS and PTH, whereby acute RAAS stimulation raised PTH and acute RAAS inhibition lowered PTH.  The magnitude of these interactions was modulated by vitamin D status and ACE inhibition, both of which have been shown to modulate the local tissue-RAAS and responsiveness of tissues to AngII. Although elevated PTH levels have been observed to decline following treatment of PA, spironolactone therapy did not lower PTH in our healthy population without PA. Improving the understanding of normal physiologic relationships between the RAAS and calcium-regulatory hormones may advance the pathophysiologic understanding of PA and hyperparathyroidism.

Nothing to Disclose: JMB, JSW, LP, GHW, RKG, GKA, AV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: We thank our funding sources for supporting this research: K23 HL111771-01 (A.V), a Brigham and Women’s Hospital Biomedical Research Institute Grant (A.V.), K23 HL08236-05 (J.S.W.), K24 HL103845 (G.K.A.) and a Harvard Medical School Research Fellowship (J.M.B.).  This project was supported by Clinical Translational Science Award U54LM008748 and grant M01-RR02635 to Harvard University and Brigham and Women’s Hospital from the National Center for Research Resources, and the Specialized Center of Research in Molecular Genetics of Hypertension Grant P50HL055000.