PRIMARY HYPERPARATHYROIDISM: NON-CLASSICAL MANIFESTATIONS

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): "Classical" primary hyperparathyroidism is associated with calcifications in the cardiovascular system and increased cardiovascular mortality. The evolution of primary hyperparathyroidism into a largely asymptomatic disorder has led to a significant body of research to reveal how and to what extent some of the classical target organs of the hyperparathyroid process may still be affected, despite the lack of overt evidence for dysfunction. The skeleton, for example, has clear and specific effects of parathyroid hormone excess, despite the disappearance of the skeletal hallmark of "classical" primary hyperparathyroidism, osteitis fibrosa cystica. These features would not have been discovered without utilizing a systematic approach with state-of-the-art methodologies. This proposal takes advantage of this same paradigm to determine whether the modern phenotype of primary hyperparathyroidism still poses a risk to the cardiovascular system. Using state-of-the-art techniques chosen for their documented value in predicting cardiovascular outcomes, we will assess not only structural abnormalities (commonly seen in severe primary hyperparathyroidism), but also functional evidence of increased vascular stiffness. Furthermore, in a randomized clinical trial, we will determine whether the abnormalities demonstrated are reversible with cure of mild primary hyperparathyroidism. Finally, we will describe a cohort of more severely affected yet asymptomatic patients, in order to complete the profile of cardiovascular involvement in modern-day primary hyperparathyroidism. Investigation of cardiovascular manifestations of primary hyperparathyroidism was identified as an important direction for future research by the 2002 NIH Workshop on Primary Hyperparathyroidism. A successful test of our hypothesis that key cardiovascular manifestations are present, and regress after surgical cure, could well alter the current standard-of-care for evaluation and management of this important metabolic bone disorder.