""""""""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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066329-02
Application #
7054055
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Malozowski, Saul N
Project Start
2005-04-15
Project End
2010-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
2
Fiscal Year
2006
Total Cost
$506,961
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Walker, Marcella D; Cong, Elaine; Kepley, Anna et al. (2014) Association between serum 25-hydroxyvitamin D level and subclinical cardiovascular disease in primary hyperparathyroidism. J Clin Endocrinol Metab 99:671-80
Walker, Marcella D; Nickolas, Thomas; Kepley, Anna et al. (2014) Predictors of renal function in primary hyperparathyroidism. J Clin Endocrinol Metab 99:1885-92
Carrelli, A L; Walker, M D; Di Tullio, M R et al. (2013) Endothelial function in mild primary hyperparathyroidism. Clin Endocrinol (Oxf) 78:204-9
Walker, Marcella Donovan; Rubin, Mishaela; Silverberg, Shonni J (2013) Nontraditional manifestations of primary hyperparathyroidism. J Clin Densitom 16:40-7
Walker, M D; Rundek, T; Homma, S et al. (2012) Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism. Eur J Endocrinol 167:277-85
Iwata, Shinichi; Walker, Marcella Donovan; Di Tullio, Marco R et al. (2012) Aortic valve calcification in mild primary hyperparathyroidism. J Clin Endocrinol Metab 97:132-7
Carrelli, Angela L; Walker, Marcella D; Lowe, Hyesoo et al. (2011) Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study. Stroke 42:2240-5
Costa, Aline G; Cremers, Serge; Rubin, Mishaela R et al. (2011) Circulating sclerostin in disorders of parathyroid gland function. J Clin Endocrinol Metab 96:3804-10
Walker, M D; Fleischer, J B; Di Tullio, M R et al. (2010) Cardiac structure and diastolic function in mild primary hyperparathyroidism. J Clin Endocrinol Metab 95:2172-9
Bilezikian, John P; Silverberg, Shonni J (2010) Normocalcemic primary hyperparathyroidism. Arq Bras Endocrinol Metabol 54:106-9

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