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      Hyperparathyroidism: Cancer and Mortality

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          Abstract

          Hyperparathyroidism is a commoner endocrinopathy today with a large number of asymptomatic patients in contrast to the scenario five decades ago. Surgery is indicated for patients fulfilling the NIH criteria who are mostly symptomatic while individuals with mild disease are managed conservatively. Several studies indicate increased risk of malignancy involving several sites and related mortality in primary hyperparathyroidism (PHPT) with the risk persisting for several years after surgery. PHPT is associated with structural & functional cardiac abnormalities and premature death from increased cardiovascular disease with risk normalising only several years after surgery. Mortality risk is associated with pre-operative serum calcium & parathormone and parathyroid adenoma weight. However, the issue of existence of similar risk and surgical benefit in mild PHPT is mired in controversy although some studies have shown an association and beneficial trends with surgery. With current evidence, it would be prudent to follow up PHPT patients for malignancy and cardiovascular disease and possibly adopt a more liberal attitude towards surgery.

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          Most cited references16

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          Hyperparathyroid and hypoparathyroid disorders.

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            Primary hyperparathyroidism and heart disease--a review.

            Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in 85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as constipation, fatigue and weakness are well-known complications. However, in Western Europe and North America, patients with pHPT are nowadays usually discovered during an early, asymptomatic phase of the disease. It has been reported that patients suffering from symptomatic pHPT have increased mortality, mainly due to an overrepresentation of cardiovascular death. pHPT is reported to be associated with hypertension, disturbances in the renin-angiotensin-aldosterone system, and structural and functional alterations in the vascular wall. Recently, studies have indicated an association between pHPT and heart disease, and studies in vitro have produced a number of theoretical approaches. An increased prevalence of cardiac structural abnormalities such as left ventricular hypertrophy (LVH) and valvular and myocardial calcification has been observed. Associations have been found between PTH and LVH, and between LVH and serum calcium. LV systolic function does not seem to be affected in patients with pHPT, whereas any influence on LV diastolic performance needs further evaluation. The aim of this review is to clarify the connection between pHPT and cardiac disease.
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              Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years.

              The natural history of mild hyperparathyroidism is incompletely clarified. Consistent hypercalcemia was found in 172 patients (aged 28-86 years) participating in population-based screenings in both 1969 and 1971. Mortality until 1994 was compared with 344 matched, normocalcemic controls from the study population. Altogether, 55 case-control pairs underwent biochemical analysis in 1992, whereas 86 patients had died, 8 were lost to follow-up, and 23 had undergone parathyroid operation. Mortality was higher (P = .015) in patients younger than 70 years. Cardiovascular diseases were over-represented causes of death. The hazard ratio for hypercalcemia as an independent cause of cardiovascular mortality was 1.72 (95% CI, 1.24-2.37; P < .001). The initially mild hypercalcemia in patients (2.67 +/- 0.07 mmol/L) decreased over time (P = .0001), whereas the serum calcium value remained constant in the controls. Serum calcium and serum parathyroid hormone values in patients were higher than controls at the follow-up (P < .0001, .01, respectively). All but 17 patients were normocalcemic in 1992, and only 2 (1.4%) developed a serum calcium value higher than 3 mmol/L. Mild hypercalcemia in patients followed up for more than 2 decades is accompanied by premature cardiovascular death despite trends to spontaneous resolution. The principal cause of hypercalcemia probably is primary hyperparathyroidism, but mechanisms contributing to its regression over time are speculative.
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                Author and article information

                Journal
                Indian J Endocrinol Metab
                Indian J Endocrinol Metab
                Indian Journal of Endocrinology and Metabolism
                Indian Journal of Endocrinology and Metabolism
                Medknow Publications & Media Pvt Ltd (India )
                2230-8210
                2230-9500
                December 2012
                : 16
                : Suppl 2
                : S217-S220
                Affiliations
                [1] Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research, Kolkata, India
                Author notes
                Corresponding Author: Dr. Sujoy Ghosh, 244 A, J C Bose Road, Kolkata - 700 020, India. E-mail: drsujoyghosh2000@ 123456gmail.com
                Article
                IJEM-16-217
                10.4103/2230-8210.104042
                3603029
                23565381
                cf2959cd-1ebf-4177-a5c1-b3fba68c5b7a
                Copyright: © Indian Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Endocrinology & Diabetes
                hyperparathyroidism,cancer,mortality
                Endocrinology & Diabetes
                hyperparathyroidism, cancer, mortality

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