Metabolic Disturbances in Relation to Serum Calcium and Primary Hyperparathyroidism

• Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases.In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated.In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium.In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, serum calcium is associated with decreased insulin sensitivity. Parathyroidectomy has positive effects on several, but not all, of the investigated metabolic parameters.

Nyckelord

Surgery

Primary hyperparathyroidism

Parathyroidectomy

Insulin sensitivity

Lipoproteins

Glucose metabolism disorders

Bone density

Calcium

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