Clinical presentation of primary hyperparathyroidism in Europe--nationwide cohort analysis on mortality from nonmalignant causes

Abstract

Primary hyperparathyroidism (PHPT) in developing countries is characterized by severe skeletal and renal complications and apparent mortality. This is in contrast with the Western hemisphere where research interests, rather than characteristics of PHPT, seem to differ between regions. In Europe, the "nontraditional" aspects of mild-to-moderate PHPT have attracted particular attention. These symptoms and signs include risk factors for cardiovascular disease such as hypertension, phenotype IV lipoproteinemia, insulin resistance, cardiac and vascular dysfunction, and morbidity in cardiovascular diseases. Mortality in cardiovascular diseases has been found to be increased in studies that include over 6500 European patients; this risk could not be verified in North American patients. By use of the nationwide Cancer Registry and Causes-of-Death Registry, mortality was analyzed in 10,995 Swedish patients (> 20 years of age) subjected to extirpation of single parathyroid adenoma of PHPT during 1958-1997. The Swedish population standardized for age, sex, and calendar year was used as control. The first postoperative year was excluded from the analysis. In total, the study included 102,515 observed person-years in the patients. Results verify an increased risk of dying after operation for PHPT (standard mortality ratio, 1.2; 95% CI, 1.19-1.27). The increased risk persisted far beyond 15 years postoperatively and occurred in both sexes and in all investigated age groups. Principal causes of excess mortality were cardiovascular diseases, diabetes mellitus, and urogenital diseases in all age groups. However, in patients operated on between 1985 and 1997 (n = 6386), overall mortality did not differ from that of the normal population, although there was maintained excess death in stroke, diabetes mellitus, and urogenital diseases. These findings infer that modern paradigms of surgical treatment normalize the risk of dying from PHPT. This improvement may be a late consequence of liberalized calcium screenings that were introduced about 30 years ago and indicate that operation at early disease stages may offer a survival advantage. An association between diabetes mellitus and PHPT is substantiated.