Cardiovascular disease and adrenergic dysfunction in mild primary hyperparathyroidism

Abstract: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death, but the underlying mechanisms are incompletely understood. The aim of this thesis was to investigate cardiovascular parameters and adrenergic function in mild PHPT compared to healthy controls subjects before and after curative parathyroidectomy (PTX). Forty-nine patients with mild PHPT (serum calcium 2.7 ± 0.1 mmol/L) and 48 control subjects, matched for age and sex, were examined; patients before PTX and up to 1 year postoperatively; control subjects at inclusion. Examinations comprised 24-hour ambulatory blood pressure (BP) measurements, 24-hour electrocardiogram with Holter monitoring, and echocardiography and measurements of circulating catecholamines at rest and after physical stress. At baseline, the patients showed signs of structural and functional heart disturbances and reduced catecholamine response to physical stress, which had not normalized at follow-up 6 months after PTX. The patients also showed signs of impaired heart rate variability (HRV). This, however, normalized after PTX. Patients being treated for hypertension showed an increase in BP after PTX, whereas BP decreased in normotensive patients. Echocardiographic, HRV-related and adrenergic parameters correlated with preoperative serum levels of PTH, contrary to hypertension. The results demonstrate reversible impairment of HRV and a previously unknown adrenergic dysfunction in PHPT, as well as the first clinical evidence of a chronotropic PTH effect. The results also demonstrate a hitherto unknown risk of BP increase after PTX in PHPT patients on antihypertensive treatment. These factors should be considered in the ongoing controversy regarding the management of patients with mild, so-called “asymptomatic” PHPT.