From the Department of Clinical Science and Education, Södersjukhuset and the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden CARDIOVASCULAR ASPECTS IN MILD PRIMARY HYPERPARATHYROIDISM AND THE OUTCOME AFTER PARATHYROIDECTOMY

Data on the extent and clinical significance of cardiovascular abnormalities in primary hyperparathyroidism (PHPT) are conflicting. The main objective of this thesis was to evaluate the cardiovascular function in patients with mild PHPT without other known risk factors and to analyze the effect of parathyroid adenomectomy. Our second aim was to analyze whether an elevated parathyroid hormone level induces any acute effect on endothelial function. In a prospective case-control design, 51 consecutive PHPT patients without any known cardiovascular risk factor were compared to 51 randomly enrolled healthy controls. The patients were re-examined 15±4 months after parathyroid adenomectomy, when parathyroid hormone and calcium levels had normalized. Vitamin D deficiency, defined as 25-OH-D < 50 nmol/L, was found in 77% of the patients compared to 20% of the controls; 40% of the PHPT patients were still vitamin D deficient at follow-up. Systolic blood pressure and triglyceride levels were higher in cases compared to controls and decreased after parathyroid adenomectomy. Cardiac morphology and function, evaluated by echocardiography and Doppler tissue imaging, were normal in both groups but the systolic myocardial velocities were higher in the PHPT group at baseline. Both systolic and diastolic blood pressure correlated to the PTH and calcium levels. Structural properties and function of the carotid and radial arteries, evaluated by ultrasound and pulse-wave analysis, were normal in both groups and did not change after parathyroid adenomectomy. Biomarkers of inflammation, coagulation and endothelial function were normal in both groups. The forearm blood flow response to metacholin and nitroprusside, analyzed in young healthy subjects, was not altered during parathyroid hormone infusion. In conclusion, patients with mild PHPT without known cardiovascular risk factors had normal cardiovascular structure and function but a higher systolic myocardial performance at baseline which decreased after parathyroid adenomectomy. Vitamin D deficiency was more common in cases. Parathyroid adenomectomy had an overall positive effect on blood pressure, vitamin D status and triglyceride level. However, based on our results, we have no evidence that cardiovascular complications can be prevented by parathyroid surgery in PHPT patients without known cardiovascular diseases and risk factors. We registered no vasoactive effect mediated by PTH alone. LIST OF PUBLICATIONS This thesis is based on the following original studies, which will be referred to in the text by their Roman numerals: I. Farahnak P, Lind L, Marttala K, Nilsson I-L. Parathyroid Hormone’s Acute Effect on Vasodilatory Function. Clinical Medicine Insights: Endocrinology and Diabetes 2010;3:37–42. II. Farahnak P, Ring M, Caidahl K, Farnebo L-O, Eriksson M J, Nilsson I-L. Cardiac function in mild primary hyperparathyroidism and the outcome after parathyroidectomy. European Journal of Endocrinology 2010;163: 461–467. III. Ring M, Farahnak P, Gustavsson T, Nilsson I-L, Eriksson M J, Caidahl K. Arterial structure and function in mild primary hyperparathyroidism before and after parathyroidectomy. Manuscript. IV. Farahnak P, Lärfars G, Sten-Linder M, Nilsson I-L. Mild primary hyperparathyroidism: Vitamin D deficiency and cardiovascular risk markers. Accepted.