Mikkel Pretorius1, Karolina Lundstam2, Ansgar Heck1, Morten W Fagerland3, Kristin Godang4, Charlotte Mollerup5, Stine L Fougner6, Ylva Pernow7, Turid Aas8, Ola Hessman9, Thord Rosén10, Jörgen Nordenström11, Svante Jansson12, Mikael Hellström2, Jens Bollerslev1. 1. Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway (M.P., A.H., J.B.). 2. Department of Radiology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, and Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden (K.L., M.H.). 3. Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway (M.W.F.). 4. Section of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway (K.G.). 5. Clinic of Breast and Endocrine Surgery, Center HOC, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (C.M.). 6. Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway (S.L.F.). 7. Department of Molecular Medicine and Surgery, Department of Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (Y.P.). 8. Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway (T.A.). 9. Department of Surgery and Centre for Clinical Research of Uppsala University, Västmanland Hospital, Västerås, Sweden (O.H.). 10. Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden (T.R.). 11. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (J.N.). 12. Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden (S.J.).
Abstract
BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.
BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.
Authors: Christina Lenschow; Andreas Wennmann; Anne Hendricks; Christoph-Thomas Germer; Martin Fassnacht; Andreas Buck; Rudolf A Werner; Lars Plassmeier; Nicolas Schlegel Journal: Langenbecks Arch Surg Date: 2022-08-09 Impact factor: 2.895