STUDIES ON CURRENT TOPICS IN THE MANAGEMENT OF PRIMARY HYPERPARATHYROIDISM

The aim of this thesis on primary hyperparathyroidism (PHPT) was to improve preoperative imaging, to evaluate the effect of parathyroidectomy on health-related quality of life, and to investigate parathyroid carcinoma and its incidence in Finland. PHPT is due to a parathyroid adenoma (in 80%), hyperplasia in two or more glands (15 20%) or, rarely, to parathyroid carcinoma. The only definitive treatment is an operation, which is indicated if surgical criteria are met. Preoperative imaging localizing the pathological gland(s) in the neck allows 70% of parathyroidectomies to be targeted. Otherwise, all four parathyroid glands are explored. In our retrospective study of 269 PHPT patients who have undergone primary operation, the planar 123iodine/99mTechnetium(Tc)-sestamibi scintigraphy and 99mTc-sestamibi scintigraphies were accurate in 61% and 34% of patients, respectively. The cure rate was 93%, but 61% in those with multigland disease (16% of the cohort). Before reoperation, preoperative imaging decreases the risk of surgery complications is higher. In our prospective study of 21 PHPT patients planned for reoperation, the imaging results were accurate in 59% of 123iodine/99mTc-sestamibi scintigraphies, in 19% of 99mTc-sestamibi-SPECT/CT, in 65% of 11C-methionine-PET/CT, and in 40% of selective venous sampling studies (SVS). False positives were present in nearly half (9 out of 20) of SVSs but only in one PET/CT study. In our prospective study of 124 PHPT patients, the preoperative health-related quality of life (HRQoL) studied with the 15D- instrument was lower than in a comparable sample of the general Finnish population (n=4295). It increased after surgery and was sustained in a one-year follow-up. Serum calcium and parathormone concentrations did not correlate with the preoperative level or the postoperative change of HRQoL. Parathyroid carcinoma (PC) is an extremely rare endocrine cancer. Our national research group collected and re-evaluated all 32 PC cases and their tissue specimen diagnosed in Finland between 2000 and 2011. We compared these to 28 atypical adenoma and 72 age- and gender-adjusted parathyroid adenoma cases. We noticed that the incidence of PC has markedly increased in recent decades, with one case in 1 000 000 persons per year between 2010 and 2013. Tissue Micro Array (TMA) analysis was performed on all tissue samples. Mutation analysis of the CDC73 gene related to PC, performed on 56% and 57% PC and atypical adenomas respectively, was positive in 6% in both groups. PC patients had more severe clinical presentation of the disease compared to other subgroups. The presence of lymph node metastasis at diagnosis, negative parafibromin staining, and a proliferation index of over 5% seemed to be related to a more aggressive disease. At the seven-year follow-up, 21% had a recurrence of PC, and half of the patients were operated on 2-4 times. The mortality of the PC group did not differ from other subgroups. In the atypical adenoma group, one had a recurrence and two had a persistent disease, all requiring reoperations. In conclusion, the use of a thyroid-specific tracer like 123Iodine improves the accuracy of planar 99mTc-MIBI scintigraphy. Before reoperation, if ultrasound and scintigraphy findings are discordant or negative, 11C-methionine-PET/CT is recommended. The HRQoL in PHPT patients is reduced compared to healthy controls, but it improves significantly after operation. The incidence of parathyroid carcinoma is increased and it is often related to a severe PHPT. Although PC patients need reoperations, the prognosis of our cohort seems better than previously reported.