Primary hyperparathyroidism : nonclassical symptoms and benefits from parathyroidectomy

Primary hyperparathyroidism (PHPT) is characterized by an inadequate increase in calcium and parathyroid hormone levels in blood. The cause is usually a benign tumor, parathyroid adenoma, and the only curative treatment is parathyroidectomy (PTX). PHPT is sometimes associated with a spectrum of neuropsychiatric and musculoskeletal so called nonclassical symptoms. The aim of this thesis was to explore the impact of nonclassical symptoms and to validate the benefits of PTX with a focus on PHPT patients without obligate indication for surgical treatment.

Paper I. Observational study including 110 patients (median age 62 years; 82.7% [n=91] females) aiming to evaluate a method for predicting the outcome of nonclassical symptoms after PTX. Intervention: Calcimimetic treatment, four weeks, 30-60 mg daily. Outcome Measures: A panel of tests assembled to assess psychiatric status, cognitive function and muscle strength performed: at baseline, during study medication, six weeks and six months after PTX. Study medication resulted in normocalcemia and improvements of nonclassical symptoms that correlated well with the postoperative outcome (positive predictive values (PPV)74-96%). The positive effects increased over time.

Paper II. A sub-analysis of 35 patients with cognitive decline defined in Study I. Seventeen patients achieved normal cognitive scores six months postoperatively. PPV ranged from 80 to 94%. NPV varied between 22-92%. Short-term calcimimetic treatment was found feasible to predict improvements of nonclassical symptoms after PTX.

Paper III. A retrospective casecontrol study and a prospective cohort study aiming to map out psychiatric comorbidity as reflected by dispensing of symptomatic medication. Data from national registries in 8279 cases of PTX between the years 2008-2017 and a population cohort matched (1:10) were analyzed. The results revealed a more comprehensive drug dispensing within 3 years before PTX (benzodiazepines OR:1.40 and selective serotonin reuptake inhibitors (SSRI) OR:1.38) with a decreasing trend postoperatively but still remained higher than in the control cohort also after PTX. This study implies that psychiatric comorbidity should be considered in PHPT patients and continued medication for mental symptoms should be reevaluated after PTX.

Paper IV. A case-control study of dental comorbidities in patients treated with PTX 2011-2016 (n=982) compared to a population cohort (n=2944). The number of interventions were similar in the cohorts but PHPT patients with calcium levels in the upper quartile (≥1.51 mmol/L) had an increased risk for tooth loss by extraction (IRR 1.85; 95% CI 1.39-2.46). Female gender was an independent risk factor for tooth loss by extraction (IRR 1.34). Paper IV draws special attention to PHPT patients with high calcium levels and poor dental health. Further research is needed in this field.

List of scientific papers

I. Koman A, Ohlsson S, Bränstrom R, Pernow Y, Bränstrom R & Nilsson IL. Short-term medical treatment of hypercalcaemia in primary hyperparathyroidism predicts symptomatic response after parathyroidectomy. British Journal of Surgery. 2019.
https://doi.org/10.1002/bjs.11319

II. Koman A, Bränstrom R, Pernow Y, Bränstrom R & Nilsson IL. Prediction of cognitive response to surgery in elderly patients with primary hyperparathyroidism. British Journal of Surgery Open. 2021;5(2):zraa029.
https://doi.org/10.1093/bjsopen/zraa029

III. Koman A, Bränstrom R, Pernow Y, Bränstrom R, Nilsson IL & Fredrik Granath. Neuropsychiatric comorbidity in primary hyperparathyroidism before and after parathyroidectomy – a population study. [Submitted]

IV. Koman A, Näsman P, Discacciati A, Ekbom A, Nilsson IL, Sandborgh-Englund G. Increased risk for tooth extraction in primary hyperparathyroidism and hypercalcemia: A population study. Clinical Oral Investigations. 2020;24(8):2755-2761.
https://doi.org/10.1007/s00784-019-03137-y