Increased mortality in so-called mild' primary hyperparathyroidism: a population-based study
Ning Yu, Peter Donnan, Michael Murphy & Graham Leese
Previous studies have reported increased cardiovascular disease, fractures and renal stones for patients with primary hyperparathyroidism (PHPT). These studies are mainly based on patients referred to specialist centres or unselected PHPT patients. We specifically aimed to assess the risk for patients mild PHPT, in whom treatment is usually not recommended. Using the unique patient identifier, which is used for all medical contacts in Tayside, data linkage of records from biochemistry, nuclear imaging, prescribing data, hospital admissions and deaths was undertaken. For patients with a raised serum calcium an algorithm using parathyroid hormone concentration and urine calcium excretion was used to define patients with PHPT. From 1997 to 2006 we identified 1683 patients (73% female) who had a calcium <2.9 mmol/l, had no co-morbidities that would warrant parathyroidectomy in the NIH guidelines, did not undergo parathyroidectomy, and as such were classified as having mild PHPT. It is possible that some may have had symptoms. 1409 patients had a serum calcium <2.8 mmol/l. When validated against case note review, there was 99.4% agreement in the diagnosis of PHPT. All subjects with mild PHPT had an increased risk of all-cause mortality (standardized mortality ratio 2.62, 95% CI 2.392.86) and cardiovascular mortality (SMR 2.68, 95% CI 2.343.05), with similar findings for those with a calcium of <2.8 mmol/l. Subjects with mild PHPT had increased risk of cardiovascular (standardised incidence ratio; 2.53), cerebrovascular disease (3.1), renal dysfunction (14.1), renal stones (4.9) psychiatric disease (5.6) and fractures (2.0) compared to the age- and sex-adjusted general population and after adjustment for pre-existing co-morbidities. This observational study suggests that subjects with mild PHPT had increased mortality and morbidity compared to the general population. It is possible that a more aggressive strategy to the management of PHPT may be warranted if these findings can be confirmed.