Context: Rising evidence of the increased risk in mild PHPT suggests that serum calcium, which has been a main surgical criterion, maybe not an accurate indicator of disease severity or at least, not a reliable predictive factor of its long-term consequences. This study aims to identify the best biochemical predictor of adverse outcomes in untreated PHPT.
Outcome measures and methods: Primary outcomes considered were all-cause mortality, fatal and non-fatal cardiovascular (CVD). Secondary outcomes were nine hospital-admitted co-morbidities, including cerebrovascular disease, hypertension, renal failure, renal stones, psychiatric condition, fractures, osteoporotic fractures, cancer, and diabetes. Data was examined using survival analysis. Potential biochemical predictors tested were baseline serum calcium, PTH, creatinine and alkaline phosphatase (ALP) and other covariates considered were gender, age at diagnosis, socio-economic status, previous usage of bisphosphonates, and previous co-morbidities.
Results: From 1997 to 2006, we identified 2097 untreated PHPT patients (mean age, 68.4 years; 60.9% female) with a total follow-up of 7338 person-years, in Tayside, Scotland. The baseline calcium was 2.65 mmol/l and PTH was 10.3 pmol/l. In total, 648 (30.9%) patients had died during the follow up, 249 (38.4%) of fatal CVD. PTH was the only significant (indicated as P<0.05) risk factor in ALL primary and secondary outcomes observed adjusting for other covariates. Serum creatinine and ALP predicted mortality outcomes in the short term (≤3 years) but not long term. In addition, high baseline serum creatinine and ALP were also associated with increased risk of hypertension, renal failure, fractures and cancer. Calcium was only associated with increased risk of all cause mortality in the short term but had no significant impact on other outcomes.
Conclusion: Baseline PTH, rather than calcium, predicts long-term outcomes in untreated PHPT and will have a significant impact on the justification optimal management of the condition.