Symptomatic versus asymptomatic primary hyperparathyroidism: A systematic review and meta-analysis

Purpose: Primary hyperparathyroidism (PHPT) is the underlying etiology for 90% of patients with hypercalcemia. PHPT patients have traditionally been characterized as being symptomatic or asymptomatic. However, we submit that even “asymptomatic” patients may still have clinical features, posing the idea of coining asymptomatic disease as a misnomer. This paper presents a systematic review and meta-analysis elucidating the differences between asymptomatic and symptomatic PHPT in the literature. Methods: A comprehensive literature search was conducted in PubMed, Cochrane, and Web of Science databases for articles published from 2012 to 2022. Inclusion criteria consisted of all studies comparing symptomatic and asymptomatic PHPT patients. Two reviewers independently evaluated the literature using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The level of evidence was determined using the Oxford Center for Level of Evidence-Based Medicine. Data were extracted, and a meta-analysis was performed. I² index was employed for heterogeneity. Results: There were 18 studies included, with a total of 4238 patients. The average age of patients included was 56.37, with 25.7% of the cohort being male. Several studies reported clinical features even for the “asymptomatic” group. Patients in the symptomatic group tended to have higher levels of PTH and calcium. The asymptomatic group had greater levels of vitamin D. There was observed heterogeneity between the studies. Conclusions: More extreme PTH, calcium values, and low vitamin D levels were seen in patients with symptomatic disease. However, asymptomatic patients occasionally exhibited clinical features. Therefore, the terminology of “asymptomatic” disease is likely inappropriate for these patients.