Up to 10% of primary hyperparathyroidism (pHPT) is genetically determined. Genetic testing is recommended for patients under 40yrs but this is not universally accepted. This study describes the nature of pHPT in under 40s and the genetic yield in a UK tertiary centre.

A retrospective observational study of a prospectively collected database of patients under 40, that underwent first-time surgery for pHPT over 10 years was conducted. Patients with known mutations, with renal disease or on lithium were excluded. Data collected included pre-operative biochemistry, imaging, operative findings and outcomes. Where genetic testing was performed, the mutations tested were MEN1, MEN2, CASR, CDC73, CDKN1A, CDKN1B, CDKN2B and CDKN2C.

1692 parathyroidectomies were performed in the study period, of whom 232 were under 40yrs. Following exclusions, 167 patients were analysed. Mean pre-operative calcium was 2.9mmol/l(2.55-4.8); mean PTH was 19.9nmol/l(4.8-131.2). An adenoma was localised (ultrasound and Sestamibi) in 51 patients (30.5%). 96 patients (57.5%) underwent genetic testing, of which 10.4% were positive. The median age of patients with positive genetics was 33.5yrs(17-38). Overall cure rate was 96.4%(161/167); 6 patients (3% of the cohort) experienced recurrence. Of those genetically tested, the cure rate in the genetics negative group was 90%, compared to 94.2% in the positive group. 26.7% of patients with negative genetics had >1 abnormal gland excised, compared to 100% of genetics positive patients.

Patients under 40yrs have less positive localisation, more multiple gland disease and 1:10 have a genetic mutation. Genetic testing is justified to aid surgical planning. Negative tests may adversely affect outcomes.