Background: Familial isolated hyperparathyroidism (FIHPT) is a rare syndrome linked to HRPT2 mutations, with a variable extent of parathyroid involvement. Extensive parathyroidectomy is usually indicated, but single-gland involvement is often reported. Recently, loss of parafibromin expression (caused by HRPT2 inactivating mutations) has been suggested as a distinguishing feature of FIHPT. This study aimed to evaluate the extent of parathyroid involvement and parafibromin expression in FIHPT.
Methods: Twelve patients from 3 FIHPT families underwent bilateral neck exploration, selective excision of macroscopically enlarged parathyroids, and biopsy of the remaining glands. Parafibromin expression was evaluated and compared with that in normal parathyroids and in adenomas arising in sporadic hyperparathyroidism.
Results: Pathology confirmed single-gland involvement in all cases (11 adenomas and 1 carcinoma). Limited parathyroidectomy achieved a cure in 91.6% (1 persistent case of parathyroid carcinoma). After a mean follow-up of 9.4 years, all remaining patients are disease free, although 3 underwent successful reoperation for single-gland long-term recurrence. Parafibromin expression was absent in all macroscopically affected glands from FIHPT patients, but present in normal parathyroids and in adenomas arising in sporadic hyperparathyroidism.
Conclusions: Loss of parafibromin expression is a distinguishing marker of parathyroid involvement in FIHPT. Single-gland involvement often occurs; limited parathyroidectomy is effective and achieves long disease-free periods.