Primary Hyperparathyroidism in MEN1 Patients: a Cohort Study with Longterm Follow-up on Preferred Surgical Procedure and the Relation with Genotype

Objective: To identify the optimal surgical strategy for multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (pHPT). To describe the course of postoperative hypoparathyroidism and to assess whether genotype is associated with persistent/recurrent pHPT.

Background: Surgery is the preferred treatment in MEN1-related pHPT, but the surgical procedure of choice is still uncertain.

Methods: This retrospective cohort study was performed at the Departments of Endocrinology of the University Medical Centers of Utrecht and Nijmegen, the Netherlands. Patients were selected from the Dutch MEN1 database, including all patients 16 years or older treated for MEN1 from 1990 to 2009. Data were collected by medical record review.

Results: Seventy-three patients underwent parathyroid surgery. Persistent/recurrent pHPT occurred in 53% after less than 3 parathyroids resected (<SPTX), 17% after subtotal resection (SPTX), and 19% after total resection with autotransplantation (TPTX). Persistent (≥6 months) postoperative hypoparathyroidism occurred in 24% after <SPTX, 39% after SPTX, and 66% after TPTX. Median duration of hypoparathyroidism was 1.5 years, in 65% successful cessation of vitamin D/calcium was possible, even after more than 10 years. After <SPTX, patients with nonsense or frameshift mutations in exons 2, 9, and 10 had a significantly lower risk of persistent/recurrent pHPT than patients with other mutations. After SPTX/TPTX persistence/recurrence did not differ with genotype. After SPTX/TPTX persistence/recurrence was more frequent (P = 0.07) in patients without bilateral transcervical thymectomy (TCT).

Conclusions: SPTX with bilateral TCT is the procedure of choice for MEN1-related pHPT. Genotype seems to affect the chance of recurrence. Postoperative hypoparathyroidism lasting 6 months or more should not be considered permanent in MEN1.