Should routine analysis of the MEN1 gene be performed in all patients with primary hyperparathyroidism under 40 years of age?

Background: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to present with primary hyperparathyroidism (1 degrees HPT) at a young age, mandating bilateral exploration of the parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history. Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be managed with the same pre- and perioperative strategy as used for sporadic primary HPT of any age. Our aim was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with apparent sporadic 1 degrees HPT.

Methods: A retrospective review was undertaken of all patients who underwent surgery for 1 degrees HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were under the age of 40. Thirty-three patients provided informed consent to a detailed personal and family history, physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients underwent genetic analysis.

Results: Of the 21 patients who consented to genetic analysis, the mean age was 30.8 years (range = 18-39 years with 43% younger than 30). These patients had no suspicious family or personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia. All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients (91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient (4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient was found to have double adenomas at surgery with subsequent histological confirmation. The overall prevalence of MEN1 mutation in all patients under 40 was 13%.

Conclusion: Although young age is often the only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We propose that these patients be managed with the same preoperative and surgical approach as those presenting with sporadic 1 degrees HPT of any age.