Endocrine Abstracts

Background and objective: Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by a broad clinical spectrum. Previous multi-center studies, that analyzed large groups of patients with MEN 1 have been reported before but long term follow up data of these patients focusing exclusively on primary hyperparathyroidism (PHPT) are scarce.

Patients and Methods: In this retrospective cohort study we include all patients with PHPT in the context of MEN1 that were under regular follow up in our institution.

Results: Our cohort consisted of 68 patients (39 males and 29 females), with a mean age at MEN1 diagnosis of 39 ± 13.06 years. Obvious family history of MEN1 was present in 76.7% of the patients. Besides PHPT, pancreatic neuroendocrine tumors were the most commonly neoplasm encountered in 80% of patients (62% non-functioning), followed by pituitary adenomas in 66% (micro 73%, non-functioning 49%). The mean age at PHPT diagnosis was 35.2 ± 14.0 years. Fifteen patients developed osteoporosis (22%), 22 (64.7%) nephrolithiasis and one nephrocalcinosis. Parathyroidectomy was performed in 57 patients (82.3%). At the initial parathyroid surgery the majority of patients had subtotal parathyroidectomy (61.4%, n=35). Long term remission of PHPT was reported in 32 patients (56%), persistence in 7 (12.2%), and recurrent disease in 18 patients (31.5%) at a median follow-up of 4 years (1 to 21 years). Reoperation for recurrent disease was performed in 11 of the 18 patients (61%), and permanent hypoparathyroidism occurred in 11 patients (19.2%%). A total of 23 patients (33.8%) were treated with a calcimimetic agent with favorable results on serum calcium levels, including both first-line and second-line treatment in unoperated patients and persistent or recurrent disease, respectively. Gene analysis was performed in 44 patients (63%) and a variant known to cause MEN1 was identified in 34 patients (77.2%) while 5 (11.3%) had a variant of uncertain significance. No genotype – phenotype associations were reported, albeit the number of patients was small (n=34).

Conclsions: PHPT in the context of MEN1 involves a multiglandular disease and remains a therapeutic challenge over long term for treating physicians, as recurrent disease can develop even after 20 years of follow up. Collection of clinical, biochemical, and genetic characteristics of MEN1 in referral centers at a national level is critical for the optimal management of these patients.