Paediatric and Young Adult Manifestations and Outcomes of Multiple Endocrine Neoplasia Type 1

Madhuni Herath; Venkat Parameswaran; Michael Thompson; Michelle Williams; John Burgess


Clin Endocrinol. 2019;91(5):633-638. 

In This Article

Abstract and Introduction


Context: Multiple endocrine neoplasia 1 (MEN 1) is an autosomal dominant disease presenting as hyperplasia and neoplasia of parathyroid, pituitary and enteropancreatic tissues. Over 90% of gene carriers develop phenotypic disease by age 30 years, potentially with onset of asymptomatic disease during childhood and adolescence.

Objective: To describe the paediatric and young adult manifestations of MEN 1.

Design: Descriptive retrospective study of 180 patients with a common MEN1 genotype. The paediatric and young adult (age <22 years) manifestations were determined using hospital records and disease surveillance data.

Results: Primary hyperparathyroidism (PHPT) was identified in 42 patients (mean age 17.2 ± 3.3 years). Parathyroidectomy was performed in 16 (38.1%; mean age 17.8 ± 3.2). Four patients experienced recurrent PHPT (25%), and six (37.5%) developed permanent hypoparathyroidism. Pituitary disease was identified in 13 patients. Prolactinoma was found in nine patients (mean age 16.6 ± 2.6 years) of whom four (44.4%) had macroprolactinoma. Two patients required surgical intervention; dopamine agonists showed efficacy in six patients. Two patients with Cushing's disease were successfully treated surgically. Three patients with nonfunctioning pituitary microadenoma managed conservatively. Pancreatic neuroendocrine neoplasms (pNENs) were diagnosed in 12 patients (mean age 17.0 ± 2.6 years): three patients with insulinoma successfully resected (two resected and one exhibiting perineural invasion) and nine patients with nonfunctioning adenomas (NFAs).

Conclusion: Pituitary adenomas, PHPT and pNENs are encountered in the paediatric and young adult MEN 1 population. Successful outcomes are typically achieved using standard medical and surgical paradigms; however, parathyroidectomy was associated with a substantial complication rate.


Multiple endocrine neoplasia type 1 (MEN 1) confers an autosomal dominant predisposition to benign and malignant neoplasia of parathyroid, enteropancreatic, pituitary and adrenal tissues.[1,2] MEN 1 results from germline-inactivating mutations of MEN1, a highly penetrant tumour suppressor gene located on chromosome 11.[3] In addition to the typical endocrine phenotype, a range of nonendocrine manifestations including smooth muscle tumours, cutaneous and subcutaneous neoplasms are also reported.[4] To date, over 400 pathogenic MEN1 mutations have been identified with no overt genotype-phenotype correlation.[5–8]

Greater than 90% of MEN 1 gene carriers exhibit phenotypic disease by age 30 years.[2,8,9] Clinically evident disease appears uncommon prior to adolescence, with consensus guidelines currently recommending genetic testing and phenotype screening of confirmed MEN1 mutation carriers commencing by 10 years of age.[2,9] Recommendations have suggested testing of children as young as age 5; however, the evidence supporting surveillance screening in early childhood is limited.[10,11] Paediatric and adolescent case series for patients carrying an MEN1 mutation suggest the likelihood of developing phenotypic disease before 10 years of age is <15%, with asymptomatic primary hyperparathyroidism accounting for the majority of events and pituitary and enteropancreatic tumours occurring infrequently.[12] Malignancy and Zollinger-Ellison syndrome appear rare in the first two decades of life, suggesting that the majority of screening effort for paediatric MEN 1 patient should focus on identifying patients with primary hyperparathyroidism, prolactinoma and less commonly, clinically relevant pancreatic neuroendocrine tumours such as insulinoma.[7,13]

The guidance for therapeutic intervention in paediatric patients with mild and asymptomatic primary hyperparathyroidism (PHPT) and nonfunctioning pancreatic neuroendocrine tumours is also based on a limited number of case series and case reports.[2,11,14,15] Consequently, there is uncertainty over the merits of early parathyroidectomy versus deferral of surgical intervention until completion of skeletal maturation.[14,15] For the smaller proportion of patients with prolactinoma, Cushing's disease and insulinoma, a strong case for intervention exists as the majority of such cases are either symptomatic or at risk of complications if left untreated.

In this study, we describe the paediatric and young adult manifestations and treatment outcomes in a large MEN 1 cohort.