Giant Prolactinoma of Young Onset: A Clue to Diagnosis of MEN-1 Syndrome

Abstract

Multiple endocrine neoplasia (MEN) type 1 syndrome is an autosomal dominant disorder caused by germline mutations in MEN1 gene, characterized by tumours in endocrine and nonendocrine organs. Giant prolactinoma is defined as tumours larger than 40mm with very high prolactin secretion. We report two unrelated Sri Lankan patients (8-year-old boy and a 20-year-old female) who presented with giant prolactinomas with mass effects of the tumours. The female patient showed complete response to medical therapy, while the boy developed recurrent resistant prolactinoma needing surgery and radiotherapy. During follow-up, both developed pancreatic neuroendocrine tumours. Genetic analysis revealed that one was heterozygous for a nonsense mutation and other for missense mutation in MEN1 gene. Screening confirmed familial MEN-1 syndrome in their families. High clinical suspicion upon unusual clinical presentation prompted genetic evaluation in these patients and detection of MEN1 gene mutation. Pituitary adenomas in children with MEN-1 syndrome are larger tumours with higher rates of treatment resistance. This report emphasizes importance of screening young patients with giant prolactinoma for MEN-1 syndrome and arranging long-term follow-up for them expecting variable treatment outcomes. Sri Lanka requires further studies to describe the genotypic-phenotypic variability of MEN-1 syndrome in this population.

Giant Prolactinoma Causing Hydrocephalus and Intracranial Hypertension as First Manifestations of Multiple Endocrine Neoplasia Type 1

“…Despite the small number of MEN1-related macroprolactinoma cases in patients younger than 21 years (14, including the present case) (13–20), the frequency of giant prolactinomas at this age group is much higher (4/11; 36%) than the overall estimated prevalence (2–4%) of age-independent giant prolactinomas (8–10). These data may suggest that in younger MEN1 patients the frequency of giant prolactinomas is higher than in age-matched sporadic cases.…”

“…These data may suggest that in younger MEN1 patients the frequency of giant prolactinomas is higher than in age-matched sporadic cases. Overall, giant prolactinomas are frequently diagnosed at the fourth to fifth decades being very rare in children and adolescents (8, 13). Thus, most of the 140 giant prolactinoma cases compiled from a meta-analysis were diagnosed around 40 years of age.…”

Somatic and germline mutations in the pathogenesis of pituitary adenomas

“…However, moving beyond the MEN1 guidelines, due to the high penetrance of the syndrome, the first presentation with pituitary adenoma in up to a third of the patients, and a higher frequency in young patients with aggressive macroadenomas (96,144,146,159), genetic screening for MEN1 (and AIP), could be considered in patients with young onset, invasive macroadenomas.…”

Clinical management of difficult to treat macroprolactinomas

“…We are still lacking molecular explanations to decipher why and how MEN1 mutations lead to a lower sensitivity to DA; however, it is noteworthy to mention that histologically, MEN1mut Prolactinomas are more frequently invasive as compared to non-mutated Prolactinomas [64,65]. Evolution of Prolactinomas in MEN1mut patients are characterized by a younger age at onset, a more aggressive behavior as reflected by a higher propensity to invade surrounding structure and, in the scope of this review, a lower sensitivity to DA [66,67].…”