Clinical MEN-1 among a large cohort of patients with acromegaly

Abstract

Context: Clinical multiple endocrine neoplasia type 1 (MEN-1) is diagnosed by the presence of atleast 2 MEN-1-associated tumors. Many patients with acromegaly and clinical MEN-1 yield negativetesting for MEN1 mutations. While cases of acromegaly and primary hyperparathyroidism (PHP)with negative genetic testing have been reported, its prevalence among patients with acromegalyis undetermined, and the clinical presentation has not been well characterized.Objectives: The main goals of this study are: (1) To determine the prevalence of clinical MEN-1with PHP in patients with acromegaly and characterize their clinical features; and (2) to evaluatethe genetic basis for the coexistence of acromegaly and PHP.Design: Retrospective record review and genetic analysis.Setting: Clinical Research Centers.Participants: 414 patients with acromegaly.Interventions: Clinical evaluation and DNA sequencing for MEN1, CDKN1A, CDKN1B, CDKN2B,CDKN2C, and AIP genes.Main outcome measurements: Clinical and genetic analysis.Results: Among patients with acromegaly, clinical MEN-1, as defined by the presence of at leastone other MEN-1-associated tumor, was present in 6.6%. PHP occurred in 6.1%; more than halfhad parathyroid hyperplasia. DNA sequencing was unrevealing for genetic mutations, exceptfor 1 case of a CDC73 mutation. Acromegaly was diagnosed at an older age with a higherprevalence of malignancies (specifically breast and thyroid) in patients with coexisting PHP thanthose with isolated acromegaly.Conclusions: A distinct phenotype is described in patients with clinical MEN-1 and negativegenetic testing for mutations previously associated with this syndrome. Further studies areneeded to identify other genes that may explain the association between PHP and acromegaly.