Large-scale second-hit AIP deletion causing a pediatric growth hormone-secreting pituitary adenoma: Case report and review of literature. (August 2020)

• Record Type: Journal Article
• Authors: Gummadavelli, Abhijeet; Dinauer, Catherine; McGuone, Declan; Vining, Eugenia M.; Erson-Omay, E. Zeynep; Omay, Sacit Bulent
• Is Part Of: Journal of clinical neuroscience. Volume 78(2020)
• Page Start: 420
• Page End: 422
• Publication Date: 2020-08
• Subjects: Gigantism -- AIP -- Pituitary adenoma; Brain -- Surgery -- Periodicals; Neurosciences -- Periodicals; Nervous system -- Surgery -- Periodicals; Brain -- surgery -- Periodicals; Neurosurgical Procedures -- Periodicals; Neurosciences -- Periodicals; Electronic journals; 616.8
• DOI: 10.1016/j.jocn.2020.04.103
• Languages: English
• ISSNs: 0967-5868

Abstract

Highlights: A young boy with excessive growth spurts was diagnosed with pituitary gigantism. Successfully cured with endoscopic endonasal surgery. Genetic sequencing demonstrated germline AIP mutation and large scale Ch 11 deletion. Coincident germline and somatic mutations were significant in his phenotype. Abstract: Gigantism (early-onset acromegaly) is a rare pediatric disorder caused by a growth hormone (GH)-secreting pituitary adenoma. Approximately 50% patients of gigantism have a germline mutation, most commonly an inactivating mutation in the aryl-hydrocarbon interacting receptor protein ( AIP ) gene on chromosome 11q13.2. We present an 11-year-old male patient with a GH-secreting pituitary macroadenoma who presented with excessive growth spurts, behavioral changes, and frontal headaches. He was successfully treated with an endoscopic endonasal gross total resection and subsequently demonstrated biochemical cure. Whole-exome sequencing showed a heterozygous germline mutation in the AIP gene suggesting pituitary adenoma predisposition. Analysis of the tumor tissue revealed a large-scale deletion on chromosome 11 overlapping with AIP leading to bi-allelic AIP loss. Coincident germline and somatic AIP mutations were likely causal in formation of a GH-secreting adenoma with an aggressive phenotype. This case exemplifies the need for early diagnosis and curative surgery in the management of AIP -mutated pituitary adenomas.