Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child.

摘要: CONTEXT Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present youngest known patient with AIP-related adenoma. CASE DESCRIPTION The presented at age of 4 years apoplexy and left ptosis severe visual loss following a 1-year history abdominal pain, headaches, rapid growth. His IGF-1 level was 5× upper limit normal, his random GH 1200 ng/mL. MRI showed 43 × 24 35‒mm suprasellar extension invading cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology 2A sparsely granulated somatotropinoma negative O6-methylguanine-DNA methyltransferase positive vascular endothelial growth factor staining. Genetic testing identified heterozygous nonsense AIP mutation (p.Arg81Ter). Exome sequencing tumor revealed that it had lost entire maternal chromosome-11, rendering hemizygous for chromosome-11 therefore lacking functional copies tumor. He started on octreotide, but because rapidly regrew levels were unchanged, temozolomide initiated, intensity-modulated radiotherapy administered 5 months after surgery. Two later, bevacizumab added, resulting excellent response. Although these treatments stabilized over years, normalized only pegvisomant treatment, although access this medication intermittent. At 3.5 follow-up, gamma knife treatment administered, dose increase indicated. CONCLUSION Multimodal long-acting radiotherapy, temozolomide, bevacizumab, can control genetically driven, aggressive, childhood-onset somatotropinomas.