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

Abstract

CONTEXT:

Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma.

CASE DESCRIPTION:

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

CONCLUSION:

Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.

• Authors: Pinaki Dutta, Kavita S Reddy, Ashutosh Rai, Anil K Madugundu, Hitendra S Solanki, Anil Bhansali, Bishan D Radotra, Narendra Kumar, David Collier, Donato Iacovazzo, Prakamya Gupta, Remya Raja, Harsha Gowda, Akhilesh Pandey, Jagtar Singh Devgun, Márta Korbonits
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 8 Pg. 3539-3544 (08 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 31125088 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Endocrine Society.

Chemical References

• Intracellular Signaling Peptides and Proteins
• aryl hydrocarbon receptor-interacting protein
• Human Growth Hormone
• Bevacizumab
• pegvisomant
• Octreotide
• Temozolomide

Topics

• Adenoma (genetics, therapy)
• Antineoplastic Protocols
• Bevacizumab (therapeutic use)
• Child, Preschool
• Combined Modality Therapy
• Human Growth Hormone (analogs & derivatives, therapeutic use)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Male
• Mutation
• Octreotide (therapeutic use)
• Pituitary Gland (surgery)
• Pituitary Neoplasms (genetics, therapy)
• Radiotherapy, Adjuvant
• Temozolomide (therapeutic use)