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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3539-3544
Number of pages6
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

temozolomide
Octreotide
Radiotherapy
Surgery
Tumors
Insulin-Like Growth Factor I
Chromosomes, Human, Pair 11
Germ-Line Mutation
Pituitary Neoplasms
Neoplasms
Chromosomes
Pituitary Apoplexy
Exome
Therapeutics
Intensity-Modulated Radiotherapy
Combined Modality Therapy
Cavernous Sinus
Histology
Nonsense Codon
Methyltransferases

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child. / Dutta, Pinaki; Reddy, Kavita S.; Rai, Ashutosh; Madugundu, Anil K.; Solanki, Hitendra S.; Bhansali, Anil; Radotra, Bishan D.; Kumar, Narendra; Collier, David; Iacovazzo, Donato; Gupta, Prakamya; Raja, Remya; Gowda, Harsha; Pandey, Akhilesh; Devgun, Jagtar Singh; Korbonits, Márta.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 8, 01.08.2019, p. 3539-3544.

Research output: Contribution to journalArticle

Dutta, P, Reddy, KS, Rai, A, Madugundu, AK, Solanki, HS, Bhansali, A, Radotra, BD, Kumar, N, Collier, D, Iacovazzo, D, Gupta, P, Raja, R, Gowda, H, Pandey, A, Devgun, JS & Korbonits, M 2019, 'Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child', The Journal of clinical endocrinology and metabolism, vol. 104, no. 8, pp. 3539-3544. https://doi.org/10.1210/jc.2019-00432
Dutta, Pinaki ; Reddy, Kavita S. ; Rai, Ashutosh ; Madugundu, Anil K. ; Solanki, Hitendra S. ; Bhansali, Anil ; Radotra, Bishan D. ; Kumar, Narendra ; Collier, David ; Iacovazzo, Donato ; Gupta, Prakamya ; Raja, Remya ; Gowda, Harsha ; Pandey, Akhilesh ; Devgun, Jagtar Singh ; Korbonits, Márta. / Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child. In: The Journal of clinical endocrinology and metabolism. 2019 ; Vol. 104, No. 8. pp. 3539-3544.
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AU - Reddy, Kavita S.

AU - Rai, Ashutosh

AU - Madugundu, Anil K.

AU - Solanki, Hitendra S.

AU - Bhansali, Anil

AU - Radotra, Bishan D.

AU - Kumar, Narendra

AU - Collier, David

AU - Iacovazzo, Donato

AU - Gupta, Prakamya

AU - Raja, Remya

AU - Gowda, Harsha

AU - Pandey, Akhilesh

AU - Devgun, Jagtar Singh

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N2 - 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.

AB - 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.

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