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Resistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant
Kriti Joshi1,2, Adrian F Daly3, Albert Beckers3
1Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Background:
Somatotropinomas are rare in childhood and frequently associated with genetic mutations. AIP mutations are found in 20-25% cases and cause aggressive somatotropinomas, often resistant to somatostatin analogues.
Aims:
To assess responses to multimodal therapy including pegvisomant in 2 children with sporadic somatotropinomas due to AIP mutations.
Case Description:
We report 2 children, a boy aged 13 and a girl aged 10, with rapid growth, visual impairment, and growth hormone hypersecretion. Magnetic resonance imaging confirmed a pituitary macroadenoma with parasellar extension in both. Despite multiple surgical attempts to debulk tumour mass, residual tumour persisted. Genetic analysis showed two different AIP mutations (patient 1: c.562delC [p.Arg188Glyfs*8]; patient 2: c.140_ 163del24 [p.Gly47_Arg54del8]). They were initially treated with a long-acting somatostatin analogue (octreotide LAR 30 mg/month) and cabergoline as a dopamine agonist, with the later addition of pegvisomant titrated up to 20 mg/day and with radiotherapy for long-term control. Somatostatin analogue was ceased due to patient intolerance and lack of control. Patient 1 had normalization of insulin-like growth factor-1 (IGF-1) after 5 months of combined therapy with pegvisomant and cabergoline. For patient 2, normalization of IGF-1 was achieved after 2 months of cabergoline and pegvisomant.
Conclusion:
AIP-associated tumours can be resistant to management with somatostatin analogues. Pegvisomant can safely be used, to normalize IGF-1 levels and help control disease.
Insights
Children with AIP mutation somatotropinomas, resistant to somatostatin analogues, achieved normalized IGF-1 levels with pegvisomant and cabergoline. This multimodal therapy offers a safe and effective treatment option for aggressive pituitary tumors.
Area of Science:
- Pediatric Endocrinology
- Oncology
- Genetics
Background:
- Somatotropinomas are rare pediatric pituitary tumors often linked to genetic mutations.
- AIP gene mutations are implicated in 20-25% of cases, leading to aggressive tumors resistant to somatostatin analogues.
Observation:
- Two children (13-year-old boy, 10-year-old girl) presented with rapid growth, visual impairment, and hypersecretion of growth hormone.
- Both had pituitary macroadenomas with parasellar extension and distinct AIP mutations.
- Initial treatment with somatostatin analogues and cabergoline, followed by pegvisomant and radiotherapy, was administered after surgical debulking failed to achieve complete tumor removal.
Findings:
- AIP-associated somatotropinomas demonstrated resistance to somatostatin analogue therapy.
- Combined therapy with pegvisomant and cabergoline successfully normalized insulin-like growth factor-1 (IGF-1) levels in both patients.
- Patient 1 achieved normalization within 5 months, while Patient 2 normalized within 2 months.
Implications:
- Pegvisomant offers a safe and effective therapeutic option for managing aggressive, somatostatin analogue-resistant somatotropinomas in children.
- This multimodal approach, including pegvisomant, can help normalize IGF-1 levels and control disease progression in pediatric AIP mutation-associated pituitary tumors.
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