Background: Somatotropinomas are rare in childhood and are frequently associated with genetic mutations. AIP mutations are found in 2025% cases of sporadic pediatric adenomas and are most commonly associated with GH secreting tumours that are large, aggressive and may be resistant to medical therapy.
Objective and hypotheses: To assess response to Pegvisomant, a GH receptor antagonist in two children with sporadic somatotropinomas due to AIP mutation, where resistance to somatostatin is a recognized phenomenon.
Method: We report two children, a 13-year-old boy and a 10-year-old girl who presented with rapid growth and visual compromise and were found to have evidence of GH hypersecretion. MRI confirmed presence of a pituitary macroadenoma with parasellar extension in both cases. Multiple surgical attempts were needed to debulk tumour mass. Residual tumour in cavernous sinus was not amenable to further surgery. Genetic analysis showed deletion in the AIP gene is both cases, patient 1-c.562delC (p.Arg188Glyfs*8) and patient 2- c.140_163del24 (p.Gly47_Arg54del8). They were initially treated with long acting somatostatin analogues (Sandostatin LAR 60 mg/week). Pegvisomant was subsequently started, at 10 mg per day subcutaneously, increased to 20 mg/day. Sandostatin was ceased due to patient intolerance and lack of biochemical control of GH excess. Radiotherapy was administered to both, as definitive treatment, for long term disease management.
Results: Patient 1 had normalisation of IGF1 to 64.8 nmol/l (20.0370.98) after 5 months of combined therapy with pegvisomant and cabergoline. Patient 2 was controlled after 2 months of cabergoline and pegvisomant, with normalisation of IGF1 to 34.4 nmol/l (12.1459.29). Her clinical course was complicated by cholelithiasis and abnormal liver function, induced by somatostatin and which resolved after cholecystectomy.
Conclusion: AIP mutation associated tumors are resistant to medical management with somatostatin receptor ligands. Pegvisomant can safely used in this situation to normalise IGF1 levels and help in disease control.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology