Kriti Joshi1,2, Adrian F Daly3, Albert Beckers3, Margaret Zacharin4,5. 1. Murdoch Children's Research Institute, Parkville, Victoria, Australia. 2. The Royal Children's Hospital, Parkville, Victoria, Australia. 3. Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium. 4. Murdoch Children's Research Institute, Parkville, Victoria, Australiamargaret.zacharin@rch.org.au. 5. The Royal Children's Hospital, Parkville, Victoria, Australiamargaret.zacharin@rch.org.au.
Abstract
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.
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.
Authors: Ericka B Trarbach; Giampaolo Trivellin; Isabella P P Grande; Felipe H G Duarte; Alexander A L Jorge; Felipe Barjud Pereira do Nascimento; Heraldo M Garmes; Marcia Nery; Berenice B Mendonca; Constantine A Stratakis; Marcello D Bronstein; Raquel S Jallad Journal: Pituitary Date: 2020-11-06 Impact factor: 4.107
Authors: Selveta Sanne van Santen; Adrian F Daly; Michael Buchfelder; Roland Coras; Yining Zhao; Albert Beckers; Aart Jan van der Lely; Leo J Hofland; Rutger K Balvers; P van Koetsveld; Marry Marrigje van den Heuvel-Eibrink; Sebastian Johannes Cornelis Martinus Maria Neggers Journal: AACE Clin Case Rep Date: 2021-12-16