Background: We describe our experience in medical therapy for invasive somatotroph pituitary macroadenomas in 8 children or adolescents presenting with acromegaly/gigantism, in terms of growth and IGF-I levels control.
Patients: Eight children, aged 5 to 17 years (median 12.4 years), presented with growth hormone (GH) hypersecretion related to somatotroph pituitary macroadenomas with cavernous sinus invasion in 6/8. Genetic testing revealed AIP mutation in only 3 out of 8.
Results: Two children with hyperprolactinemia received cabergoline in addition to other therapies. In 4/8, transphenoidal surgery was performed as first-line treatment but was incomplete in all cases. Three of them were then treated with somatostatin analogs (SA) that were ineffective on growth and unable to normalize IGF-I levels. So, 2 children underwent pituitary radiation therapy and in the 3rd the adjunction of pegvisomant therapy to SA allowed normalization of IGF-I levels. The 4th child, aged 8 years, was treated with pegvisomant alone after surgery: this quickly led to a dramatic reduction in IGF-I levels (from 558 to 115 ng/ml) and growth arrest (<2 cm/year). She then entered puberty spontaneously and, since 2 years, titration of pegvisomant allows to perfectly control her growth velocity. Four children were treated medically as first-line therapy, three with SA and one with SA and pegvisomant. SA alone were ineffective in normalizing IGF-I levels and growth velocity in all three children. Surgical tumor debulking followed by re-initiation of SA allowed normalization of GH secretion and growth arrest in one of them. The two others received pegvisomant in combination with SA that allowed normalization of IGF-I levels and growth arrest only in one. In the other, growth arrest was only achieved after surgical debulking of the tumor. The patient who received a first-line combination of SA and pegvisomant, experienced a rapid normalization of IGF-I levels and tumor size decreased.
Conclusion: In childhood acromegaly, pegvisomant alone or in combination with SA appears to be more effective in stunting growth than SA alone. In case of invasive macroadenoma in children, in the absence of visual impairment, surgical debulking can be delayed and a combination therapy with pegvisomant and SA may be a good option as first-line therapy.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology