Case Report: Case series: growth hormone replacement for severe growth hormone deficiency during BRAF inhibitor therapy in pediatric low-grade glioma: long-term follow-up

Pediatric low-grade gliomas (pLGGs) involving the hypothalamic-pituitary region frequently result in endocrine dysfunction, particularly growth hormone deficiency (GHD), due to tumor location and treatment-related effects. Growth hormone replacement therapy (GHRT) is generally considered after a period of disease stability, whereas its use during active oncologic therapy remains controversial, including during BRAF inhibitor (BRAFi) treatment. We describe two pediatric patients with severe GHD who received GHRT during ongoing vemurafenib, a BRAFi, for progressive chiasmatic-hypothalamic pLGG. The first patient, a girl diagnosed in infancy with desmoplastic infantile ganglioglioma, developed severe GHD after biopsy, chemotherapy, partial tumor debulking, and targeted therapy, together with multiple additional endocrine deficiencies. The second patient, a boy with pilocytic astrocytoma, was diagnosed with severe GHD after multimodal treatment, including partial and subtotal surgical resections, chemotherapy, radiotherapy, and targeted therapy. In both cases, low-dose GHRT was initiated after multidisciplinary assessment, documented radiological stability before GHRT initiation, and family counseling regarding the absence of direct safety data during active BRAFi therapy. Treatment was titrated over two months, with regular IGF-1 monitoring and close endocrine and oncologic surveillance. During approximately six years of concomitant GHRT and vemurafenib exposure, growth stabilized and lipid parameters improved, whereas catch-up growth remained limited and bone outcomes were complex, with increased bone mineral content but persistent or worsening lumbar DXA-derived impairment. No tumor progression or secondary malignancies were detected during the reported follow-up. These two cases add to the limited evidence on GHRT administration during BRAFi therapy by documenting prolonged concomitant GHRT and vemurafenib exposure in children with severe confirmed GHD and previously progressive chiasmatic-hypothalamic pLGG. However, the limited sample size and observational nature of this report preclude conclusions about safety or efficacy. Larger prospective studies are needed to define which patients may benefit and under which monitoring conditions GHRT could be considered during BRAFi therapy.