Reversible Growth Hormone Excess in Two Girls with Neurofibromatosis Type 1 and Optic Pathway Glioma

Abstract

Background: A total of 12 children with neurofibromatosis type 1 (NF-1) with optic pathway glioma (OPG) and growth hormone (GH) excess are reported to date, but no data exist on the long-term outcome. We describe 2 girls with NF-1 with OPG and GH excess treated with somatostatin analogue (SSa) who maintained a normal GH axis after stopping SSa therapy. Methods: The diagnosis ofGH excess was established from auxological data, persistently high levels of insulin-like growth factor 1 (IGF-1) and a lack of GH suppression during an oral glucose tolerance test. Results: Both patients were started on SSa treatment. During treatment, growth deceleration and normal IGF-1 levels were documented. The first case stopped treatment following the development of SSa side effects. The second case interrupted SSa when, closed to her final height, a normal IGF-1 level was documented. While off treatment, both cases maintained normal IGF-1 levels and appropriate growth velocity for their age and development, with normal GH secretion on biochemical testing. Both cases received treatment for central precocious puberty. Conclusion: GH excess in NF-1 children with OPG can be reversed and only short-term SSa therapy may be required. The aetiology remains undetermined, but the course suggests a hypothalamic dysfunction.

Growth Hormone Excess in Children with Optic Pathway Tumors Is a Transient Phenomenon

“…This finding of GH excess resolution is similar to that of a recent report of GH excess in 2 girls with NF1 and OPT [7]. In that report, the 2 patients were each treated with somatostatin analogues and achieved normalization of IGF-1 levels and growth velocity.…”

“…Furthermore, the natural history of GH excess in children in the setting of OPT has not been extensively described. In a recent report of 2 children with NF1-associated OPT and GH excess treated with somatostatin analogs, the GH excess resolved [7]. Whether GH excess is a temporary condition in these children is an important clinical question.…”

Endocrine Long-Term Follow-Up of Children with Neurofibromatosis Type 1 and Optic Pathway Glioma

“…Among the other endocrinopathies reported in our study, we found 2 NF1 children with OPG who had reversible GHE [26]. GHE is a rare disease in childhood, but can be more frequent in NF1 children and may increase their oncological risk or promote the growth of an existing tumour [37, 38].…”

“…On the other hand, the pathogenesis of GHD in NF1 patients with OPG is not known, but its reversed course suggests different mechanisms, and a functional “geographical” effect of OPG on GH production could be hypothesised. Reversible GHE has been recently described by our group in 2 girls with NF1 and OPG [26]. In patients with GHE and OPG, it has been hypothesised that the presence of OPG inhibits SS tone, allowing an unregulated release of GH [27].…”

Growth Disturbances in Childhood Cancer Survivors

“…Careful consideration must be taken when determining whether to initiate therapy by balancing the risk of prolonged exposure to elevated GH levels in tumors known to have GH receptors [112, 121] with the potentially transient nature of the GH excess [111, 122]. …”