Endocrine Aspects of Neurofibromatosis Type 1

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with a highly variable phenotype and a prevalence of about one in 3–4.000. NF1 is characterised by typical cutaneous manifestations and a wide spectrum of somatic, cognitive and social-emotional complications. Typical endocrinal pathology occurs in NF1 patients, and may either lead to the diagnosis of NF1 or the diagnosis of its complications. The aim of this article is to review endocrine complications of NF1 and their management. Short stature is commonly seen in NF1 individuals, without clear aetiology. It may have association with altered function of the hypohalamic pituitary somototropin axis (growth hormone deficit occurs 100 times more frequently than in normal population), or precocious puberty, and skeletal deformities. Tall stature may be resulting from deletion of the whole NF1 gene, or a symptom of precocious puberty of GH excess, either or without glioma in optic pathway or hypothalamus. Precocious puberty is a well-known complication of NF1. It is associated with the presence of an OPG but can also occur in the absence of an OPG. NF1 related endocrine tumours include pheochromocytomas, and pancreatic neuroendocrine tumours. NF1 individuals know a decreased bone mineral density, related to endocrinal causes, but also from formation and function of osteoblasts. Specific osseous complications of NF1 include spinal deformity, and pseudo arthrosis due to fracture of dysplastic long bones. In conclusion endocrine symptoms may be alarming signs of NF1 related pathology. After exclusion of underlying pathology, management of endocrine problems is similar to that in children without NF1. However, management requires specific consideration of the full spectrum of complications of NF1.