Diversity of endocrine disorders in pat ients with neurofibromatosis in childhood: case reports

Neurofibromatosis type 1 is a disorder characterized by an increased risk of formation of
benign and malignant tumors due to the gene mutation on chromosome 17q11.2. During embryogenesis the gene product – neurofibromin regulates the proliferation and maturation of glial and neuronal progenitors. Loss of neurofibromin leads to activation of proto-oncogene, resulting in increased risk of tumor development. The incidence is described to be as 1:2,500 - 1:3,500 live births. It is an autosomal dominant disorder that affects the bone, nervous system, soft tissues, and skin. About 50% of children with Neurofibromatosis type 1 are affected by brain gliomas involving the visual pathways and/or the hypothalamic region. Brain Magnetic resonance imaging may reveal optic pathway gliomas, astrocytomas. About 50% of children with Neurofibromatosis type 1 are affected by brain gliomas involving the visual pathways and/or the hypothalamic
region. Growth hormone deficiency is described as more common in children with Neurofibromatosis type 1, compared to the general population. Individuals with Neurofibromatosis type 1 are predisposed to brain tumors, and the vast majority of these tumors are pilocytic astrocytomas of the optic pathways and brainstem. Central precocious puberty development seems to be due to the near hypothalamic or suprasellar optic gliomas, leading to a premature activation of hypothalamic-pituitary-gonadal axis. The mechanism of growyh hormone deficiency is also connected with either tumor lesions or to insufficiency of growth hormone and IGF-1 due to loss of neurofibromin action in the pituitary cells. In the current work we describe two different endocrine disorders in children with Neurofibromatosis type 1, stressing the diversity of endocrine clinical presentation of the same main disease. The theory of central precocious puberty development in children with optic gliomas near to hypothalamic region is explained by interference with tonic central nervous system inhibition of the hypothalamic-pituitary-gonadal axis, resulting in the premature activation of the puberty. Described clinical cases present the heterogeneity and unpredictable progression of clinical features in children with Neurofibromatosis type 1. We underline the need of a careful diagnostic follow-up in all children with Neurofibromatosis type 1,
particularly with an optic gliomas to recognize early symptoms of secondary endocrine disorders and early perform an appropriate treatment.