Introduction:Up to 20% of children with neurofibromatosis type 1 (NF1) develops low-grade optic pathway gliomas(OPGs) that can result in neuroendocrinopathy.
The aim of the study was to identify prognostic factors for developing neuroendocrinopathies in patients with NF1 and OPGs before any treatment.
Methods: Records of 117 children with NF1 and OPGs followed at 4 Italian centers between 1997-2016 were retrospectively reviewed. We studied those endocrinopathies occurring before radiation therapy, chemo-therapy or surgery. OPGs were classified according to the modified Dodge classification (MDC).
Results: The NF1 median age at diagnosis was 1.8 years (range 0.1-12.8) and at diagnosis of OPGs was 4.2 years (range 0.4-13.7). Median follow-up was 9 years (range 0.2-35).
109/117(93.1%) OPGs were MDC1, 73/117(62.3%) MDC2, and 53/117(45.2%) MDC3/4. The chiasm was involved in 73(62%) tumors, hypothalamus in 37(32%).
Endocrine disorders were identified in 35(29.9%) children. Median age at diagnosis of endocrinopathies was 7.8 years (range 1.4-12.9 years). Among patients with endocrine disorders, the proportion of patients who later underwent any treatment for OPGs (both chemotherapy and/or surgery) was higher than in those without endocrine disorders (65.8%vs24.4%; P=0.0001).
Considering the entire population the cumulative proportion of patients free from endocrine disease at 10 years of follow-up was 65.9%. Endocrine free survival declined up to 8 years post OPGs diagnosis. Hypothalamic involvement was the stronger single independent predictor of endocrine disorders (HR:7.48(95%CI:3.5-15.85),P<0.0001). Another independent predictor was age at OPGs diagnosis < 5 years (HR:2.51(1.09-5.8),p:0.03). Central precocious puberty (CPP) was diagnosed in 25 (14 males) children (71.4%) (median age 8years;range:3.5-10.5), followed by GHD in 4(11.4%) children (median age 9.4 years;range 8.4-11.5), diencephalic syndrome in 4(11.4%) children (median age 4.6 years;range 1.4-5.8), growth hormone hypersecretion in 2(5.7%) children (median age 4 years; range 3.9-4.1).
Conclusions: Endocrine disorders are common in patients with NF1 and OPGs independently from any treatment. Hypothalamic involvement and young (<5 years) age at OPGs diagnosis were predictors of endocrine disorders. CPP was the most prevalent diagnosis while GHD was not common as previously described. A high index of suspicion for very rare endocrine disorders such as diencephalic syndrome and growth hormone hypersecretion is important in these patients, especially in younger ones.
Patients with OPGs and endocrine disorders,because of the frequent hypothalamic involvement, need a particularly careful follow-up as they are more at risk to need treatment,both CT and surgery.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology