ESPE Abstracts

Background: Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder affecting 1:3000 individuals. Endocrine comorbidities have been reported in 1%-3% of all NF1 patients. In children, central precocious puberty (CPP) is the most frequent endocrinopathy (3%). Other endocrinological problems associated with this condition are short stature, growth hormone (GH) deficiency/excess, calcium-phosphate metabolism derangement and decreased bone mineral density.

Aim: To establish the prevalence of endocrine disorders in children and young adults with NF1 and their possible relationship with the presence of optic glioma.

Methods: This monocentric retrospective study evaluated 151 NF1 patients (81 boys and 70 girls) aged between 3 and 25.4 years (median chronological age 11.9 years, range IQ 8.8-16) with genetically confirmed NF1. Clinical and hormonal/biochemical data at last evaluation were retrieved from medical records. The neuroradiological presence of glioma was also recorded. Lumbar spine bone mineral apparent density (LS-BMAD) was measured by Dual energy X-ray absorptiometry (DXA) and expressed as Standard Deviations Score (SDS) calculated for chronological and bone age.

Results: Endocrine disorders were observed in 47% of patients. The most prevalent comorbidities were short stature (14.6%) and CPP (10%). Persistent short stature was observed in 10% of patients who reached adult height (AH). GH deficiency or IGF-I levels > 2 SDS were detected both in 5.3%. Primary hypothyroidism was recorded in 12/119 cases (10%). Decreased bone mineral density (BMAD< -2 SDS) was present in 14/102 patients (13.7%) and hypovitaminosis D in 92%, 8% of whom had 25 hydroxyvitamin D (25OHD) levels <10 ng/ml, though not correlated each other. Out of 81 boys, gynecomastia was reported in 14%, 3 of whom were prepubertal. Among neuroradiologically evaluated patients, 32/133 (24%) had glioma. CPP and high IGF-I levels appeared to be significantly associated with the presence of optic glioma(P = 0.02).

Conclusion: The present study, evaluating a wide cohort of NF1 subjects both during childhood and transition, shows that endocrine comorbidities are far more common than previously reported. Short stature is highly prevalent, even after AH achievement. In pre-pubertal patients, CPP and GH/IGF-I axis derangement are the most frequent alterations. Independently from age, the decrease in BMAD is not significantly correlated with low serum 25OHD levels. Though CPP and high IGF-I levels are associated with presence of glioma, present results demonstrate that nearly half of NF1 patients presents endocrine disorders, not necessarily supported by a neuroradiological picture. Thus, a thorough endocrine evaluation and follow up are mandatories.