Endocrine Abstracts

Neurofibromatosis 1 (NF1) is a rare disease determined by mutations in the RAS-MAPK pathway. It can cause precocious or delayed puberty.

Case 1: A 11 years 9 months old girl known with Neurofibromatosis – Noonan Syndrome (NF-NS) was admitted for severe growth deficit (-5.14 SDS). She had over 20 café au lait spots, hypertelorism, pterigium colli, B1 P1. At 18 months she had had surgery for pulmonary stenosis and after that a left ventricular tumor proved to be neurofibroma at biopsy. She had low IGF1, normal thyroid function and empty sella on MRI. Her bone age was 8. hGH therapy was started with satisfactory results. After 2 years, at a bone age of 13 she showed no signs of puberty. A triptorelinum test was negative. She was diagnosed with delayed puberty and estrogen was started with good results.

Case 2: A 5 years old boy was admitted for pubertal evaluation. The clinical exam showed a tall child (+2.79 SDs) with café au lait spots and subcutaneous neurofibromas. He was G4 P2 with a 25 ml testicular volume. A triptorelinum test confirmed central precocious puberty. Bone age was 10. The cerebral MRI showed multiple neurofibromas and a hamartoma in the third ventricle. He was diagnosed with NF1 and central precocious puberty. Treatment with triptorelinum was started. At 7 years he presented a seizure and a MRI showed an infiltrative tumor in the right thalamus. The biopsy showed a pilocytic astrocytoma. Radiotherapy and chemotherapy were started and continued for 18 months with monthly iv treatment. The evolution was favorable and a MRI after the completion of treatment showed no residual tumor. At the age of 9.6 years treatment with triptorelinum was stopped and puberty resumed. He was 1.65 DSD with a bone age of 13.

Conclusions: NF1 can cause all types of pubertal abnormalities and patients should be monitored closely.