Endocrine Abstracts

Background: Neurofibromatosis 1 (NF-1) is an autosomal-dominant multisystemic neurocutaneous disorder. It has long been appreciated that NF-1 is associated with endocrine conditions. The well reported endocrine conditions in NF-1 are growth hormone deficiency, central precocious puberty, pheochromocytoma and gastrointestinal neuroendocrine tumors including insulinoma. Furthermore, individuals with NF-1 are at increased risk of some malignancies including soft tissue sarcomas, peripheral nerve sheath tumors and gastrointestinal stromal tumors (GISTs). These tumors are known to cause non-islet cell tumor cell hypoglycemia (NICTH) due to excessive secretion of insulin like growth factor 2. Here, we describe 2 cases of different endocrine disorders in patients with NF 1.

Case description: Case 1: A 33-year-old lady presented with ischemic stroke. She had elevated blood pressure. But she did not have classic triad of symptoms or spells suggestive of pheochromocytoma. Further assessment revealed the presence of multiple café-au-lait patches, neurofibromas, axillary freckling and bilateral lisch nodules concluding the diagnosis of NF-1. Investigations into the possibility of pheochromocytoma confirmed it with elevated urinary metanephrines more than 5 times the normal upper reference range and large left adrenal tumor. She underwent adrenalectomy and histology further supported the diagnosis of pheochromocytoma. Case 2: A 57-year-old male with NF-1 was evaluated for recurrent major hypoglycemic events and concurrent symptoms of melena, loss of appetite, loss of weight and lethargy for 3-month duration. He was diagnosed to have metastatic GIST. Parallel assessment for frequent spontaneous hypoglycemia made the diagnosis of NICTH with suppressed levels of insulin, c-peptide and beta-hydroxy butyrate with low IGF-1 and positive glucagon challenge test. As the tumor was surgically non-curable, imatinib was started. Due to recurrent level-3 hypoglycemia with hospital admissions, he was initiated on high dose prednisolone. There was initial improvement in hypoglycemia with steroids but after 6 months he gradually deteriorated with gastrointestinal symptoms as well as hypoglycemia and succumbed to death after one year of diagnosis.

Conclusion: Though there are no specific recommendations for surveillance of patients with NF-1, physicians should have a high-index of suspicion in those with symptoms suggestive of endocrine conditions and appropriate screening tests should be performed.