SAT-324 An Unusual Association between Pheochromocytoma and Hyperparathyroidism in a Patient with Neurofibromatosis Type 1: A Possible Co-Occurrence of Two Hereditary Endocrine Tumor Syndromes

Background: Patients with neurofibromatosis type 1 (NF1) have increased risk of developing various types of endocrine tumors including pheochromocytoma; however, an association with hyperparathyroidism is a rare entity. We present an unusual combination of pheochromocytoma and hyperparathyroidism in a NF-1 patient; a double mutation or digenic inheritance in hereditary endocrine syndromes is proposed. Clinical case: A 66-year-old woman with clinical features of NF1 presented with alteration of consciousness. Physical examination was unremarkable except a large lower abdominal mass and normotension. Severe hypercalcemia (15.02 mg/dL) with markedly elevated parathyroid hormone (PTH 1,550.6 pg/mL; 15-68.3) levels was revealed. A neck ultrasonography showed a 1.6-cm well-defined heterogeneous hypoechoic lesion at postero-inferior aspect of right thyroid lobe corresponding to the result from Tc99m MIBI parathyroid scintigraphy suggestive of parathyroid adenoma. CT whole abdomen revealed a huge uterine myoma and an accidental finding of a 2.5-cm well-defined enhancing nodule at right adrenal gland. Pheochromocytoma was diagnosed by an elevated of 24-h urine metanephrine (771.1 ug; < 276.1) with a normal level of 24 h-urine normetanephrine (273.7 ug; < 668.7). Genetic study showed a heterogeneous mutation at Gly681Ser in exon 11 of RET gene. The co-existence of NF1 and multiple endocrine neoplasia type 2A (MEN2A) was proposed. Laparoscopic right adrenalectomy was performed and its pathological findings confirmed the diagnosis of pheochromocytoma. Subsequently, total parathyroidectomy with thyroidectomy was done with its pathological study showing a parathyroid adenoma, multinodular goiter without the evidence of medullary thyroid carcinoma. The patient refused to perform the treatment for her myoma uteri. During the follow-up period, she has remained asymptomatic with calcium/vitamin D and thyroid hormone replacement without an evidence of pheochromocytoma or hyperparathyroidism recurrence. Conclusion: Our patient has the distinctive features of pheochromocytoma and primary hyperparathyroidism in the patient carrying the double mutations in NF1 and RET gene. This gene-gene interaction may explain the phenotype variability among the affected patients with the hereditary endocrine tumor syndromes.