MON-383 NF1 and PHTS Co-Occurrence: A Unique Case and Management Challenges

Abstract Disclosure: A. Razzeto: None. H. Mejia: None. N.A. Borja: None. Z.C. Hannoush: None. Introduction: Neurofibromatosis type 1 (NF1) and PTEN Hamartoma Tumor Syndrome (PHTS) are autosomal dominant disorders that predispose to various neoplasms. NF1, affecting 1 in 3,000, has been linked to subclinical hypothyroidism and rarely to thyroid nodules/cancer, primary hyperparathyroidism, and pheochromocytoma/paraganglioma. PHTS, affecting 1 in 200,000 individuals, is associated with an increased incidence of benign thyroid nodules and differentiated thyroid cancer. The co-occurrence of these syndromes has not been previously reported, and this case highlights the complexities of managing a patient with both. Case Presentation: A 33-year-old Eastern European male with NF1 and a history of multiple neurofibroma resections, optic nerve gliomas, history of metastatic testicular cancer, lung teratoma, and colonic polyposis presented with an incidental thyroid mass in surveillance CT. He denied compressive neck symptoms and was clinically and biochemically euthyroid (TSH 2.35 mcIU/mL). Physical exam demonstrated macrocephaly, diffuse neurofibromas, café-au-lait macules, and a large left thyroid mass. Thyroid ultrasound revealed a bilateral goiter with multiple hypoechoic nodules (largest 4.8 cm, left lobe). Laboratory evaluation revealed normal calcium, calcitonin, metanephrine and normetanephrine levels. Further genetic testing revealed he was heterozygous the pathogenic variants NF1 c.1381C>T (p.Arg461*) and PTEN c.253+1G>T. Due to the significantly elevated lifetime risk of follicular and papillary thyroid cancer associated with PHTS ranging between 3% and 14%, the patient was counseled regarding FNA/thyroidectomy but opted for close surveillance. Most recently, he developed PTH-dependent hypercalcemia (Ca 11.3 mg/dL, corrected Ca 10.7 mg/dL; PTH 95 pg/mL) with normal GFR. Further workup for primary hyperparathyroidism is pending. Conclusion: This is the first reported case of co-occurring NF1 and PHTS. The patient's multinodular goiter, prior malignancy, and increased risk for thyroid cancer and other endocrine disorders due to his dual genetic diagnoses require individualized management. Despite declining intervention, close surveillance is crucial. Presentation: Monday, July 14, 2025