THU506 A Not-So-Simple Case Of Hyperparathyroidism

Abstract

Abstract Disclosure: P.J. Bhatt: None. S. Rabiei: None. V. Kantorovich: None. Multiple endocrine neoplasia 1 (MEN-1) is a rare autosomal dominant disorder caused by an inactivating mutation of the MEN-1 tumor suppressor gene and is associated with tumors of the parathyroid (95%), endocrine pancreas (40-70%) and anterior pituitary (30-40%). Primary hyperparathyroidism is the most frequent and earliest expression of MEN1 syndrome with a typical onset at age 20-25 in inherited cases, reaching 100% penetrance after age 50. Current guidelines recommend genetic testing in all individuals with primary hyperparathyroidism diagnosed at a young age, with multiglandular disease, or with family history of primary hyperparathyroidism. A 58 year old female with a history of L. breast cancer, pulmonary embolisms, DM2, and recurrent nephrolithiasis was diagnosed with primary hyperparathyroidism at age 36 and had a parathyroidectomy with 3.5 gland removal and later a total thyroidectomy. She continued to be symptomatic and was found to have an ectopic parathyroid gland in her chest requiring parathyroid gland reimplantation 18 years later. After 3 years, she was admitted for a CHF exacerbation and a pancreatic tail lesion was incidentally discovered. There was no mention of pancreatic lesions prior to this reading. Family history was pertinent for a father with nephrolithiasis. Her daughter had recurrent nephrolithiasis, hyperparathyroidism and was found to have a MEN 1 variant of uncertain significance, prompting the patient to seek genetic counseling. 22 years after her initial diagnosis of hyperparathyroidism, she tested positive for a likely pathologic heterozygous variant mutation of the MEN1 gene called 1747C>T. At endocrinology follow-up, she was asymptomatic. Labs showed elevated Chromogranin A at 1,799 ng/ dL [<311] and gastrin 174pg/mL [</=100]. FSH, LH, prolactin, free alpha subunit, cortisol, and IGF-1 were normal. Further imaging confirmed a DOTATATE-avid 1.1cm nodular lesion in the pancreatic tail, concerning for a neuroendocrine tumor. MEN1 gene mutation is associated with MEN1 syndrome, familial isolated hyperparathyroidism and has an autosomal dominant predisposition to thyroid cancer and paraganglioma-pheochromocytoma syndrome. The 1747C>T sequence change creates a premature translational stop signal in the MEN1 gene and disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation. Upon diagnosis of multiglandular hyperparathyroidism, the patient should have been sent for genetic testing and instead, became an example of a multisystem failure to identify and provide necessary testing and treatment. Until her variant diagnosis, her pancreatic tumor was not identified as such. The main cause of mortality in MEN-1 patients is malignant spread of neuroendocrine tumors, hence early detection and prompt treatment are of the utmost importance to preserve quality of life and improve survival. Presentation: Thursday, June 15, 2023