SUN-078 When Endocrine and Genetic Disorders Collide: Acromegaly with Recurrent Pituitary Macroadenoma and Familial Papillary Thyroid Carcinoma

Abstract Disclosure: E. Nkwenya: None. Acromegaly, a rare endocrine disorder caused by a growth hormone (GH)-secreting pituitary macroadenoma, leads to excessive GH and insulin-like growth factor 1 (IGF-1) levels. This hormonal overproduction promotes abnormal cell proliferation, metabolic dysregulation, and organ enlargement, increasing the risk of cardiovascular disease and malignancies, particularly thyroid and colorectal cancers. Early diagnosis and management, including surgical and pharmacological interventions, are crucial to reducing morbidity and mortality.We present a 54-year-old male with acromegaly, recurrent pituitary macroadenomas, and a strong familial history of malignancies. Initially diagnosed at age 37, he presented with headaches, diplopia, bilateral extremity weakness, weight loss, erectile dysfunction, and fatigue. His family history included first-degree relatives with papillary thyroid cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, and colonic polyps. Physical examination revealed features of acromegaly. Laboratory testing confirmed elevated IGF-1 levels (595 ng/mL; reference: 100-300 ng/mL), and MRI showed a 4 cm suprasellar pituitary macroadenoma. Echocardiography revealed left ventricular hypertrophy, and bone density testing showed osteoporosis, though bisphosphonate treatment was declined. Colonoscopy was unremarkable.The patient underwent transsphenoidal tumor resection, which confirmed an IGF-1-secreting pituitary macroadenoma and craniopharyngeal duct remnant. Persistent IGF-1 elevation (595 to 776 ng/mL) required somatostatin analogs, subtotal tumor resection, and radiation therapy. Pegvisomant ultimately normalized IGF-1 levels (106 ng/mL), and MRIs showed stable residual tumor tissue. The patient later developed melanoma in situ, benign lung nodules, and gallbladder polyps. At age 46, thyroid nodules were detected, and total thyroidectomy confirmed Stage I papillary thyroid carcinoma, with no recurrence on surveillance imaging. Recently, he sustained an occipital skull fracture from a fall.The association between acromegaly and thyroid malignancy is linked to IGF-1’s antiapoptotic effects on thyroid follicular cells. The patient’s multiple neoplasms and significant family history of malignancies can be attributed to IGF-1 cell proliferation and possibly a genetic predisposition to tumorigenesis. Germline mutations in the AIP gene have been implicated in familial and early-onset acromegaly, warranting genetic evaluation. This case highlights the need for a multidisciplinary approach to optimize management and investigate underlying genetic contributions to tumorigenesis in acromegaly. Presentation: Sunday, July 13, 2025