Abstract Disclosure: M.P. Lieberman-Ulm: None. M.A. Yanez-Bello: None. V.S. Lagari-Libhaber: None. Background: Parathyroid adenomas are often detected in asymptomatic patients without palpable neck mass and are responsible for 80 to 85% of cases of primary hyperparathyroidism. Oversized or “Giant” parathyroid adenomas (GPAs) are defined as parathyroid adenomas that weigh more than 3.5 g. These are rare, representing less than 1.5% of parathyroid adenomas. The majority of reported cases of GPAs are associated with elevation of PTH and calcium levels, though usually not as high as is seen in patients with parathyroid carcinoma, where PTH levels typically reach greater than three times the upper limit of normal and serum calcium greater than 14 mg/dL. Clinical Case: A 73-year-old man presented with altered mental status and was found to have severe hypercalcemia (serum calcium 20.5 mg/dL, albumin 4.4 g/dL) and AKI stage III (eGFR 16 mL/min/1.73m2). Physical exam showed palpable, mobile, left-sided fullness, and further lab evaluation revealed intact PTH of 2,934 pg/mL, vitamin D, 25-OH of 24.8 ng/mL, and PTHrP of 14 ng/mL. Phosphorous level was not collected prior to treatment. Neck ultrasound was unremarkable. CT revealed a 9 cm hypodense lesion inseparable from the posterior aspect of the left thyroid lobe extending inferiorly to the posterior mediastinum at the level of the carina. Sestamibi scan showed scintigraphic evidence of parathyroid adenoma in the left tracheoesophageal groove. Patient was treated with IV fluids, zoledronic acid, calcitonin, cinacalcet and furosemide in addition to receiving hemodialysis on arrival. He then underwent resection of the mediastinal parathyroid gland. Pathology revealed parathyroid adenoma (16.6 g) without evidence of gross or microscopic invasion into adjacent structures, vascular or perineural invasion. Size greater than 3.5 g classified this mass as a giant parathyroid adenoma. Post-operatively, the patient’s PTH and corrected calcium normalized (17 pg/mL and 9.4 mg/dL, respectively). Conclusion: Giant parathyroid adenomas are a rare cause of primary hyperparathyroidism. Generally, parathyroid adenomas present with less severe clinical and biochemical characteristics than those of parathyroid carcinomas. However, the characteristics of GPA can be similar to parathyroid carcinoma, and differentiating between the two can be challenging. Parathyroid masses are differentiated with histologic diagnosis along with haematoxylin and eosin stain findings. In the case of our patient, his clinical picture was suggestive of parathyroid carcinoma given the severity of his disease, but pathology revealed parathyroid adenoma. Additionally, his calcium and PTH levels normalized after parathyroidectomy. This case may be representative of rare, aggressive giant parathyroid adenoma, however close follow up is imperative to ensure patient does not develop metastatic disease in the future, which would suggest underlying malignancy all along. Presentation: 6/2/2024