Abstract Background Pituitary adenomas co-secreting GH, Prolactin and ACTH are rare. Clinical Case A 38-year-old male with a past medical history of depression and type 2 diabetes mellitus was seen in the endocrinology clinic for an evaluation of acromegaly. In the preceding four years, the patient had experienced an enlargement of his hands and feet, hyperhidrosis, development of an underbite, snoring, daytime somnolence, erectile dysfunction, headaches, and blurry vision. His visual fields were normal. Physical exam: BP 137/85, BMI 39 kg/m2. He had coarse facial features, acral changes of his hands and feet, and wide spacing of his teeth. There was a notable absence of facial plethora, abdominal obesity with thin extremities, proximal muscle weakness, purple abdominal striae, and galactorrhea. Initial laboratory results: GH 16.9 ng/mL (0.05-3 ng/ml), IGF-1 1,109 ng/mL (82-242 ng/mL), Prolactin (PRL) 96.9 ng/ml (5-20 ng/ml), testosterone 34 ng/dL (200-1000 ng/dL), LH 2.3 miu/ml (1.4–12 miu/ml), FSH 4.8 miu/ml (1.5-12 miu /ml), ACTH 197.6 pg/mL (7.2- 63.3 pg/mL), 0800 cortisol 16.2 ug/dL (5-29 ug/dL), 24-hour urine free cortisol 56.84 mcg (3.5-40 mcg), HS salivary cortisol 0.242 (<0.359 ug/dL), overnight 1 mg Dexamethasone suppression test cortisol 6.9 mcg/dL (< 1.8 mcg/dL), normal Free T4 and TSH, and A1c 9.7%. A pituitary MRI revealed a 3.9 cm lobulated, intra and supra-sellar mass with mass effect on the optic chiasm and 75% encasement of the left supra-clinoid internal carotid artery. Neurosurgery performed an endoscopic, endonasal partial resection of the pituitary tumor. The histology was diagnostic of an adenoma, and immunohistochemical staining was positive for GH and PRL, but not ACTH. Post-op lab results: GH 1.07 ng/ml, IGF-1 353 ng/ml, PRL 9.6 ng/ml, testosterone 41 ng/dL, ACTH 68.2 pg/ml, cortisol 4.5 ug/dL, 24-hr urine free cortisol 8 mcg, HbA1c 5.7%. Discussion The intent of this case presentation is to report the rare finding of a pituitary tumor co-secreting GH, ACTH, and Prolactin. The diagnosis of acromegaly was confirmed by significant elevations of GH and IGF-1. The diagnosis of subclinical Cushing's disease was confirmed by elevated ACTH level, 24-hr urine free cortisol, and failed dexamethasone suppression test. The elevated PRL may have been due to tumor PRL secretion or stalk effect. The reduction of these parameters after surgery corroborated the presence of pleurihormonal secretion. This patient's findings support screening for co-secretion of multiple pituitary hormones in patients with acromegaly. Reference Pleurihormonal ACTH-GH Adenoma: Case Report and Systematic Literature Review World Neurosurg 2018 114: 158-164 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.