Endocrine Abstracts

JOINT2843

Primary therapy in Cushing’s disease consists of transsphenoidal surgery but when the tumor is aggressive, patients can undergo targeted radiotherapy. Due to its late effect, medical therapy like metyrapone is an option for managing hypercortisolism till radiotherapy is achieving maximal therapeutic effect, limited because of poor tolerability and lack of data regarding long-term efficacy. To document the significant changes on metyrapone in our patient we used: body weight, systolic blood pressure, ability of doing squats, Quality of Life, Beck Depression Inventory assessment, glycosylated hemoglobin test (HbA1c) along with biochemical parameters. The patient is a 56-year-old female with medical history of severe psychiatric symptoms (major depression, episodes of hypomania) and cognitive impairment along with proximal muscle weakness and metabolic complications: obesity, uncontrolled type 2 diabetes, resistant hypertension, all caused by pituitary adenoma diagnosed in February 2022. In April 2022 the patient was referred to neurosurgery for transsphenoidal pituitary surgery. The immunohistochemistry was positive for ACTH with high proliferative index (ki-67: 14%). Postsurgical MRI scan indicated residual tumor presence. A second and third surgery attempts couldn’t control hypercortisolism. In August 2023 she started stereotactic pituitary radiation followed by metyrapone, initially 250 mg daily then titrated up to 250 mg twice/day, well tolerated. We documented the changes before and after initiating metyrapone treatment: weight loss was 13 kg, diabetes was controlled with metformin and GLP-1 analogue (HbA1c from 10.1% to 6%), proximal muscle strength increased from 1 to 5 squats, maximum systolic blood pressure was 150 mmHg. Psychiatric symptoms ameliorated, concentration, comprehension, verbal control and spatial abilities improved. Regarding biochemical changes: plasma ACTH decreased from 132.9 pg/ml to 64.58 pg/ml, 24-hour urinary free cortisol from 172.51mg/24h to 52.2mg/24h, morning serum cortisol normalized (20.76mg/dl) as well as late-evening salivary cortisol (0.18mg/dl). She continues with 500 mg metyrapone per day with a favorable evolution. Neurosurgery in tertiary centers is the first line treatment in Cushing’s disease and should remain the mainstay of its management, followed by radiotherapy in aggressive cases. Only few medications have been proven to be beneficial as a bridge therapy while waiting for the effect of stereotactic pituitary radiation to be complete and metyrapone could be one of them.