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Adrenal (Excluding Mineralocorticoids)

SAT-493 - Short-Term Steroidogenesis Inhibition with High-Dose Metyrapone Therapy to Improve Clinical Outcomes Prior to Surgical Resection of Cortisol-Producing Adrenocortical Carcinoma

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Rashelle Ripa, MD: No financial relationships to disclose


Introduction:
Adrenocortical carcinoma (ACC) is a rare malignancy that can present with excess hormone secretion. Cortisol-producing ACC can cause severe Cushing’s syndrome with metabolic and cardiovascular complications, increasing preoperative risk. Experience with adrenal steroidogenesis inhibitors for preoperative control of cortisol excess in ACC is limited due to the rarity of this condition. We report a case of severe ACTH-independent Cushing’s syndrome secondary to cortisol-producing ACC successfully managed with short-term preoperative metyrapone therapy.

Case Presentation:
A 44-year-old female with a history of type 2 diabetes mellitus, hypertension, morbid obesity, and heart failure presented with intractable back pain and was found to have multiple thoracic and lumbar compression fractures. CAT scan of abdomen with and without contrast incidentally revealed a heterogeneous, partially calcified right adrenal mass measuring 8.9 cm, which had increased from 7 cm over two months prior, and a paraspinal abscess. Clinical evaluation demonstrated florid features of Cushing’s syndrome, including uncontrolled hyperglycemia, hypertension, dorsocervical fat pad, facial rounding, abdominal striae, hirsutism, easy bruising, and amenorrhea. Biochemical evaluation confirmed ACTH-independent hypercortisolism, with markedly elevated serum cortisol of 45 µg/dL (normal range 5.3-22.5), suppressed ACTH < 5 pg/ml (normal range 6-50), elevated 24-hour urinary free cortisol level of 1,842 µg/24 (normal range 4-50), cortisol level of 32.8 µg/dLfollowing 1 mg dexamethasone demonstrated failure to suppress.

Plasma metanephrine and aldosterone levels were normal. In addition to antibiotic therapy, high-dose metyrapone 1,000 mg three times daily was initiated, titrated up to 1500 mg three times daily, resulting in rapid biochemical improvement, with serum cortisol decreasing to 8.19 µg/dL, normalization of 24-hour urine free cortisol, along with reduction in insulin and antihypertensive requirements, and stabilization of potassium levels. Patient received dexamethasone 0.5 mg orally daily (block and replace therapy) when AM cortisol decreased to < 10 µg/dL. Due to prolonged QT interval of 582 ms (normal QTc < 460) and concurrent amiodarone therapy, osilodrostat was not indicated. The patient subsequently underwent open right adrenalectomy. Pathology confirmed high-grade adrenocortical carcinoma with necrosis, periadrenal adipose tissue invasion, and vascular invasion.

Discussion:
This case highlights the critical role of short-term (less than two weeks) preoperative adrenal steroidogenesis inhibition in managing hypercortisolism associated with ACC. High-dose metyrapone rapidly controlled cortisol excess, leading to improvement in clinical and biochemical parameters and optimization prior to surgery in a medically complex patient.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*