MON-477 - ACTH Independent Cushing Syndrome Complicated by Cardiogenic Shock and Heart Transplantation: Challenges in Management.

Endogenous Cushing syndrome is associated with significant cardiovascular morbidity and mortality. Management is very complex in critically ill patients requiring major surgeries or organ transplantation, where control of hypercortisolism must be balanced with the need for supraphysiologic glucocorticoid therapy. We report a case of ACTH-independent Cushing syndrome complicated by end stage heart failure and cardiogenic shock requiring heart transplantation.
A 28-year-old woman with a history of mild cognitive dysfunction, obesity, and bilateral adrenal nodules was admitted with acute-onset heart failure (ejection fraction 20%) and cardiogenic shock. During evaluation for congestive heart failure, she was found to have hypercortisolemia. She required intensive care unit (ICU) care throughout her hospitalization.
Clinically, she exhibited classic Cushingoid features, including centripetal obesity, facial plethora, dorsocervical fat pad, wide violaceous abdominal striae, hirsutism, scalp hair thinning, and irregular menses. Biochemical testing showed elevated late-night salivary cortisol (448 and 671 ng/dL), 24-hour urinary free cortisol of 125.4 µg/24 h, and failure to suppress on dexamethasone testing (1-mg cortisol 18 µg/dL; 2-mg cortisol 16.9 µg/dL; 8-mg cortisol 21.5 µg/dL with dexamethasone level 4040 ng/dL). ACTH was persistently suppressed ( < 5 pg/mL), consistent with ACTH independent Cushing syndrome. Aldosterone and renin were elevated, attributed to heart failure.
CT scan showed stable bilateral adrenal adenomas (right: two 1.8cm nodules; left: two 2.8 cm nodules). Pituitary MRI was negative except for a small pineal cyst. Genetic testing showed a CTNNB1 mutation. Androgen levels and plasma metanephrines were normal.
She underwent aortic valve replacement and aortic arch repair, after which her serum cortisol increased to 34.4 µg/dL. She was initially treated with an etomidate infusion, followed by metyrapone once cortisol improved. Despite the surgery, her cardiac function continued to deteriorate, necessitating heart transplantation for survival. Due to her critical cardiac status, she was not considered a candidate for adrenalectomy prior to transplantation.
Her case was reviewed in a multidisciplinary tumor board, focusing on the need for controlling endogenous hypercortisolism while simultaneously requiring supraphysiologic glucocorticoid dosing in the peri/post-transplant period, likely indefinitely. A block and replace strategy was selected. Post-transplant, she received an etomidate infusion for five days while on high-dose glucocorticoids. As steroids were gradually tapered, she was transitioned to metyrapone as a bridge to definitive adrenalectomy.
Other medications were contraindicated due to concerns for hepatotoxicity, QTc prolongation, and interactions with post-transplant immunosuppressive therapy.

*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.*