(12.10) Recurrent ACTH-Dependent Cushing Syndrome After Bilateral Adrenalectomy

Cushing Syndrome (CS), characterized by excessive cortisol production, poses a significant challenge due to its clinical manifestations and comorbidities. Bilateral adrenalectomy (BLA) is considered a definitive treatment for ACTH-Dependent Cushing Syndrome (ACTH-D-CS) when other therapeutic options are contraindicated or failed. However, few patients may experience persistent or recurrent hypercortisolism despite this radical intervention. Recurrent ACTH-D-CS after BLA is rare and uncommon.

Case(s) Description : 34-year-old female with a history of ACTH-D-CS s/p TSPR and gamma knife radiation therapy, central hypothyroidism, hypogonadotropic hypogonadism, osteoporosis, hyperparathyroidism, and hyperaldosteronism presented to our clinic for recurrent ACTH-D-CS. Patient was being treated with ketoconazole and cabergoline after failed radiation therapy. Labs showed 8 PM Cortisol 51 (2.9-17.3 ug/dL) and ACTH 317 (6-50pg/mL). The patient had laparoscopic total BLA since medical therapy failed. Pathology showed bilateral adrenal gland hyperplasia. After surgery, she was treated with glucocorticoids that were tapered down to physiological doses of hydrocortisone and fludrocortisone. Later, patient stopped both medications due to uncontrolled hypertension and started on antihypertensive medications. She had the following clinical presentation then: multiple bone fractures, chronic fatigue and weight gain. Labs showed AM total cortisol of 29.2 (4.0-22.0 mcg/dL), free cortisol of 1.60 (0.07-0.93 mcg/dL), ACTH of 252 (6 - 50 pg/mL), 24-hour urine free cortisol of 94.1 (4.0 - 50.0 mcg/24 h). CT with and without contrast with adrenal protocol showed the presence of the remnant right adrenal gland. Patient had an open right adrenalectomy, and the residual right adrenal gland was removed. Pathology was benign. Post-operatively, labs showed AM total cortisol of 7.5 (4.6-20.6 mcg/dL), free cortisol of 0.15 (0.07-0.93 mcg/dL) and ACTH of 448 (6 - 50 pg/mL). Patient has responded well to physiological hydrocortisone and fludrocortisone regimen.

Discussion : BLA is the treatment of choice for ACTH-D-CS when other therapies have failed. Our patient had recurrent hypercortisolism after the first BLA. Recurrent/Persistent CS is very rare as BLA is usually successful. (3) It is known that remnant adrenal tissue might regenerate, and cortisol levels might become detectable after ceasing exogenous steroids with some patients being able to discontinue glucocorticoid replacement. (1,2,4) This case demonstrates that as clinicians we should be aware of the possibility of recurrent ACTH-D-CS even after BLA. We need further data to establish biochemical and radiological surveillance guidelines for CS recurrence.