Increased Weight Loss With the Combination of Levoketoconazole and Semaglutide in a Patient With Mild Hypercortisolism.

BACKGROUND/OBJECTIVE: A patient with obesity, anxiety, depression, and hyperandrogenism, diagnosed with mild hypercortisolism of unknown etiology, had increased weight loss with the combination of levoketoconazole and semaglutide. CASE REPORT: A 21-year-old female with a history of polycystic ovary syndrome, anxiety, depression, and obesity presented with irregular menstrual cycles, acne, and excess body hair. Her weight at initial visit was 275 lbs, with physical examination showing moon facies, dorsocervical fat pad, supraclavicular fat pad, and abdominal striae. Medications included sertraline 100 mg daily and metformin 500 mg daily, which was increased; spironolactone was added, and Ozempic 0.25 mg subcutaneously weekly was started and titrated up to 1 mg subcutaneously weekly. The patient lost 42 lbs with Ozempic but plateaued. A dexamethasone suppression test showed a non-suppressed adrenocorticotropic hormone 10 (reference: 7.2-63.3) and morning cortisol 6.7 ng/dL (reference: <1.8 ng/dL). The 24-hour urinary free cortisol was high normal 42 μg per 24 hours (reference: 6-42 μg per 24 hours) with a negative magnetic resonance imaging and computed tomography scan for pituitary or adrenal tumors. A diagnosis of hypercortisolism of unknown origin was made, with the decision to treat with levoketoconazole. The patient lost an additional 47 lbs, resulting in a total weight loss of 89 lbs while on levoketoconazole and semaglutide, and the cortisol levels normalized. DISCUSSION: Limited literature exists on the management of hypercortisolism without an identifiable source. Our case shows that combined use of levoketoconazole and semaglutide resulted in significant weight loss and improvement of biochemical and psychological parameters. CONCLUSION: Hypercortisolism may mimic other diagnoses, and further exploration is needed about possible additive effects of levoketoconazole with semaglutide.