Demacort® is mixture of betamethasone (high-potency corticosteroid) and clotrimazole (antifungal agent), an inhibitor of CYP3A4, which can inhibit the metabolism of betamethasone. Interaction of these drugs may result in decreased clearance of betamethasone and increased risk for adverse events such as iatrogenic Cushing’s syndrome. A 26-year-old female was admitted to the hospital due to rapid weight gain after application of Demacort®. During a period of one month, she showed weight gain of 30 kg and developed several Cushingoid appearances. The result of an overnight dexamethasone suppression test was negative, thus, endogenous Cushing’s syndrome was ruled out. A negative cortisol response was observed for the rapid ACTH stimulation test; therefore, we made a diagnosis of iatrogenic Cushing’s syndrome combined with additional secondary adrenal insufficiency.