False Positive Cushing's Syndrome in a 16-Year-Old Male

Abstract

Introduction: Cushing syndrome is an endocrine disorder characterized by prolonged exposure to high levels of glucocorticoids, either from endogenous overproduction or exogenous sources. It presents with symptoms such as rapid weight gain, central obesity, muscle weakness, and hypertension. The diagnosis requires a combination of clinical, biochemical, and imaging tests. Dexamethasone suppression testing is pivotal in diagnosing hypercortisolism, but its accuracy may be affected by pharmacokinetic factors, such as drug interactions. This case report discusses a false-positive diagnosis of Cushing syndrome in a 16-year-old male, caused by the pharmacokinetic interference of carbamazepine, an enzyme-inducing medication. Case Presentation: A 16-year-old male with psychiatric comorbidities (bipolar disorder and epilepsy) presented with rapid weight gain, a hallmark symptom of Cushing syndrome. Initial laboratory testing revealed elevated cortisol and adrenocorticotropic hormone (ACTH) levels, with partial cortisol suppression during the low-dose dexamethasone suppression test, suggesting an ACTH-dependent cause of hypercortisolism. Imaging studies of the pituitary and adrenal glands were negative for abnormalities. High-dose dexamethasone suppression and 24-hour urinary free cortisol (UFC) levels further supported the diagnosis of hypercortisolism. A detailed medication review revealed the patient was taking carbamazepine, a CYP3A4 enzyme inducer, which could have accelerated the metabolism of dexamethasone and led to inadequate suppression of cortisol, producing falsely elevated levels. Conclusions: Carbamazepine, through its enzyme-inducing effect on CYP3A4, likely interfered with the dexamethasone suppression test, leading to false-positive results for Cushing syndrome. Following the discontinuation of carbamazepine, the patient’s cortisol levels normalized, weight stabilized, and the signs of Cushing syndrome resolved. Alternative psychiatric medications were initiated without further endocrine abnormalities. This case emphasizes the importance of considering pharmacokinetic interactions, such as those with enzyme-inducing drugs, when diagnosing Cushing syndrome. Clinicians should carefully review medications in patients with suspected hypercortisolism and consider these interactions when interpreting biochemical test results. A comprehensive medication review and interdisciplinary collaboration are crucial for accurate diagnosis, avoiding unnecessary interventions, and improving patient outcomes. The case advocates for tailored diagnostic protocols in similar clinical scenarios.