Understanding Challenges in Management of Hypercortisolism
An expert discusses how diagnosing hypercortisolism is challenging due to its nonspecific symptoms, fluctuating hormone levels, and complex testing requirements that often delay accurate detection and treatment.
By
Bob Busch, MD
| Published on October 22, 2025
3 min read
Identifying and diagnosing hypercortisolism presents significant clinical challenges due to its variable presentation, overlapping symptoms with common disorders, and the complex physiology of cortisol regulation. Early manifestations such as weight gain, fatigue, hypertension, and mood changes are nonspecific and can mimic more prevalent conditions like obesity, depression, or metabolic syndrome. This often leads to delayed or missed diagnosis. Furthermore, the cyclical or intermittent nature of cortisol secretion can produce fluctuating symptoms and laboratory values, complicating interpretation of diagnostic tests. Physicians must maintain a high index of suspicion and carefully consider hypercortisolism when multiple, progressive features—such as facial rounding, proximal muscle weakness, or easy bruising—occur concurrently.
Biochemical testing adds another layer of complexity. The recommended screening tests—such as the 24-hour urinary free cortisol, late-night salivary cortisol, and low-dose dexamethasone suppression test—each have limitations related to sensitivity, specificity, and variability among patients. Factors including stress, sleep disturbances, obesity, alcoholism, and certain medications can produce false-positive or false-negative results. Moreover, differentiating between true Cushing syndrome and pseudo-Cushing states (caused by chronic stress, depression, or alcoholism) requires nuanced clinical judgment and repeat testing to confirm cortisol dysregulation. These diagnostic hurdles often necessitate multidisciplinary collaboration among endocrinologists, radiologists, and laboratory specialists.
Even after biochemical confirmation, identifying the underlying etiology—whether pituitary, adrenal, or ectopic—can be difficult. Imaging studies may reveal incidental findings or fail to detect small tumors, and dynamic testing such as the CRH stimulation or inferior petrosal sinus sampling is technically demanding and not universally available. As a result, many patients endure prolonged diagnostic journeys before receiving definitive treatment. These challenges highlight the need for increased awareness, improved diagnostic algorithms, and access to specialized endocrine care to ensure timely and accurate identification of hypercortisolism.
