- Cushing’s syndrome is an endocrine disorder caused by prolonged exposure to excessive levels of cortisol, a glucocorticoid hormone produced by the adrenal glands. Cortisol plays a central role in regulating metabolism, immune response, blood pressure, and the body’s stress response. When present in excess, however, it disrupts these systems, leading to a wide array of clinical symptoms.
- Cushing’s syndrome can result either from endogenous overproduction of cortisol by the body or from exogenous (iatrogenic) sources, most commonly the prolonged use of glucocorticoid medications prescribed for conditions such as asthma, rheumatoid arthritis, or autoimmune diseases.
- The underlying causes of endogenous Cushing’s syndrome are diverse. The most common is Cushing’s disease, which refers specifically to cortisol overproduction due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. In this condition, the pituitary gland produces excessive ACTH, which overstimulates the adrenal glands, leading to hypercortisolism. Other causes include adrenal tumors (adenomas or carcinomas) that directly secrete cortisol, and ectopic ACTH syndrome, where non-pituitary tumors (such as small-cell lung carcinoma) produce ACTH inappropriately. Distinguishing between these sources is essential for diagnosis and treatment planning.
- Clinically, Cushing’s syndrome presents with a distinctive constellation of symptoms and physical changes. Patients often develop central obesity with disproportionate fat accumulation in the face (producing the characteristic “moon face”), upper back (“buffalo hump”), and abdomen, while limbs remain relatively thin due to muscle wasting. Other hallmark features include thin, fragile skin that bruises easily, wide purplish striae (stretch marks) on the abdomen and thighs, hypertension, and glucose intolerance or diabetes mellitus. Osteoporosis, menstrual irregularities, hirsutism in women, decreased libido, and mood disturbances such as depression or irritability are also common. Children with Cushing’s syndrome may exhibit growth retardation.
- The diagnosis of Cushing’s syndrome requires a careful combination of clinical evaluation, biochemical testing, and imaging studies. Common screening tests include the dexamethasone suppression test, late-night salivary cortisol measurement, and 24-hour urinary free cortisol levels. Once hypercortisolism is confirmed, additional tests help determine whether the cause is ACTH-dependent (pituitary or ectopic source) or ACTH-independent (adrenal tumor). Imaging techniques such as MRI of the pituitary and CT scans of the adrenal glands or chest are used to localize the source.
- Treatment depends on the underlying cause. For Cushing’s disease, transsphenoidal surgery to remove the pituitary adenoma is the preferred option. Adrenal tumors may be treated with surgical removal, while ectopic ACTH-producing tumors require excision or management of the primary malignancy. In cases where surgery is not feasible or incomplete, medications that inhibit cortisol synthesis (e.g., ketoconazole, metyrapone, mitotane) or block its effects may be used. Radiation therapy to the pituitary or bilateral adrenalectomy may be considered in refractory cases. When caused by long-term glucocorticoid use, gradual withdrawal or dose reduction is necessary to prevent adrenal insufficiency.
- If untreated, Cushing’s syndrome can have serious complications, including cardiovascular disease, severe infections, osteoporosis-related fractures, and psychological disorders, significantly reducing life expectancy. However, with early diagnosis and appropriate treatment, prognosis can improve dramatically, although some long-term effects—such as metabolic syndrome, osteoporosis, or cognitive changes—may persist.
