Cushing's syndrome is a complex hormonal disorder caused by prolonged exposure to excessive levels of cortisol, a steroid hormone produced primarily by the adrenal glands.
Cortisol plays essential roles in regulating metabolism, immune response, blood pressure, and the body's reaction to stress.
Causes and Pathophysiology
Pituitary adenomas: Benign tumors on the pituitary gland releasing excess adrenocorticotropic hormone (ACTH), stimulating adrenal cortisol production. This specific form is known as Cushing's disease and accounts for about 70% of endogenous cases.
Adrenal tumors: Benign or malignant growths of the adrenal cortex that autonomously produce cortisol.
Ectopic ACTH secretion: Tumors such as the lung can produce ACTH unrelated to pituitary control, prompting adrenal cortisol overproduction.
Clinical Manifestations
Cushing's syndrome presents with distinctive but diverse symptoms reflecting cortisol's widespread effects on tissues:
Morphological changes: Central obesity with accumulation of fatty in the trunk, upper back, face (creating a rounded “moon face”), accompanied by thin arms and legs from muscle wasting.
Skin alterations: Fragile and thinning skin prone to bruising, slow wound healing, and characteristic reddish-purple stretch marks (striae) primarily on the abdomen and thighs.
Musculoskeletal symptoms: Proximal muscle weakness impairing mobility and bones demineralization leading to osteoporosis and fractures.
Endocrine dysfunction: Women may experience menstrual irregularities or amenorrhea and hirsutism (excess facial/body hair). Men commonly have reduced libido, infertility, and erectile dysfunction.
Metabolic disturbances: Cortisol-induced insulin resistance can result in hyperglycemia and diabetes mellitus. Hypertension is common due to cortisol's potentiation of vasoconstrictive hormones.
Neuropsychiatric effects: Patients frequently suffer from fatigue, depression, anxiety, irritability, cognitive impairment, and sleep disturbances, which can precede other symptoms.
Diagnosis and Evaluation
Diagnosis of Cushing's syndrome requires a high index of suspicion followed by biochemical testing to confirm hypercortisolism. Common tests include:
- Late-night salivary cortisol level assessment.
- Dexamethasone suppression test to evaluate cortisol feedback inhibition.
Dr. Lynnette Nieman, a leading expert in Cushing's syndrome, emphasized, "Early diagnosis and treatment are critical, because delays in therapy are associated with increased morbidity and mortality." Her insight underscores the importance of clinical vigilance to improve outcomes through timely intervention.
Cushing's syndrome is a rare but serious disorder marked by prolonged cortisol excess from various origins. It affects multiple physiological systems causing characteristic physical, metabolic, and neuropsychiatric changes. Diagnosis is confirmed by specialized hormone testing and imaging to determine the underlying cause.
While challenging, early recognition and precise treatment tailored to the source of hormone production can mitigate the significant health risks associated with the disorder and improve quality of life for patients.
