Cushing's syndrome

Overview

Cushing's syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol, a steroid hormone produced by the adrenal glands. Cortisol plays an essential role in regulating metabolism, blood pressure, and the body’s response to stress. When the body is exposed to excessive cortisol, either due to internal overproduction or external sources such as corticosteroid medications, it leads to a wide range of physical and metabolic abnormalities. Cushing's syndrome can affect individuals of all ages but is most commonly diagnosed in adults between the ages of 30 and 50, and it occurs more frequently in women.

Causes

Cushing's syndrome can result from both endogenous (internal) and exogenous (external) sources of cortisol:

• Exogenous causes: The most common cause is long-term use of corticosteroid medications (such as prednisone) for conditions like asthma, lupus, or rheumatoid arthritis.

• Endogenous causes: Include:

  • Cushing's disease: Caused by a pituitary tumor that secretes excess adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce more cortisol.

  • Adrenal tumors: Benign or malignant tumors of the adrenal glands that produce cortisol independently of ACTH.

  • Ectopic ACTH syndrome: ACTH is produced by non-pituitary tumors, often in the lungs (e.g., small cell lung carcinoma).

Symptoms

Cushing's syndrome presents with a wide range of symptoms due to the systemic effects of elevated cortisol. Common signs and symptoms include:

• Weight gain: Especially around the abdomen, face (moon face), and upper back (buffalo hump)

• Thin, fragile skin: That bruises easily and heals slowly

• Striae: Wide, purple stretch marks on the abdomen, thighs, or breasts

• Muscle weakness: Especially in the upper arms and thighs

• Facial rounding and fullness

• Increased fat around the neck and decreased fat in the limbs

• High blood pressure and blood sugar levels

• Osteoporosis: Increased risk of bone fractures

• Mood changes: Depression, anxiety, irritability

• Irregular menstrual periods or amenorrhea in women

• Decreased libido and erectile dysfunction in men

• Hirsutism: Excessive hair growth in women on the face and body

Diagnosis

Diagnosing Cushing's syndrome involves a combination of clinical assessment, laboratory testing, and imaging studies to determine the cause of cortisol excess. Diagnostic steps include:

• Initial screening tests:

  • 24-hour urinary free cortisol test

  • Late-night salivary cortisol test

  • Low-dose dexamethasone suppression test (DST)

• ACTH levels: Measured to differentiate between ACTH-dependent and ACTH-independent causes

• High-dose dexamethasone suppression test: Helps distinguish Cushing’s disease from ectopic ACTH secretion

• Imaging:

  • MRI of the pituitary gland if Cushing’s disease is suspected

  • CT scan of the adrenal glands or chest to identify tumors

Treatment

Treatment depends on the underlying cause of Cushing's syndrome. Options include:

• Reducing corticosteroid use: Gradual tapering of exogenous steroids under medical supervision if they are the cause

• Surgery:

  • Transsphenoidal surgery to remove pituitary adenomas (for Cushing’s disease)

  • Adrenalectomy for adrenal tumors

  • Resection of ectopic ACTH-secreting tumors when possible

• Radiation therapy: For residual or inoperable pituitary tumors

• Medications: To control cortisol production, such as ketoconazole, metyrapone, mitotane, or mifepristone

• Hormone replacement therapy: May be needed if adrenal glands are removed

Prognosis

With timely diagnosis and appropriate treatment, the prognosis for Cushing’s syndrome can be favorable. However, untreated or prolonged exposure to high cortisol levels can lead to serious complications such as cardiovascular disease, diabetes, osteoporosis, and severe infections. Post-treatment recovery varies, some symptoms like hypertension and glucose intolerance may take months to improve, and long-term monitoring is often necessary. In cases of Cushing’s disease, there is a risk of recurrence, requiring ongoing follow-up care.