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Cushing's Syndrome

Cushing's syndrome is a collection of signs and symptoms resulting from prolonged exposure to high levels of glucocorticoids such as cortisol. This condition can be caused by endogenous factors, such as tumours, or exogenous factors, such as prolonged use of corticosteroid medications.

Signs and Symptoms

Cushing's syndrome presents with a variety of symptoms that reflect the body's response to excess cortisol. These include:

  • High blood pressure
  • Central obesity: Weight gain primarily around the trunk and face, leading to a "moon face" and a "buffalo hump" on the back.
  • Muscle weakness and bone loss: Cortisol causes protein breakdown, leading to muscle wasting and osteoporosis.
  • Skin changes: These include reddish-purple stretch marks (striae), acne, and fragile skin that bruises easily and heals poorly.
  • Facial plethora: A round, red face often due to increased blood flow and capillary dilation.
  • Psychiatric symptoms: Depression, anxiety, and cognitive difficulties are common.
  • Menstrual irregularities: Women may experience hirsutism, amenorrhea, or oligomenorrhea.
Facial appearance of a patient with iatrogenic Cushing's syndrome
Facial appearance of a 30 year old female patient with iatrogenic Cushing's syndrome.
Symptoms of Cushing's syndrome
Symptoms of Cushing's syndrome.
Increased hair and stria in a patient with Cushing's syndrome
Increased hair and stria in a 30 year old female patient with iatrogenic Cushing's syndrome.
Features of Cushing syndrome in an infant
Features of Cushing syndrome including a round face, acne, reddish skin, central obesity, and poor muscle tone.

Causes

Cushing's syndrome can be caused by both exogenous and endogenous factors:

Exogenous

  • Medication: The most common cause is the prolonged use of glucocorticoid medications for conditions like asthma or rheumatoid arthritis.

Endogenous

  • Pituitary adenomas: Known as Cushing's disease, where a benign tumour in the pituitary gland produces excessive ACTH, stimulating cortisol production.
  • Adrenal tumours: These can autonomously secrete cortisol.
  • Ectopic ACTH production: Non-pituitary tumours, such as small cell lung cancer, can produce ACTH.

Diagnosis

Diagnosing Cushing's syndrome involves several steps:

  1. Medical History and Physical Examination: Checking for medication use and characteristic physical signs.
  2. Laboratory Tests:
    • 24-hour urinary free cortisol test: Measures cortisol levels in the urine.
    • Low-dose dexamethasone suppression test: Assesses cortisol suppression after administering dexamethasone.
    • Late-night salivary cortisol test: Measures cortisol levels late at night when they should be low.
  3. Imaging:
    • MRI or CT scans: To detect pituitary or adrenal tumours.
Diagnostic algorithm of suspected Cushing's syndrome
Diagnostic algorithm of suspected Cushing's syndrome.

Treatment

Treatment depends on the underlying cause:

  • Medication-Induced: Gradual reduction of corticosteroid dosage under medical supervision.
  • Pituitary Adenomas (Cushing's Disease): Surgical removal of the adenoma. Post-surgery, patients may require steroid replacement therapy temporarily.
  • Adrenal Tumours: Surgical removal of the adrenal gland(s). In cases where surgery is not feasible, medications like ketoconazole or metyrapone can be used to reduce cortisol production.
  • Ectopic ACTH Production: Treatment focuses on the underlying tumour, which may involve surgery, chemotherapy, or radiation.
Management algorithm of Cushing's disease
Management algorithm of Cushing's disease.

Prognosis

With appropriate treatment, most cases of Cushing's syndrome have a good prognosis, and life expectancy can be normal. However, untreated Cushing's syndrome can lead to severe complications like hypertension, diabetes, osteoporosis, and increased susceptibility to infections, which can significantly impact quality of life and longevity.


Self-assessment MCQs (single best answer)

What is the most common cause of Cushing's syndrome?



Which of the following is a characteristic sign of Cushing's syndrome?



Which test is commonly used to initially screen for Cushing's syndrome?



What is a distinguishing feature of Cushing's disease compared to other forms of Cushing's syndrome?



Which symptom is NOT typically associated with Cushing's syndrome?



What is the primary treatment for Cushing's syndrome caused by a pituitary adenoma?



Which condition may present with features of Cushing's syndrome due to excess exogenous steroid use?



Which hormone is typically elevated in Cushing's disease but not in adrenal adenoma-induced Cushing's syndrome?



What is the preferred method for visualising a pituitary adenoma in a patient suspected of having Cushing's disease?



Which of the following is a potential complication of untreated Cushing's syndrome?



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