Cushing syndrome: causes, types, clinical diagnosis and management

Cushing’s syndrome is a hormonal condition induced by chronic exposure to elevated cortisol levels. It can be caused by a variety of situations that enhance cortisol production, as well as the use of exogenous glucocorticoids.

What is Cushing syndrome?

Cushing’s syndrome is a condition induced by chronic exposure of the body’s tissues to high quantities of the hormone cortisol. It can be caused by glucocorticoid use or by cortisol-producing tumors or adrenocorticotropic hormone (ACTH), which promotes cortisol production.

Feature of Cushing syndrome including a round face, acne, reddish skin

Causes of Cushing syndrome

Exogenous (iatrogenic) Cushing’s Syndrome:

• Glucocorticoid drugs: Chronic use of corticosteroid drugs (e.g., prednisone) to treat illnesses such as asthma, rheumatoid arthritis, and lupus.

Endogenous Cushing’s Syndrome:

• Pituitary Adenoma (Cushing’s Disease) is a benign tumor of the pituitary gland that secretes an excess of adrenocorticotropic hormone (ACTH), boosting adrenal gland cortisol production.
• Ectopic ACTH Syndrome occurs when non-pituitary malignancies (such as small cell lung cancer) generate ACTH.
• Adrenal Tumors: Adrenal adenomas or carcinomas create excess cortisol in the absence of ACTH.

Types Cushing syndrome

ACTH-dependent Cushing Syndrome:

• Cushing Disease is caused by a pituitary adenoma.
• Ectopic ACTH Syndrome refers to the release of ACTH by non-pituitary malignancies.

ACTH-independent Cushing’ Syndrome:

• Adrenal Adenoma/Carcinoma: A tumor in the adrenal gland that produces too much cortisol.
• Primary Pigmented Nodular Adrenocortical Disorder (PPNAD): A rare adrenal gland condition.
• McCune-Albright Syndrome is a genetic condition that affects bones, skin, and the endocrine system.

Clinical Diagnosis

Clinical presentation:

• Weight gain: Obesity in the center, moon face, and buffalo hump.
• Skin changes include thinning, easy bruising, and purple striae (stretch marks).
• Musculoskeletal: Muscle weakness; osteoporosis.
• Metabolic conditions include hypertension, glucose intolerance, and diabetes.
• Reproductive issues include irregular menstruation and hirsutism (excess hair growth) in women.
• Neuropsychiatric symptoms include mood swings, sadness, and cognitive abnormalities.

Diagnostic Tests:

• The 24-Hour Urinary Free Cortisol Test measures cortisol excretion in urine.
• The Late-Night Salivary Cortisol Test measures cortisol levels in saliva late at night.
• The Low-Dose Dexamethasone Suppression Test measures cortisol levels following dexamethasone injection.
• ACTH Levels: Indicates if Cushing’s syndrome is ACTH-dependent or independent.

Imaging Studies:

• MRI of the Pituitary Gland: Used to detect pituitary adenomas.
• Adrenal CT or MRI: Used to detect adrenal tumors.
• Chest and abdominal imaging are used to discover ectopic ACTH-producing tumors.

Management

1. Treatment of Underlying Cause:

Pituitary Adenomas (Cushing’s Disease):

• Surgery: Transsphenoidal removal of the pituitary tumor.
• Radiation Therapy: For residual or recurrent tumors.
• Medications: To control cortisol production (e.g., ketoconazole, metyrapone).

Ectopic ACTH Syndrome:

• Surgery: To remove the ACTH-secreting tumor.
• Medical Therapy: To control cortisol levels if surgery is not feasible.

Adrenal Tumors:

• Surgery: Adrenalectomy to remove adrenal adenomas or carcinomas.
• Medications: Mitotane for adrenal carcinoma.

2. Medical Management for Hypercortisolism:

• Medications: Ketoconazole, metyrapone, mitotane, mifepristone to reduce cortisol production or block its effects.

3. Management of Complications:

• Osteoporosis treatment includes calcium and vitamin D supplements, as well as bisphosphonates.
• Antihypertensive medicines.
• Diabetes involves monitoring blood glucose levels and using drugs to regulate them.

Monitoring and Follow-up:

• Regular follow-up appointments to check cortisol levels, manage problems, and alter treatment as needed.
• Psychological support and counseling can help with mood swings, sadness, and other mental health disorders.

Frequently Asked Question (FAQ)

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