Understanding Cushing’s Syndrome: Causes, Symptoms, and Treatments
Cushing’s Syndrome
Overview
Cushing’s syndrome develops when the body produces excessive cortisol. This can also occur from taking high doses of cortisol or other steroid hormones.
Causes and Risk Factors
The most frequent cause is the side effect of anti-inflammatory steroids for conditions like asthma or rheumatoid arthritis.
The second most common cause is Cushing’s disease. This occurs when the pituitary gland overproduces adrenocorticotropic hormone (ACTH), stimulating the adrenal glands to produce cortisol.
Cushing’s disease is more common in women.
Other causes of Cushing’s syndrome include:
- Pituitary or adrenal gland tumor
- Tumor elsewhere in the body (ectopic Cushing’s syndrome)
Symptoms
Symptoms can vary, but may include:
- Central obesity (protruding abdomen with thin arms and legs)
- Acne or skin infections
- Backache
- Buffalo hump (fat accumulation between shoulders)
- Facial hair growth
- Headache
- Impotence (men)
- Menstrual cessation (women)
- Mental changes
- Purple stretch marks on the abdomen, thighs, and breasts
- Moon face (round, red, full face)
- Thin, easily bruised skin
- Weakness
- Unintentional weight gain
- Bone pain or tenderness
- Fatigue
- High blood pressure
- Muscle atrophy
- Red skin spots
- Flushing or redness
Diagnosis
Blood glucose and white blood cell counts may be elevated, while potassium levels may be low.
Tests to confirm high cortisol levels include:
- Blood cortisol test
- Dexamethasone suppression test
- Urine cortisol test
Tests to determine the cause may include:
- Abdominal CT scan
- Corticotropin evaluation
- Pituitary MRI
Treatment
Treatment depends on the underlying cause.
Corticosteroid-induced Cushing’s syndrome:
- Slowly decrease the medication dose under medical supervision, if possible.
Cushing’s syndrome caused by a pituitary or ACTH-secreting tumor:
- Surgical removal of the tumor
- Radiation therapy after tumor removal (in some cases)
- Hydrocortisone (cortisol) replacement therapy (after surgery and sometimes lifelong)
Cushing’s syndrome caused by an adrenal tumor:
- Surgical removal of the tumor
- Medications to block cortisol release if the tumor cannot be removed
Prognosis
Tumor removal may lead to full recovery, but recurrence is possible.
Survival for ectopic tumors depends on the tumor type. Untreated Cushing’s syndrome can be life-threatening.
Complications
- Diabetes
- Pituitary tumor enlargement
- Osteoporosis-related fractures
- High blood pressure
- Kidney stones
- Serious infections
Additional Information
Cushing’s syndrome is characterized by a moon face, central obesity affecting the face, neck, and abdomen, limb muscle atrophy, hypertension, diabetes mellitus, osteoporosis, kidney stones, and capillary fragility resulting in easy bruising. When caused by a pituitary adenoma, it can also lead to headaches and vision impairment if the optic chiasm is compressed. Primary hyperaldosteronism causes hypertension and low blood potassium (hypokalemia), leading to fatigue, heart arrhythmias, muscle cramps, and hormonal pheochromocytoma. Pheochromocytoma causes significant hypertension, often appearing in crises accompanied by headaches, tremors, cold hands and feet, sweating, abdominal pain, and chest pain. The intensity can be severe enough to cause myocardial infarction or cerebral hemorrhage. Adrenal fatigue can cause dizziness, hypotension (especially upon standing), and dark-colored skin folds and oral mucosa in Addison’s disease. Non-functioning adrenal tumors (those that don’t produce hormones) may be asymptomatic or cause abdominal discomfort due to compression.
Diagnosis involves blood and urine tests. In Cushing’s syndrome, a lack of circadian rhythm of cortisol in the blood and elevated urinary cortisol are typical. The origin is determined by measuring ACTH, cortisol suppression with dexamethasone, and a CRH test. Hyperaldosteronism evaluates renin (suppressed in primary aldosteronism) and aldosterone levels in the blood at baseline and after stimulation with ambulation or diuretics. Urine aldosterone is also measured over 24 hours and should be elevated. Pheochromocytoma presents with increased blood and urine catecholamines and elevated vanillylmandelic acid (a catecholamine metabolite) in urine. A clonidine suppression test for blood catecholamines may be necessary. Primary adrenal insufficiency is diagnosed by confirming low cortisol levels between 8 and 10 a.m., accompanied by elevated ACTH and a lack of response to intravenous ACTH injection. After functional diagnosis, morphological studies are needed. CT scans help visualize the adrenal glands for size or lymph alterations, as in adenomas or carcinomas. In hyperaldosteronism, selective catheterization of the adrenal veins may be necessary. In Cushing’s syndrome with high ACTH, an MRI is performed to locate the ACTH-producing pituitary adenoma. If not visualized, inferior petrosal sinus catheterization may be needed to confirm the source of increased ACTH secretion in the pituitary.
Treatment initially involves antagonizing the effects of hormonal hypersecretion. In Cushing’s syndrome, ketoconazole, an antifungal, reduces cortisol synthesis. Spironolactone, which blocks aldosterone’s action, is used in primary hyperaldosteronism. Pheochromocytoma requires drugs that block catecholamine receptors, especially alpha-blockers like phenoxybenzamine, prazosin, or doxazosin. Beta-blockers like propranolol are used in a second phase. After several days of drug treatment and clinical stabilization, definitive treatment can begin. In adenoma and carcinoma cases, surgery, now often laparoscopic, is performed. If Cushing’s syndrome is due to an ACTH-producing pituitary adenoma, it is usually removed transsphenoidally (through the sphenoid bone) if its size allows. Addison’s disease is treated with oral hydrocortisone to replace cortisol. Patients with aldosterone deficiency also need fluorohydrocortisone. Patients with Cushing’s syndrome due to chronic corticosteroid use should gradually reduce their dose if possible. These patients and those with Addison’s disease may need additional corticosteroids during intercurrent illnesses (surgery, infection).