Cushing’s syndrome leads to hypercortisolism (exponential increase in cortisol levels) in the body. An untreated or improperly managed Cushing’s syndrome can cause serious complications in the body.
- Cortisol is a stress hormone released by the adrenal glands during stressful events.
- It regulates the sleep-wake cycle and the body’s response to inflammation.
- Persistent high levels of cortisol can damage the body.
What is Cushing’s syndrome?
Cushing's syndrome is a rare hormonal illness that occurs when the body's tissues are repeatedly exposed to high doses of the hormone cortisol. Cortisol is generated by the adrenal glands and helps the body respond to stress. The hormone helps maintain blood pressure and cardiovascular function, as well as regulates protein, carbohydrate, and fat metabolism.
Cushing’s syndrome is caused by the excess release of adrenocorticotrophic hormone (ACTH). Pituitary adenomas or benign or noncancerous tumors of the pituitary gland emit excessive levels of ACTH. Tumors of the adrenal glands and other organs (such as the lungs) release ACTH. This is referred to as ectopic ACTH syndrome. Some people may have a genetic predisposition for tumors of one or more endocrine glands, which can lead to Cushing’s syndrome.
- Cushing's syndrome affects approximately 10 to 15 people out of 1 million each year.
- It mostly affects individuals aged between 20 and 50 years.
- Women are more prone to it than men.
What are the symptoms of Cushing’s syndrome?
The symptoms of Cushing’s syndrome include:
- Severe fatigue
- Growth retardation in children
- A rounded face
- Weight around the torso, shoulders, and neck
- Insomnia
- Edema
- Muscle weakness and back pain
- High blood sugar or diabetes
- High blood pressure
- Skin problems:
- Slow wound healing
- Bruising
- Stretch marks on the abdomen, hips, and thighs
- Thinning of skin
- Reduced bone density (osteoporosis)
- Decreased memory
- Irritability
- Mood swings
- Hirsutism (women)
- Decreased libido
- Irregulated body temperature
How is Cushing’s syndrome diagnosed?
The doctor will do a thorough medical evaluation that includes an investigation of the individual's medical history and a physical exam.
The first step to diagnosing Cushing's syndrome is to detect high cortisol levels in the body.
The following tests help determine cortisol levels in the body:
- Salivary cortisol testing
- Urinary-free cortisol test
- Dexamethasone suppression test
- Blood tests
- Corticotropin-releasing hormone stimulation test
Additional testing, such as CT or MRI scans, can help determine whether a tumor is causing Cushing’s syndrome. Some pituitary tumors are too small to be identified on imaging and must be removed through the petrosal sinus (small sinus veins that drain from the pituitary).
How is Cushing’s syndrome treated?
Cushing’s syndrome treatment differs from person to person based on the underlying reason. If a glucocorticoid drug causes the condition, it will be gradually tapered to avoid an adrenal crisis caused by an abrupt drop in cortisol levels. The glucocorticoid could be switched to another steroid class or anti-inflammatory.
Medications
The FDA has approved adrenostatic medicines, mitotane, and osilodrostat, for the treatment of Cushing’s syndrome. Osilodrostat works primarily by suppressing the action of 11-hydroxylase, the last enzyme in the route that leads to cortisol production. It inhibits the production of aldosterone by blocking the enzyme 18-hydroxylase.
However, many drugs that exhibit adrenostatic activity, including ketoconazole, metyrapone, aminoglutethimide, and etomidate, help treat Cushing’s syndrome but do not have FDA approval. These medications can suppress the formation of corticotroph pituitary adenomas and restore normal hypothalamic-pituitary-adrenal axis function by inhibiting one or more steroidogenic enzymes.
Surgery
When Cushing’s syndrome is caused by a tumor, the tumor is surgically removed. If surgery is not an option (for example, because the tumor has spread) or does not improve symptoms, radiation treatment could be used. Following the removal of a pituitary tumor, the person is on cortisol supplementation for 6 to 18 months. If both adrenal glands are removed, people will require cortisol and other hormone replacement for the rest of their lives.
Cushing’s syndrome is usually curable because it is caused by long-term glucocorticoid usage. Despite adequate therapy, many people have persistent Cushing’s syndrome symptoms, such as muscular weakness or cognitive impairment.
Cushing's Syndrome. https://columbiasurgery.org/conditions-and-treatments/cushings-syndrome
Cushing Syndrome. https://www.uhhospitals.org/health-information/health-and-wellness-library/article/Diseases-and-Conditions/cushings-syndrome
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