Cushing syndrome is a rare but serious hormonal disorder that affects thousands of people worldwide. This condition occurs when the body produces too much cortisol, a hormone that plays a crucial role in metabolism, stress response, and immune function. Left untreated, Cushing syndrome can have a significant impact on a person’s health and quality of life, making it essential to recognize and address its symptoms early.
This article aims to provide a comprehensive overview of Cushing syndrome, exploring its causes, diagnosis, and treatment options. We’ll delve into the various factors that can lead to this condition, including pituitary tumors, adrenal gland issues, and long-term use of corticosteroid medications. Additionally, we’ll discuss the diagnostic process, which often involves a series of tests to confirm the presence of excess cortisol in the body. Finally, we’ll examine the available treatment approaches, ranging from medication to surgery, that can help manage Cushing syndrome and improve patients’ overall well-being.
What is Cushing Syndrome?
Cushing syndrome is a rare but serious hormonal disorder that occurs when the body has too much of the hormone cortisol for a prolonged period. Cortisol, often referred to as the “stress hormone,” plays a crucial role in metabolism, stress response, and immune function. When cortisol levels remain persistently high, it can lead to a range of physical and mental changes.
The most common cause of Cushing syndrome is the use of glucocorticoid medications, which are used to treat inflammatory conditions like asthma and rheumatoid arthritis. However, the condition can also result from tumors in the pituitary gland, adrenal glands, or other parts of the body that secrete excess cortisol or adrenocorticotropic hormone (ACTH), which stimulates cortisol production.
Symptoms
Cushing syndrome can cause a wide array of symptoms, which may vary among individuals depending on the underlying cause. Some of the most common signs and symptoms include:
- Rapid weight gain, particularly in the face, abdomen, and upper back
- Fatty deposits between the shoulders (buffalo hump) and in the face (moon face)
- Purple or pink stretch marks on the skin
- Thinning and fragility of the skin, which bruises easily
- Slow wound healing
- Acne and facial hair growth in women
- Muscle weakness and fatigue
- Mood changes, such as irritability, anxiety, and depression
- High blood pressure and blood sugar levels
- Osteoporosis and increased risk of fractures
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Types
There are two main types of Cushing syndrome:
- Exogenous Cushing Syndrome: This type is caused by factors outside the body, most commonly due to the long-term, high-dose use of glucocorticoid medications. When these medications are discontinued or reduced, the symptoms typically subside.
- Endogenous Cushing Syndrome: This type results from factors within the body, such as tumors in the pituitary gland (Cushing disease), adrenal glands, or other organs that secrete excess cortisol or ACTH. Cushing disease, caused by a pituitary tumor, accounts for about 70% of endogenous Cushing syndrome cases in adults.
Prompt diagnosis and treatment of Cushing syndrome are essential to prevent complications and improve patients’ quality of life. Treatment options depend on the underlying cause and may include surgery, radiation therapy, and medications that reduce cortisol production or block its effects.
Causes of Cushing Syndrome
Cushing syndrome has two main etiologies: exogenous hypercortisolism and endogenous hypercortisolism. Exogenous hypercortisolism, the most common cause of Cushing syndrome, is mostly iatrogenic and results from the prolonged use of glucocorticoids. Endogenous Cushing syndrome results from excessive production of cortisol by adrenal glands and can be ACTH-dependent and ACTH-independent.
Exogenous Causes
The most common cause of exogenous Cushing syndrome is due to people taking cortisol-like medications. These drugs are used to treat inflammatory disorders such as asthma and rheumatoid arthritis. They also suppress the immune system after an organ transplant. This type of Cushing syndrome is temporary and goes away after the patient has finished taking the cortisol-like medications.
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Endogenous Causes
Endogenous Cushing syndrome, in which the adrenal glands produce too much cortisol, is uncommon. It usually comes on slowly and can be difficult to diagnose. This type of Cushing syndrome is most often caused by hormone-secreting tumors of the adrenal glands or the pituitary, a gland located at the base of the brain. In the adrenal glands, the tumor (usually non-cancerous) produces too much cortisol.
ACTH-dependent cortisol excess due to a pituitary adenoma is called Cushing disease, and it is responsible for 80% of endogenous Cushing syndrome. Most tumors that produce ACTH originate in the pituitary gland but sometimes non-pituitary tumors, usually in the lungs, can also produce too much ACTH and cause ectopic Cushing syndrome.
Adrenal hyperplasia, adenoma, and carcinoma are major causes of ACTH-independent Cushing syndrome. An ACTH level greater than 20 pg/mL (4.4 pmol/L) is consistent with ACTH-dependent Cushing syndrome. An ACTH level between 5 and 20 pg/mL is equivocal.
Diagnosis and Testing
Diagnosing Cushing syndrome involves a thorough evaluation of the patient’s symptoms, physical examination findings, and laboratory test results. The diagnostic process aims to confirm the presence of excess cortisol and identify the underlying cause.
The initial step in diagnosing Cushing syndrome is a comprehensive physical examination. Physicians look for characteristic signs such as moon-like facies, easy bruising, purple skin striae, and hirsutism. Additionally, they assess the patient’s blood pressure, as hypertension is a common feature of Cushing syndrome. In some cases, enlarging pituitary adenomas in Cushing’s disease may affect cranial nerves II, III, IV, and VI, leading to visual disturbances or eye movement abnormalities.
Laboratory tests play a crucial role in confirming the diagnosis of Cushing syndrome. The best screening test is a 24-hour urine collection with analysis for urinary free cortisol excretion. Elevated levels of urinary free cortisol, particularly values more than three times the upper limit of normal, strongly suggest Cushing syndrome.
Once the diagnosis of Cushing syndrome is established, imaging studies are performed to localize the source of excess cortisol production. If an adrenal tumor is suspected, an abdominal CT scan is recommended. For patients with suspected pituitary Cushing’s disease, a contrast-enhanced MRI of the pituitary gland is the imaging modality of choice. However, it is important to note that normal-appearing pituitaries may occur in some patients with Cushing’s disease due to diffuse hyperplasia of ACTH-producing cells or small microadenomas that are not visible on imaging studies.
In cases where the source of ACTH excess remains unclear, additional procedures such as inferior petrosal sinus sampling (IPSS) may be necessary. IPSS involves obtaining blood samples from the veins draining the pituitary gland to measure ACTH levels and lateralize the source of ACTH production.
The diagnosis of Cushing syndrome requires a comprehensive approach that integrates clinical findings, biochemical testing, and imaging studies. Accurate diagnosis is essential for guiding appropriate treatment and improving patient outcomes.
Treatment Options
The type of treatment for Cushing syndrome depends on the underlying cause of the high cortisol levels. If a tumor is causing Cushing syndrome, the healthcare provider may suggest surgery or radiation. Another option is for the healthcare provider to prescribe medication that slows down the production of cortisol.
Medication
Adding drugs that reduce cortisol or taking away drugs that can cause Cushing syndrome are potential treatment options. Medical therapy for Cushing syndrome is not a cure and may not completely improve all of the symptoms of too much cortisol. Medicines to control cortisol production at the adrenal gland include:
- Osilodrostat (Isturisa)
- Levoketoconazole (Recorlev)
(Mifeprex) is approved for people with Cushing syndrome who have type 2 diabetes or high blood sugar. It does not lower the amount of cortisol the body makes but blocks the effect of cortisol on tissues.
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Surgery
If Cushing syndrome is caused by a tumor, the healthcare provider may recommend removing the tumor with surgery. Pituitary tumors are often removed by a neurosurgeon, who may do the operation through the nose. ACTH-producing tumors in other parts of the body may be removed with regular surgery or using less-invasive approaches with smaller incisions.
If an ACTH-producing tumor isn’t found, or if one can’t be fully removed and Cushing syndrome continues, the healthcare provider may recommend removing the adrenal glands. This is called a bilateral adrenalectomy. This procedure immediately stops the body from making too much cortisol. After both adrenal glands are removed, the patient may need to take medicines to replace cortisol and another adrenal hormone called aldosterone for the rest of their life.
Radiation therapy
If the surgeon can’t totally remove a pituitary tumor, radiation therapy may be needed along with surgery. Radiation also may be used for people who can’t have surgery. Radiation can be given in small doses over six weeks, or with a single, high dose of radiation. In both cases, the healthcare provider can plan the procedure in a way that reduces radiation exposure to other tissues.
Cortisol levels may take years to return to normal after radiation therapy. During this time, the patient may need to take cortisol medications in the form of hydrocortisone tablets. They may be able to stop the medications after six to 18 months.
In summary, the treatment options for Cushing syndrome aim to normalize cortisol levels and manage the symptoms. The choice of treatment depends on the underlying cause and may involve medication, surgery, or radiation therapy. Close monitoring and follow-up with healthcare providers are essential for the best outcomes.
Conclusion
Cushing syndrome has a significant impact on a person’s health and well-being, making early detection and proper treatment crucial. This hormonal disorder, caused by excess cortisol in the body, can stem from various sources, including medication use, pituitary tumors, or adrenal gland issues. To diagnose Cushing syndrome, doctors use a mix of physical exams, lab tests, and imaging studies to pinpoint the root cause and craft an effective treatment plan.
Managing Cushing syndrome often involves a tailored approach, which may include stopping certain medications, surgery to remove tumors, or using drugs to lower cortisol levels. The goal is to bring cortisol production back to normal and ease the symptoms that come with this condition. With the right care and ongoing follow-ups, many people with Cushing syndrome can see big improvements in their health and quality of life.