Cushing syndrome and cancer
Cushing syndrome, also known as hypercortisolism, is an endocrine disorder characterized by prolonged exposure to elevated cortisol levels in the body. This condition can arise from various factors, including the use of exogenous steroids, specific tumors that produce adrenocorticotropic hormone (ACTH), or adrenal gland tumors. The disorder is associated with a range of symptoms such as rapid weight gain, thinning skin, muscle weakness, excessive hair growth, and psychological disturbances, which can significantly impact quality of life.
In the context of cancer, Cushing syndrome can occur due to ectopic ACTH syndrome, where tumors, often in the lungs or other locations, secrete ACTH, leading to increased cortisol production. The annual incidence of endogenous Cushing syndrome is estimated at 40 to 70 cases per million individuals, with most cases attributed to the use of glucocorticoids. Diagnosis typically involves urinary free cortisol tests, salivary cortisol measurements, and imaging studies to identify tumors. Treatment options may include reducing steroid use, surgical intervention for tumors, radiation therapy, and medications to manage cortisol levels. While untreated Cushing syndrome can be life-threatening, appropriate treatment can lead to symptom relief and improved health outcomes.
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Cushing syndrome and cancer
ALSO KNOWN AS: Cushing’s syndrome, hypercortisolism, hyperadrenocorticism, Itsenko-Cushing syndrome
RELATED CONDITIONS: Polycystic ovary syndrome, pseudo-Cushing’s syndrome, leukocytosis, hyperglycemia, hypokalemia, hypercoagulability, small-cell lung cancer
DEFINITION: Cushing syndrome is an endocrine disorder that results from prolonged exposure of the body to high levels of the hormone cortisol.
Risk factors: People who take exogenous steroids, like people with arthritis or organ transplant patients, and families that show an inherited tendency to develop endocrine gland tumors are at risk of developing Cushing syndrome. Individuals taking glucocorticoid or corticosteroid medicines like prednisone, dexamethasone, or prednisolone for long periods are also at increased risk. The presence of tumors that produce the protein hormone adrenocorticotropic (ACTH) causes Cushing's syndrome to develop. Additionally, the herbal supplement Artri King has been linked to Cushing's syndrome.
Etiology and the disease process: The adrenal glands lie on top of the kidneys, and the hormone cortisol is made by the outer layer (cortex) of the adrenal glands. Cortisol maintains blood sugar levels and blood pressure, reduces the inflammatory response, balances the activity of insulin, and regulates the metabolism of proteins, sugars, and fats. It also helps the body respond to stress and is found in high levels in women in their last three months of pregnancy, highly trained athletes, and people suffering from depression.
Cortisol secretion by the adrenal glands is tightly regulated. A peptide hormone called corticotropin-releasing hormone (CRH) is released into the bloodstream by a portion of the brain called the hypothalamus. CRH signals to the anterior lobe of the pituitary gland, which lies just below the hypothalamus, to release ACTH. Circulating ACTH signals to the adrenal cortex cells to release cortisol. Normal blood cortisol levels shut off CRH and ACTH release by the hypothalamus and anterior lobe of the pituitary gland, respectively. Perturbation of this negative feedback control loop can abnormally increase blood cortisol levels.
Particular tumors of the anterior lobe of the pituitary (pituitary adenomas) that secrete increased amounts of ACTH cause most cases of Cushing syndrome (Cushing disease). Tumors outside the pituitary also can secrete increased amounts of ACTH (ectopic ACTH syndrome). Lung tumors cause more than half these cases. Sometimes adrenal gland tumors can cause Cushing syndrome. adrenocortical carcinomas cause high blood cortisol levels and rapid onset of symptoms.
Incidence: The majority of Cushing syndrome cases are due to exogenous glucocorticoids. The annual incidence of endogenous Cushing syndrome is estimated at 40 to 70 cases per 1 million individuals.
Symptoms: Symptoms of Cushing syndrome include rapid weight gain concentrated around the face (moon face) and trunk; excessive sweating; thinning of the skin that causes easy bruising, poor healing, and stretch marks; muscle weakness, particularly in the shoulders and hips; excessive hair growth in women; and fat pad deposition on the back of the neck and collar bone (buffalo hump). Excess cortisol also causes insomnia, infertility, and psychological disturbances that range from euphoria to psychosis and also commonly include depression, anxiety, and panic attacks. Complications include bone loss and osteoporosis, high blood pressure, kidney stones, type II diabetes, and unusual infections as a result of suppression of the immune system.
Screening and diagnosis: The urinary free cortisol (UFC) test determines free cortisol concentrations in the urine over twenty-four hours. Urinary cortisol concentrations above three to four times the normal level (50 to 100 micrograms a day) are highly suggestive of Cushing syndrome. However, measuring cortisol in saliva at nighttime has become more popular. High salivary cortisol levels are also indicative of Cushing syndrome.
The dexamethasone suppression test determines the location of the abnormality. Dexamethasone mimics the physiological effects of cortisol, inhibiting ACTH release by the anterior lobe of the pituitary gland and decreasing cortisol production. If an ectopic source of cortisol production exists, then dexamethasone administration should not decrease blood or urine cortisol levels. Low-dose and high-dose dexamethasone tests are combined, and if there is no change in cortisol levels before and after dexamethasone administration for either test, an adrenal or ectopic ACTH-producing tumor is indicated. No change for the low-dose test and normal suppression in the high-dose test indicate a pituitary tumor. The CRH stimulation test further distinguishes between pituitary and ectopic ACTH-producing tumors. After an injection of CRH, patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol, but those with ectopic ACTH syndrome and cortisol-secreting adrenal tumors show no such response.
If the endocrine tests are positive for Cushing syndrome, computed tomography scans of the chest and abdomen or magnetic resonance imaging of the pituitary gland can detect tumors of the adrenal glands or pituitary gland that might be producing excessive cortisol or ACTH. Bone mineral density tests may also aid in the diagnosis of Cushing's syndrome while detecting the common complication of bone loss or osteoporosis.
Treatment and therapy: Reducing the use of corticosteroid drugs can ameliorate the symptoms of exogenous Cushing syndrome. In the case of endogenous Cushing syndrome, surgery is recommended for tumors producing ACTH or cortisol. Radiation therapy is sometimes required to completely extirpate the tumor. Drugs that reduce cortisol production, such as ketoconazole (Nizoral), levoketoconazole (Recorlev), osilodrostat (Isturisa), mitotane (Lysodren), or metyrapone (Metopirone), can normalize cortisol blood levels and are given before surgery for those who are quite ill or to those for whom surgery and radiation were not completely successful. For Cushing syndrome patients with type II diabetes, Mifepristone (Korlym or Mifeprex) is appropriate. The twice-a-day Pasireotide (Signifor) injection is available for patients who cannot take oral medications.
Prognosis, prevention, and outcomes: If left untreated, Cushing syndrome is lethal, but with treatment, most patients experience some relief of symptoms and cortisol normalization.
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