Which exogenous conditions are responsible for increased cortisol secretion
Cushing's syndrome is a disorder caused by the body’s exposure to an excess of the hormone cortisol. Cortisol affects all tissues and organs in the body. These effects together are known as Cushing's syndrome. Show
Cushing’s syndrome can be caused by overuse of cortisol medication, as seen in the treatment of chronic asthma or rheumatoid arthritis (iatrogenic Cushing’s syndrome), excess production of cortisol from a tumor in the adrenal gland or elsewhere in the body (ectopic Cushing’s syndrome) or a tumor of the pituitary gland secreting adrenocorticotropic hormone (ACTH) which stimulates the over-production of cortisol from the adrenal gland (Cushing’s disease). Cortisol is a normal hormone produced in the outer portion of the adrenal glands. When functioning correctly, cortisol helps the body respond to stress and change. It mobilizes nutrients, modifies the body's response to inflammation, stimulates the liver to raise blood sugar and helps control the amount of water in the body. Cortisol production is regulated by the ACTH produced in the pituitary gland. Prevalence of Cushing’s Syndrome
Underlying CausesPituitary Adenomas — Cushing’s DiseasePituitary adenomas are benign tumors of the pituitary gland that secrete increased amounts of ACTH causing excessive cortisol production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing, MD, in his book The Pituitary Body and Its Disorders, Cushing’s disease is the most common cause of spontaneous Cushing’s syndrome, accounting for 60-70 percent of all cases. Some benign or malignant (cancerous) tumors that arise outside the pituitary gland can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors (malignant adenomas or carcinoids) cause more than 50 percent of these cases. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors and medullary carcinomas of the thyroid. An abnormality of the adrenal glands, such as an adrenal tumor, may cause Cushing's syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood. Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing's syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones including cortisol and adrenal androgens. Adrenocortical carcinomas often cause very high hormone levels and a rapid onset of symptoms. Familial Cushing's SyndromeMost cases of Cushing's syndrome are not genetic. However, some individuals may develop Cushing's syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In primary pigmented micronodular adrenal disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In multiple endocrine neoplasia type I (MEN I), hormone-secreting tumors of the parathyroid glands, pancreas and pituitary gland can occur. Cushing's syndrome in MEN I may be due to a pituitary, ectopic or adrenal tumor. Signs and Symptoms Associated with Cushing’s Syndrome/Disease:
The diagnosis of Cushing's syndrome is based on clinical suspicion combined with a review of the patient’s medical history, physical examination and laboratory tests to help determine the existence of excessive levels of cortisol. A patient suspected of having Cushing’s syndrome must initially have an appearance suggestive of excess cortisol production combined with an elevated 24-hour urinary excretion of cortisol. In assessing the physical features of Cushing’s syndrome, it can often be beneficial to compare old and recent photographs to reveal the classic changes in facial and body appearance associated with this disorder. The following tests can help determine if there are excessive levels of cortisol being produced:
After a definitive diagnosis has been made, the source must then be determined. The first step in distinguishing the underlying cause is the measurement of ACTH. Patients with ACTH-secreting tumors will either have a normal or elevated level of ACTH. In contrast, patients with an excess of adrenal cortisol will have a subnormal level. Performing a high-dose dexamethasone suppression test may be helpful in this situation. This test, similar to the low-dose dexamethasone suppression test, involves taking a high dose of dexamethasone (8 mg) at 11 p.m. then having blood drawn to screen for the presence of cortisol the following morning. In normal patients, the morning level of cortisol will again be very low. Patients with pituitary tumors will also suppress their serum cortisol level, but those with adrenal tumors will maintain a high level of cortisol production. A high level of cortisol points to a non-pituitary source. Despite the tests described above, distinguishing a pituitary from a non-pituitary ACTH-secreting tumor can be diagnostically challenging. The majority of patients with ACTH-secreting tumors have a pituitary lesion that is often very small. The following tests are recommended:
Treatment of Cushing's SyndromeTreatment of Cushing’s syndrome depends on the underlying cause of excess cortisol but may perhaps include surgery, radiation, chemotherapy or the use of cortisol-inhibiting drugs. If the cause is iatrogenic, from long-term use of glucocorticoid hormones to treat another disorder, the physician will gradually reduce the dose of the externally administered steroid to the lowest dose adequate for control of that disorder. Once control is established, the dose of glucocorticoid hormones may be given on alternate days to lessen side effects for the patient. Treatment of Cushing’s DiseaseMicrosurgical resection of an ACTH-secreting pituitary adenoma is the optimum treatment for Cushing’s disease with cure rates of 80-90 percent if a tumor is found. Surgery is most often done through a transnasal transsphenoidal approach, which will not leave a visible scar. This type of surgery may be performed, per the surgeon’s preference, using either a minimally invasive operating microscope or with the use of an endoscope. Partial removal of the pituitary gland (subtotal hypophysectomy) may be used in patients without clearly identifiable adenomas. In patients to whom a remission is not obtained after surgery, the use of various medications that can inhibit cortisol production may be used, such as: These agents are not as effective as surgery and are considered a second–line course of treatment. In some patients who are particularly resistant to all forms of therapy, removal of the adrenal glands bilaterally (bilateral adrenalectomy) may be considered. Post-surgery, with successful tumor removal, the production of ACTH drops below normal. This decrease is natural and temporary, and patients are prescribed a synthetic form of cortisol such as hydrocortisone or prednisone to compensate this change. Most patients can discontinue replacement therapy within six to 12 months, but others may require the use of oral steroids for several years to, possibly, their lifetime. Patients who need adrenal surgery may also require steroid replacement therapy. One additional treatment option in patients who have failed surgical procedures or are too high risk medically to bring to surgery is radiation therapy. Radiation therapy, which is administered over a six-week period to the pituitary gland, has yielded improvement in 40-50 percent of adults and up to 85 percent of children. Stereotactic radiosurgery has also been found to be an effective treatment for patients with ACTH-secreting pituitary adenomas. A recent study demonstrated endocrine remission in 54 percent of patients and tumor-growth control in 96 percent. However, ongoing observation is required to monitor for tumor growth, disease recurrence, the development of new hormone deficiencies and damage to the optic pathways and brain. Cushing’s Syndrome/Disease ResourcesThe AANS does not endorse any treatments, procedures, products or physicians referenced in these patient fact sheets. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific neurosurgical advice or assistance should consult his or her neurosurgeon, or locate one in your area through the AANS’ Find a Board-certified Neurosurgeon” online tool. What causes increased cortisol?Causes of higher-than-normal cortisol levels and Cushing's syndrome include: Taking large amounts of corticosteroid medications, such as prednisone, prednisolone or dexamethasone, for treatment of other conditions. Tumors that produce adrenocorticotropic hormone (ACTH). These are usually found in your pituitary gland.
What stimulates cortisol secretion?Cortisol secretion is regulated by the HPAC, such that neurosecretory cells in the hypothalamic paraventricular nucleus release corticotropin releasing factor into the pituitary stalk, causing ACTH release by the anterior pituitary, resulting in increased rates of adrenal cortisol production.
What stimulus causes the release of cortisol?The release of cortisol is triggered by physical or psychological stress. The function of cortisol is to prepare the body for action in response to stress, and among its effects are an increase in blood pressure, an increase in blood sugar, and a suppression of the immune system.
Which of the following causes the secretion of cortisol quizlet?High levels of ACTH hormone are detected in the adrenal glands and stimulate the secretion of cortisol, causing blood levels of cortisol to rise.
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