Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, round red faces, fat bumps between the shoulders, weak muscles, weak bones, pimples, and brittle skin that heal badly. Women may have more hair and irregular menstruation. Sometimes there are mood swings, headaches, and chronic fatigue.
Cushing's syndrome is caused by drugs such as excessive cortisol such as prednisone or tumors that produce or produce excessive cortisol production by the adrenal gland. Cases caused by pituitary adenomas are known as Cushing's disease. This is the second most common cause of Cushing's syndrome after treatment. A number of other tumors can also cause Cushing. Some of these are associated with congenital abnormalities such as some type 1 endocrine neoplasia and the Carney complex. Diagnosis requires a number of steps. The first step is to examine the drug a person uses. The second step is to measure cortisol levels in urine, saliva or in the blood after taking dexamethasone. If the test is not normal, cortisol may be measured late at night. If cortisol remains high, blood tests for ACTH can be performed.
Most cases can be treated and cured. If due to medication, this can often be stopped slowly. If caused by a tumor, it can be treated with a combination of surgery, chemotherapy, and/or radiation. If the pituitary is affected, other medications may be needed to replace the missing function. With care, life expectancy is usually normal. Some, among whom surgery can not lift all tumors, have an increased risk of death.
About two to three people per million are affected each year. It most often affects people aged 20 to 50 years. Women are affected three times more often than men. The mild degree of overt production of cortisol without obvious symptoms, however, is more common. Cushing's syndrome was first described by Harvey Cushing in 1932. Cushing's syndrome can also occur in other animals including cats, dogs, and horses.
Video Cushing's syndrome
Signs and symptoms
Symptoms include rapid weight gain, especially on the trunk and face with frugal limbs (central obesity). Common signs include the growth of fat pads along the collarbone, at the back of the neck ("buffalo hump" or lipodystrophy), and on the face ("face of the moon"). Other symptoms include excessive sweating, capillary dilation, skin thinning (which causes easy bruising and dryness, especially the hands) and mucous membranes, purple or red striae (weight gain in Cushing's syndrome stretches the skin, thin and weak, causes bleeding) on ​​the stem body, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (male-pattern male hair growth), bald and/or very dry and brittle hair. In rare cases, Cushing can cause hypocalcaemia. Excess cortisol may also affect the system and other endocrine causes, for example, insomnia, inhibited aromatase, reduced libido, male impotence, and amenorrhoea/oligomenorrhea and infertility in women due to androgen increases. Studies also show that the resulting amenorrhea is due to hypercortisolism, which feeds back into the hypothalamus resulting in a decrease in GnRH release rate.
Cognitive conditions, including memory dysfunction and attention, as well as depression, are commonly associated with increased cortisol, and may be an early or endogenous Cushing indicator. Depression and anxiety disorders are also common.
Other striking and troublesome skin changes that may arise in Cushing's syndrome include facial acne, susceptibility to superficial fungal infections (dermatophytes and malassezia), and a purplish-type atrophic striae in the abdomen.
Other signs include increased urination (and accompanied by increased thirst), persistent high blood pressure (due to increased vasoconstriction effect of cortisol from epinephrine) and insulin resistance (especially common with the production of ACTH outside the pituitary), leading to high blood sugar and insulin resistance that can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cortisol may also exhibit mineralocorticoid activity in high concentrations, aggravate hypertension and cause hypokalemia (common in ectopic ACTH secretion) and hypernatremia (elevated Na-ion concentration in plasma). Furthermore, excessive cortisol can cause gastrointestinal disorders, opportunistic infections, and wound healing disorders associated with cortisol suppression of the immune response and inflammation. Osteoporosis is also a problem in Cushing's syndrome because osteoblast activity is inhibited. In addition, Cushing's syndrome can cause joint pain and pain, especially in the hips, shoulders, and lower back. Cushing's syndrome includes all the causes of increased cortisol leading to sickness. Cushing's disease is a special type of Cushing's syndrome caused by a pituitary tumor causing excessive production of ACTH (adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, resulting in disease status. Cushing's disease due to excessive ACTH can also cause hyperpigmentation. This is due to the production of Melanocyte-Stimulating Hormone as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Or, it is proposed that the high level of ACTH ,? -lipotropin, and -lipotropin, which contains weak MSH function, may work on melanocortin receptors 1. Cushing disease variants can be caused by ectopics, ie extrapituitally, ACTH production from, for example, small cell lung cancer. When Cushing's syndrome is caused by increased cortisol at the level of the adrenal gland (via adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In this case, ACTH levels remain low and no hyperpigmentation develops. While all Cushing's disease gives Cushing's syndrome, not all Cushing's syndrome is caused by Cushing's disease.
Brain changes such as cerebral atrophy may occur. This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and highly correlated with psychopathologic personality changes.
- Fast weight gain
- Moodiness, irritability, or depression
- Muscle and bone weakness
- Memory dysfunction and attention
- Osteoporosis
- Diabetes mellitus
- Hypertension
- Immune suppression
- Sleeping disorders
- Menstrual disorders such as amenorrhea in women
- Infertility in women
- Impotence in men
- Hirsutism
- Baldness
- Hypercholesterolemia
Maps Cushing's syndrome
Cause
Some possible causes of Cushing's syndrome are known.
External versus internal
The most common cause of Cushing's syndrome is the taking of glucocorticoids prescribed by health care practitioners to treat other diseases (called iatrogenic Cushing's syndrome). This can be a corticosteroid treatment effect of various disorders such as asthma and rheumatoid arthritis, or in immunosuppression after organ transplantation. Synthetic ACTH administration is also possible, but ACTH is less commonly prescribed because of lower costs and utilities. Although rare, Cushing's syndrome can also be caused by the use of medroxyprogesterone acetate. In Cushing's form, atrophy of the adrenal gland due to lack of stimulation by ACTH, because glucocorticoids decrease ACTH production regulation. Cushing's syndrome in childhood usually results from the use of glucocorticoid drugs.
Endogen Cushing's syndrome results from some of the body's own system disorders that secrete cortisol. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands.
- In the Cushing pituitary, benign pituitary adenomas secrete ACTH. It is also known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.
- In Cushing adrenal, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.
- Tumors outside the normal pituitary-adrenal system can produce ACTH (sometimes with CRH) that affects the adrenal gland. This etiology is called ectopic or paraneoplastic Cushing disease and is seen in diseases such as small cell lung cancer.
- Finally, rare cases of tumors secreting CRH (without ACTH secretion) have been reported, which stimulate the production of ACTH pituitary.
Pseudo-Cushing's Syndrome
Increased total cortisol levels can also be caused by estrogen found in oral contraceptive pills containing a mixture of estrogen and progesterone, leading to Pseudo-Cushing syndrome. Estrogen can cause an increase in cortisol binding globulin and thus cause total cortisol levels to rise. However, the total free cortisol, which is an active hormone in the body, measured by 24-hour urine collection for urine-free cortisol, is normal.
Pathophysiology
The hypothalamus is in the brain and the pituitary gland is just below it. The paraventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropin (ACTH). The ACTH travels through the blood to the adrenal glands, where it stimulates the release of cortisol. Cortisol is secreted by the adrenal gland cortex from an area called the fasciculata zone in response to ACTH. Increased levels of cortisol provide negative feedback on CRH in the hypothalamus, which decreases the amount of ACTH released from the anterior pituitary gland.
In fact, Cushing's syndrome refers to excess cortisol from any etiology (as a syndrome meaning group of symptoms). One of the causes of Cushing's syndrome is the adenoma that secretes cortisol in the adrenal gland cortex (primary hypercortisolism/hypercortism). Adenomas cause blood levels of cortisol to become very high, and negative feedback on the pituitary of high levels of cortisol causes ACTH levels to be very low.
Cushing's disease refers only to secondary hypercortisolism due to the overproduction of ACTH from corticotrophic pituitary adenoma (secondary hypercortisolism/hypercortism) or due to hypothalamic production of CRH (tertiary hypercortisolin releasing hormone) (hypercortisolism/tertiary hypercortism). This causes blood levels of ACTH to increase along with cortisol from the adrenal glands. ACTH levels remain high because the tumors are unresponsive to negative feedback from high levels of cortisol.
When Cushing's syndrome is due to ACTH additionally known as ectopic Cushing syndrome. This can be seen in paraneoplastic syndrome.
When Cushing's syndrome is suspected, both dexamethasone suppression tests (dexamethasone administration and determination of cortisol and ACTH levels), or 24-hour urine measurement for cortisol offer the same level of detection. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and the blood sample is tested, cortisol & gt; 50 nmol/l (1.81 Âμg/dl) would be an indication of Cushing's syndrome because ectopic cortisol or ACTH sources (such as adrenal adenomas) exist that are not inhibited by dexamethasone. A new approach, recently cleared by the US FDA, is a 24-hour dose of cortisol sampling, which may be just as sensitive, as salivary cortisol levels at night are high in cushingoid patients. Other pituitary hormone levels may need to be confirmed. Performing a physical examination to determine visual field defects may be necessary if pituitary lesions are suspected, which may suppress the optic chiasm, causing typical typontal hemianopia.
When one of these tests is positive, a CT scan of the adrenal gland and MRI of the pituitary gland is performed to detect the presence of adrenal or pituitary adenomas or incidentaloma (incidental invention of harmless lesions). Adrenal gland scintigraphy with iodocholesterol scanning is sometimes necessary. Occasionally, determining levels of ACTH in various veins in the body by venous catheterization, working toward the pituitary (a sinus petrosal sampling) is required. In many cases, tumors that cause Cushing's disease are less than 2 mm and are difficult to detect using MRI or CT imaging. In one study of 261 patients with confirmed pituitary disease, only 48% of pituitary lesions were identified using MRI prior to surgery.
Plasma CRH levels are inadequate at diagnosis (with possible exceptions from tumors that secrete CRH) due to peripheral dilution and binding to CRHBP.
Diagnosis
Cushing's syndrome can be confirmed through a variety of tests that include:
- Dexamethasone suppression test
- Saliva cortisol level
Treatment
Most cases of Cushingoid symptoms are caused by corticosteroid drugs, such as those used for asthma, arthritis, eczema and other inflammatory conditions. As a result, most patients are effectively treated by carefully reducing (and eventually stopping) the drugs that cause the symptoms.
If adrenal adenomas are identified, they may be removed surgically. A corticotrophic pituitary adenoma that secretes ACTH should be removed after diagnosis. Regardless of the location of adenoma, most patients require postoperative steroid replacement at least temporarily, because long-term depletion of the pituitary ACTH and normal adrenal tissue do not recover soon. Obviously, if both adrenals are removed, replacement with hydrocortisone or prednisolone is a must.
In patients who are unsuited or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (eg ketoconazole, metyrapone) but they have limited efficacy. Mifepristone is a strong type II glucocorticoid receptor antagonist and, because it does not interfere with homeostatic normal cortisol type I receptor transmission, may be very useful for treating the cus- tive effects of Cushing's syndrome. However, this drug faces considerable controversy because of its use as abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who were not candidates for surgery, or who did not respond to prior surgery, with a warning that mifepristone should not be used by pregnant women.
Adrenal removal in the absence of a known tumor is sometimes done to remove excess cortisol production. On several occasions, this eliminates negative feedback from previous occult pituitary adenomas, which begin to grow rapidly and result in extreme ACTH levels, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome.
Epidemiology
Cushing's syndrome caused by treatment with corticosteroids is the most common form. Cushing's disease is rare; a study in Denmark found the incidence of less than one case per million people per year. However, asymptomatic microadenomas (less than 10 mm) of the pituitary are found in about one in six individuals.
People with Cushing's syndrome have increased morbidity and mortality compared with the general population. The most common cause of death in Cushing's syndrome is cardiovascular events. People with Cushing's syndrome have nearly 4 times increased cardiovascular mortality compared with the general population.
Other animals
For more information on the shape on the horse, see pituitary pars intermedia dysfunction.
See also
- Addison's disease
- adrenal insufficiency (hypokortisolism)
References
External links
- Information from Epg Online
Source of the article : Wikipedia
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