1.

adrenal crisis the adrenal cortex produces 3 steroid hormones: glucocorticoids (cortisol), mineralocorticoids (aldosterone, 11-deoxycorticosterone), and androgens (dehydroepiandrosterone). The androgens are relatively unimportant in adults, and 11-deoxycorticosterone is a fairly weak mineralocorticoid in comparison with aldosterone. The primary hormone of importance in acute adrenal crisis is cortisol; adrenal aldosterone production is relatively minor. Cortisol enhances gluconeogenesis and provides substrate through proteolysis, protein synthesis inhibition, fatty acid mobilization, and enhanced hepatic amino acid uptake. Cortisol indirectly induces insulin secretion to counterbalance hyperglycemia but also decreases insulin sensitivity. Cortisol exercises a significant anti-inflammatory effect by stabilizing lysosomes, reducing leukocytic responses, and blocking cytokine production. Phagocytic activity is preserved, but cell-mediated immunity is diminished, in situations of cortisol deficiency. Finally, cortisol facilitates free-water clearance, enhances appetite, and suppresses adrenocorticotropic hormone (ACTH) synthesis. Aldosterone is released in response to angiotensin II stimulation via the renin-angiotensin-aldosterone system, hyperkalemia, hyponatremia, and dopamine antagonists. Its effect on its primary target organ, the kidney, is to promote reabsorption of sodium and secretion of potassium and hydrogen. The mechanism of action is unclear; an increase in the sodium- and potassium-activated adenosine triphosphatase (Na+/K+ ATPase) enzyme responsible for sodium transport, as well as increased carbonic anhydrase activity, has been suggested. The net effect is to increase intravascular volume. The reninangiotensin-aldosterone system is unaffected by exogenous glucocorticoids, and ACTH deficiency has a relatively minor effect on aldosterone levels. Adrenocortical hormone deficiency results in the reverse of these hormonal effects, producing the clinical findings of adrenal crisis. Primary adrenocortical insufficiency occurs when the adrenal glands fail to release adequate amounts of these hormones to meet physiologic needs, despite release of ACTH from the pituitary. Infiltrative or autoimmune disorders are the most common cause, but adrenal exhaustion from severe chronic illness also may occur. Secondary adrenocortical insufficiency occurs when exogenous steroids have suppressed the hypothalamic-pituitary-adrenal (HPA) axis. Too rapid withdrawal of exogenous steroid may precipitate adrenal crisis, or sudden stress may induce cortisol requirements in excess of the adrenal glands' ability to respond immediately. In acute illness, a normal cortisol level may actually reflect adrenal insufficiency because the cortisol level should be quite elevated. Bilateral massive adrenal hemorrhage (BMAH) occurs under severe physiologic stress (eg, myocardial infarction, septic shock, complicated pregnancy) or with concomitant coagulopathy or thromboembolic disorders.

2. About prognosis: The 'prognosis' of Cushing's syndrome usually refers to the likely outcome of Cushing's syndrome. The prognosis of Cushing's syndrome may include the duration of Cushing's syndrome, chances of complications of Cushing's syndrome, probable outcomes, prospects for recovery, recovery period for Cushing's syndrome, survival rates, death rates, and other outcome possibilities in the overall prognosis of Cushing's syndrome. Naturally, such forecast issues are by their nature unpredictable. Prognosis of Cushing's syndrome: Many cases can be cured. Results depend on the underlying cause and severity of the problem. Prognosis for Cushing's syndrome: The prognosis for individuals with Cushing's syndrome varies depending on the cause of overproduction of cortisol. With treatment, most individuals with Cushing's syndrome show significant improvement, while improvement for others may be complicated by various aspects of the causative illness. Some kinds of tumors may recur. Most cases of Cushing's can be cured

3. Treatment depends on the specific reason for cortisol excess and may include surgery, radiation, chemotherapy or the use of cortisol-inhibiting drugs. If the cause is long-term use of glucocorticoid hormones

to treat another disorder, the doctor will gradually reduce the dosage to the lowest dose adequate for control of that disorder. Once control is established, the daily dose of glucocorticoid hormones may be doubled and given on alternate days to lessen side effects.

Pituitary Adenomas

Several therapies are available to treat the ACTH-secreting pituitary adenomas of Cushing's disease. The most widely used treatment is surgical removal of the tumor, known as transsphenoidal adenomectomy. Using a special microscope and very fine instruments, the surgeon approaches the pituitary gland through a nostril or an opening made below the upper lip. Because this is an extremely delicate procedure, patients are often referred to centers specializing in this type of surgery. The success, or cure, rate of this procedure is over 80 percent when performed by a surgeon with extensive experience. If surgery fails, or only produces a temporary cure, surgery can be repeated, often with good results. After curative pituitary surgery, the production of ACTH drops two levels below normal. This is a natural, but temporary, drop in ACTH production, and patients are given a synthetic form of cortisol (such as hydrocortisone or prednisone). Most patients can stop this replacement therapy in less than a year.

For patients in whom transsphenoidal surgery has failed or who are not suitable candidates for surgery, radiotherapy is another possible treatment. Radiation to the pituitary gland is given over a 6-week period, with improvement occurring in 40 to 50 percent of adults and up to 80 percent of children. It may take several months or years before patients feel better from radiation treatment alone. However, the combination of radiation and the drug mitotane (Lysodren) can help speed recovery. Mitotane suppresses cortisol production and lowers plasma and urine hormone levels. Treatment with mitotane alone can be successful in 30 to 40 percent of patients. Other drugs used alone or in combination to control the production of excess cortisol are aminoglutethimide, metyrapone, trilostane and ketoconazole. Each has its own side effects that doctors consider when prescribing therapy for individual patients.

Ectopic ACTH Syndrome

To cure the overproduction of cortisol caused by ectopic ACTH syndrome, it is necessary to eliminate all of the cancerous tissue that is secreting ACTH. The choice of cancer treatment - surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these treatments - depends on the type of cancer and how far it has spread. Since ACTH-secreting tumors (for example, small cell lung cancer) may be very small or widespread at the time of diagnosis, cortisol-inhibiting drugs, like mitotane, are an important part of treatment. In some cases, if pituitary surgery is not successful, surgical removal of the adrenal glands (bilateral adrenalectomy) may take the place of drug therapy.

Adrenal Tumors

Surgery is the mainstay of treatment for benign as well as cancerous tumors of the adrenal glands. In Primary Pigmented Micronodular Adrenal Disease and the familial Carney's complex, surgical removal of the adrenal glands is required.

4. complication cushing

High blood pressure High blood pressure means that the bodys blood flow is causing too much pressure against artery walls. Up to 80% of people with Cushings syndrome have high blood pressure. Though seen more often in adults, high blood pressure is also very common in children with Cushings syndrome.1

Ways to manage: Treatment to normalize cortisol + standard blood pressure medicine

Diabetes Many people with Cushings syndrome develop problems with the way their body processes sugars. These are called glucose metabolism disorders, and they include diabetes, a condition caused by too much sugar (glucose) in the blood. Diabetes occurs in 20% to 50% of people with Cushings syndrome.1 Ways to manage: Treatment to normalize cortisol + changes in diet (as directed by a doctor); may also include medicine to reduce blood sugar

Obesity Obesity is the term used for a high body mass index (that is, the amount of fat in the body). In people with Cushings syndrome, obesity can develop particularly in the middle part of the body (around the abdominal area), while arms and legs can be thin.1 Obesity occurs in more than 90% of people with Cushings syndrome.4 Ways to manage: Treatment to normalize cortisol + changes in diet and/or appropriate medicines/exercise

High cholesterol and triglycerides In people with Cushings syndrome, excess cortisol can cause an increase in cholesterol and triglycerides. As a result, cholesterol and triglycerides build up in arteries, making it more difficult for blood to flow to the heart.1 Ways to manage: Treatment to normalize cortisol + dietary changes, exercise, and cholesterolreducing medicine

Excess clotting of the blood Blood clots are soft, thick masses of blood that form to prevent too much bleeding (for instance, at the site of a wound). However, excess cortisol can cause the blood to form unneeded clots. These extra clots can block arteries, affecting blood flow to the heart.1 Ways to manage: Treatment to normalize cortisol + anticlotting medicine when needed (for instance, right before and after an operation)

Osteoporosis

Osteoporosis means that bones become fragile and can fracture easily. Around 50% of people with Cushings syndrome are reported to have osteoporosis.1

Ways to manage: Treatment to normalize cortisol + antiresorptive osteoporosis medicine + daily requirements of calcium and vitamin D

Psychological and mental changes From 50% to 80% of people with Cushings syndrome are reported to experience major depression. Cushings syndrome can also cause other mood disorders such as mania, memory problems, anxiety and, in children, obsessive-compulsive disorder.1

Ways to manage: Treatment to normalize cortisol + therapy and medicines for specific psychological symptoms (depression or anxiety) Cushings syndrome can also cause other complications. For example, Cushings syndrome may reduce thyroid function (called hypothyroidism), cause infertility in both men and women, and prevent children from growing normally in height.1 In 80% to 85% of people with endogenous Cushings syndrome, the cause is excess ACTH produced by a pituitary or other tumor. Treatment to reduce ACTH levels will, in turn, reduce cortisol to normal levels which is very important in managing the complications of Cushings syndrome.1mplication