Cushing Syndrome

Cushing syndrome occurs when your body has too much of the hormone cortisol over time. This can result from taking oral corticosteroid medication. Or your body might produce too much cortisol.
Too much cortisol can cause some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin. Cushing syndrome can also result in high blood pressure, bone loss and, on occasion, type 2 diabetes.
Treatments for Cushing syndrome can return your body's cortisol levels to normal and improve your symptoms. The earlier treatment begins, the better your chances for recovery.

1. Memoona Arshad Group 11 – 6 th Sem ISM – IUK Presented to : Uvaidulaeva F.T Cushing Syndrome

2. Cushing syndrome occurs when your body has too much of the hormone cortisol over time. This can result from taking oral corticosteroid medication. Or your body might produce too much cortisol . Too much cortisol can cause some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin. Cushing syndrome can also result in high blood pressure, bone loss and, on occasion, type 2 diabetes. Treatments for Cushing syndrome can return your body's cortisol levels to normal and improve your symptoms. The earlier treatment begins, the better your chances for recovery. Overview

3. There are two main etiologies of Cushing syndrome: Endogenous hypercortisolism Endogenous Cushing syndrome results from excessive production of cortisol by adrenal glands and can be ACTH-dependent and ACTH-independent . exogenous hypercortisolism . Exogenous hypercortisolism , the most common cause of Cushing syndrome, is mostly iatrogenic and results from the prolonged use of glucocorticoids . ACTH-secreting pituitary adenomas (Cushing disease) and ectopic ACTH secretion by neoplasms are responsible for ACTH-dependent Cushing. Adrenal hyperplasia, adenoma, and carcinoma are major causes of ACTH-independent Cushing syndrome. Etiology

4. When stimulated by ACTH, the adrenal gland secretes cortisol and other steroid hormones. ACTH is produced by the pituitary gland and released into the petrosal venous sinuses in response to stimulation by corticotropin -releasing hormone (CRH) from the hypothalamus  ( according to image on next slide ). ACTH is released in a diurnal pattern that is independent of circulating cortisol levels: peak release occurs just before awakening, and ACTH levels then decline throughout the day. Control of CRH and ACTH release is maintained through negative feedback by cortisol at the hypothalamic and pituitary levels. Neuronal input at the hypothalamic level can also stimulate CRH release. Pathphysiology

5. Although the adenomas of Cushing's disease secrete excessive amounts of ACTH, they generally retain some negative feedback responsiveness to high doses of glucocorticoids . Ectopic sources of ACTH, usually in the form of extracranial neoplasms , are generally not responsive to negative feedback with high doses of glucocorticoids . However , some overlap exists in the response to negative feedback between pituitary and ectopic sources of excessive ACTH. Cushing's syndrome is categorized as ACTH dependent or ACTH independent  ( according to table on next slide ). This division is convenient for organizing the work-up of patients with suspected hypercortisolism . Pathphysiology (Contd..)

6. ACTH Dependent ACTH Independent Cushing's disease Iatrogenic Ectopic ACTH syndrome Adrenal adenoma Ectopic corticotropin -releasing hormone syndrome* Micronodular hyperplasia * Macronodular hyperplasia* Classification of Cushing's Syndrome ACTH = adrenocorticotropin hormone. *—Accounts for 1 percent or less of cases .

7. Depression, alcoholism, medications, eating disorders and other conditions can cause mild clinical and laboratory findings, similar to those in Cushing's syndrome, termed “pseudo-Cushing's syndrome .” The laboratory and clinical findings of hypercortisolism disappear if the primary process is successfully treated. Dexamethasone , an exogenous glucocorticoid , is used to test for Cushing's syndrome. This gluococorticoid does not interfere with cortisol assays but induces similar physiologic responses . Pathphysiology (Contd..)

8. The most common symptoms of this condition are: weight gain fatty deposits, especially in the midsection, the face (causing a round, moon-shaped face), and between the shoulders and the upper back (causing a buffalo hump) purple  stretch marks on the breasts, arms, abdomen, and thighs thinning skin that bruises easily skin injuries that are slow to heal acne Fatigue muscle weakness Signs & Symptoms

9. In addition to the common symptoms above, there are other symptoms that may sometimes be observed in people with Cushing’s syndrome. These can include: high blood sugar increased thirst increased urination osteoporosis high blood pressure (hypertension) a  headache mood swings anxiety irritability depression an increased incidence of infections Signs & Symptoms (Contd..)

10. Cushing’s syndrome can be particularly difficult to diagnose. This is because many of the symptoms, like weight gain or fatigue, can have other causes. Additionally , Cushing’s syndrome itself can have many different causes. Your healthcare provider will review your medical history. They’ll ask questions about symptoms, any health conditions you may have, and any medications you may be prescribed. They’ll also perform a physical exam where they’ll look for signs like buffalo hump, and stretch marks and bruises . Diagnosis

11. The doctor may order laboratory tests, including: 24-hour urinary free cortisol test For this test, you’ll be asked to collect your urine over a 24-hour period. The levels of cortisol will then be tested. Salivary cortisol measurement In people without Cushing’s syndrome, cortisol levels drop in the evening. This test measures the level of cortisol in a saliva sample that’s been collected late at night to see if cortisol levels are too high. Low-dose dexamethasone suppression test For this test, you’ll be given a dose of dexamethasone late in the evening. Your blood will be tested for cortisol levels in the morning. Normally, dexamethasone causes cortisol levels to drop. If you have Cushing’s syndrome, this won’t occur . Lab Tests

12. Imaging tests CT or MRI scans can provide images of your pituitary and adrenal glands to detect abnormalities, such as tumors . Petrosal sinus sampling This test can help determine whether the cause of Cushing syndrome is rooted in the pituitary or somewhere else. For the test, blood samples are taken from the veins that drain the pituitary gland ( petrosal sinuses). A thin tube is inserted into your upper thigh or groin area while you're sedated and is threaded to the petrosal sinuses. Levels of ACTH are measured from the petrosal sinuses and from a blood sample taken from the forearm. If the ACTH level is higher in the sinus sample, the problem stems from the pituitary. If the ACTH levels are similar between the sinuses and forearm, the root of the problem lies outside of the pituitary gland. Lab Tests (Contd..)

13. Most cases of Cushingoid symptoms are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions. Consequently , most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms . If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic  pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly , if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative. Treatment

14. In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostasis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushing's syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women. In March 2020, Isturisa (osilodrostat) oral tablets a 11-beta-hydroxylase enzyme inhibitor was approved by FDA for treating those patients who cannot undergo pituitary surgery or for patients who underwent surgery but continue to have the disease. Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol . In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation . This clinical situation is known as Nelson's syndrome. Treatment (Contd..)

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16. Diet Although dietary changes won’t cure your condition, they can help to keep your cortisol levels from rising even more or help to prevent some complications . Prevention

17. Some dietary tips for those with Cushing’s syndrome include: Monitor your calorie intake Keeping track of your calorie intake is important since weight gain is one of the main symptoms of Cushing’s syndrome. Try to avoid drinking alcohol. Alcohol  consumption has been linked with a rise in cortisol levels, particularly in heavy drinkersTrusted Source, according to a 2007 study. Watch your blood sugar. Cushing’s syndrome can lead to high blood glucose, so try not to eat foods that can cause a rise in blood sugar. Examples of foods to focus on eating include vegetables, fruits, whole grains, and fish. Cut back on sodium. Cushing’s syndrome is also associated with high blood pressure (hypertension). Because of this, try to limit your sodium intake. Some easy ways to do this include not adding salt to food and carefully reading food labels to check sodium content. Make sure to get enough calcium and vitamin D. Cushing’s syndrome can weaken your bones, making you prone to fractures. Both calcium and vitamin D can help to strengthen your bones . Prevention (Contd..)

18. Cushing’s Syndrome: Signs, Causes, and Treatment (healthline.com) Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation - American Family Physician (aafp.org) Cushing’s Syndrome/Disease – Causes, Symptoms, Diagnosis and Treatments (aans.org) Cushing syndrome - Symptoms and causes - Mayo Clinic Cushing Syndrome - StatPearls - NCBI Bookshelf (nih.gov) Diagnostic Approach to Cushing Disease (medscape.com) References

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