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Adrenal gland disorders ADRENAL GLAND • Either of two small, dissimilarly shaped endocrine glands, one located above each kidney, consisting of the cortex, which secretes several steroid hormones, and the medulla, which secretes epinephrine. • The adrenal cortex :produces corticosteroids which include glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androgens (primarily dehydroepiandrosterone and androstenedione). • Function is regulated by the neuroendocrine hormones from the pituitary, hypothalamus and renin-angiotensin system. • Adrenal androgens--chief physiologic activity occurs after conversion to testosterone. • The adrenal medulla :is composed of chromaffin cells, which synthesize and secrete catecholamines (mainly epinephrine and lesser amounts of norepinephrine). • • Chromaffin cells also produce bioactive amines and peptides (eg, histamine, serotonin, chromogranins, neuropeptide hormones Epinephrine and norepinephrine(( the major effector amines of the sympathetic nervous system)), are responsible for the “flight or fight” response (ie, chronotropic and inotropic effects on the heart; bronchodilation; peripheral and splanchnic vasoconstriction with skeletal muscular vasodilation; metabolic effects including glycogenolysis, lipolysis, and renin release). • Excess quantities of epinephrine and norepinephrine are produced in pheochromocytoma . Function of the gland • HORMONE FUNCTION • ALDOSTERONE: Renal : Na & Cl reabsorption; K excretion • GI : Na absorption • GLUCO-CORTICOIDS: Increase serum glucose by gluconeogenesis & glycogenolysis especially during STRESS • Blocks inflammation(lymphokines) • Counteracts effect of histamine-inflammation • sex HORMONE: Physiologically insignificant • Becomes useful during menopause in women SYMPTOMATOLOGY ALDOSTERONE DEFICIENCY Decrease in plasma volume leading to dehydration. Hypotension to shock. Increased K. CORTISOL DEFICIENCY ANOREXIA, N/V, ABDOMINAL PAIN, WT LOSS, LETHARGY HYPOGLYCEMIA HYPOTENSION HYPERKALEMIA, WEAK PULSE HYPERPIGMENTATION IMPAIRED STRESS TOLERANCE SEX HORMONE DEFICIENCY LOSS OF BODY HAIR LOSS OF LIBIDO OR IMPOTENCE MENSTRUAL & FERTILITY DISORDER ADRENAL CORTEX DISORERS ADRENAL INSUFFICIENCY ADRENAL CRISIS CUSHING’S SYNDROME ALDOSTERONISM ADDISON’S DISEASE • Is a hormone deficiency caused by damage to the outer layer of the adrenal gland (adrenal cortex). • Addison's disease is a disorder that results in the body producing insufficient amounts of certain hormones produced by the adrenal glands. • Sometimes, Addison's disease also involves insufficient production of aldosterone, one of the mineralocorticoid hormones. • • • Insufficiency of corticosteroids can be total when the operation of all hormones drops out, and partial fallout of activity of one adrenal hormone. Addison's disease can be life-threatening. Addison's disease can occur at any age, but is most common in people ages 30 to 50. ETIOLOGY • Autoimmune processes -80% of cases-corticosteroid, aldost,androgen-all • Pituitary failure( atrophy, necrosis)-no HYPERKALEMIA/PIGMENTATION • TB, Syphilis, coccid mycosis ,Histoplasmosis, CMV(AIDS) • Tumor ,Metastases , Amyloidosis, Hemochromatosis • Hemorrhage-warfarin, shock, major surgery, antiphospholipid. • Drugs that block corticosteroid synthesis (eg, ketoconazole). • All groves syndrome-achalasia, alacrima,neurologic disease. • Addison's disease may coexist with diabetes mellitus or hypothyroidism. Destruction of adrenal gland Mineralocorticoid & glucocorticoid deficiency Mineralocorticoid deficiency ↑ in urinary excretion of Na, ↓ in urinary excretion of K Inability to concentrate urine, with electrolyte imbalance Glucocorticoid deficiency Disturbances in carbohydrate, fat and protein metabolism, decrease liver glycogen severe dehydration plasma hypertonicity, acidosis, hypotension circulatory collapse Hypoglycaemia and anorexia SIGNS & SYMPTOMS • A. Manifestation, connected with the falling of mineral corticoids: • 1) DEHYDRATION develops owing to loss of sodium ions (decreases rearbsortion) with the loss of water (polyuria). • 2) HYPOTENSION - by decrease of circulating blood volume. • 3) HEMOCONCENTRATION is connected with liquid loss, results to disorders of microcirculation and hypoxia. • 4) Decreasing of kidney blood circulation is stipulated by increase of arterial pressure with disturbances of glomerular filtration and development of intoxication (nitrogenemia); • 5) HYPERKALEMIA -- by decrease secretion of potassium ions and their output from the damaged cells. • B. Manifestations by disorders of glucocorticoid function of adrenal: • Muscle weakness and fast tiredness • Decrease of ability to remove water during water load (water poisoning). • Weight loss and decreased appetite • HYPOTENSION -- (permissive reaction on catecholamine’s)90% • Darkening of the skin (HYPERPIGMENTATION-- bronzed disease) • Diffuse tanning over nonexposed as well as exposed areas over knuckles, elbows, knees, nail beds, palmer creases, and posterior neck. • Nipples and areolar darken, new scars pigmented ,skin in pressure areas • Depression , emotional changes, mental irritability. • Salt craving EXAMINATION &DIAGNOSIS • Examine for hyperpigmentation: Hand: palmar creases Mouth and lips Areas usually covered by clothing: nipple Areas irritated by belts, straps, collars or rings • Look for vitiligo • Look for sparse axillary hair and pubic hair • Examine the abdomen for adrenal scar • Examine blood pressure for postural hypotension • Signs of critical deterioration (Addisonian crisis): – Shock (low BP, tachycardia) – hypothermia • SCREENING AND DIAGNOSIS • Doctor will talk first about the medical history and the signs and symptoms. • If doctor thinks that patient may have Addison's disease, He may undergo some of the following tests: • Blood test. • ACTH stimulation test. • Insulin-induced hypoglycemia test. • Imaging tests. • BLOOD TEST: • Measuring blood levels of sodium, potassium, cortisol and ACTH gives the doctor an initial indication of whether adrenal insufficiency may be causing the signs and symptoms. • A blood test can also measure antibodies associated with autoimmune Addison's disease. ACTH stimulation test This test involves measuring the level of cortisol in the blood before and after an injection of synthetic ACTH. If adrenal glands are damaged, the ACTH stimulation test shows that the output of cortisol in response to synthetic ACTH is blunted or nonexistent. TREATMENT • • • • • • • If patient receive an early diagnosis of Addison's disease, treatment may involve taking prescription corticosteroids. Because the body isn't producing sufficient steroid hormones, doctor may have recommend to take one or more hormones to replace the deficiency. Cortisol is replaced using hydrocortisone (Cortef), prednisone or cortisone. Fludrocortisone (Florinef) replaces aldosterone, which controls the body's sodium and potassium needs and keeps the blood pressure normal. In addition, doctor may recommend treating androgen deficiency with an androgen replacement called dehydroepiandrosterone. Some studies indicate that, for women with Addison's disease, androgen replacement therapy may improve overall sense of wellbeing, libido and sexual satisfaction. These hormones are given orally in daily doses that mimic the amount body normally would make, thereby minimizing side effects. If ill with vomiting and can't retain oral medications, may need corticosteroid injections. CUSHING’S SYNDROME Sustained over production of glucocorticoids by adrenal gland from ACTH by pituitary tumor Excessive glucocorticoid administration. • Cushing's Disease: Is the result of a pituitary tumor and the inappropriate production of ACTH. Cushing's Syndrome: Causes the same symptoms, but is a disorder marked by overproduction of adrenal hormones, Cushing’s syndrome is all other forms of Cushing’s. CLINICS DIAGNOSIS: • 24-hour urine cortisol: 24-hour urine cortisol (or urine free cortisol) is often used to evaluate overall cortisol production. One out of four 24-hour urine samples may be normal and other testing may have to be performed. Like the midnight cortisol test, it is recommended that this test be repeated if results are abnormal, to avoid false positives. • Midnight plasma cortisol and late-night salivary cortisol measurements: Normally, cortisol production is suppressed at midnight but in Cushing syndrome, this does not happen. Therefore, an elevated blood (plasma) level at midnight suggests Cushing syndrome. Blood is the preferred sample, but this usually requires a hospital stay. Alternatively, a saliva sample can be collected late at night at home and then tested. It is recommended that a sample be collected three nights in a row. If only a single sample is collected and tested, the test should be repeated if the result is outside the established reference range, to confirm the results and to avoid false positives. • Dexamethasone suppression screening test: Dexamethasone is a synthetic steroid that mimics cortisol in the feedback inhibition of corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) production. A normal response to dexamethasone is suppression of cortisol secretion. • Dexamethasone can be used in different dosages for different purposes as a diagnostic test. One version involves giving a fairly low dose (1 mg) at bedtime to prevent the rise in ACTH and cortisol that normally occurs during sleep. Between 8 and 9 am the next morning, a blood sample is drawn and the cortisol level is measured. In healthy individuals, the level will be low (suppressed); in those with Cushing syndrome, the level will not be suppressed TREATMENT • Reducing corticosteroid use. • Surgery. If the cause of Cushing syndrome is a tumor, your doctor may recommend complete surgical removal. Pituitary tumors are typically removed by a neurosurgeon, who may perform the procedure through your nose. • Radiation therapy: Radiation can be given in small doses over a six-week period, or with a technique called stereotactic radiosurgery (Gamma Knife surgery). In the latter procedure, administered as a single treatment, a large dose of radiation is delivered to the tumor, and the radiation exposure to surrounding tissues is minimized. • Medication:Medications to control excessive production of cortisol at the adrenal gland include ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone) • Mifepristone (Korlym) is approved for people with Cushing syndrome who have type 2 diabetes or glucose intolerance. Mifepristone does not decrease cortisol production, but it blocks the effect of cortisol on your tissues. • The newest medication for Cushing's is pasireotide (Signifor), and it works by decreasing ACTH production from a pituitary tumor. This medication is given as an injection twice daily. It's recommended if pituitary surgery is unsuccessful or cannot be done • Ketoconazole (600 to 1200 mg/day) • metyrapone(2-3 g/day) • Mitotane(2-3 G/day)- slow onset Thanks for your optimal attention!