Adrenal disorders

Cortisol is a normal hormone produced in the outer portion, or cortex, of the adrenal glands, located above each kidney. The normal function of cortisol is to help the body respond to stress and change. It mobilizes nutrients, modifies the body’s response to inflammation, stimulates the liver to raise the blood sugar, and it helps control the amount of water in the body. Another adrenal cortex hormone, aldosterone, regulates salt and water levels which affects blood volume and blood pressure. Small amounts of androgens (male hormones) are also normally produced in the adrenal cortex. Cortisol production is regulated by adrenocorticotrophic hormone (ACTH), made in the pituitary gland, which is located just below the brain.

Catechalomines: Activity Stimulates the “fight or fight” reaction Increased plasma glucose levels Increased cardiovascular function Decreased gastrointestinal and genitourinary function

The adrenal gland is divided into two parts, adrenal cortex and medulla. The adrenal cortex secretes androgen, mineralocorticoids (eg, aldosteron) and glucocorticoids (eg, cortisol). The adrenal medulla secretes catecholamines (eg, epinephrine, norepinephrine, dopamine).

MEDULLA -----sympathetic system CORTEX Zona Glomerulosa- Renin-Angiotensin-Aldosterone Axis Zonae Fasciculata/Reticularis-Hypothalamic –pituitary-Adrenal Axis

Steroid actions Amino acid catabolism (muscle wasting)… gluconeogenesis in the liver.. Hyperglycemia… increased insulin output… eventual beta cell failure… fat deposition… diabetes Ca resorption, impairment of Ca absorbtion, increased renal Ca excretion…. osteoporosis Increased gastric acidity… ulcer formation or aggravation K loss and Na retention… edema and hypertension Initially increased antibody release.. Eventually decreased antibody production, lymphocytopenia, eosinopenia, neutrophelia, polycythemia… susceptibility to infections Maintenance of arteriolar tone and blood pressure

Mineralocorticoids Aldosteron is primarily involved with fluid and electrolyte balance The principle stimulus for aldosterone is angiotensin ll. Aldosteron secretion causes sodium reabsorption in the distal renal tubule in exchange for potassium and hydrogen ions. The net effects are, fluid retention, decrease in plasma potassium and metabolic alkalosis.

Cushing’s Syndrome

Excessive stimulation of glucocorticoid receptors Most common iatrogenic (predinisolone) Non-iatrogenic rare

Aetiology ACTH –dependent Pit.Adenoma secretingACTH(Cushing dis.) Ectopic ACTH(bronchial carcinoid,small -cell lung Ca) Iatrogenic (ACTH therapy) Non-ACTH –dependent Iatrogenic (Chronic steroid therapy) Adrenal adenoma Adrenal carcinoma

Pseudo-cushings syndrome(cortisol excess as part of another illness Alcohol excess Major depressive illness Primary obesity

Major Clinical Features in Cushing’s Syndrome Weight gain, Central obesity Moon face and plethora Muscular weakness, especially proximal Depression and psychosis Oligomenorrhoea or amenorrhoea in females Hirsuties Striae, acne, skin-thinning, bruising Polyuria, nocturia decreased libido and impotence in males Hypertension diabetes or impaired glucose tolerance Loss of heigh and osteoporosis

investigations Biochemical evaluation of Cushing syndrome: a-Urinary free cortisol excretion over 150 ug\ day. b- dexamethasone suppression test; glucocorticoids inhibit secretion of hypothalamic CRH and pituitary ACTH but do not directly affect adrenal cortisol production. The overnight 1-mg dexamethasone suppression test requires administration of 1 mg of dexamethasone at 11 PM with subsequent measurement of cortisol level at 8 am.4 In healthy individuals, the serum cortisol level should be less than 2.2 ug/dL (exclude cushing).

c- loss of circadian rhythm of cortisol secretion Normal values, 10-25 ug\ml in the morning, 2-10 ug\ml in the evening, elevated serum cortisol at 11 PM can be an early finding. d-Recently, measuring salivary cortisol level has gained interest, as it is a simple and convenient way of obtaining a nighttime sample. levels less than 1.3-1.5 ng/mL exclude Cushing syndrome.

Imaging studies Others CT or MRI brain and abdomen Chest X ray Chest CT Others Tumour markers

Treatment SURGERY *Transsphenoidal removal of pituitary tumors, or Bi-adrenalectomy .. *Pituitary irradiation is employed when transsphenoidal surgery is not successful or not possible Adrenal tumour Lap.removal Patients with endogenous Cushing syndrome who undergo resection of pituitary, adrenal, or ectopic tumors should receive stress doses of glucocorticoid in the intraoperative and immediate postoperative period

*lifelong glucocorticoid and mineralocorticoid replacement is necessary in those patients who undergo bilateral adrenalectomy. MEDICAL(Metyrapone, Ketoconazole) Few weeks prior to surgery Nonresectable tumour Radiation Cytotoxic

Adrenal Insufficiency

Pathophysiology Addison disease is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed. Frequency The prevalence of Addison disease is 40-60 cases per 1 million population.

Age The most common age at presentation in adults is 30-50 years Age The most common age at presentation in adults is 30-50 years. Sex Idiopathic autoimmune Addison disease tends to be more common in females and children.

Causes of Adrenal Insufficiency Primary Idiopathic (Addison disease) Tuberculosis Fungal infections Adrenal hemorrhage Congenital adrenal hypoplasia Sarcoidosis Amyloidosis Metastatic neoplasia Others

Causes of Adrenal Insufficiency Secondary After exogenous glucocorticoids After the cure of Cushing syndrome (removing endogenous glucocorticoids) Hypothalamic and pituitary lesions

Major Clinical Features in Adrenal Insufficiency Weakness Skin Mucous membrane and skin pigmentation, darkening of hair freckling, vitiligo, pigment accentuation at nipples, and friction areas, pigment concentration in skin creases and in scars Loss of weight, emaciation, anorexia, vomiting, diarrhea Hypotension Salt craving Hypoglycemic episodes

Acute Adrenal crises Acute circulatory shock Sever hypotension ,hyponatremia , Hyperkalemia and in some cases hypoglycemia,hypercalcemia.cramps,vomiting,diarrhea,unexplained fever may be present.Often pp by infection or surgery

Investigations --Random plasma cortisol --Short ACTH stimulation test; In patients with Addison disease, both cortisol and aldosterone show minimal or no change in response to ACTH. --ACTH assay --Plasma renin activity and aldosterone --Lab tests hyponatremia Hyperkalemia metabolic acidosis

-elevated (BUN) and creatinine due to the hypovolemia with decreased glomerular filtration rate. -Hypoglycemia -adrenal autoantibodies may be present Imaging study Chest x-ray-- TB CT abdomen

Treatment The goals of pharmacotherapy are to reduce morbidity and to prevent complications e.g adrenal crisis; 1- corticosteroid replacement Cortisol 15mgam 5mgpm 2- mineralocorticoid: Fludrocortisone 0.05-0.1 mg PO qd; some patients may only require alternate-day dosing. 3-In acute adrenal crises medical emergency IV hydroctisone and IV fluids (NS and 10% dextrose +treat pp factor