Addison's disease Ahmed Salam Lectures Medical Student “TSU” WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Definition: Addison's disease, also known as primary adrenal insufficiency and hypocortisolism is a long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones. Addison's disease is a disorder that occurs when your body produces insufficient amounts of certain hormones produced by your adrenal glands. In Addison's disease, your adrenal glands produce too little cortisol and often insufficient levels of aldosterone as well. Also called adrenal insufficiency, Addison's disease occurs in all age groups and affects both sexes. Addison's disease can be life- threatening. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Pathogenesis: adrenal glands are composed of two sections. The interior (medulla) produces adrenaline-noradrenaline hormones. The outer layer (cortex) produces a group of hormones called corticosteroids, which include: Glucocorticoids. These hormones, which include cortisol, influence your body's ability to convert food fuels into energy, play a role in your immune system's inflammatory response and help your body respond to stress. Mineralocorticoids. These hormones, which include aldosterone, maintain your body's balance of sodium and potassium to keep your blood pressure normal. Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, libido and a sense of well-being in both men and women. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT So Addison's disease results when adrenal glands are damaged, producing insufficient amounts of the hormone cortisol and often aldosterone as well. Primary adrenal insufficiency: occurs when the cortex is damaged and doesn't produce its hormones in adequate quantities , is most commonly the result of the body attacking itself (autoimmune disease). immune system views the adrenal cortex as foreign, something to attack and destroy. Other causes of adrenal gland failure may include : Tuberculosis, Spread of cancer to the adrenal glands, Bleeding into the adrenal glands, which may present as adrenal crisis without any preceding symptoms. WWW.GREATASSIMPLEMEDICINE.COM

Secondary adrenal insufficiency : G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Secondary adrenal insufficiency : Another more common cause of secondary adrenal insufficiency occurs when people who take corticosteroids for treatment of chronic conditions, such as asthma or arthritis, abruptly stop taking the corticosteroids. Addisonian crisis: untreated Addison's disease, an addisonian crisis may be provoked by physical stress, such as an injury, infection or illness. WWW.GREATASSIMPLEMEDICINE.COM

Signs and symptoms When to see a doctor: G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Signs and symptoms When to see a doctor: Darkening areas of skin (hyperpigmentation) Severe fatigue Unintentional weight loss Gastrointestinal problems, such as nausea, vomiting and abdominal pain Lightheadedness or fainting Salt cravings Muscle or joint pains WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Addison's disease symptoms usually develop slowly, often over several months, and may include: Extreme fatigue Weight loss and decreased appetite Darkening of your skin (hyperpigmentation) Low blood pressure, even fainting Salt craving Low blood sugar (hypoglycemia) Nausea, diarrhea or vomiting Abdominal pain Muscle or joint pains Irritability Depression Body hair loss or sexual dysfunction in women WWW.GREATASSIMPLEMEDICINE.COM

Pain in your lower back, abdomen or legs. G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Acute adrenal failure (addisonian crisis):Sometimes, however, the signs and symptoms of Addison's disease may appear suddenly. In acute adrenal failure (addisonian crisis), the signs and symptoms may also include: Pain in your lower back, abdomen or legs. Severe vomiting and diarrhea, leading to dehydration. Low blood pressure. Loss of consciousness. High potassium (hyperkalemia) and low sodium (hyponatremia). WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT WWW.GREATASSIMPLEMEDICINE.COM

Investigation: G.S.M MEDICAL LECTURES/ Addison's disease Blood test AHMED SALAM MD STUDENT Investigation: Blood test Assessment of glucocorticoid : random plasma cortisol is usually low in patient with adrenal insufficiency. ACTH stimulation test. This test involves measuring the level of cortisol in your blood before and after an injection of synthetic ACTH. ACTH signals your adrenal glands to produce cortisol. If your adrenal glands are damaged, the ACTH stimulation test shows that your output of cortisol in response to synthetic ACTH is limited or nonexistent. Assessment of mineralocorticoids: electrolyte measurement shows hyponatraemia occur in both aldosterone and cortisol deficiency , hyperkalaemia is common , plasma renin and aldosterone should measure and shows renin is high and aldosterone low or either lower part of normal range. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Assessment of androgens: measure of dehydroepiandrosterone (DHEA) and androstenedrosterone the levels are highest n the morning. Adrenal autoantibodies: are positive in autoimmune adrenal failure. Tuberculosis cause adrenal calcification HIV Test: is a risk factor for infection are present. Insulin-induced hypoglycemia test: The test involves checking your blood sugar (blood glucose) and cortisol levels at various intervals after an injection of insulin. In healthy people, glucose levels fall and cortisol levels increase. Imaging tests undergo a computerized tomography (CT) scan of your abdomen to check the size of your adrenal glands and look for other abnormalities that may give insight to the cause of the adrenal insufficiency. Your doctor may also suggest an MRI scan of your pituitary gland if testing indicates you might have secondary adrenal insufficiency. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Management: Glucocorticoid replacement: oral hydrocortisone (cortisol) 15-20 mg daily in divided dose side-effect: excess weight gain and hyperpigmentation. Mineralocorticoid replacement: fludrocortisone (9a- fluoro-hydrocortisone) usual dose 0.05-0.15 mg daily , measurement: blood pressure , plasma electrolytes and plasma renin. Androgen replacement: androgen replacement with DHEA (50 mg/day) side- effect: acne and hirsutism . WWW.GREATASSIMPLEMEDICINE.COM

Management of adrenal crisis(urgent case): G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Management of adrenal crisis(urgent case): Correct volume depletion: IV saline to normalize blood pressure and pulse. Replace glucocorticoids: IV hydrocortisone 100 mg. Correct other metabolic abnormalities: IV 10% glucose . WWW.GREATASSIMPLEMEDICINE.COM

Case report presentation: G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Case report presentation: A 63-year-ol woman presented to the hospital and she compline: increasing darkening of the skin. Dizziness. nausea with occasional vomiting and progressive weight loss over eight months prior to presentation. easy fatigability. There were no headaches, blurred vision, and neither loss of consciousness nor change in her bowel habit. The medical history and systemic review revealed no abnormality and were not significant as to the likely cause of her disease state. WWW.GREATASSIMPLEMEDICINE.COM

Physical examination: G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Physical examination: Physical examination revealed an elderly lady: Pale. generalized hyperpigmentation especially on the face, oral mucosa, palmar creases and knuckles. No features of malnutrition or hypovitaminosis and also There was no significant peripheral lymphadenopathy. systemic examination: pulse of 106 bpm blood pressure 100/60 mmHg supine and 70/40mmHg sitting. All other systems were essentially normal. WWW.GREATASSIMPLEMEDICINE.COM

Laboratory investigations: G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Laboratory investigations: Na+ 136 mmo/L Cl- 100 mmo/L K+ 3.4 mmo/L . note are the anaemia (haemoglobin10gm/dl), with normal red cell morphology. ESR 58mm/hr (Westergreen method). fasting blood sugar was 76mg. total serum protein of 7.8g/L (albumin-3.4g/L and globulin 4.4g/L). Plasma cortisol was undetectable at 0 and 30 minutes of cosyntropin administration (0.25 mg). HIV screening was negative. WWW.GREATASSIMPLEMEDICINE.COM

Radiological diagnostic; G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Radiological diagnostic; Radiological diagnostic tests included; abdominal ultrasound, which was reported as showing normal liver, spleen, pancreas and pelvic organs. computerised tomography scan (CT) of the abdomen showed a non-enhancing oval shaped left suprarenal mass with calcification and an ipsilateral hypoplastic but functional left kidney. The conclusion was a suprarenal tumour-adenoma or adrenocortical carcinoma to exclude tuberculous adrenalitis. A CT brain scan was normal. the CT abdominal findings suggestive of adrenal tuberculosis. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Discussion : first described the clinical features of primary adrenal insufficiency, Hence the term Addison’s disease. The characteristic form resulting from primary adreno-cortical insufficiency distinguishes Addison’s disease from other forms of adrenal insufficiency which may result from pituitary or hypothalamic diseases , with decrease in adrenocorticotrophic hormone (ACTH) secretion and consequent adrenal cortex atrophy. The commonest causes of Addison’s disease are autoimmune and tuberculous adrenalitis . Others are fungal infection, metastatic neoplasia, haemochromatosis and congenital adrenal hyperplasia. WWW.GREATASSIMPLEMEDICINE.COM

G.S.M MEDICAL LECTURES/ Addison's disease AHMED SALAM MD STUDENT Management: she commenced on anti-tuberculous drugs, but Ten days after admission, she had nausea, vomiting, fever with chills and extreme lethargy. Cardiovascular examination showed a tachycardia, low volume pulse, BP 70/40 mmHg and blood film showed trophozoites of plasmodium falciparum. so then managed with : intravenous fluids (dextrose in saline). Antimalarials. antibiotics and hydrocortisone. She made remarkable recovery and was maintained on oral prednisolone and fludrocortisone. WWW.GREATASSIMPLEMEDICINE.COM