Adrenal insufficiency
ObjectivesAt the end of this lecture, the student should be able to:Define adrenal insufficiency Recognize the causes of adrenal insufficiency.Describe clinical presentation of Addison’s disease. List the investigations and outline the management plan of Addison’s disease.Describe the clinical features and treatment of adrenal crisis.
CASE SCENARIO
A 32-year-old woman with known hypothyroidism is admitted to hospital. Her Blood pressure is 86/53 mmHg and her pulse 100 bpm. Investigations reveal: Serum sodium 126 mmol/L (137-144) Serum potassium 5.8 mmol/L (3.5-4.9) Serum glucose 3.0 mmol/L (3.0-6.0) 1- What is the most likely diagnosis? 2- What is the most appropriate investigation to confirm your diagnosis?Definition
There is a decrease in the secretion of cortisol and or aldosteroneClinical suspicion is important because the presentation of AI may be insidious and subtleClinical diagnosis is frequently delayed or missed early if unrecognized, may present in a life-threatening crisis with acute cardiovascular collapse (adrenal crisis)prevalence of well-documented, permanent adrenal insufficiency is 5 in 10,000 in the general populationClassification Secondary (low ACTH) Hypothalamic or pituitary disease: Chronic glucocorticoid excess (endogenous or exogenous) Pituitary tumors (active and inactive adenomas, carcinoma) Mass lesions affecting the hypothalamic-pituitary region: Craniopharyngioma, meningioma, metastases Pituitary irradiation Autoimmune hypophysitis Pituitary apoplexy/hemorrhage Pituitary infiltration (TB, actinomycosis, sarcoidosis, histiocytosis X, Wegener's granulomatosis, metastases
Primary adrenal insufficiency (high ACTH)(Addison’s disease)Autoimmune:Isolated autoimmune adrenalitis (30- 40%) Polyglandular syndrome 1 &2 (60- 70%)Infection:TB, HIV, CMV, cryptococcosis, histoplasmosis, coccidioidomycosisAIDSMetastasesBilateral adrenalectomy
Rare causes: Lymphoma Adrenal hemorrhage in meningococcal sepsis (Waterhouse-Friderichsen syndrome) Amyloidosis, sarcoidosis Hemochromatosis Imparied Steriodiogensis CAH Drugs (Mitotane, aminoglutethimide, etomidate, ketoconazole, suramin
Addison’s disease First discovered by Thomas Addison in 1855 First described as an infection of the adrenal gland- most commonly TB. Now instead of infection, its most commonly characterized by an autoimmune destruction of the adrenal glands
Epidemiology
Addison’s disease is a rare and chronic disease.6-110 cases diagnosed per 100,000 in the world per year. 1.4 million deaths per year around the world. Usually effects 30-50 year-olds, but can be seen in all ages.
Clinical Features
Signs and Symptoms Caused by Mineralocorticoid Deficiency (Primary AI Only) Abdominal pain, nausea, vomiting Dizziness, postural hypotension Salt craving Low blood pressure, postural hypotension Increased serum creatinine (due to volume depletion) Hyponatremia HyperkalemiaSigns and Symptoms Caused by Adrenal Androgen DeficiencyLack of energyDry and itchy skin (in women)Loss of libido (in women)Loss of axillary and pubic hair (in women)Other Signs and SymptomsHyperpigmentation (primary AI only) [due to excess of pro- opiomelanocortin (POMC)–derived peptides]Alabaster-colored pale skin (secondary AI only) (due to deficiencyof POMC-derived peptides)
Acute adrenal insufficiency Occurs after a prolonged period of nonspecific complaints More frequently observed in patients with primary AI. Postural hypotension may progress to hypovolemic shock. Adrenal insufficiency may mimic features of acute abdomen with abdominal tenderness, nausea, vomiting, and fever. In some cases, decreased responsiveness, progressing to stupor and coma.
Addisonian Crisis: Severely low blood pressure (shock) Hyperkalemia Hyponatremia Hypoglycemia Hypercalcemia Unexplained fever, diarrhea, vomiting Coma and death Precipitated by infection, surgery or intercurrent disease
Management
It is a medical emergencyIV fluid (normal saline 1 L/h with continuous cardiac monitoring and 10% dextrose)Hydrocortisone 100 mg bolus followed by 100–200 mg hydrocortisone over 24 h infusion or i.v doses until GI symptoms improve then start oral therapyMineralocorticoid replacement can be initiated once the daily hydrocortisone dose has been reduced to <50 mgTreat precipitating causeDiagnosis of AI
Determined by low level of adrenal hormone after stimulation with synthetic ACTH hormone tetracosactide Short Test: 250 micrograms of tetracosactide or cosyntropin (ACTH 1-24), i.m or i.v injectionBlood cortisol levels at 0, 30 and 60 minACTH at 0 minNormal is 500–550 nmol/L (18–20 µg/dL) 30–60 minutes after ACTH stimulationFor Ddx: Plasma ACTH, renin, aldosterone Adrenal Autoantibody MRI pituitary CT or MRI of adrenals CBC Blood Ca and glucose Thyroid function test CXR HIV test Serum Na and K
Treatment
Replacement ( always need glucocorticoids and usually mineralcorticoid therapy) Hydrocortison orally 15 mg at morning and 5 mg at evening Doses change according to lifestyle: doubling the routine oral dose in the case of intercurrent illness with fever - IV hydrocortisone injection at a daily dose of 100 mg in cases of prolonged vomiting, surgery, or trauma Have to carry emergency injection of hydrocortisone and card/bracelet indentifying their conditionMineralocorticoid replacement in primary AI (100–150 g fludrocortisone). The adequacy of treatment can be evaluated by measuring BP, sitting and standing to detect a postural drop indicative of hypovolemia, serum Na, k, and plasma renin should be measured regularly.Adrenal androgen replacement is an option in patients with lack of energy, and in women with loss of libido. - It can be achieved by once-daily administration of 25–50 mg DHEA. Treatment is monitored by measurement of DHEAS, androstenedione, testosterone.