### Date : 2024-06-01 14:36 ### Topic : Addison's disease #medicine #endocrinology ---- ### Pathophysiology Addison's disease, or primary adrenal insufficiency, is characterized by the destruction or dysfunction of the adrenal cortex. This leads to deficiencies in glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens. The most common cause is autoimmune adrenalitis, accounting for approximately 70-90% of cases. Other etiologies include infectious diseases (e.g., tuberculosis, HIV), metastatic malignancies, adrenal hemorrhage (e.g., Waterhouse-Friderichsen syndrome), and genetic disorders (e.g., congenital adrenal hyperplasia). ### Symptoms and Clinical Presentation 1. **Glucocorticoid Deficiency (Cortisol)** - Fatigue, weakness - Weight loss, anorexia - Hypoglycemia - Nausea, vomiting, abdominal pain - Neuropsychiatric symptoms (depression, irritability, cognitive impairment) 2. **Mineralocorticoid Deficiency (Aldosterone)** - Hypotension, particularly orthostatic - Hyponatremia - Hyperkalemia - Salt craving - Dehydration 3. **Adrenal Androgen Deficiency** - More noticeable in females due to lack of peripheral androgen synthesis - Loss of axillary and pubic hair - Decreased libido ### Diagnostic Workup 1. **Initial Screening** - **Morning Serum Cortisol and ACTH Levels**: Low cortisol levels (<3 mcg/dL) with elevated ACTH levels (>200 pg/mL) suggest primary adrenal insufficiency. 2. **ACTH Stimulation Test** - **Synthetic ACTH (Cosyntropin) Administration**: Measure baseline cortisol, then administer 250 mcg of cosyntropin IV or IM, and measure cortisol levels at 30 and 60 minutes. A normal response is a rise in cortisol to >18-20 mcg/dL. Failure to achieve this indicates adrenal insufficiency. 3. **Electrolyte Panel** - Hyponatremia and hyperkalemia are common findings. - Hypoglycemia may also be present. 4. **Autoimmune Workup** - **21-Hydroxylase Antibodies**: Present in autoimmune adrenalitis. 5. **Imaging** - **CT/MRI of Adrenal Glands**: To assess for adrenal calcification, hemorrhage, or mass. ### Management 1. **Glucocorticoid Replacement** - **Hydrocortisone**: Typically administered in divided doses (e.g., 15-25 mg/day in two or three doses, with the largest dose in the morning). - Alternatively, prednisone or dexamethasone can be used, but with caution due to their longer half-lives and potential for overtreatment. 2. **Mineralocorticoid Replacement** - **Fludrocortisone Acetate**: Usually 0.05-0.2 mg/day. Dosage is adjusted based on blood pressure, electrolytes, and plasma renin activity. 3. **Education and Stress Dosing** - Patients must be educated on increasing glucocorticoid doses during illness, surgery, or stress (e.g., doubling or tripling the dose). - Emergency medical identification and an injectable emergency supply of hydrocortisone or dexamethasone for adrenal crisis. 4. **Monitoring** - Regular follow-up to assess symptom control, side effects, and biochemical parameters. - Monitor blood pressure, electrolytes, and glucose levels periodically. - Annual screening for other autoimmune conditions, especially thyroid dysfunction. ### Adrenal Crisis Management 1. **Immediate Treatment** - **IV Hydrocortisone**: 100 mg bolus, followed by 200 mg/24 hours as continuous infusion or intermittent boluses. - **IV Fluids**: Normal saline to correct volume depletion and hyponatremia; dextrose-containing fluids if hypoglycemia is present. 2. **Subsequent Care** - Transition to oral glucocorticoids once the patient is stable and able to take oral medications. - Evaluate and manage any underlying precipitating factors (e.g., infection, trauma). Understanding the complexity of Addison's disease and ensuring meticulous management and patient education is critical to improving outcomes and preventing potentially life-threatening adrenal crises. Regular monitoring and adjusting therapy based on clinical response and biochemical parameters are essential components of effective long-term management.