Addison’s disease and adrenal insufficiency
Overview
Hypofunction of adrenal gland caused by primary (Addison’s disease) or secondary adrenal insufficiency. Causes of adrenal insufficiency include: autoimmune dysfunction (Graves’ disease) or autoimmune polyendocrine syndrome, tuberculosis, bilateral adrenalectomy and medications (ketoconazole, phenytoin, rifampin, phenobarbital).
Pathophysiology
Occurs when adrenal glands do not produce enough cortisol and, in some cases, aldosterone. Primary adrenal insufficiency (Addison’s disease) usually causes...
- Destruction of all regions of adrenal cortex
- Deficiencies of cortisol, aldosterone, and androgens
- Compensatory increases in corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH)
Autoimmune dysfunction causes 80–90% of cases in developed countries; tuberculosis is leading cause in developing countries. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g. phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. Secondary adrenal insufficiency usually results from exogenous corticosteroid use, leading to suppression of hypothalamic-pituitary-adrenal axis and decreased ACTH release, resulting in impaired androgen and cortisol production.
Diagnosis
Laboratory tests
Using the short cosyntropin stimulation test, an increase in cortisol level to 18 mcg/dL (500 nmol/L) or more rules out adrenal insufficiency. Patients with Addison’s disease have an abnormal response to the short cosyntropin stimulation test. Plasma ACTH levels are usually 400–2000 pg/mL in primary insufficiency and normal to low (5–50 pg/mL) in secondary insufficiency. A normal cosyntropin-stimulation test does not rule out secondary adrenal insufficiency. Insulin hypoglycemia test, metyrapone test, and CRH stimulation test are sometimes performed.
Pharmacotherapy
Inform patients of expected outcome, treatment complications, proper medication use and adherence, and potential side effects.
For adrenal insufficiency ㅡ Corticosteroids, use hydrocortisone, cortisone, or prednisone at the lowest effective dose twice daily to mimic normal diurnal adrenal rhythm of cortisol production. Starting total daily doses: hydrocortisone 15–25 mg, cortisone acetate 25–37.5 mg, or prednisone 2.5 mg. Give 2/3 of dose in the morning and 1/3 of dose 6–8 hours later. May use fludrocortisone acetate 0.05–0.2 mg orally once daily to replace mineralocorticoid loss and prevent hyperkalemia. If parenteral therapy is necessary, give deoxycorticosterone trimethylacetate in oil 2.5–5 mg IM every 3–4 weeks. Because most adrenal crises occur after glucocorticoid dose reductions or lack of stress-related dose adjustments, patients receiving corticosteroid replacement should add 5–10 mg hydrocortisone (or equivalent) to their normal daily regimen shortly before strenuous activities, such as exercise. During severe physical stress (e.g., febrile illness, after accidents), patients should double their daily dose until recovery. Treatment of secondary adrenal insufficiency is identical to primary disease treatment, except that mineralocorticoid replacement is usually not necessary.
For acute adrenal insufficiency ㅡ Acute adrenal insufficiency (adrenal crisis or addisonian crisis) is an endocrine emergency. Stressful situations, surgery, infection, and trauma may increase adrenal requirements, especially in patients with underlying adrenal or pituitary insufficiency. Most common cause of adrenal crisis is abrupt withdrawal of exogenous glucocorticoids in patients receiving chronic treatment that resulted in hypothalamic-pituitary-adrenal-axis suppression. Parenteral hydrocortisone is corticosteroid of choice because of combined glucocorticoid and mineralocorticoid activity. Starting dose is 100 mg IV by rapid infusion, followed by continuous infusion (usually 10 mg/hr) or intermittent bolus of 100–200 mg every 24 hours. Continue IV administration for 24–48 hours. If patient is stable at that time, start oral hydrocortisone 50 mg every 6–8 hours, followed by tapering to chronic replacement needs. If fluid replacement is required, give dextrose 5% in normal saline solution IV at a rate to support blood pressure. If hyperkalemia is present after hydrocortisone maintenance phase, provide mineralocorticoid supplementation with fludrocortisone acetate 0.1 mg daily. Patients with adrenal insufficiency should carry a card or wear a bracelet or necklace that contains information about their condition. Ensure easy patient access to injectable hydrocortisone or glucocorticoid suppositories for emergency use or during times of physical stress, such as febrile illness or injury.
Monitoring
Assess patient symptoms every 6–8 weeks to assess adequacy of glucocorticoid replacement. Reduction in excess pigmentation is a good clinical indicator of successful therapy. Development of Cushingoid features indicates excessive replacement. Most patients are able to lead normal lives with hormone replacement therapy.
References
- Salvatori, R. (2005). Adrenal Insufficiency. JAMA, [online] 294(19), pp.2481–2488. Available at: https://jamanetwork.com/journals/jama/article-abstract/201863
