Primary adrenocortical insufficiency

PREVALENCE: 5 cases/100,000 persons
PREDOMINANT SEX: Female:male ratio of 2:1

• Hyperpigmentation: more prominent in palmar creases, buccal mucosa, pressure points (elbows, knees, knuckles), perianal mucosa, and around areolas of nipples
• Hypotension
• Generalized weakness
• Amenorrhea and loss of axillary hair in females

• Autoimmune destruction of the adrenal glands (80% of cases)
• Tuberculosis (15% of cases)
• Carcinomatous destruction of the adrenal glands
• Adrenal hemorrhage (anticoagulants, trauma, coagulopathies, pregnancy, sepsis)
• Adrenal infarction (arteritis, thrombosis)
• Other: sarcoidosis, amyloidosis, postoperative, fungal infections, AIDS (adrenal insufficiency develops in 30% of patients with AIDS)

Sepsis, hypovolemic shock, acute abdomen, apathetic hyperthyroidism in the elderly, myopathies, GI malignancy, major depression, anorexia nervosa, hemochromatosis, salt-losing nephritis, chronic infection

• If the clinical picture is highly suggestive of adrenocortical insufficiency, the diagnosis can be made with the rapid ACTH (Cortrosyn) test:

1.Give 250 µg ACTH by IV push and measure cortisol levels at 0 and 30 min.
2.Cortisol level <18 30="30" 60="60" adrenal="adrenal" at="at" br="br" dl="dl" g="g" insufficiency.="insufficiency." is="is" min="min" of="of" or="or" suggestive="suggestive">3.Measure plasma ACTH. A high ACTH level confirms primary adrenal insufficiency.

1.Normal or low plasma ACTH level following rapid ACTH (Cortrosyn test)
2.Absence of hyperpigmentation
3.No significant impairment of aldosterone secretion (because aldosterone secretion is under control of the renin-angiotensin system)
4.Additional evidence of hypopituitarism (e.g., hypogonadism, hypothyroidism)

• Increased potassium, decreased sodium and chloride
• Decreased glucose
• Increased BUN/creatinine ratio (pre-renal azotemia)
• Mild normocytic, normochromic anemia, neutropenia, lymphocytosis, eosinophilia (significant dehydration may mask hyponatremia and anemia)
• PPD and antiadrenal antibodies

• Chest x-ray examination may reveal a small heart.
• Abdominal x-ray film: adrenal calcifications may be noted if the adrenocortical insufficiency is secondary to TB or fungus.
• Abdominal CT scan: small adrenal glands generally indicate either idiopathic atrophy or long-standing TB, whereas enlarged glands are suggestive of early TB or potentially treatable diseases.

• Perform periodic monitoring of serum electrolytes, vital signs, and body weight; liberal sodium intake is suggested.
• Periodic measurement of bone density may be helpful in identifying patients at risk for the development of osteoporosis.
Patients should carry a Medic Alert bracelet and an emergency pack containing hydrocortisone 100 mg ampule, syringe, and needle. Patients and partners should be educated on how to give IM injection in case of vomiting or coma.

Addisonian crisis is an acute complication of adrenal insufficiency characterized by circulatory collapse, dehydration, nausea, vomiting, hypoglycemia, and hyperkalemia.

1.Draw plasma cortisol level; do not delay therapy while waiting for confirming laboratory results.
2.Administer dexamethasone sodium phosphate 4 mg q12h or hydrocortisone 100 mg IV q6h for 24 hr; if patient shows good clinical response, gradually taper dosage and change to oral maintenance dose (usually prednisone 7.5 mg/day).
3.Provide adequate volume replacement with D5 NS solution until hypotension, dehydration, and hypoglycemia are completely corrected. Large volumes (2 to 3 L) may be necessary in the first 2 to 3 hr to correct the volume deficit and hypoglycemia and to avoid further hyponatremia.
Identify and correct any precipitating factor (e.g., sepsis, hemorrhage).

• Give hydrocortisone 15 to 20 mg PO every morning and 5 to 10 mg in late afternoon or prednisone 5 mg in morning and 2.5 mg hs.
• Give oral fludrocortisone 0.05 mg/day to 0.20 mg/day: this mineralocorticoid is necessary if the patient has primary adrenocortical insufficiency. The dose is adjusted based on the serum sodium level and the presence of postural hypotension or marked orthostasis.
• Instruct patients to increase glucocorticoid replacement in times of stress and to receive parenteral glucocorticoids if diarrhea or vomiting occurs. Typical supplementation varies from 25 mg PO qd of hydrocortisone for minor medical and surgical stress to 50–100 mg IV hydrocortisone every 8 hr for sepsis-induced hypotension or shock.
• The administration of dehydroepiandrosterone 50 mg PO qd improves well-being and sexuality in women with adrenal insufficiency.

• Lifelong medical supervision is necessary to monitor adequacy of therapy and prevent complications.
• Adrenal function is rarely recovered.
• Life expectancy is in the normal range if adequately treated.

Patient education material may be obtained from the National Addison’s Disease Foundation, 505 Northern Blvd., Suite 200, Great Neck, NY 11021, phone: (516) 487-4992.

Cousin DB, Wood KE: Corticosteroid supplementation for adrenal insufficiency. JAMA 287:236, 2002.