Primary Adrenal Insufficiency

For 2 weeks, a 43-year-old white female had worsening nausea and multiple episodes of vomiting. Her symptoms began with increased malaise and decreased appetite. The emesis was unrelated to meals and was sometimes accompanied by mild abdominal distention. She had occasional fevers but denied any recent contact with ill persons. She also reported a 12-lb weight loss, decreased energy level, and an increased tan complexion over the past several months.

The patient's medical history included 2 cesarean deliveries. Her mother had type 2 diabetes mellitus and a "thyroid disorder." Her father's medical history was unknown. She was taking no medications.

The patient appeared very thin and had diffuse hyperpigmentation (A; physician's hand is shown for comparison), poor dentition, dark gingiva, and notable areas of increased pigmentation on her buccal mucosa (B and C). Heart rate was 114 beats per minute; temperature, 36.1°C (97°F); blood pressure, 82/61 mm Hg; and respiration rate, 16 breaths per minute. There was minimal abdominal distention; normal bowel sounds; and no abdominal tenderness, guarding, or rigidity. The remainder of the examination findings were normal.

Initial laboratory results showed the following levels: sodium, 113 mEq/L; potassium, 5.3 mEq/L; chloride, 82 mEq/L; bicarbonate, 22 mEq/L; blood urea nitrogen, 15 mg/dL; creatinine, 0.6 mg/dL; and serum glucose, 50 mg/dL. The complete blood cell count was normal. A random cortisol level was 2.48 µg/dL (normal, 5 to 18 µg/dL). There was no obstruction or acute findings detected on abdominal x-ray films.

Primary adrenal insufficiency with an acute adrenal crisis was suspected. Initially, the patient was stabilized with intravenous normal saline and corticosteroids. A follow-up adrenocorticotropic hormone (ACTH) stimulation test revealed a poststimulation cortisol level of 1.71 µg/dL at 30 minutes and 1.70 µg/dL at 60 minutes. Later, her ACTH level was 689 pg/mL (normal, 9 to 52 pg/mL); the aldosterone level was less than 1 ng/dL (normal, 2 to 9 ng/dL supine, 2 to 35 ng/dL upright). These results confirmed the diagnosis.

Adrenal disorders are divided into 2 categories: those caused by end-organ dysfunction (primary adrenal insufficiency or Addison disease), and those caused by abnormal ACTH production (secondary adrenal insufficiency).¹ The most common cause of Addison disease is autoimmune adrenalitis, which results from glandular destruction by cytotoxic T lymphocytes. Primary adrenal insufficiency may be associated with other autoimmune polyglandular syndromes. Because this patient had a family history of diabetes mellitus and a thyroid disorder, which are commonly present in persons with autoimmune polyglandular syndrome type II, she will be further evaluated for hypothyroidism, hypoparathyroidism, diabetes, and hypogonadism. Other causes of adrenal insufficiency (eg, hemorrhagic infarction, metastatic disease, infectious adrenalitis) result in symptoms once there is greater than 90% involvement of both glands.¹

When adrenal insufficiency is suspected, basal morning plasma cortisol levels may be obtained. Levels of less than 3 µg/dL are highly suggestive of the diagnosis. Patients with these levels may not need additional testing. This is also true in patients with a plasma cortisol level of greater than 19 µg/dL, which essentially rules out the disorder.² However, if the diagnosis is uncertain or if further confirmation is desired, ACTH stimulation testing may be performed.

An abdominal CT scan should be obtained to further evaluate the cause of primary adrenal insufficiency. Enlarged glands or calcification may indicate infection, hemorrhage, or metastatic disease.

Treatment for primary adrenal insufficiency involves the replacement of both glucocorticoids and mineralocorticoids. Some advocates also recommend replacement of androgens in women.^1,2 This patient responded well to therapy with glucocorticoids and mineralocorticoids.

All patients with adrenal insufficiency should be instructed to increase their dose of medication (3 times the regular dose for 3 days) during periods of acute illness and to have prefilled syringes of dexamethasone available for administration in the event they are unable to take oral medication.

References:

REFERENCES:

1.

Williams GH, Dluhy RG. Disorders of the adrenal cortex. In: Braunwald E, Fauci AS, Kasper DL, et al, eds.

Harrison's Principles of Internal Medicine.

New York: McGraw-Hill; 2001:2084-3000.

2.

Oelkers W. Adrenal insufficiency.

N Engl J Med.

1996;335:1206-1212.