A 40-year-old woman comes to your office complaining that “I always feel nauseated and I get tired real fast even when I’m at home just puttering around. This has been going on for about 3 months.” She also tells you that “I’ve been vomiting quite a bit and I don’t have an appetite. The only good thing about all this is that I’ve lost 15 pounds.” After some discussion, she informs you that she has been married for 10 years and denies any extramarital affairs. However, before she got married she admits that “I was pretty wild and would pick up the cutest guy in the bar and take him home for the night. I took mega doses of antibiotics to prevent sexually transmitted diseases and I loved to use amyl and butyl nitrite to heighten my orgasm.” The woman does not seem to be very concerned about her condition as she says, “Doc, just give me something for this nausea and vomiting and I’ll be good to go. I want to lose another 15 pounds.” What is the most likely diagnosis?
Differentials • Acquired immunodeficiency syndrome (AIDS), hemochromatosis, pituitary hypofunction
Relevant Physical Examination Findings • Blood pressure 100/70 mm Hg reclined; 80/60 mm Hg standing (orthostatic hypotension) • Increased pigmentation on her knuckles, knees, and elbows • Areolae are bluish-black • Axillary and pubic hair is sparse • No lymphadenopathy
Relevant Lab Findings
• Blood chemistry:
- hemoglobin (Hgb) 16 g/dL (high);
- hematocrit (Hct) 53% (high); Na 105 mEq/L (low);
- K 6.5 mEq/L (high);
- HCO3– 19 mEq/L (low);
- blood urea nitrogen (BUN) 26 mg/dL (high);
- fasting glucose 45 mg/dL (low);
- serum ferritin 200 ng/mL (normal);
- morning plasma cortisol 3 mg/dL (low);
- morning plasma ACTH 200 pg/mL (high) • Human immunodeficiency virus (HIV) test: negative • Purified protein derivative (PPD) test: negative • Computed tomography (CT) scan: small, noncalcified adrenal glands
Addison Disease (Primary Adrenocortical Insufficiency) • Addison disease (AD) is commonly caused by the autoimmune destruction of the adrenal cortex resulting in a deficiency of cortisol, aldosterone, and dehydroepiandrosterone. Skin hyperpigmentation is seen as a result of increased MSH, which is a byproduct of ACTH synthesis in the adenohypophysis. The deficiency of cortisol results in the following: contributes to orthostatic hypotension; mild pressor effect on the heart and vasculature; hypoglycemia because cortisol plays a role in gluconeogenesis; nausea; vomiting; anorexia; weight loss; and an increase in ACTH levels because cortisol controls ACTH secretion by a negative feedback loop.
The deficiency of aldosterone results in the following: hyponatremia, hypovolemia, decreased cardiac output, decreased renal blood flow, azotemia, andhyperkalemia (which can lead to cardiac dysrhythmia). Aldosterone acts on the principal cells of the cortical collecting ducts in the kidney and causes increased Na reabsorption(tubular fluid S plasma). Aldosterone also acts on the principal cells of the cortical collecting ducts in the kidney and causes increased K secretion (plasma S tubular fluid). A definitive diagnosis of AD is indicated by low cortisol levels, low aldosterone levels, low dehydroepiandrosterone levels, and high ACTH levels.
• Some AIDS patients (20%) present with cortisol resistance and adrenal insufficiency. The HIV test rules out AIDS in this case. Some believe that megadoses of antibiotics, amyl and butyl nitrites, and multiple blood transfusions may destroy CD4 lymphocytes and lead to AIDS.
• Hemosiderin is a golden brown hemoglobin-derived pigment consisting of iron. Iron is absorbed mainly by surface absorptive cells within the duodenum, transported in the plasma by a protein called transferrin, and normally stored in cells as ferritin, which is a protein–iron complex. During iron overload, intracellular ferritin undergoes lysosomal degradation, in which the ferritin protein is degraded and the iron aggregates within the cell as hemosiderin in a condition called hemosiderosis. The more extreme accumulation of iron is called hemochromatosis, which is associated with liver and pancreas damage. Hemochromatosis can be observed in patients with increased absorption of dietary iron, impaired utilization of iron, hemolytic anemias, and blood transfusions. Clinical findings of hemochromatosis include cirrhosis of the liver, diabetes, and increased skin pigmentation (bronze diabetes).
• Pituitary hypofunction (secondary adrenocortical insufficiency) presents with many of the same symptoms as AD because the adrenal cortex is under control of the adenohypophysis. A definitive diagnosis of pituitary hypofunction is indicated by low cortisol levels, normal aldosterone levels (because the zona glomerulosa of the adrenal cortex is controlled by the renin-angiotensin system), low dehydroepiandrosterone levels, and low ACTH levels. Since ACTH levels are low, MSH will not be increased so that no increased skin pigmentation would be observed.