Pagana: Mosby’s Manual of Diagnostic and Laboratory Tests, 7th Edition

Addison’s Disease

Case Studies With Answers

This 32-year-old white professional female was noted to have increasing melanosis affecting her skin and gums. She noted that she had become weaker over the past several weeks. She complained of nausea, occasional vomiting, and anorexia. She experienced a 10-pound weight loss in the last 8 weeks. She complained of a relative recent onset of moderate high-back pain. She has noted constipation but has no other gastrointestinal symptoms. She noted early satiety. Over the last 2 years she has developed Reynaud’s phenomena.

Her physical exam reveals a thin woman with a dark tan (she recently returned from a vacation in the Caribbean). She weighed 90 lbs and was 5ʹ2ʺ tall. She had very little axillary hair but had all normal primary and secondary sexual characteristics. There was evidence of a melanotic gum line around her teeth. The creases of her hands were hypermelanotic. The remaining physical examination was normal.

Studies	Results	
CBC	Normal	
Chemical profile	Normal except:
Na = 129 (normal: 136–145 mEq/L)
K = 5.1 (normal: 3.5–5 mEq/L)
Albumin 3.0 (normal: 3.5–5 g/dL)	
EGD	Mild gastritis	
Gastric emptying	Delayed gastric emptying	
CT scan abdomen	Adrenal glands not visible	
CT scan of the brain	No pituitary tumor	
Cortisol 8 am	2 mcg/dL (normal: 5–23 mcg/dL)	
ACTH 8 am	3,200 pg/mL (normal: <80 pg/mL)	
Aldosterone	10 ng/dL (normal: 5–30 ng/dL)	
21-Hydroxylase antibodies	5 Units/mL (normal: <1 Units/mL)	
ANA	Positive 1:120 (normal: negative at 1:40 dilution)	
T4 (Free)	2.5 ng/dL (normal: 0.8–2.8 ng/dL)	
TSH	4 microUnits/mL (normal: 2–10 microUnits/mL)	

Diagnostic Analysis

With the low cortisol level, the diagnosis of Addison’s disease was made. Her ACTH was high, indicating secondary adrenal failure. ACTH has actions comparable to melanocytic-stimulating hormone thus causing hyperpigmentation, and elevated levels of ACTH caused this woman to be very darkly tanned. No pituitary tumor was found indicating that this was primary adrenal failure. Her elevated ANA and hydroxylase antibodies indicated that she had an autoimmune cause of her Addison’s disease. The small or absent adrenal glands noted on CT scan corroborated autoimmune destruction of her adrenal glands.

Although one of her main presenting symptoms was upper GI dysfunction, no pathology, such as peptic disease, was found. Her reduced gastric transit was caused by her Addison’s disease.

Critical Thinking Questions

1.	Of all the tests this young woman had, which single test would be easiest, most diagnostic, and would have explained her entire symptom complex?
Cortisol

2.	What other adrenal function test could have been performed to assist in the diagnosis of this woman’s adrenal failure?
Cortisol stimulation test. An increase in plasma cortisol levels after the infusion of an ACTH-like drug indicates that the adrenal gland is normal and capable of functioning if stimulated. In that case the cause of adrenal insufficiency would lie within the pituitary gland (hypopituitarism, which is called secondary adrenal insufficiency). If little or no rise in cortisol levels occurs after the administration of the ACTH-like drug, the adrenal gland is the source of the problem and cannot secrete cortisol.

3.	What is the difference between primary and secondary Addison’s disease, and how can the two be separated?
Primary adrenal insufficiency (Addison’s disease) is caused by pathology/disease of the adrenal gland (such as adrenal hemorrhage, infarction, autoimmunity, metastatic tumor, surgical removal of the adrenal glands, or congenital adrenal enzyme deficiency). Secondary adrenocortical insufficiency, on the other hand, is a condition in which there is an insufficiency of adrenocorticotropic hormone (ACTH) which, in turn, prevents the body from producing enough cortisol. ACTH is produced by the pituitary gland. This gland is controlled by the hypothalamus in the brain. Most common of secondary adrenocortical insufficiency are pituitary tumors, craniopharyngiomas, surgery to remove a tumor, radiation therapy to the pituitary, and cysts in the pituitary.

4.	Why was this woman’s sodium low and her potassium elevated?
Cortisol has a mineralocorticoid (aldosterone-like) effect. Cortisol acts on the kidneys to provide active reabsorption of sodium and secretion of potassium. Patients with Addison’s disease cannot reabsorb sodium and waste potassium in their urine.

List of Cases