Adrenal Insufficiency

Definition 

• Primary Adrenal Failure, a.k.a Addison’s disease is a disease of adrenal glands

  • Sr. cortisol, & Sr. aldosterone are decreased.

  • ACTH is increased.

  • Problem is in the adrenals, the hypothalamus - pituitary is O.K

• Secondary Adrenal insufficiency due to d/o in pituitary or hypothalmus

  • Often have other associated sx like HA, visual field loss.

  • Sr. Cortisol and ACTH is decreased.

  • Sr. Aldosterone is normal.

Etiology

• Primary adrenal failure most often due to autoimmune adrenalitis, which is associated with other endocrine deficits (polyglandular syndrome), hypothyroidism. Infections such as tuberculosis and histoplasmosis may also cause adrenal failure.

• Hemorrhagic adrenal infarction may occur in the postoperative period, in coagulation disorders and hypercoagulable states, and in sepsis. Adrenal H'ge often causes abdominal or flank pain and fever. CT abdomen scan with and without contrast usually reveals high-density bilateral adrenal masses.

• AIDS, caused by disseminated CMV, mycobacterial or fungal infection, or adrenal lymphoma.

• Other less common etiologies include adenoleukodystrophy, that causes adrenal failure in young males, and drugs such as ketoconazole and etomidate that inhibits steroid synthesis.

• Secondary adrenal failure most often due to glucocorticoid therapy. ACTH suppression may persist for a year after therapy is stopped. Any disorder of the pituitary or hypothalamus can cause ACTH deficiency, but other evidence of these disorders is usually obvious.

Diagnosis

• Primary adrenal insufficiency should be suspected in patients presenting with anorexia, nausea, vomiting, weight loss, weakness, fatigue, hypotension, hyponatremia, hyperkalemia. 

• Symptoms may be chronic, but shock may develop suddenly, and is fatal unless promptly treated. Often this adrenal crisis is triggered by illness, injury, or surgery. The symptoms are mainly due to cortisol deficiency and occurs in both primary and secondary adrenal failure.

• Hyperpigmentation (due to marked ACTH excess) and hyperkalemia and volume depletion (due to aldosterone deficiency) occur only in primary adrenal failure.

Acute AI: potentially fatal.

• Sx: Shock like state. Anorexia, fatigue, malaise, weakness, N/V/D, fever or labile temperatures (hyper or hypothermia), orthostatic hypotension, hyponatremia, hyperkalemia, hypoglycemia, and hypercalcemia.

• Acute AI can occur in Pt. with chronic AI, by infection or injury.

Chronic AI sx include anorexia, fatigue, malaise, weakness, N/V/D, vague abdominal pain, muscle cramps, salt craving, weight loss, hyperpigmentation, hypotension, vitiligo, hyponatremia, hyperkalemia. Calcification of ear cartilage is often seen in Pts with long-standing adrenal insufficiency. - Hyperpigmentation is 2° ACTH excess – melanotrophic. - Hyperkalemia and volume depletion is 2° decreased aldosterone

Screening tests: Check basal levels of Sr. cortisol and aldosterone. Sr. ACTH.

A morning plasma cortisol level of <10 mcg/dL in an acutely ill patient is definitive evidence of adrenal insufficiency. Conversely, a random cortisol level of >20 mcg/dL is usually interpreted as evidence of intact adrenal function and rules out AI.

Cortrosyn (synthetic subunit of ACTH) stimulation test.

• Cortrosyn test (a.k.a cortisone, cosyntropin, ACTH stimulation test)

• Obtain a 4-mL fasting venous blood sample at 8:00 a.m.

• Administer Cosyntropin, 250 mcg IV or IM.

• Obtain additional 4-mL blood specimens at 30 after administration of Cortrosyn.

• Normal response is expected stimulation of adrenal cortisol resulting in rise in Sr. cortisol levels > 20 mcg/dL. The normal cortisol response after Cosyntorpin must be at least 2 x baseline level. Normally aldosterone level parallel cortisol levels.

• In adrenal hyperplasia there is an increase of cortisol levels of 3 to 5 times the normal.

• Absent or blunted response is seen in 

  • Addison’s disease (1° Adrenal insufficiency)

  • Hypopituitarism (2° Adrenal insufficiency)

  • Adrenal carcinoma, adenoma

• The distinction between primary and secondary adrenal failure is usually clinically clear.

  • Hyperkalemia, hyperpigmentation, or other autoimmune endocrine deficits indicate primary adrenal failure, whereas deficits of other pituitary hormones, symptoms of pituitary mass (e.g., headache, visual field loss), or known pituitary or hypothalamic disease indicate secondary adrenal failure. If unclear, the plasma ACTH level distinguishes primary adrenal failure (in which it is markedly elevated) from secondary adrenal failure (in which it is low).

• Peripheral eosinophilia is common finding in 1° AI

• Electrolyte abnormalities is often seen in 1° AI > 2° AI

Other labs

• TSH, thyroid antimicrosomal abs, PPD, CT abdomen: calcification of adrenal suggest H’ge or infection. X-ray head