Hypoadrenal Crisis and the Stress Management of the Patient on Chronic Steroid Therapy
Neil Aronin
I. HYPOADRENAL CRISIS
A. General principles.
1. The adrenal glands secrete five types of hormones, but two are critical in the intensive care unit (ICU) setting.
a. Aldosterone has a major effect on electrolyte balance.
b. Cortisol promotes gluconeogenesis and has many other actions.
c. Both are life sustaining; deficiency of either can result in a hypoadrenal crisis.
2. Hypoadrenal crisis can occur as an acute event in individuals lacking previous adrenal problems.
3. A high index of suspicion arises in patients who have inadequate responses to initial therapies.
4. Severe illnesses that contribute to ICU admission (e.g., sepsis, acute respiratory failure) might interfere with traditional tests of adrenal function.
5. There is no unified alogorithm of treatment.
B. Etiology.
1. The most common cause of primary adrenal failure, Addison disease, is autoimmune and is often known before the ICU admission.
2. Other causes of adrenal failure offer a difficult diagnosis in the ICU. These include overwhelming sepsis; hemorrhage secondary to trauma, circulating anticoagulants, or anticoagulant therapy; tuberculosis; fungal disease; amyloidosis; acquired immune deficiency syndrome; antiphospholipid syndrome; infarction; irradiation; metastatic disease; or drugs.
3. Critical illness can cause or bring out adrenal insufficiency.
4. The most common cause of secondary adrenal insufficiency is suppression of corticotrophin (adenocorticotrophic hormone [ACTH]) release by prior glucocorticoid therapy.
a. There are no cutoffs on duration of glucocorticoid therapy, its route of administration, and its dosage that can cause adrenal cortical atrophy and inadequate reserve.
C. Pathophysiology.
1. The adrenal cortex secretes aldosterone from the zona glomerulosa and cortisol from the zona fasciculata.
2. Aldosterone promotes the reabsorption of sodium and the secretion of potassium and hydrogen ion in the distal renal tubule.
a. It is controlled mainly by the renin-angiotensin system.
b. Glucocorticoid suppression of ACTH, and therefore cortisol in the zona fasciculata, does not suppress aldosterone in the zona glomerulosa.
c. Aldosterone deficiency results in sodium wasting, with concomitant loss of water and an increase in renal reabsorption of potassium. A decrease in plasma volume and dehydration occurs, with subsequent increases in blood urea nitrogen (BUN) and plasma renin activity.
3. Glucocorticoids promote gluconeogenesis and protein wasting and increase the excretion of free water by the kidney.
a. In large doses, glucocorticoids bind to mineralocorticoid receptors, increasing sodium reabsorption and potassium and hydrogen ion excretion.
b. Glucocorticoids act on the central nervous system, to affect the sense of well-being, appetite, and mood. They inhibit ACTH release through hypothalamic and pituitary actions.
c. Glucocorticoids have direct effects on the cardiovascular system and maintain blood pressure, although mechanisms are not established. Critical illness and glucocorticoid deficiency affect common physiologic systems.
d. Excess glucocorticoids cause lymphopenia, leukocytosis, and eosinopenia; can lead to osteoporosis and reduction of hypercalcemia; and can impair host defenses to infections.
e. A decrease in circulating levels of cortisol causes a marked increase in levels of ACTH and β-lipotropin, from which melanocyte-stimulating hormone activity increases. In long-standing adrenal insufficiency, the skin, especially creases and scars, develops hyperpigmentation.
f. Low plasma cortisol is also associated with the following:
i. Orthostatic hypotension, which can progress to frank shock in a crisis.
ii. Hypoglycemia and an increase in sensitivity to insulin.
D. Diagnosis.
1. Clinical manifestations that suggest adrenal insufficiency include the following:
a. A history of increasing weakness, lassitude, fatigue, anorexia, vomiting, and constipation (with hypoadrenal crisis, diarrhea can occur).
b. Patients who present with adrenal hypofunction in crisis are hypotensive (volume depletion) or in frank shock; they generally have a fever, sometimes high, and may be stuporous or comatose.
c. In individuals whose loss of adrenal function occurs precipitously (adrenal hemorrhage due to an infection, anticoagulant therapy, trauma, or after surgery), no hyperpigmentation is seen but flank pain is often present.
