Abstract
Acute adrenal insufficiency, although not common, is an often unrecognized disorder in critically ill patients. Even minor degrees of adrenal insufficiency can increase the mortality of critically ill or injured patients. Here, after presenting a typical case, the condition is defined, and recognition, management, and prevention are discussed. The risk of developing acute adrenal insufficiency is also discussed.
Keywords
adrenal crisis, adrenal insufficiency, hypothalamic-pituitary-adrenocortical axis, refractory hypotension, stress dose steroids
Case Synopsis
A 68-year-old, 5-foot 10-inch, 100-kg man develops refractory hypotension toward the end of a laparotomy to remove the left colon because of recurrent diverticulitis and suspected peridiverticular abscess. The patient remains intubated at the end of the procedure and is taken to the intensive care unit (ICU), where a pulmonary artery catheter is placed and transthoracic echocardiogram (TTE) is obtained. The pulmonary artery occlusion pressure is 6 mm Hg, systemic vascular resistance is 475 dynes/cm 5 , cardiac output is 10 L/min, and cardiac index is 6 L/min/m 2 . TTE shows a hyperdynamic left ventricle with end-systolic cavity obliteration, a small hypercontractile right ventricle, and a small inferior vena cava with marked respiratory variations. The patient is mechanically ventilated and has a heart rate of 128 beats per minute in sinus rhythm and blood pressure of 88/42 mm Hg on infusions of norepinephrine 0.1 μg/kg per minute, epinephrine 0.1 μg/kg per minute, and vasopressin 0.03 units per minute. The patient’s medical history is remarkable for hypertension and type 2 diabetes chronically treated with lisinopril and glucophage, respectively. Both were withheld on the day of surgery. Shortly after his admission to the ICU, a diagnostic test was performed and a new medication was added to the therapeutic regimen. After several hours the patient was hemodynamically stable and vasopressors had been discontinued.
Problem Analysis
Definition
Adrenal insufficiency (AI) is a relatively rare but potentially life-threatening condition that can be quiescent until unmasked by medical stressors such as sepsis, traumatic insults, hemorrhagic shock, or surgical stress.
Sir Thomas Addison described primary AI in 1855. Approximately a century later Harvey Cushing developed the concept of secondary AI. Causes for primary and secondary AI are listed in Box 1.1 .
Primary Adrenal Insufficiency
Autoimmune
Polyglandular autoimmune syndrome types I and II
Infectious
Tuberculosis
Histoplasmosis
Blastomycosis
Coccidiomycosis
Cryptococcosis
Human immunodeficiency virus
Cytomegalovirus
Mycobacterium avium-intracellulare
Cryptococcus
Toxoplasmosis
Kaposi sarcoma
Fibrosis
Infarction
Adrenal hemorrhage
Waterhouse-Friderichsen syndrome
Lupus anticoagulant
Antiphospholipid antibodies
Immune thrombocytopenic purpura
Heparin induced
Thrombocytopenia
Anticoagulants
Metastatic disease
Lung
Gastric
Breast
Malignant melanoma
Lymphoma
Drugs
Decreased steroid synthesis
- •
Metyrapone
- •
Aminoglutethimide
- •
Mitotane
- •
Etomidate ∗
∗ Still unproven and therefore speculative.
- •
Ketoconazole
- •
Increased steroid catabolism
- •
Rifampin
- •
Dilantin
- •
Phenobarbital
- •
Familial
Familial glucocorticoid deficiency
Adrenoleukodystrophy
Adrenomyeloneuropathy
Iatrogenic
Bilateral surgical removal
Bilateral embolization
Secondary Adrenal Insufficiency
Exogenous steroid administration (often referred to as tertiary or iatrogenic)
Pituitary or hypothalamic diseases
Infiltrative tumor (adenoma)
Sarcoid
Hemorrhage
Autoimmune
Isolated ACTH deficiency
Surgical
Pituitary surgery
Removal of a functioning adrenal adenoma
ACTH, Adrenocorticotropic hormone.
The hypothalamic-pituitary-adrenocortical (HPA) axis ( Fig. 1.1 ) regulates the amount of cortisol released by the adrenals. The cycle begins with the release of corticotropin-releasing factor (CRF) from the hypothalamus, which stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH then stimulates the release of cortisol from the adrenal cortex at a rate of about 20 mg/day. Cortisol (or a synthetic analog) acts on the hypothalamus to inhibit the release of CRF and on the anterior pituitary to inhibit the release of ACTH. The associated diurnal variation in cortisol release peaks in the morning and midafternoon and then tapers off to a nadir in the evening. Although normal adults secrete about 5 to 10 mg/m 2 of cortisol (or hydrocortisone) each day, during periods of acute stress the adrenal cortex can secrete as much as 100 mg/m 2 per 24 hours.
