Michael P. Kefer
PATHOPHYSIOLOGY
Adrenal insufficiency may be acute or chronic, and results when the physiologic demand for glucocorti-coids and mineralocorticoids exceeds the supply from the adrenal cortex.
The pituitary secretes adrenocorticotropic hormone (ACTH) and associated melanocyte-stimulating hormone (MSH).
ACTH stimulates the adrenal cortex to secrete cortisol (and aldosterone to a minor degree). Cortisol has negative feedback on the pituitary to inhibit secretion of ACTH and MSH.
Cortisol is the major glucocorticoid. It has a key role in maintaining blood glucose levels by decreasing glucose uptake and stimulating proteolysis and lipolysis for gluconeogenesis. Cortisol is necessary for the proper function of catecholamines on cardiac muscle and arterioles. Cortisol also controls body water balance.
Aldosterone is the major mineralocorticoid. The renin-angiotensin system and serum potassium regulate its secretion. ACTH has a minor effect.
The adrenal cortex as a source of androgens is much more important in women than men.
Adrenal insufficiency is described as primary or secondary based on whether the insufficiency occurs at the level of the adrenal glands or pituitary, respectively.
Adrenal crisis is the acute, life-threatening form of adrenal insufficiency.
Congenital adrenal hyperplasia results from an enzyme deficiency in cortisol production. In 95% of cases the deficient enzyme is 21-hydroxylase.
CLINICAL FEATURES
Manifestations of primary adrenal insufficiency, which are due to cortisol and aldosterone deficiency, include weakness, dehydration, hypotension, anorexia, nausea, vomiting, weight loss, and abdominal pain.
Hyperpigmentation of both exposed and nonexposed skin and mucous membranes occurs as a result of uninhibited MSH secretion in conjunction with ACTH.
Androgen deficiency in women manifests as thinning of pubic and axillary hair.
Secondary adrenal insufficiency results from inadequate secretion of ACTH (which is accompanied by MSH), with resultant cortisol deficiency. Aldosterone levels are not significantly affected because of regulation through the renin-angiotensin system. Therefore, hyperpigmentation and hyperkalemia are not seen.
Clinical features of adrenal crisis are as described above, but to the extreme and accompanied by shock and altered mental status.
Congenital adrenal hyperplasia presents in the first month of life with nonspecific symptoms of lethargy, vomiting, poor feeding, and poor weight gain. Examination reveals dehydration, hyperpigmentation, and, in females, clitoromegaly.
DIAGNOSIS AND DIFFERENTIAL
All patients with adrenal insufficiency have low plasma cortisol levels.
Diagnosis of primary adrenal insufficiency and congenital adrenal hyperplasia is based on clinical features and laboratory investigation revealing hyponatremia, hyperkalemia, hypoglycemia, anemia, metabolic aci-dosis, and prerenal azotemia.
Secondary adrenal insufficiency is similarly diagnosed except hyperkalemia is not seen as there is no aldosterone deficiency, and hyperpigmentation is not seen as MSH levels are low along with ACTH levels.
The most common cause of adrenal insufficiency and adrenal crisis is adrenal suppression from prolonged steroid use with either abrupt steroid withdrawal or exposure to increased physiologic stress such as injury, illness, or surgery.
Adrenal suppression can occur with steroids given by any route (oral, topical, intrathecal, or inhaled).
It may take up to 1 year for the hypothalamic-pituitary-adrenal axis to recover following prolonged suppression with steroid treatment.
Differential diagnosis of primary and secondary adrenal insufficiency is listed in Tables 134-1 and 134-2, respectively.
TABLE 134-1 Causes of Primary Adrenal Insufficiency
TABLE 134-2 Causes of Secondary Adrenal Insufficiency
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treatment of acute adrenal insufficiency is outlined in Table 134-3.
Neonates with congenital adrenal hyperplasia are treated with normal saline 20 milligrams/kg bolus for hypovolemia, hydrocortisone 25 mg IV/IO for steroid deficiency, and 10% dextrose 5 mL/kg for hypoglycemia.
TABLE 134-3 Treatment Guide for Adrenal Insufficiency
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 137, “Hypoglycemia and Metabolic Emergencies in Infants and Children,” by Nadeemuddin Qureshi, Mohammed Al-Mogbil, and Osama Y. Kentab and Chapter 225, “Adrenal Insufficiency and Adrenal Crisis,” by Alzamani Mohammed Idrose.