Adrenal insufficiency

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Clinical symptoms and signs of adrenal insufficiency depend upon the rate and extent of loss of adrenal function, whether mineralocorticoid production is preserved, and the degree of stress. The onset of adrenal insufficiency is often very gradual and it may go undetected until an illness or other stress precipitates adrenal crisis.

Adrenal crisis

The syndrome of adrenal crisis (acute adrenal insufficiency) in adults may occur in the following scenarios: (a) In a previously undiagnosed patient with primary adrenal insufficiency who has been subjected to serious infection or other acute, major stress; (b) In a patient with known primary adrenal insufficiency who does not take more glucocorticoid during an infection or other major illness, or has persistent vomiting caused by viral gastroenteritis or other gastrointestinal disorders; (c) After bilateral adrenal infarction or bilateral adrenal hemorrhage; (d) Less frequently in patients with secondary or tertiary adrenal insufficiency during acute stress, but is sometimes seen with acute cortisol deficiency due to pituitary infarction; and (e) In patients who are abruptly withdrawn from doses of glucocorticoid that cause secondary adrenal insufficiency. Importantly, this includes not only oral but inhaled medications.

Clinical manifestations

The predominant manifestation of adrenal crisis is shock, but the patients often have nonspecific symptoms such as anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, fever, confusion or coma. Hypoglycemia is a rare presenting manifestation of acute adrenal insufficiency; it is more common in secondary adrenal insufficiency caused by isolated corticotropin (ACTH) deficiency. Patients with long-standing adrenal insufficiency who present in crisis may be hyperpigmented (due to chronic ACTH hypersecretion) and have weight loss, serum electrolyte abnormalities, and other manifestations of chronic adrenal insufficiency. The major hormonal factor precipitating adrenal crisis is mineralocorticoid, not glucocorticoid, deficiency, and the major clinical problem is hypotension. Thus, adrenal crisis can occur in patients who are receiving physiologic or even pharmacologic doses of synthetic glucocorticoid if their mineralocorticoid requirements are not adequately satisfied. In addition, patients with secondary adrenal insufficiency, in whom aldosterone secretion is usually normal, rarely present in adrenal crisis. Although it is not primarily responsible, glucocorticoid deficiency can contribute to hypotension by causing decreased vascular responsiveness to angiotensin II and norepinephrine, decreased synthesis of renin substrate, and increased prostacyclin production.

Chronic adrenal insufficiency

Patients with chronic primary adrenal insufficiency may have symptoms and signs of glucocorticoid, mineralocorticoid, and in women, androgen deficiency. In contrast, patients with secondary or tertiary adrenal insufficiency usually have normal mineralocorticoid function. The diagnosis is usually obvious in patients with the full-blown syndrome of adrenal insufficiency. However, its onset is often insidious, with the gradual development of symptoms, most of which are nonspecific. In its early stage, therefore, diagnosis may be difficult. The clinical presentation of primary adrenal insufficiency is discussed separately.

Common features — The most common clinical features of chronic primary adrenal insufficiency are listed below. Regardless of the immediate complaint, most patients with adrenal insufficiency have the following: (a) Chronic malaise; (b) Lassitude; (c) Fatigue that is worsened by exertion and improved with bed rest; (d) Weakness that is generalized, not limited to particular muscle groups; (e) Anorexia; and (f) Weight loss.

The weight loss is primarily due to anorexia, but dehydration may contribute. The amount of weight lost can vary from 2 to as much as 15 kg and may not become evident until adrenal failure is advanced. The patient may also be very sensitive to opioid, analgesic or sedative drugs, or may recover very slowly from illnesses or operations that do not precipitate adrenal crisis.

Notes & References

[1] Jacobs TP, Whitlock RT, Edsall J, Holub DA. Addisonian crisis while taking high-dose glucocorticoids. An unusual presentation of primary adrenal failure in two patients with underlying inflammatory diseases. JAMA 1988; 260:2082.

[2] Zuckerman-Levin N, Tiosano D, Eisenhofer G, et al. The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: a study in isolated glucocorticoid deficiency. J Clin Endocrinol Metab 2001; 86:5920.

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Stawicki SP

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