The most important factor in diagnosing hypoadrenalism in the intensive care unit (ICU) setting is a high index of clinical suspicion as its clinical presentation is usually non-specific. Previous or present use of corticosteroids, use of anticoagulants, a history of tuberculosis, metastatic malignancy, and (ongoing) sepsis are among the conditions that may be associated with acute hypoadrenalism and should rouse this suspicion. Adrenal crisis should be considered in (septic) shock that is unresponsive to volume expansion and vasopressor agents and in (postoperative) patients with unexplained abdominal complaints, fever, and/or hypotension. Clinical features of chronic hypoadrenalism when present (e.g. hyperpigmentation) and laboratory findings are helpful. However, in acute cases laboratory abnormalities are often less pronounced than in chronic hypoadrenalism. Hyponatremia with a high urinary sodium concentration, hyperkalemia, and hypoglycemia are important clues to the diagnosis of hypoadrenalism. The sodium-to-potassium ratio will almost always be below 30. However, hyperkalemia is not a feature of secondary hypoadrenalism. Eosinophilia, leukocytosis, increased blood urea and calcium concentrations, and a mild metabolic acidosis support the diagnosis of hypoadrenalism, but these abnormalities (with the exception of eosinophilia) are common in critically ill patients. The basis of the diagnosis of adrenal insufficiency depends on the demonstration of inadequate cortisol production. A basal cortisol concentration below 275 mmol/l (<10 g/dl) strongly suggests the diagnosis, and a level of 550 nmol/l (20 g/dl) or above argues strongly against it. However, in virtually all patients in whom the diagnosis is considered, a short ACTH (tetracosactrin) stimulation test should be performed because of the variable and pulsatile nature of the response of the hypothalamic-pituitary-adrenal axis to stress. The test involves the intravenous administration of 0.25 mg tetracosactrin and measurement of plasma cortisol concentrations before stimulation and 30 and/or 60 min afterwards. A rise in plasma cortisol concentration between 30 and 60 min to a peak of at least 600 mmol/l or more virtually excludes primary hypoadrenalism ( Patel et a/ 1991).
This is an accurate and safe diagnostic test in the ICU setting. However, an adequate response does not eliminate secondary/tertiary adrenal insufficiency of recent onset. Measurement of ACTH levels prior to the ACTH test will show low-normal or decreased concentrations in these cases. Available provocative tests, which centrally stimulate the hypothalamic-pituitary-adrenal axis, are the insulin-induced hypoglycemia and metyrapone tests ( Grilnspggn..land..l.Bi!jer.l19l9l4). They can help to discriminate between primary and secondary/tertiary hypoadrenalism but are not practical in the ICU. A corticotropin-releasing hormone stimulation test can test the ability to secrete sufficient ACTH, but an exaggerated and prolonged ACTH response is observed in primary hypothalamic disorders. Prolonged ACTH stimulation tests can also be helpful in distinguishing primary from secondary/tertiary adrenal insufficiency, but their use in critically ill patients is rather cumbersome.
In addition to laboratory investigations, diagnostic imaging modalities such as computer tomography and magnetic resonance imaging are useful in the diagnosis of adrenal insufficiency. Both techniques are able to identify anatomical lesions in the area of the hypothalamic-pituitary-adrenal axis.
Was this article helpful?