Part of “CHAPTER 14 – ADRENOCORTICOTROPIN: PHYSIOLOGY AND CLINICAL ASPECTS“

In states of possible autonomous ACTH hypersecretion, dexamethasone is used to inhibit ACTH secretion, and the plasma cortisol concentration or urinary cortisol excretion can be used to estimate ACTH secretory function (see Chap. 74). This technique is used in the diagnosis and differential diagnosis of Cushing syndrome and has been used to demonstrate hypercortisolism in melancholic depression.

Many stimuli have been used to stimulate ACTH secretion for clinical diagnostic purposes. Indications include Cushing syndrome and hypoadrenalism. The most frequently used test of HPA reserve is the cosyntropin stimulation test. This test is based on the rationale that if adrenal cortisol reserves are normal, the hypothalamic CRH and pituitary ACTH reserves must also be normal. Typically 250-μg ACTH (1–24) is administered intravenously and cortisol levels measured at baseline, 30 minutes, and 60 minutes. If plasma cortisol levels rise above 19 μg/dL at 30 (or 60) minutes, this is interpreted as a normal adrenal response. Peak cortisol levels of 16 μg/dL at 60 minutes occur after intramuscular cosyntropin.54 In general, this is used to demonstrate both pituitary ACTH-secretory integrity and normal adrenal-cortisol secretory function, because adrenal atrophy develops rapidly in states of ACTH deficiency. An abnormal cosyntropin test is highly specific for adrenal insufficiency. In cases of pituitary or hypothalamic damage, in which sufficient time may not have passed to allow adrenal atrophy from ACTH deprivation, the cosyntropin test is normal.

However, glucocorticoid deficiency crises have occurred in individuals with a normal cosyntropin test, especially in patients with central hypoadrenalism (pituitary or hypothalamic causes) who may be mistakenly diagnosed as normal in as many as 40% of cases.55 Low sensitivity of the 250-μg cosyntropin test has led to studies using a lower, more physiologic,
1-μg dose, which produces cortisol responses in normal subjects comparable to those obtained with 250-μg cosyntropin and appears more reliable in the diagnosis of central adrenal insufficiency.56 A safe, reliable single test for assessing the functional reserve of the HPA axis57 is still not available. Therefore, good clinical judgment is needed to select the correct test, or combination of tests, to determine whether there is an abnormality of HPA axis function.