Diagnostic predicament of secondary adrenal insufficiency

To propose an approach for the diagnosis of secondary adrenal insufficiency (AI) by presentation of 2 clinical cases and review of the literature.

We describe 2 patients who were considered to have a normal hypothalamic-pituitary-adrenal axis on the basis of an appropriate response to the high-dose (250 microg) cosyntropin stimulation test (HST), with use of a cutoff value of 20 microg/dL. Our first patient had undergone resection of a 4-cm pituitary tumor a few months previously, and the second patient had hyponatremia with empty sella syndrome. Both patients, however, had strong clinical evidence suggestive of secondary AI. On testing by the insulin tolerance test (ITT) in the first patient and the overnight metyrapone test (OMT) in the second patient, secondary AI was diagnosed. We reviewed the literature to compare the utility of the different tests for the diagnosis of secondary AI.

An 8 AM serum cortisol value less than 5 microg/dL or above 13 microg/dL and a stimulated cortisol level less than 16 microg/dL on both the low-dose cosyntropin stimulation test (LST) and the HST as well as above 22 microg/dL on the LST and above 30 microg/dL on the HST can reliably predict the functional status of the hypothalamic-pituitaryadrenal axis in chronic secondary AI. Values between these cutoff points may necessitate further assessment with the OMT or ITT based on clinical suspicion.

We recommend a 3-step diagnostic approach, with the first 2 steps performed together-starting with the 8 AM basal cortisol determination in conjunction with either the LST (preferably) or the HST. In cases of an indeterminate response coupled with a strong clinical suspicion, the final step should be definitive testing with the OMT or ITT.