COMPARISON OF LOW AND HIGH-DOSE CORTICOTROPIN STIMULATION TESTS IN PATIENTS WITH PITUITARY DISEASE

Tetracosactin [corticotropin-(1-24)] is used for clinical testing of a drenocortical responsiveness. The usual dose [high dose test (HDT)] is 250 mu g. With this test, patients with mild secondary adrenal insuff iciency are usually not identified, thus putting them at risk of an ad renal crisis in stressful situations. It was recently reported that a tetracosactin test with approximately 1 mu g [low dose test (LDT)] ide ntifies patients with mild forms of pituitary-adrenal insufficiency. W e performed both the HDT and the LDT in 35 control subjects and in 44 patients with pituitary disease, mostly pituitary tumors. In these pat ients, more sensitive reference tests for evaluating the pituitary-adr enal axis (insulin-induced hypoglycemia, metyrapone, and CRH tests) we re also performed. In the HDT, plasma cortisol was measured 30 and 60 min after tetracosactin injection; in the LDT (0.5 mu g/m(2) body surf ace area), plasma cortisol was measured 20, 30, 40, 50, and 60 min pos tinjection. In 6 control subjects, tetracosactin plasma levels were al so measured after injection. In the HDT, the correlation between 30 an d 60 min cortisol levels was extremely high (r = 0.991; P < 0.0001), b ut the correlation of the LDT with the HDT at 30 min was also highly s ignificant (r = 0.948; P < 0.0001). The lower normal limit of cortisol responses (means of controls minus 2 SD) at 30 min was lower in the L DT by 3.1 mu g/dL (85 nmol/L) than in the HDT. Compared with the refer ence tests, the diagnostic sensitivities of the HDT and the LDT were a lmost identical. Both tests identified patients with moderately to sev erely pathological insulin and metyrapone tests, but not those with sl ightly pathological reference tests. In the HDT, plasma tetracosactin rose to more than 60,000 mu g/mL shortly after injection. In the LDT, it rose to 1,900 pg/mL. Both concentrations stimulate cortisol (supra- ) maximally. Together, these data show that in pituitary disorders the results of the LDT and the HDT are almost identical. Plasma tetracosa ctin levels in the LDT still rise to levels that maximally stimulate t he adrenal. Tetracosactin testing with low or high doses cannot genera lly replace the more expensive and cumbersome insulin or metyrapone te sts.