Comparison of the Low Dose Short Synacthen Test (1 μg), the Conventional Dose Short Synacthen Test (250 μg), and the Insulin Tolerance Test for Assessment of the Hypothalamo-Pituitary-Adrenal Axis in Patients with Pituitary Disease

Abstract

There is still uncertainty about what is the most appropriate test for assessment of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate the insulin tolerance test (ITT), but this is unpleasant and resource intensive, and may occasionally give misleading results. The conventional [250 microg tetracosactrin, ACTH-(1-24)] short synacthen test (SST) has been used as a simple alternative to the ITT, but it has produced some falsely reassuring results with potentially serious consequences. A low dose [1 microg tetracosactrin, ACTH-(1-24)] short synacthen test (LDSST) has recently been advocated as a more reliable and safer alternative to ITT. Some studies, however, have failed to demonstrate any difference between SST and LDSST. The purpose of this study was to assess the clinical usefulness of LDSST compared to SST and ITT in patients with pituitary disease. We studied 64 patients with suspected or proven pituitary disease. All patients underwent SST and LDSST. Forty-two patients underwent ITT. There was a high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; P < 0.0001), the ITT and SST 30 min cortisol levels (r = 0.83; P < 0.0001), and the LDSST peak cortisol response and the SST 30 min cortisol level (r = 0.85; P < 0.0001). In the LDSST, all but six patients achieved maximal cortisol response by 30 min. A plasma cortisol cut-off of 600 nmol/L is more helpful than 500 nmol/L for clinical decision-making using either the SST 30 min cortisol level or the LDSST peak cortisol response. The sensitivity of the LDSST was 100% (cortisol response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring results. SST (pass cortisol level, >600 nmol/L) was less sensitive than LDSST, it produced 2 of 64 (3%) falsely reassuring results. Even the ITT (pass cortisol level, >500 nmol/L) failed to identify one patient with clinically evident cortisol deficiency. The results of this study indicate that both SST and LDSST, at a cortisol cut-off of 600 nmol/L, are safe for the purpose of clinical decision-making with regard to steroid replacement therapy in patients with pituitary disease. As the LDSST produced no falsely reassuring decisions, we suggest that this could replace the SST and ITT for initial evaluation of the HPA axis in patients with pituitary disease. We suggest administering 1 microg tetracosactrin, i.v., with sampling at 0, 20, and 30 min.

Long-term metabolic, endocrine, and neuropsychological outcome of hematopoietic cell transplantation for Wolman disease

“…7,13 The adrenocorticotropin stimulation test is used to evaluate adrenal cortisol production. The standard-dose ACTH stimulation test (250 mg cosyntropin) is typically used to diagnose primary adrenal insufficiency, while the low-dose ACTH stimulation test (1 mg cosyntropin) is more sensitive than the standard-dose test [14][15][16][17] and thus may be more appropriate for diagnosis of subtle adrenal insufficiency, including secondary adrenal insufficiency or adrenal suppression, to test for adrenal recovery. A peak cortisol response 420 mg per 100 ml is generally considered normal, and 18-20 mg per 100 ml is considered borderline.…”

The diagnosis and investigation of adrenal insufficiency in adults

“…60,71,86 -91 The majority of these divergent responses occur in patients who show poststimulation cortisol values of between 500 and 650 nmol/L. 92,93 In one recent study of 148 patients at risk of developing secondary adrenal insufficiency due to cranial irradiation, pituitary surgery or concomitant glucocorticoid therapy, only one patient with a normal synacthen response (30 min cortisol .550 nmol/L) and one patient with a borderline result (510-550 nmol/L at 30 min) developed clinical adrenal insufficiency. 94 Based on these observations, the false-negative rate for the synacthen test is ,1%.…”

“…Furthermore, as the ITT is not 100% sensitive, there may be infrequent patients who pass the ITT but who are later found to have adrenal insufficiency. 76,93 A study of patients following pituitary surgery found six of a group of 41 who failed the low-dose (1 mg) synacthen test one week after surgery subsequently passed the ITT at 4 -6 weeks postsurgery. 75 In contrast, three of 40 patients had a normal response to the standard-dose synacthen test but a subnormal response to the ITT.…”

Adrenal Insufficiency In Critically Ill Patients

“…20,21 It is prepared by diluting the 250-μg vial in 250 ml of normal saline to obtain a concentration of corticotrophin (ACTH) 1 mcg/ml and using a 1-ml syringe to accurately draw a dose. The syringes can be kept at 4°C for up to 4 months without any decline in biologic activity 22 .…”