The low-dose (1 μg) Cosyntropin Test (LDT) for Primary Adrenocortical Insufficiency: Defining the Normal Cortisol Response and Report on First Patients with Addison Disease Confirmed with LDT

Abstract

The validity of low-dose 1 microg cosyntropin test (LDT) is reported mainly for the assessment of secondary adrenocortical insufficiency (AI). Likewise the hypothalamic-pituitary disorders, early diagnosis of the initial or partial stages of primary AI has an important role. The aim of study was to: 1) establish the normal cut-off level at which the stimulated plasma cortisol (FP) in LDT excludes primary AI; 2) compare the results in elderly subjects to those in younger ones; 3) compare the results between normal and obese subjects; and 4) verify the established cut-off values on the sample of patients suspected to have primary AI. 110 subjects (99 women and 11 men, aged 19-80 years, mean 46.2+/-16.1 years, without suspicion for impairment of the hypothalamo-pituitary-adrenal axis were recruited to undergo the LDT in standard conditions. Control group consists of 30 patients (22 women and 8 men, aged 7-58 years, mean 38.4+/-10.6 years) evaluated in whom for suspicion of primary AI as suggested by LDT was confirmed by supplemental investigations (elevated ACTH levels, positive autoantibodies against 21-hydroxylase, mutational analysis of corresponding genes). The mean peak FP level at 30 min (FP (30)) of the subjects was 675+/-85 nmol/L (95% CI=659 to 691 nmol/L), thus reference values expressed as mean+/-2 SD were 505-845 nmol/L. There was a significant negative correlation between basal FP values (FP (0)) (434+/-105 nmol/L) and the absolute FP incremental (FP (Delta)) response varying from 52 to 553 nmol/L (median 230 nmol/L) (r=-0.71; P<0.001). FP (30) was higher in elderly subjects (n=27) in comparison to younger subjects (n=25) (689+/-88 nmol/L vs. 642+/-63 nmol/L, u=2.11, P<0.05) due to higher FP (Delta) (274+/-116 nmol/L vs. 175+/-112 nmol/L; u=4.02, P<0.01) ; FP (30) levels in obese subjects (n=27) did not differ from those with normal BMI (n=33) (694+/-100 nmol/L vs. 667+/-65 nmol/L, u=1.31, P>0.05). We did not find any correlation between body weight or body surface area and FP (0), FP (30) or FP (Delta). Post-stimulation FP (30) levels in the control group varied from 0 to 354 nmol/L with median 64 nmol/L (25 (th) percentile 10 nmol/L; 75 (th) percentile 165 nmol/L) and were entirely distinctive from those of the subjects without adrenal impairment ( P<0.001). Taking the mean -2 SD result as a threshold, FP value of 500 nmol/L can be consider as cut-off at 30 min in the LDT for defining the intact adrenocortical function, independently of age and body weight, body surface area.