The low-dose (1 microg) cosyntropin test (LDT) for primary adrenocortical insufficiency: Defining the normal cortisol response and report on first patients with Addison disease confirmed with LDT.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Department of Endocrinology, National Institute of Endocrinology and Diabetology, Lubochna, Slovakia. mikulas.pura@nedu.sk
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D000224:Addison Disease / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001830:Body Surface Area; D003366:Cosyntropin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013255:Steroid 21-Hydroxylase / Q000097:blood; D055815:Young Adult
D003366:Cosyntropin; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone