Reliability of the Low Dose Synacthen Test in Children Undergoing Pituitary Function Testing

Abstract

Background: There are few data in the paediatric literature on the normal Cortisol response to stimulation during the low dose synacthen test (LDST) (1 pg). Aim: To examine the Cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs). Methods: A retrospective review of results in children with short stature and normal growth hormone levels.Results: Of 33 children tested, seven had suboptimal Cortisol responses based on accepted criteria (peak <500 nmol/1) -a false positive rate of 21%. Only three of these children had a repeat LDST, which was normal in all cases. The peak Cortisol response (median 633, range, 417-1052 nmol/1) was inversely correlated with age (r = -0.44, ρ <0.05). Conclusion: One in five tests did not meet normal criteria. This false positive rate (21%) should be borne in mind when interpreting synacthen tests to prevent overdiagnosis of adrenal insufficiency. KEY WORDSlow dose synacthen, adrenal insufficiency

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

“…In healthy adults, the peak cortisol response following a low-dose ACTH test is !500 nmol/l in 7% of the population (23). In children, using a similar threshold, this value may be up to 21% (21). In our cohort, 18% of the patients 'failed' their ITT in terms of cortisol, utilising a standard 500 nmol/l cut-off.…”

“…It has been proposed that a small sample size and the assumption that the relationship between ACTH and cortisol is linear rather than logarithmic may be responsible for such an observation (18). It has also been reported that the response to exogenous ACTH in childhood varies with age (19,20,21,22) and pubertal status (19); however, in some of these studies, ACTH was not dosed by body surface area and thus a relatively larger dose in younger children was a possible confounding factor (19,21,22). Our data also suggest that the cortisol response to the ITT is influenced by age and that the use of a single age threshold of 500 nmol/l (a value extrapolated from adult practice) across the entire paediatric age group is inappropriate.…”

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

“…With regard to ACTH stimulation testing, there was some variability amongst the cosyntropin dose (low or high) used in the studies, but within the studies testing methods were consistent. This test (either iteration) has been criticized for yielding significant false-positive results [47-49]. Therefore, our estimates of HPA axis suppression are likely conservative overestimates of the actual proportion of clinically significant AI.…”

The Intramuscular Glucagon Stimulation Test Does Not Provide Good Discrimination between Normal and Inadequate ACTH Reserve When Used in the Investigation of Short Healthy Children

“…Peak cortisol levels have been shown to decrease with age and to vary by sex and pubertal status after high-dose ACTH stimulation test [25] and after ITT [15,26]. Mushtaq et al [27] reported an inverse correlation between cortisol response to the 1-μg ACTH test and age in children with short stature and normal GH levels. In a recent study that investigated the cortisol response to the 1-μg ACTH test following treatment with supraphysiological doses of glucocorticoids, the peak-stimulated cortisol level was greater in the children aged <6 years than in the older children, possibly due to a shorter duration of glucocorticoid treatment [28].…”

“…Indeed, some authors claim the 1-μg ACTH test is equivalent in sensitivity to the ITT in terms of assessing adequacy of the stress response in adults [21]. However, the low dose has technical limitations [35] and its superiority over the standard dose ACTH test is still a matter of debate in adults [20,21] and in children [27,36]. Two major reviews on this subject including predominantly adult studies reached dissimilar conclusions [16,37].…”