Lack of sensitivity of the 1‐μg low‐dose <scp>ACTH</scp> stimulation test in a paediatric population with suboptimal cortisol responses to insulin‐induced hypoglycaemia

O’Grady, Michael J.; Hensey, Conor; Fallon, M.; Hoey, Hilary; Murphy, Nuala; Costigan, Colm

doi:10.1111/j.1365-2265.2012.04474.x

Cited by 7 publications

(8 citation statements)

References 48 publications

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“…Data from 33 short, normal children report that a peak cortisol value of 500 nmol/L gives a false positive rate as high as 21%, with median cortisol concentrations being 633 nmol/L, range 417–1052 30. The specificity of the LDSST in a study of 35 normal children and young adults, age 17.8 years (6.7–34.3), was 94% at a peak cortisol concentration of 415 nmol/L,3 and a cut-off value closer to 400 nmol/L has been supported in other observational studies 24…”

Section: Diagnostic Tests Of Adrenal Functionmentioning

confidence: 58%

The diagnosis and treatment of adrenal insufficiency during childhood and adolescence

2016

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The diagnosis and treatment of adrenal insufficiency in childhood and adolescence poses a number of challenges. Clinical features of chronic adrenal insufficiency are vague and non-specific, and mimic many other causes of chronic ill health. A range of diagnostic tests are available for the assessment of adrenal function, all of which have advantages and disadvantages. Cortisol responses to these tests may vary with age and between genders. Knowledge of normal cortisol levels during health and ill health in childhood is also limited, and the cortisol replacement therapies available in clinical practice enable only crude mimicry of physiological patterns of cortisol secretion. An awareness of the limitations of diagnostic tests and treatments is important, and critical clinical assessment, integrating clinical and biochemical data, is essential for the diagnosis and treatment of children with suspected adrenal insufficiency. The aim of this review is to draw on data from clinical studies to inform a pragmatic approach to the child presenting with symptoms of chronic adrenal insufficiency. Clinical features of primary and secondary adrenal insufficiency, and syndromes associated with these diagnoses are described. Factors to consider when selecting a diagnostic test of adrenal function and interpretation of test results are considered. Finally, the limitations of cortisol replacement therapy are also discussed.

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Section: Diagnostic Tests Of Adrenal Functionmentioning

confidence: 58%

The diagnosis and treatment of adrenal insufficiency during childhood and adolescence

2016

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“…Some authors claim that the low-dose ACTH stimulation test is equivalent in sensitivity to the ITT in terms of assessing adequacy of the stress response in adults. Previous studies in children have disputed this, however (27,28,29), and suggested that higher cortisol thresholds may be necessary for the low-dose ACTH stimulation test compared with the ITT. In light of the findings of our study, the effects of age will also have to be taken into account in calculating appropriate thresholds for the low-dose ACTH stimulation test in future studies involving children and adolescents.…”

Section: Discussionmentioning

confidence: 76%

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

O’Grady

Hensey

Fallon

et al. 2013

European Journal of Endocrinology

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Objective: Based on adult data, a peak cortisol response R500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age. Design: The present study was a retrospective cohort study. Methods: Retrospective analysis of children and adolescents aged %18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic-pituitary-adrenal axis impairment (peak cortisol value !400 nmol/l) or using systemic glucocorticoids were excluded. Results: Two hundred and twenty-three tests were analysed. Peak cortisol responses R500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (rZK0.15, PZ0.03). A peak cortisol response !500 nmol/l was significantly less common in patients aged !12 years (9/97 (9%) vs 31/126 (25%); PZ0.004). In children aged !12 years, the median (5th-95th centiles) peak cortisol values were 610 (480-806) nmol/l compared with 574 (442-789) nmol/l in children aged R12 years (P!0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (PZ0.0004)). Conclusions: Use of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.

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“…The included studies were all cohort studies involving children being investigated because they were at risk of developing central HPA axis insufficiency. Five of the studies5 30 33–35 used the ITT as reference standard, two studies31 32 used metyrapone as the reference test and one study10 used hCRH as the reference standard. The dose of Synacthen and sampling times used in the LDSST varied in the studies (see table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Using the QUADAS-2 assessment criteria,25 four of the studies5 32–34 were judged to be at low risk of bias but had some concerns regarding applicability while the other four studies10 30 31 35 included were judged to be at risk of bias but having low concerns regarding applicability.…”

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children

Agwu

Dwan

2016

Arch Dis Child

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Lack of standardisation of assays and protocols with regard to timing, frequency and dose has resulted in diagnostic inaccuracies. There is no clear evidence to indicate that LDSST is superior to SSST in the assessment of HPA axis in children. The choice of either SSST or LDSST should be individualised based on clinical judgement for each patient. This systematic review has identified the need for a well-designed, adequately powered, randomised controlled trial on the use of diagnostic tests used in assessing HPA axis in children.

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Lack of sensitivity of the 1‐μg low‐dose ACTH stimulation test in a paediatric population with suboptimal cortisol responses to insulin‐induced hypoglycaemia

Abstract: The 1-μg LDSST lacks sensitivity in detection of secondary adrenal insufficiency in children when compared to the gold-standard ITT.

Cited by 7 publications

References 48 publications

The diagnosis and treatment of adrenal insufficiency during childhood and adolescence

The diagnosis and treatment of adrenal insufficiency during childhood and adolescence

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

A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children

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