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A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children
  1. Sze May Ng1,2,
  2. Juliana Chizo Agwu3,
  3. Kerry Dwan4
  1. 1Department of Paediatrics, Southport and Ormskirk NHS Trust, Ormskirk, UK
  2. 2Institute of Translational Medicine, University of Liverpool, Liverpool, UK
  3. 3Department of Paediatrics, Sandwell and West Birmingham NHS Trust, West Bromwich, UK
  4. 4Department of Biostatistics, University of Liverpool, Liverpool, UK
  1. Correspondence to Dr Sze May Ng, Department of Paediatrics, Southport and Ormskirk NHS Trust, Wigan Road, Ormskirk, Lancashire L39 2AZ, UK;{at}


Background The diagnostic value of tests used in assessing hypothalamic-pituitary-adrenal axis (HPA) in children remains controversial.

Design A systematic review and meta-analysis with receiver-operated-characteristic curve was undertaken to assess the diagnostic values of conventional standard dose 250 μg tetracosactrin (ACTH), short Synacthen test (SSST) and/or low-dose Synacthen test (LDSST) in the assessment of HPA insufficiency in children. Studies eligible for inclusion were any study that compared the use of the LDSST and/or SSST in the assessment of central adrenal insufficiency in children compared with reference standard test.

Results There were no randomised trials found. SSST resulted in higher specificity and positive likelihood ratio than LDSST. The LDSST had a higher sensitivity (86% vs 61%) but a lower specificity (88% vs 99%) than the SSST, but there was high heterogeneity from the LDSST studies with various doses of Synacthen used.

Conclusions 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.

  • adrenal
  • synacthen
  • ACTH
  • cosyntropin
  • cortisol

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