Aims The low-dose Short Synacthen test is a popular diagnostic test of adrenal insufficiency in children. It is employed by 82% of UK paediatric endocrinologists. Although various dosing strategies exist, 1 mcg is most commonly employed, however none of the low-dose forms of Synacthen are commercially available. A ‘British Society for Paediatric Endocrinology and Diabetes’ survey revealed 14 different methods for diluting 250 mcg/ml ampoules. We investigated whether the various dilution strategies result in differences in the resultant Synacthen dose administered.
Methods The ten most popular dilution methods were tested, encompassing different diluents (0.9% saline n=9, 5% dextrose n=1), single (n=6) and double (n=4) dilution strategies and varying initial quantities of Synacthen (0.1 to 1 ml). Each method was made up five times under simulated ward conditions and three samples were taken from different parts of the bag of resultant solution. Samples were frozen then batch-analysed on an hACTH radioimmunoassay validated for Synacthen. All samples were diluted to 250 pg/ml (most sensitive part of the assay measuring range) and the coefficient of variation (CV) calculated.
Results There was marked variation in Synacthen detected from the three samples taken from the same solution (CV 13.4%– 194.6%) suggesting inadequate mixing, the five preparations of the same method, suggesting batch to batch variation, and between the ten different preparation methods (CV range 24.2%–163.7%) suggesting divergence between methods. Estimates of the likely Synacthen dose, if administered to patients, ranged from less than 0.04 mcg to more than 2 mcg.
Conclusion Considerable variation was observed both within and between dilution methods. Variables, which may affect the actual dose of Synacthen administered, include: poor dilution technique, inappropriate dilution strategies, pharmaceutical manufacturer variation, use of inaccurate ward equipment, volume inconsistencies, lack of adequate mixing and lack of a controlled environment. We recommend low-dose Synacthen be made up under laboratory conditions and call for a commercial preparation of 1 mcg Synacthen.
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