Endocrine Abstracts

Background: The low-dose short synacthen test (LDSST) is the most popular diagnostic test for adrenal insufficiency in UK. Although various dosing strategies exist 1 μg is most commonly employed but not commercially available. A BSPED survey revealed 14 different methods for diluting the 250 μg/ml ampoules. We investigated whether differing dilution strategies, made up using standard ward not laboratory equipment, result in differences in Synacthen dose administered.

Method: 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 initial quantities of Synacthen (0.1–1 ml) used. Each was made up five times by the same investigator and three samples taken from the resultant solution. Samples were frozen then batch analysed on an ACTH RIA validated for Synacthen. All samples were diluted down to 250 pg/ml (most sensitive part of the assay measuring range), with 0.9% saline and the variance calculated (coefficient variation (CV)).

Results: There was variation in the Synacthen detected from the three samples taken from the same solution (CV range 3.4–107.5%) suggesting mixing issues, the five preparations of the same method, suggesting batch to batch variation, and between the ten different preparation methods (CV range 22.9–89.8%). The method utilizing 5% Dextrose as diluent had 14 of its 15 samples off the top of the assay range. Estimates of the likely Synacthen dose, if administered to patients, range from <0.04 μg to more than 2 μg.

Discussion: Considerable variation was observed both within and between dilution methods. There are numerous variables which may affect the actual dose of Synacthen administered: pharmaceutical manufacturer variation, use of inaccurate ward equipment causing drawing up inaccuracies, volume inconsistencies and lack of adequate mixing. We recommend low-dose Synacthen be made up under laboratory conditions and call for a commercial preparation of 1mcg Synacthen.