Towards a non-invasive short Synacthen test
Charlotte Elder1, Trevor Johnson2, Martin Loxley3, Jerry Wales1 & Neil Wright2
Introduction: A 2009 BSPED survey revealed that 90% use a low dose Synacthen test (LDST) and 44% had noticed increased referrals of asthmatic children prescribed inhaled corticosteroids (ICS). Approximately 21% of UK children have asthma of whom 70% are prescribed ICS (10% at high dose). There is an increasing need for a simple, less invasive, alternative to the LDST to evaluate their adrenal function. We are developing a non-invasive LDST, with Synacthen administered nasally and cortisol measured in saliva.
Methods: We performed three Synacthen tests on 12 healthy, adult males. On the first visit volunteers received 1 μg i.v. Synacthen, the second and third visits 100 and 25 μg intranasal Synacthen respectively. During a 3 h test 14-paired samples of blood and saliva were taken. All volunteers were dexamethasone suppressed enabling us to measure Synacthen on an ACTH RIA.
Results: We achieved a median AUC0180 min with 100 μg intranasal Synacthen, 20% of that following a 1 μg i.v. dose, (6% with 25 μg), this gave a bioavailability of 0.20.24%. The Cmax was 17.9 and 11 pg/ml respectively compared with 169 pg/ml i.v. Tmax was 17.5 and 10 min respectively compared with 5 min i.v. On analysis of the 1 μg i.v. data we observed considerable variability in mean peak plasma Synacthen (261.6 pg/ml S.D. 104.9). The timing of the peak cortisol varied, occurring at 30 min in 50%. There was no relationship between peak Synacthen and peak cortisol, despite correction for BMI and BSA. None of our participants achieved a cortisol above 450 nmol/l, which we believe is a blunting effect of dexamethasone.
Conclusion: We have shown considerable variability in the 1 μg i.v. LDST. The doses of intranasal Synacthen chosen in our study did not reach bioequivalence with the 1 μg LDST. However the test was well tolerated and easy to administer and so with increased dose holds considerable promise.