Endocrine Abstracts

Introduction: The short Synacthen test (SST) is a popular diagnostic investigation for adrenal insufficiency (AI). Cannulation and blood sampling are required making it invasive, time-consuming and resource-intensive. Salivary cortisol is a well-established alternative to serum sampling. We have developed a non-invasive alternative to the 1 μg SST, using a novel formulation of Synacthen (with a nasal drug enhancer, chitosan) given nasally and utilising saliva to measure the cortisol response.

Methods: We undertook a pharmacokinetic dose escalation study with five doses of nasal Synacthen (tetracosactide): 25, 100, and 100 mcg with chitosan, 500 and 500 μg with chitosan, administered to 12 healthy adult males on different occasions and compared them to a 1 μg i.v. test. During each 3-h visit, 15-paired blood and saliva samples were taken and measurements of plasma Synacthen, serum cortisol and salivary cortisol and cortisone made. Volunteers were dexamethasone suppressed enabling measurement of Synacthen on an ACTH RIA.

Results: The 25 and 100 μg doses showed minimal absorption. Addition of the chitosan improved bioavailability and cortisol response but dose escalation increased the absorption of nasal Synacthen more than the chitosan. The 100 μg with chitosan and 500 μg formulations showed a comparable cortisol response to the 1 μg i.v. dose. Nasal administration of the 500 μg Synacthen with chitosan formulation resulted in the highest bioavailability and was the only dose in which all volunteers attained a peak serum cortisol of more than 500 nmol/l. Salivary cortisol and cortisone samples had a close and reliable relationship with serum samples. Salivary cortisone was the more sensitive marker of adrenocortical response at lower values.

Conclusions: Synacthen is absorbed nasally and appears safe and well tolerated. Nasally administered 500 μg Synacthen with chitosan and salivary cortisol or perhaps cortisone sampling at 60, 75, and 90 min may provide a useful alternative to the low-dose SST.