A patient study to determine the effectiveness of a needle-free test for the diagnosis of adrenal insufficiency

INTERVENTION: Participants will attend 2 separate visits and will receive a different drug (either 500µg nasal tetracosactide (Nasacthin) or 250µg IV tetracosactide (Synacthen) (or 145µg/m2 for paediatric participants)) at each visit in an open‐label, randomised sequence, determined in advance of the first visit via an integrated randomisation function within the study’s secure web‐based data capture system. For each drug, there is a single administration on the day of the visit. The nasal formulation (Nasacthin) is administered using a primed mucosal atomiser device, 0.1ml to each nostril (total volume 0.2ml). Synacthen is administered via the cannula as a slow bolus. All participants will be asked to complete a short questionnaire during each visit to explore the acceptability and tolerability of the study drug and will also receive a safety telephone call from a member of the study team 24‐48 hours after each visit to check for any adverse events. Participants will also have the option to take part in a focus group held at the end of the study to explore the acceptability, usability and tolerability of the Nasacthin test. CONDITION: Adrenal insufficiency ; Nutritional, Metabolic, Endocrine PRIMARY OUTCOME: The proportion of participants with adrenal insufficiency (AI) diagnosed by the Nasacthin Test (Positive Percent Agreement) using serum cortisol at baseline and 30 minutes post‐drug administration, measured using liquid chromatography with tandem mass spectrometry (LC‐MS/MS). To be included in the analysis, participants will have been confirmed to have AI by assessment of serum cortisol at 30 minutes following the Synacthen test. SECONDARY OUTCOME: 1. Frequency of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) by treatment arm, as reported by participants up to 48 hours after each study visit. Any SAEs/SUSARs will be followed to the point of resolution.; 2. Analysis of participant and healthcare professional acceptability, usability and tolerability of the Nasacthin test, measured using non‐validated questionnaires completed by participants at the end of each study visit and by healthcare professionals at the end of the study; and optional participant and stakeholder focus groups held at the end of the study. INCLUSION CRITERIA: 1. Known adrenal insufficiency 2. Basal cortisol <100 nmol/L or peak on SST <200 nmol/L at time of diagnosis or since in last 6 months 3. Able to comply with passive drool salivary sampling requirements 4. Able to provide signed written informed consent 5. Age 4‐75 years