A randomized controlled crossover study comparing synthetic porcine and human secretins with biologically derived porcine secretin to diagnose Zollinger-Ellison Syndrome

Background: Although biologically-derived porcine secretin is approved for the diagnosis of Zollinger-Ellison Syndrome, it is no longer available in t he United States. Pure human and porcine secretins have now been synthesize d and new drug applications have been filed with the Federal Drug Administr ation (FDA). Methods: In the current study we compared secretin testing results in six c onfirmed Zollinger-Ellison Syndrome patients using the biologically-derived product and both synthetic products (human and porcine) in a three-way, ra ndomized, single-blind Latin-squares crossover study. Results: Using the FDA-approved criterion for positive secretin testing (i. e. a serum gastrin concentration increase of > 110 pg/mL), there was comple te agreement between all three agents for all patients. With the more strin gent NIH criterion (i.e. a serum gastrin concentration increase of > 200pg/ mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically-derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% incr ease in serum gastrin concentration). The time to peak serum gastrin concen tration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum gastrin concentrations showed a single statistically significant difference (the ch ange from baseline at 15 min between synthetic human and synthetic porcine secretin, P = 0.0274). Statistically significant changes from baseline occu rred at 1, 2 and 5 min for biologically-derived porcine secretin and at 2 a nd 5 min for both synthetic porcine and synthetic human secretin, in keepin g with the expected time curve for positive tests. All three agents were we ll-tolerated. Conclusions: These data suggest that either synthetic secretin product, whe n released onto the United States market, can be used to confirm Zollinger- Ellison Syndrome.