Secretin
Also known as: ChiRhoStim, Sqrtmid, synthetic human secretin, synthetic porcine secretin, RO 25-1553, secretin (human), secretin (porcine)
Gastrointestinal peptide hormone; secretagogue; diagnostic agent; Class B G protein-coupled receptor (GPCR) agonist
What it is
Secretin is a hormone used by gastroenterologists to test pancreatic function and diagnose conditions like Zollinger-Ellison syndrome. Injected during endoscopy, it prompts the pancreas to release bicarbonate-rich fluid that doctors collect and measure. Synthetic secretin (ChiRhoStim) has been FDA-approved since 2004 for diagnostic use only.
The scientific side
Secretin is described as a 27-amino acid peptide hormone secreted by S cells in the duodenum in response to acidic chyme entering the small intestine. It acts via the secretin receptor (SCTR), a Class B G protein-coupled receptor expressed predominantly on pancreatic ductal cells, cholangiocytes (biliary epithelium), and gastric chief cells. Receptor activation couples to Gs, stimulating adenylate cyclase and elevating intracellular cyclic AMP (cAMP), which in turn activates protein kinase A (PKA) and drives chloride-bicarbonate exchange via CFTR and anion exchangers on ductal cell apical membranes (PMID 25332973, 14673718). The primary physiological effect is stimulation of large-volume, bicarbonate-rich fluid secretion from pancreatic ductal cells — the basis of all secretin-stimulation diagnostic tests. Pancreatic bicarbonate output neutralizes gastric acid in the duodenum and creates an optimal pH environment for pancreatic enzyme activity. Secretin also inhibits gastric acid secretion and gastric motility (PMID 14673718), stimulates bile flow from liver cholangiocytes, and plays a homeostatic role in hepatic biliary secretion; large cholangiocytes uniquely express SCTR and secretin modulates biliary secretion, cholangiocyte proliferation, senescence, and hepatic fibrosis in cholestatic liver disease models (PMID 32737904). Beyond the GI tract, secretin functions as a neuropeptide: SCTR transcripts are distributed throughout the brain including cerebral cortex, hippocampus, hypothalamus, and cerebellum, where secretin acts as a retrograde messenger facilitating GABAergic transmission and modulating motor functions (PMID 12392059). More recently, secretin has been shown to act on interstitial cells of Cajal (ICC-DMP) in the deep muscular plexus via cAMP-PKA-mediated inhibition of calcium transients, suppressing excitatory enteric neurotransmission and slowing small intestinal contractions (PMID 41198902). Secretin also modulates satiety through a brown adipose tissue-brain axis: exogenous secretin activates brown adipocytes, reduces caudate glucose uptake, improves inhibitory control, and downregulates neural responses to food cues — suggesting a role in appetite regulation beyond the gut (PMID 36764966, 34671320). The evolutionary origins of the secretin-SCTR axis appear to trace to amphibians, with secretin and its receptor having undergone independent evolutionary trajectories (PMID 24868104).
Class: Gastrointestinal peptide hormone; secretagogue; diagnostic agent; Class B G protein-coupled receptor (GPCR) agonist
Administration & storage
- Administration
- Slow intravenous bolus injection over 1 minute (standard for all approved diagnostic indications)Intravenous infusion (used in some autism and metabolic research protocols — not standard clinical practice)Not administered subcutaneously or intramuscularly in any approved or studied indication
- Storage
- Unreconstituted vials: store at controlled room temperature 20–25°C (68–77°F). After reconstitution: use immediately; discard any unused solution. Do not freeze reconstituted product. Protect from light.
- Cautions
- Acute pancreatitis has been reported rarely after secretin administration; use with caution in patients with active or suspected acute pancreatitis.,Transient decreases in blood pressure (hypotension) can occur immediately following intravenous injection; monitor vital signs during administration.,Nausea, flushing, and abdominal discomfort are the most commonly reported adverse effects during the injection.,Hypersensitivity reactions (including anaphylaxis) have been reported rarely; resuscitation equipment should be available.,Secretin is contraindicated in patients with acute pancreatitis until the episode has resolved.,Use with caution in patients with pancreatic pseudocysts — secretin-stimulated ductal pressure may theoretically exacerbate.,No dose adjustment is established for renal or hepatic impairment; use with caution in severe organ dysfunction.,Pregnancy Category C (animal data only); use only if the diagnostic benefit justifies the potential risk.
Legal & regulatory status
FDA-approved as ChiRhoStim (synthetic human secretin, 40 mcg/vial) and Sqrtmid (synthetic porcine secretin) for: (1) diagnosis of pancreatic exocrine dysfunction via the secretin-stimulation test, (2) diagnosis of…
Secretin is not listed on the current WADA Prohibited List. As an endogenous peptide hormone used exclusively for diagnostic indications at very low doses, it has no known performance-enhancing application. It is not…
No Health Canada marketing authorization identified in the reviewed literature. Secretin is not listed as an approved drug product in Canada. Diagnostic use may occur in specialized academic centers under special access…
What it's studied for
- Diagnosis of pancreatic exocrine dysfunction (chronic pancreatitis) Prospective clinical studies / FDA-approved diagnostic use
- Diagnosis of gastrinoma (Zollinger-Ellison syndrome) Clinical study / FDA-approved diagnostic use
- Autism spectrum disorder — investigated in multiple RCTs; no benefit established Multiple RCTs — negative / no benefit
- Potential therapeutic target for obesity and metabolic regulation Early clinical / preclinical
- Cholestatic liver disease — modulation of biliary secretion and fibrosis (investigational) Preclinical / translational
- Facilitation of ERCP and secretin-stimulated MRCP imaging Clinical practice — FDA-approved diagnostic use
Safety signals
- Acute pancreatitis (rare)
- Hypotension / transient blood pressure decrease
- Nausea, flushing, and abdominal discomfort
- Hypersensitivity reactions including anaphylaxis
- Absence of benefit in autism (efficacy signal — risk of inappropriate off-label use)
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 0.2 mcg/kg intravenous (ChiRhoStim) or 0.2 CU/kg (clinical secretin units) | — | Adults — secretin pancreatic function test (ePFT) | Research |
| Unspecified | 2 CU/kg intravenous (porcine secretin) or 0.4 mcg/kg (synthetic human secretin) | — | Adults — secretin provocative test for Zollinger-Ellison syndrome | Research |
| Unspecified | 1 mcg/kg intravenous | — | Adults — secretin-stimulated MRCP/ERCP imaging | Research |
| Unspecified | 0.4 mcg/kg intravenous (synthetic human secretin) or 2 CU/kg (porcine secretin) | — | Adults — autism RCTs (investigational, no benefit established) | Research |
| Unspecified | Intravenous secretin at physiologic-range doses | — | Adults — satiety/metabolic neuroimaging study | Research |
| intravenous bolus | 0.2 mcg/kg IV (pancreatic function test); 0.4 mcg/kg IV (ZES provocative test); 1 mcg/kg IV (secretin-MRCP) | single administration per diagnostic session | adults undergoing evaluation for chronic pancreatitis or suspected Zollinger-Ellison syndrome in a gastroenterology setting |