The Pancreatic Villains

Game Mode

Diagnosis Challenge

Read the labs and tap the tumor. Five patients, five tumors. No peeking at the cards first.

Glucagonoma alpha cell

Insulinoma beta cell

Somatostatinoma delta cell

VIPoma non-islet

Gastrinoma G cell

Tumor Files

The Lineup

Front: key facts. Back: mechanism + boards trap. Tap to flip.

From the Attending

Pancreatic neuroendocrine tumors (PNETs) split on what they secrete. Insulinoma · beta cell. Whipple triad: low glucose + neuroglycopenic symptoms + relief with glucose. C-peptide HIGH (endogenous). Gastrinoma (ZES) · non-beta. Refractory ulcers (especially distal duodenum/jejunum), high serum gastrin + high BAO; secretin test paradoxically raises gastrin. Glucagonoma · alpha cell. 4 Ds: dermatitis (necrolytic migratory erythema), diabetes, DVT, depression. Somatostatinoma · delta. Diabetes + cholelithiasis + steatorrhea (somatostatin shuts off insulin/CCK/secretin). VIPoma · WDHA: watery diarrhea + hypokalemia + achlorhydria. Match the hormone to the syndrome · that's the whole differential.

Alpha Cell

Glucagonoma

Pancreatic alpha-cell tumor · MEN 1

📷 NME Rash · tap to expand

Key labHigh glucose + high lipids

Classic skinNecrolytic migratory erythema

TreatmentOctreotide + resection

Part ofMEN 1 or sporadic

🔴 HALLMARK: Migrating blistering rash (NME)

tap to flip →

Why the Rash Happens

Trace It

Glucagon is catabolicTears things down for fuel. Glucagon tells your body: burn amino acids, raise blood sugar. Great in starvation, catastrophic when a tumor does it 24/7.. Excess glucagon burns amino acids for fuel. Skin needs amino acids to rebuild. No amino acids = skin breaks down, blisters, and crusts. When the depletion moves to a new area, the old spot heals and a new one erupts. That is the "migratory" part.

Board Trap

The hyperglycemia will look like type 2 diabetes at first glance. The rash is the tell. If you see a rash that migrates + diabetes + weight loss: this is glucagonoma until proven otherwise. Type 2 diabetes does not give you a migratory erosive rash.

Beta Cell

Insulinoma

Pancreatic beta-cell tumor · MEN 1

📷 Insulinoma · gross specimen · tap

LabsHigh insulin + High C-peptide

TriadWhipple triad

TreatmentResection + octreotide

🏹 HALLMARK: Fasting hypoglycemia, both insulin AND C-peptide elevated

tap to flip →

The C-Peptide Rule

Why C-Peptide Matters

ProinsulinThe precursor to insulin. Your pancreas makes proinsulin, then cleaves it into insulin + C-peptide in equal amounts. One insulin out = one C-peptide out. gets cleaved into insulin and C-peptide in a 1:1 ratio. So endogenous (your own) insulin production always comes with C-peptide attached. Exogenous injected insulin has NO C-peptide. The tumor makes more of your own insulin, so C-peptide is sky high along with insulin.

Whipple Triad

1. Symptoms of hypoglycemia during fasting. 2. Documented low blood glucose. 3. Relief with glucose administration. All three together = Whipple triad = insulinoma confirmed clinically.

Nesidioblastosis (PEDS)

Instead of one tumor, all islet cells proliferate. Seen in infants. Same result: hypoglycemia. Labs look like insulinoma but you will not find a discrete mass.

Delta Cell

Somatostatinoma

Pancreatic delta-cell tumor · MEN 1

Phase contrast microscopy of pancreatic islets of Langerhans

📷 Islets of Langerhans · tap to expand

LabsHigh somatostatin

GI effectSteatorrhea + constipation

Other effectsDiabetes + gallstones

TreatmentOctreotide + resection

🔴 HALLMARK: Somatostatin inhibits EVERYTHING

tap to flip →

The Great Inhibitor

What Somatostatin Turns Off

Somatostatin is the body's master brake pedal. It inhibits: insulin, glucagon, growth hormone, gastric acid secretion, and pancreatic enzyme secretion. When the tumor overproduces it, all those things crash. Result: blood sugar dysregulation (diabetes), no stomach acid (achlorhydria), no pancreatic enzymes (steatorrhea), bile stasis (gallstones), and motility slows to a crawl (constipation).

Memory Hook

Think of somatostatin as the "STOP" hormone. The tumor makes too much STOP, so everything that needs to go: stops. Digestion stops. Acid stops. Sugar regulation stops. That is four different problems from one hormone.

VIP Tumor

VIPoma

Vasoactive intestinal peptide tumor

CT scan of well-differentiated neuroendocrine tumor of the pancreatic tail

📷 Pancreatic NET · CT scan · tap to expand

SyndromeWDHA

Diarrhea>3 liters/day, watery

Key labHypokalemia

AcidAchlorhydria

💧 HALLMARK: WDHA = Watery Diarrhea, Hypokalemia, Achlorhydria

tap to flip →

Why So Much Water

The Mechanism

VIP triggers intestinal cells to dump chloride and water into the gut lumen. More than three liters a day. Your kidneys cannot keep up. The diarrhea washes potassium out through stool, causing hypokalemia. VIP also inhibits stomach acid secretion, causing achlorhydria. None of this is osmotic. The gut is actively secreting.

Key Board Test

To confirm VIPoma vs other secretory diarrhea: the diarrhea PERSISTS after a 48-hour fast. Osmotic diarrhea (e.g., lactose intolerance) stops when you stop eating. Secretory diarrhea (VIPoma) keeps going because the tumor keeps secreting VIP regardless of food intake.

Treatment

Octreotide buys time. Resection is the cure. Potassium replacement urgently.

G Cell

Gastrinoma

Zollinger-Ellison syndrome · MEN 1

Endoscopy showing multiple duodenal ulcers in Zollinger-Ellison syndrome

📷 ZES endoscopy · multiple ulcers · tap

LabsElevated fasting gastrin

UlcersMultiple, distal (jejunum)

Dx testSecretin stimulation

🔴 HALLMARK: Multiple ulcers + elevated gastrin at all times

tap to flip →

Zollinger-Ellison: The Anatomy

Why Multiple Ulcers

Normally gastrin is released from the stomach, works locally, and turns off. In gastrinoma, a tumor secretes gastrin constantly. Constant gastrin = constant acid production = acid floods the duodenum and even reaches the jejunum. Multiple peptic ulcers form in places they normally would not. A jejunal ulcer by itself should make you think ZE syndrome.

Secretin Stimulation Test (The Paradox)

In normal tissue, secretin suppresses gastrin. In a gastrinoma, secretin paradoxically raises gastrin. This is the confirmatory test. Secretin in, gastrin goes UP = gastrinoma. Secretin in, gastrin stays flat or drops = normal or H. pylori ulcer.

MEN 1 Link

Gastrinoma is the most common functional pancreatic tumor in MEN 1. If you see MEN 1, always screen for ZE syndrome. Rule of 3s: pituitary, parathyroid, pancreas.

Visual Pearls

Signature Moves

The three patterns boards love. One look and you should know the tumor.

Signature Move · Glucagonoma

The Furnace

Glucagon is the catabolic switch. One signal fires from the alpha cell. Three fuels rise at once.

Ignition Sequence

Glucagon fires. Watch three pathways ignite.

Pattern Locked

The 3-High Signature

One alpha-cell signal, three catabolic outputs. Type 2 diabetes only nudges the first.

Route

α-cell glucagon → liver, adipose, body

Pattern

Glucose ↑ + Lipids ↑ + Ketones ↑

Pearl

Three pinned + a migrating rash = glucagonoma. Period.

Signature Move · Insulinoma

The Crash

A beta-cell tumor pumps insulin even when blood sugar is empty. The fuel gauge falls. The brain dims.

Fasting State · Insulin Pulses

Tumor fires insulin without checking the tank.

Pattern Locked

Whipple Triad

Symptoms appear when glucose drops; relief comes only when glucose returns. The trap is the C-peptide.

Route

β-cell hyperinsulinism → CNS + sympathetic drive

Pattern

Hypoglycemia + Symptoms + Relief with glucose

Pearl

C-peptide high = tumor (endogenous). C-peptide low = factitious insulin.

Signature Move · Somatostatinoma

The Big Silence

The delta-cell tumor floods the body with the master off-switch. Four downstream systems go quiet.

Master Brake · Engaged

Insulin

Beta-cells firing

Diabetes

Gastric Acid

Parietal cells active

Achlorhydria

Pancreatic Enzymes

Lipase, amylase out

Steatorrhea

Gallbladder

Motility intact

Gallstones

Somatostatin floods the system. Each output goes dark.

Pattern Locked

The DASH Quartet

Somatostatin is the master inhibitor. Four organ outputs shut down at once. The tetrad is unique.

Route

δ-cell somatostatin → pancreas, stomach, gallbladder

Pattern

Diabetes + Achlorhydria + Steatorrhea + Gallstones

Pearl

All four together → somatostatinoma. Octreotide does the same thing on purpose.

Signature Move · VIPoma

The Flood

VIP commandeers the gut. Water, potassium, and bicarb pour out of the body. The diarrhea ignores fasting.

Secretory Storm

VIP fires from the tumor. Enterocytes dump fluid.

Pattern Locked

WDHA Storm

Cholera-like watery diarrhea, potassium falling, bicarb gone. The giveaway: a fast does not stop it.

Route

VIP → enterocyte cAMP storm → lumen secretion

Pattern

Watery diarrhea + Hypokalemia + Achlorhydria

Pearl

Persists through 48h fast = secretory, not osmotic. Replace K⁺ first, then octreotide.

Signature Move · Gastrinoma

The Acid Storm

Tumor gastrin storms the parietal cells. Acid floods the stomach, the duodenum, then burns past them.

Acid Drop · Distal Reach

Parietal cells fire under tumor gastrin. Acid drops.

Pattern Locked

Zollinger-Ellison

PPI does not hold. Ulcers march distally. The jejunal lesion is the tell.

Route

Tumor gastrin → parietal H⁺/K⁺ ATPase storm

Pattern

Refractory ulcers + Multiple sites + Diarrhea

Pearl

Jejunal ulcer = ZE until proven otherwise. Fasting gastrin > 1000 or secretin stim test.

MEN 1 · The Three Ps

All five pancreatic villains can run with this crew.

P

Pituitary

Prolactinoma most common

P

Parathyroid

Hyperparathyroid + high calcium

P

Pancreas

Gastrinoma most common

Boards trap: find one of these and screen for the other two. The MEN 1 patient who shows up for headaches has the pituitary adenoma. The same patient with kidney stones has the parathyroid adenoma. Spot any P, hunt the other two.

The Fork In The Road

The C-Peptide Trap

Same labs. Two completely different stories. C-peptide picks the side.

From the Attending

C-peptide HIGH · endogenous insulin source · insulinoma or sulfonylurea-induced (sulfa screen). C-peptide LOW · exogenous insulin (factitious or accidental injection). Always check the screen for surreptitious insulin in a healthcare worker / diabetic family member. Insulinoma workup: supervised 72-hour fast · document hypoglycemia with simultaneously inappropriately HIGH insulin, HIGH C-peptide, HIGH proinsulin. Then localize: small (<2cm), often missed on CT · endoscopic ultrasound is the modality of choice. If C-peptide is low · it's NOT insulinoma. Move on.

Patient found unconscious. Glucose 38 mg/dL. Insulin 3x normal.

↓

Check C-peptide

HIGH ↑

Insulinoma

Pancreas making it. C-peptide rides shotgun with every endogenous insulin molecule. 1:1 ratio. Image the pancreas.

LOW ↓

Injected Insulin

Someone brought insulin in from outside. Exogenous insulin has zero C-peptide. Suspect factitious. Pull the labs again.

Lock it in: insulin alone tells you nothing. C-peptide picks the side of the fork.

Now walk it as a case. Each tap reveals the next step.

A nursing unit calls you about a patient who was found unconscious with a blood glucose of 38 mg/dL. Insulin level comes back 3x the upper limit of normal. What is your next test?

C-peptide level

Repeat insulin level in 1 hour

CT abdomen to find the tumor

Exactly. C-peptide tells you whether that insulin came from the patient's own pancreas or from a syringe. That distinction changes everything: tumor vs. factitious. CT comes later, once you know which you are dealing with.

Reasonable reflex, but more insulin levels will not tell you the source. You already know insulin is high. The question is: where did it come from? C-peptide is the answer.

You are jumping ahead. CT will find a mass if there is one, but first you need to know if this is endogenous (tumor) or exogenous (injection). Half the time the answer is factitious hypoglycemia, and there is no mass to find.

C-peptide is the single most important test in hypoglycemia with high insulin. It is the fork in the road between insulinoma and self-injection.

⚠

Classic Board Setup

"A 34-year-old nurse is found unresponsive in the break room. Glucose 28 mg/dL. Insulin level: markedly elevated. C-peptide: undetectable." The boards love this vignette. The career detail (nurse, pharmacist, someone with insulin access) is the tell. Undetectable C-peptide = injected insulin = NOT insulinoma.

Memory

Memory Hooks

Tap to unblur. See if you can recall before you look.

🍏

Glucagonoma: The Rash

Glucagonoma = Glucose up + Going skin. Glucagon breaks down amino acids for fuel. Skin runs out. Rash migrates to wherever depletion is worst at the moment. No amino acids = no new skin = necrolytic migratory erythema.

tap to reveal

💉

C-Peptide: The Source Detector

C-peptide only comes with homemade insulin. If C-peptide is high: the pancreas is making too much (insulinoma or sulfonylurea). If C-peptide is undetectable: the insulin was injected from outside. Zero factory output means someone brought insulin in from the street.

tap to reveal

🧠

Somatostatinoma: The Brake

Somatostatin = STOP everything. Inhibits insulin (sugar dysregulation), glucagon, GH, gastric acid (achlorhydria), pancreatic enzymes (steatorrhea), and motility (constipation + gallstones). A somatostatinoma is the pancreas stuck with its foot on the brake 24/7.

tap to reveal

💧

VIPoma: WDHA

WDHA: Watery Diarrhea, Hypokalemia, Achlorhydria. The "Verner-Morrison syndrome." VIP dumps water and chloride into the gut non-stop. 3+ liters a day. It keeps going even when fasting. That last part separates secretory from osmotic diarrhea on boards.

tap to reveal

🔵

Gastrinoma: The Paradox

Normal tissue: secretin in, gastrin drops. Gastrinoma: secretin in, gastrin shoots UP. The gastrinoma cannot respond normally. Multiple ulcers beyond the duodenal bulb is the other giveaway. If you see a jejunal ulcer, the boards want you to think Zollinger-Ellison immediately.

tap to reveal

🌞

MEN 1: The Trio

Wermer syndrome. The three Ps: Pituitary adenoma + Parathyroid adenoma + Pancreatic endocrine tumor. All five pancreatic tumors on this page can be part of MEN 1.

tap to reveal

The One Drug

One Drug Rules Them All

Bridge to surgery for every villain on this page. Tap to reveal.

Challenge

One drug buys time before surgery for every tumor in the lineup. Which one?

Glucagonoma

Insulinoma

Somatostatinoma

VIPoma

Gastrinoma

Octreotide

a synthetic somatostatin analog

Remember somatostatin is the body's master brake pedal. Octreotide is that brake in a syringe with a long half-life. It binds somatostatin receptors on the tumor cells themselves, so it works upstream. Less hormone secreted means the downstream chaos calms down: rash heals, diarrhea slows, hypoglycemia stabilizes, ulcers get a chance to heal. Resection is still the cure. Octreotide is the bridge. One mechanism, five villains.

Clinical Evidence

What You Will See

Boards test recognition. Tap to expand.

Endoscopy showing multiple duodenal ulcers in Zollinger-Ellison syndrome gastrinoma

📷 Gastrinoma (ZES): Multiple duodenal ulcers · tap to expand

📷 Glucagonoma: Necrolytic migratory erythema (NME) · tap to expand

📷 Insulinoma: Pancreatic tumor gross pathology · tap to expand

Board Sim

Prove It

Five drawn at random per load. No running score shown. You either know it or you learn it.

From the Attending

Two stem patterns to know cold: (1) MEN1 association · any PNET in a patient with hypercalcemia (parathyroid) or pituitary symptoms (acromegaly, prolactinoma, amenorrhea) = MEN1 syndrome · tumors of 3 P's: Parathyroid, Pancreas (gastrinoma most common), Pituitary. (2) ZES + diarrhea-predominant ulcer + MEN1 family history is the classic gastrinoma vignette · localize to the gastrinoma triangle (junction of cystic + CBD, neck/body of pancreas, 2nd/3rd duodenum). Treatment first-line for PNETs: surgical resection if localized + somatostatin analogs (octreotide/lanreotide) to control symptoms. Recognize the syndrome, then recognize MEN1 lurking behind it.

Diagnosis Challenge

The Lineup

Signature Moves

The C-Peptide Trap

Memory Hooks

One Drug Rules Them All

What You Will See

Prove It

Keep Going