Pancreatic Endocrine Disorders

Pancreatic Islets & DM Patho - Islet Insights

• Islet Cells & Hormones: (📌 A-G, B-I, D-S, PP-P)
  • α-cells: Glucagon (↑glucose)
  • β-cells: Insulin (↓glucose), Amylin
  • δ-cells: Somatostatin (inhibitory)
  • PP (γ)-cells: Pancreatic Polypeptide
• Diabetes Mellitus (DM) Patho:
  • T1DM: Autoimmune β-cell destruction (insulitis, Type IV HSR) → absolute insulin deficiency. HLA-DR3/DR4.
  • T2DM: Insulin resistance + β-cell dysfunction → relative insulin deficiency. Islet amyloid (IAPP) deposition.

⭐ Insulitis (lymphocytic infiltration of islets) is pathognomonic for Type 1 DM.

Insulinoma - Sweet & Lowdown

• Most common functional PanNET; β-cell tumor secreting excess insulin.
• Clinical Features: Recurrent hypoglycemia.
  • Neuroglycopenic: confusion, blurred vision, seizures, coma.
  • Autonomic (adrenergic): sweating, palpitations, tremor, anxiety.
• Diagnosis:
  • 📌 Whipple's Triad:
    1. Symptoms of hypoglycemia.
    2. Low plasma glucose (e.g., < 50 mg/dL).
    3. Relief of symptoms with glucose administration.
  • Key Labs (during hypoglycemia): ↑ Insulin, ↑ C-peptide, ↑ Proinsulin; ↓ β-hydroxybutyrate.
  • Negative oral hypoglycemic agent screen.
• Localization: Endoscopic ultrasound (EUS) is gold standard. CT/MRI.
• Pathology: Typically solitary, benign (>90%), small (<2cm). ~5-10% associated with MEN1.
• Treatment: Surgical resection (curative). Diazoxide, octreotide for unresectable cases.

⭐ Elevated C-peptide and proinsulin levels differentiate insulinoma from factitious hypoglycemia (exogenous insulin use).

Gastrinoma (ZES) - Acid Attack!

• Gastrin-secreting neuroendocrine tumor (NET) causing Zollinger-Ellison Syndrome (ZES).
• Locations: Duodenum (most common), pancreas. Often within the "Gastrinoma triangle".
• Pathophysiology: ↑ Gastrin → parietal cell hyperplasia → massive ↑ HCl secretion.
• Clinical Features:
  • Multiple, refractory, or distal (e.g., jejunal) peptic ulcers.
  • GERD, abdominal pain.
  • Chronic diarrhea, steatorrhea (low pH inactivates pancreatic enzymes).
• Diagnosis:
  • Fasting serum gastrin (FSG): > 100 pg/mL (suspect); > 1000 pg/mL with gastric pH < 2 (diagnostic).
  • Secretin stimulation test: Paradoxical ↑ gastrin > 200 pg/mL from baseline.
  • Endoscopy: Prominent gastric folds.

⭐ Approximately 20-30% of gastrinomas are associated with Multiple Endocrine Neoplasia type 1 (MEN1).

• Treatment: High-dose Proton Pump Inhibitors (PPIs); surgical resection if localized. oka

Other PanNETs - Rare Hormone Havoc

⭐ Necrolytic migratory erythema (NME), an erythematous rash with blistering, crusting, and scaling, is a pathognomonic feature of glucagonoma.

High‑Yield Points - ⚡ Biggest Takeaways

• Insulinomas: Most common functioning PanNET, usually benign; cause hypoglycemia, Whipple's triad.
• Gastrinomas (ZES): Cause multiple peptic ulcers; often malignant and associated with MEN1 syndrome.
• Glucagonomas: Characterized by necrolytic migratory erythema, diabetes, and DVT.
• Type 1 DM: Autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency.
• Type 2 DM: Due to insulin resistance and relative insulin deficiency; islet amyloid deposition is common.
• VIPomas: Result in WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria).