Pancreatic Endocrine System

The pancreatic endocrine system is a specialized component of the pancreas responsible for producing and regulating hormones that control metabolism, blood glucose levels, and digestive functions. This system consists of clusters of hormone-secreting cells known as the islets of Langerhans, which are dispersed throughout the pancreas. Unlike the exocrine pancreas, which produces digestive enzymes, the endocrine pancreas functions in direct communication with the bloodstream, ensuring precise hormonal regulation essential for metabolic stability.

The pancreas is located in the upper abdomen, posterior to the stomach, and in close proximity to the duodenum and spleen. It is a dual-function gland, possessing both exocrine and endocrine components. The exocrine portion, composed of acinar cells and ductal structures, is responsible for secreting digestive enzymes into the duodenum to facilitate nutrient breakdown. The endocrine portion, consisting of the islets of Langerhans, plays a critical role in glucose homeostasis and metabolic regulation. The pancreas is richly vascularized and innervated, allowing for rapid hormonal secretion into circulation. Its endocrine function is tightly regulated through complex feedback mechanisms involving the hypothalamic-pituitary axis, gastrointestinal hormones, and systemic glucose levels to maintain metabolic equilibrium.

Why Cuba

In Cuba, the surgical management of pancreatic endocrine conditions is guided by a patient-specific approach that considers the type of tumor, hormonal activity, and overall disease burden. The overarching aim is to control abnormal hormone secretion, alleviate symptoms, and prevent disease progression, particularly in cases involving functional neuroendocrine tumors.

Patients benefit from a well-coordinated care pathway that includes thorough diagnostic workups, skilled surgical intervention, and structured post-operative monitoring. Cuban surgical teams emphasize precision and preservation, opting for minimally invasive techniques when appropriate to reduce recovery time and enhance the patient experience. This integrated model supports better clinical outcomes and a quicker return to normal life.

The Importance of the Pancreatic Endocrine System

The pancreatic endocrine system is composed of clusters of hormone-secreting cells known as the islets of Langerhans. These cells regulate essential metabolic functions, including:

• Beta Cells: Secretes insulin to lower blood glucose levels by facilitating glucose uptake into cells.
• Alpha cells: Secretes glucagon secretion to raise blood glucose by stimulating liver glycogen breakdown.
• Delta cells: Secretes somatostatin that inhibits the secretion of insulin, glucagon, and digestive enzymes.
• Pp cells: Secretes pancreatic polypeptide secretion to regulate pancreatic enzyme activity and gastrointestinal motility.

When tumours or functional disorders disrupt these hormone-producing cells, they can lead to severe metabolic imbalances that require surgical treatment.

Conditions That Require Pancreatic Endocrine Surgery

Pancreatic endocrine surgery is indicated for various conditions that affect hormone secretion. These include:

• Pancreatic Neuroendocrine Tumours (PNETs)

PNETs are rare tumours that arise from hormone-secreting cells in the pancreas. They can be classified as functional (hormone-producing) or non-functional (hormonally inactive).

• Insulinoma: Overproduces insulin, causing severe hypoglycemia.
• Gastrinoma (Zollinger-Ellison Syndrome): Produces excess gastrin, leading to severe stomach ulcers and acid reflux.
• Glucagonoma: Overproduces glucagon, causing hyperglycemia and a distinct skin rash.
• VIPoma (Verner-Morrison Syndrome: Produces vasoactive intestinal peptide (VIP), leading to severe watery diarrhea and dehydration.
• Somatostatinoma: Overproduces somatostatin, causing diabetes, gallstones, and nutrient malabsorption.
• Non-Functional PNETs: These tumours do not produce excess hormones but can grow large and cause pain, obstruction, or metastasis.

• Multiple Endocrine Neoplasia Type 1 (MEN1)

A genetic disorder that leads to multiple pancreatic tumours, along with parathyroid and pituitary gland involvement.

• Hereditary or Sporadic Pancreatic Endocrine Tumours
• Von Hippel-Lindau Syndrome (VHL): Can cause multiple pancreatic and adrenal tumours.
• Neurofibromatosis Type 1 (NF1): Associated with pancreatic neuroendocrine tumours.

Causes of Pancreatic Endocrine Disorders

The exact causes of pancreatic endocrine tumours and disorders vary but generally include:

• Genetic mutations: MEN1, VHL, NF1, and SDHB gene mutations increase the risk of PNETs.
• Sporadic tumour formation: Most insulinomas and gastrinomas arise randomly without a genetic component.
• Hormonal imbalances: Excessive hormone secretion can lead to tumour growth.
• Chronic inflammation or pancreatic damage: May contribute to pancreatic endocrine dysfunction.

Symptoms of Pancreatic Endocrine Tumours and Disorders

Symptoms depend on the type of hormone being overproduced.

Common Symptoms by Condition:

• Insulinoma: Frequent hypoglycemia, confusion, weakness, fainting.
• Gastrinoma: Recurrent stomach ulcers, acid reflux, weight loss.
• Glucagonoma: High blood sugar, severe skin rash (necrolytic migratory erythema).
• VIPoma: Persistent watery diarrhea, dehydration, low potassium.
• Somatostatinoma: Diabetes, gallstones, steatorrhea (fatty stools).
• Non-functional PNETs: Patients may experience abdominal pain, weight loss, and intestinal blockage due to tumour growth.

Pre-Surgical Diagnosis for Pancreatic Endocrine Surgery

Before surgery, a thorough diagnostic workup is performed to confirm the presence of pancreatic endocrine tumours and assess surgical options.

Diagnostic Tests Include:

• Hormonal Blood Tests: Measure insulin, gastrin, glucagon, VIP, somatostatin, and chromogranin A levels.
• 24-Hour Urine Hormonal Analysis: Measures hormonal metabolites excreted in urine, particularly useful for catecholamine-secreting tumours (pheochromocytomas).

Imaging Studies:

• CT Scan or MRI: Identifies tumour size and location.
• PET Scan: Detects neuroendocrine tumours with high accuracy.
• Endoscopic Ultrasound: Helps with fine-needle biopsy for tumour analysis.

Surgical Options for Pancreatic Endocrine

Surgical options for pancreatic endocrine conditions are considered when medical management is insufficient, and a targeted intervention is needed to address hormone-secreting tumours or structural abnormalities within the pancreas.

Surgery is recommended when:

• The tumour is functional and causing hormone-related symptoms.
• The tumour is non-functional but larger than 2 cm.
• The tumour is malignant or has metastatic potential.
• There is a genetic predisposition to pancreatic neuroendocrine tumours.

Pancreatic Enucleation (Minimally Invasive)

• Used for small, isolated, benign tumours, particularly insulinomas and non-functional tumours.
• Only the tumour is removed while preserving most of the pancreas, avoiding unnecessary pancreatic tissue loss.
• Laparoscopic techniques are commonly used to minimize surgical trauma, scarring, and recovery time.
• Best for tumours are less than 2 cm, especially when they are non-invasive and away from the pancreatic ducts.
• Reduces the risk of diabetes and exocrine insufficiency since pancreatic tissue is spared.

Distal Pancreatectomy (Traditional or Minimally Invasive)

• Removes the tail and/or part of the body of the pancreas, often along with the spleen if necessary.
• Used for glucagonomas, insulinomas, VIPomas, and non-functional tumours located in the tail.
• Can be performed laparoscopically or as an open surgery, depending on tumour complexity.
• When performed with spleen preservation, it reduces the risk of postoperative infections and immune compromise.
• Patients with large or malignant tumours may require regional lymph node dissection for staging.

Central Pancreatectomy (Parenchyma-Preserving Surgery)

• Used for tumours in the pancreatic neck or body, where removing only the affected segment is preferred.
• Preserves both the head and tail of the pancreas, reducing the risk of endocrine (diabetes) and exocrine (digestive enzyme) dysfunction.
• Often performed laparoscopically, though open surgery may be needed for larger tumours.
• More technically challenging due to the need for complex pancreatic reconstructions to maintain digestive function.
• Indicated for benign or low-grade malignant tumours, but not recommended for aggressive pancreatic neuroendocrine tumours (PNETs).

Whipple Procedure (Pancreaticoduodenectomy)

• A major, complex surgery primarily used for gastrinomas and tumours in the pancreatic head.
• Removes the head of the pancreas, duodenum, bile duct, gallbladder, and part of the stomach to ensure complete tumour excision.
• Performed as an open surgery depending on tumour size and patient factors.
• Requires reconstruction of the digestive tract, connecting the remaining pancreas, bile duct, and stomach to the intestines.
• Higher complication risks include pancreatic fistula, delayed gastric emptying, and nutritional challenges.