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Pathology of the Endocrine Pancreas
Pars endocrina pancreatis
For medical students2 min readUpdated 2026-10-10
Pathology of the endocrine pancreas encompasses disorders of carbohydrate metabolism (various types of diabetes mellitus) and hormonally active tumors (insulinomas). Chronic hyperglycemia in diabetes triggers a cascade of reactions leading to severe systemic damage to blood vessels, kidneys, eyes, and the nervous system.
Main SymptomChronic hyperglycemia, disrupting all types of metabolism and causing tissue hypoxia
MODY DiabetesMonogenic autosomal dominant form of the disease in young, normal-weight patients
Renal InvolvementNodular glomerulosclerosis (Kimmelstiel-Wilson syndrome) leading to nephrotic syndrome
InsulinomaThe most common endocrine tumor of the pancreas, causing hypoglycemia and erratic behavior
Classification and Pathogenesis of Diabetes Mellitus
Diabetes mellitus (DM) is the primary pathology of the endocrine pancreas. Several main pathogenetic variants are distinguished:
Type 1 DM: Occurs predominantly in individuals under 30 years of age against a background of genetic predisposition (diabetogenic HLA antigens are detected in 95% of patients). Triggers (Coxsackie viruses, rubella, toxic chemicals) initiate an autoimmune reaction. T-lymphocytes, macrophages, and specific autoantibodies cause immune inflammation of the islets (insulitis). The morphological outcome is the destruction of $\beta$-cells, islet atrophy, and absolute insulin deficiency.
Type 2 DM: Usually develops after age 40, has a polygenic nature, and is closely associated with obesity. It is based on receptor insulin resistance and relative insulin deficiency. Functional exhaustion of $\beta$-cells is promoted by pancreatic lipomatosis and the deposition of local senile amyloid. The protein amylin exhibits direct cytotoxicity toward islet cells.
MODY Diabetes: A rare monogenic form in young individuals with normal body weight, inherited in an autosomal dominant manner.
Gestational DM: Occurs during pregnancy. It carries the risk of diabetic macrosomia and fetal malformations (diabetic embryopathy).
Mitochondrial DM: Caused by point mutations in mitochondrial DNA, inherited maternally, and often associated with hearing loss or MELAS syndrome.
Systemic Changes and Diabetic Angiopathies
The key damaging factor in any type of diabetes is hyperglycemia. It activates non-enzymatic protein glycosylation and lipid peroxidation. The morphological basis for most complications is generalized vascular bed involvement—diabetic angiopathies (the cause of death in 65–85% of cases).
Diabetic Macroangiopathy: Affliction of large- and medium-sized arteries. It manifests as early, widespread atherosclerosis and Mönckeberg medial calcification (calcification of the tunica media).
Diabetic Microangiopathy: Systemic damage to capillaries and arterioles. It is characterized by marked basement membrane thickening, plasmorrhagia, and hyalinosis, leading to luminal narrowing up to complete obliteration.
These vascular disorders form specific target-organ pathologies:
Kidneys: Diabetic nephropathy, the most prominent manifestation of which is nodular glomerulosclerosis. Grossly, the kidneys are finely granular, firm, and symmetrically shrunken.
Eyes: Diabetic retinopathy. Includes microaneurysms, hemorrhages, and retinal neovascularization. It carries the risk of glaucoma and retinal detachment.
Nervous System: Diabetic neuropathy. Caused by microangiopathy of the vessels supplying the nerves (vasa nervorum). It leads to segmental demyelination, loss of sensation in the lower extremities, and the formation of neuropathic ulcers in diabetic foot syndrome.
Hormonally Active Tumors (Insulinomas)
Neoplasms originating from the endocrine cells of the islets of Langerhans are collectively called insulinomas (or islet cell tumors). These are rare tumors (1–2% of all pancreatic neoplasms). Most commonly, they have an adenoma structure. Immunohistochemical analysis is required to accurately determine the tumor's hormonal profile.
Insulinoma: The most common neuroendocrine tumor originating from $\beta$-cells. Excess insulin secretion causes severe hypoglycemic attacks. Patients suffer from morning lethargy, disorientation, epileptiform seizures, and erratic behavior followed by amnesia. All symptoms are rapidly relieved by glucose administration.
Gastrinoma: The second most frequent tumor (arising from G-cells). It features a malignant course—by the time of detection, up to 75% of patients already have metastases. Gastrin release provokes Zollinger-Ellison syndrome: marked gastric acid hypersecretion and the formation of multiple "kissing" ulcers of the stomach and duodenum, prone to bleeding and perforation. In half of cases, gastrinoma is associated with multiple endocrine neoplasia type 1 (MEN-1).
Glucagonoma: A tumor developing from $\alpha$-cells.
Mnemonic
The clinical picture of hyperinsulinism in insulinoma is easily remembered as a "glucose hangover": morning lethargy, erratic behavior, retrograde amnesia. It is "treated" just as simply—with sweets (intravenous glucose).
Frequently asked questions
What changes occur in the fundus in diabetic retinopathy?
In diabetic retinopathy, funduscopic examination reveals vascular abnormalities, hemorrhages, and optic nerve alterations.
Microaneurysms — detected in retinal capillaries and venules.
Hemorrhages — include microhemorrhages, small intraretinal, preretinal, and vitreous hemorrhages (hemophthalmos).
Exudates — formation of "hard" and "soft" ("cotton-wool") spots.
Vascular abnormalities — intraretinal microvascular abnormalities (IRMA), venous beading and loops, and neovascularization of the optic disc and retina.
Gastrinoma — associated with Zollinger-Ellison syndrome.
Pancreatic polypeptideoma.
Calcitoninoma — hypersecretes calcitonin.
ACTHoma — hypersecretes ACTH.
The cited sources do not explicitly state the cellular origin of all these tumors. B-cells secreting insulin and A-cells secreting glucagon are described in the pancreatic islets.
What clinical manifestations are characteristic of glucagonoma?
Glucagonoma is characterized by:
Necrolytic migratory erythema (necrotic rash).
Diabetes mellitus or impaired glucose tolerance.
Weight loss, cachexia, anemia.
Mucosal lesions.
What is the difference between MODY diabetes and classic type 2 diabetes mellitus?
MODY diabetes is a monogenic disorder with an autosomal dominant inheritance pattern. Unlike polygenic type 2 diabetes, it presents at a young age, patients maintain a normal body weight, and lipid metabolism disorders are virtually absent.
What is the role of amylin in the development of pancreatic pathology?
Amylin is a polypeptide produced by $\beta$-cells. In elderly patients with type 2 diabetes, it forms local senile amyloid deposits. Amylin acts as an insulin antagonist, increases insulin resistance, and exerts a direct toxic effect on islet cells, leading to their atrophy.
What is Zollinger-Ellison syndrome?
This is a clinical syndrome developing in the presence of a gastrinoma. The tumor uncontrollably secretes gastrin, leading to marked gastric acid hypersecretion and the formation of severe, recurrent, and complication-prone multiple ulcers of the stomach and duodenum.
Go deeper
Morphological and clinical characteristics of MODY diabetes variants (types 1–5)
Pathogenesis of fetal complications in gestational diabetes (diabetic macrosomia and embryopathy)
Stages of diabetic retinopathy development: from non-proliferative to proliferative forms
Comparative morphology of clinical and pathogenetic variants of diabetic foot syndrome (ischemic and neuropathic)
Pathogenesis of Mauriac syndrome in children with decompensated type 1 diabetes