Pathophysiology of Endocrine System

The Endocrine System

• The endocrine system works through chemical messengers (hormones) that are secreted directly into the circulatory system to regulate target organ function.
• The feedback loop controls the release of hormones and maintains homeostasis, a state of steady conditions vital for life.
• The endocrine system consists of various glands, including the pineal gland, thalamus/hypothalamus, pituitary gland, thyroid and parathyroid, thymus, adrenal gland, pancreas, uterus, ovaries, and testes.

Endocrine Disorders

• Endocrine disorders can be categorized into three main types:
  • Hypersecretion: excess activity of a specific hormone or hormones, which can be caused by overproduction of a hormone, glandular hypertrophy/hyperplasia, or tumors that secrete hormones.
  • Hyposecretion: reduced activity of a specific hormone or hormones, which can be caused by atrophy of glandular tissue, damage from autoimmune attack, infection, or neoplasia, or reduced hormonal stimulation of a gland.
  • Altered responsiveness of a tissue to a specific hormone, which can involve down-regulation of receptors or altered receptor/secondary messenger function.

Pancreas

• The pancreas is both an exocrine and endocrine gland.
• The endocrine cells, referred to as the islets of Langerhans, are small clusters scattered throughout the pancreas, surrounded by exocrine cells.
• The islets of Langerhans make up only 2%–3% of the mass of the pancreas, but receive 5–10 times more blood than the exocrine pancreas.
• The pancreas produces hormones that regulate glucose metabolism, including insulin and glucagon.

Diabetes Mellitus

• Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia.
• Hyperglycemia results from defects in insulin secretion, insulin action, or both.
• Diabetes mellitus is associated with secondary damage in multiple organ systems, especially the kidneys, eyes, nerves, and blood vessels.
• Prediabetes is defined as elevated blood sugar that does not reach the criterion for an outright diagnosis of diabetes.
• Prediabetes is associated with obesity, dyslipidemia, and hypertension.

Pathogenesis of Type 1 Diabetes

• Type 1 diabetes is an autoimmune disease in which islet destruction is caused primarily by immune effector cells reacting against endogenous beta cell antigens.
• The fundamental immune abnormality in type 1 diabetes is a failure of self-tolerance in T cells specific for beta cell antigens.
• Autoantibodies against beta cell antigens, including insulin and glutamic acid decarboxylase, are detected in the blood of 70% to 80% of patients.

Pathogenesis of Type 2 Diabetes

• Type 2 diabetes is a heterogeneous and multifactorial complex disease that involves interactions of genetics, environmental risk factors, and inflammation.
• The two defects that characterize type 2 diabetes are:
  • A decreased ability of peripheral tissues to respond to insulin (insulin resistance).
  • Beta cell dysfunction that is manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia.
• Insulin resistance predates the development of hyperglycemia and usually is accompanied by compensatory beta cell hyperfunction and hyperinsulinemia in the early stages of the evolution of diabetes.

Acute Manifestations

• Polydipsia, polyuria, and polyphagia (3 P’s).
• Weight loss.
• Diabetic ketoacidosis (DKA) in type 1 diabetes.
• Hyperosmolar hyperglycemic state in type 2 diabetes.
• Rarely, can be caused by unopposed secretion of growth hormone (GH) and epinephrine, or in patients on glucocorticoid therapy (steroid diabetes).
• General weakness, skin sepsis, and poor wound healing.

Chronic Complications

• Nonenzymatic glycation:
  • Small vessel disease (hyaline arteriolosclerosis, retinopathy, neuropathy, nephropathy).
  • Large vessel disease (atherosclerosis, CAD, cerebrovascular disease, peripheral vascular disease).
• Osmotic damage (sorbitol accumulation in organs with aldose reductase and or absent sorbitol dehydrogenase):
  • Neuropathy: motor, sensory, and autonomic degeneration.
  • Cataracts.

Hyperglycemic Emergencies

• Sequence of metabolic derangements leading to diabetic coma in type 1 diabetes:
  • Absolute insulin deficiency leads to a catabolic state, eventuating in ketoacidosis and severe volume depletion.
  • These derangements bring about sufficient central nervous system compromise to cause coma and eventually death if left untreated.

Hypoglycemia in Diabetes Mellitus

• Hypoglycemia: a blood sugar level below 70 milligrams per deciliter (mg/dL) or 3.9 millimoles per liter (mmol/L).
• Usually occurs in patients treated with insulin or insulin secretagogues (e.g., sulfonylureas, meglitinides) in the setting of high-dose treatment, inadequate food intake, and/or exercise.
• Neurogenic (autonomic-sympathetic activation) symptoms: diaphoresis, tachycardia, tremor, anxiety, hunger.
• Neuroglycopenic symptoms: altered mental status, seizures, death due to insufficient glucose in CNS.
• Behavioral symptoms: may occur in the absence of preceding neurogenic symptoms in patients with attenuated autonomic response (hypoglycemia unawareness).