Alterations in Endocrine Function (Thyroid & Pancreas)

Unit 11: Alterations in Endocrine Function (Thyroid & Pancreas) Pathophysiology

Overview of the Endocrine System

  • Definition: Consists of glands that synthesize and release hormones directly into the bloodstream.

  • Functionality: Works with the nervous and immune systems to regulate body responses to internal and external stimuli.

  • Role in Communication: It plays a crucial role in cellular communication.

  • Reference: See Table 40-1 for detailed hormones and their actions.

Hormones

  • Definition: Hormones are chemical messengers that initiate intracellular responses in target cells.

  • Common Features of Hormones:

    • Have specific secretion rates.

    • Only affect target cells that have specific hormonal receptors, which may be located on the plasma membrane or within the cell itself.

    • Operate within feedback loops to maintain homeostasis.

Hormone Receptors

  • Definition: Hormone receptors are proteins that bind with circulating hormones.

  • Response Mechanism: The ability of a cell to respond to a hormone depends on:

    • The quantity of receptors on or within the target cell that are specific to that hormone.

    • The affinity of said receptors for the hormone.

  • Regulation Mechanisms:

    • Up-Regulation: An increase in the number of receptors, enhancing sensitivity to the hormone.

    • Down-Regulation: A decrease in the number of receptors, diminishing sensitivity to the hormone.

Endocrine Feedback Mechanisms

  • Negative Feedback: The most common feedback mechanism.

    • Examples:

    • Glucose/Insulin

    • Calcium/Parathyroid Hormone

    • Stress Response/Cortisol

  • Positive Feedback:

    • Examples:

    • Female Reproductive Cycle

    • Labor

  • Further Learning: See pages 1042-1043 for in-depth feedback regulation.

Examples of Negative Feedback Loops

  1. Stress Response:

    • Hypothalamus releases CRH → Anterior Pituitary releases ACTH → Adrenal glands produce Cortisol → Metabolic effects.

  2. Thyroid Response:

    • Hypothalamus releases TRH → Anterior Pituitary releases TSH → Thyroid releases T4 and T3.

Basic Mechanisms of Endocrine Dysfunction

  • Hypofunction of the gland: Can occur due to ischemia, immune response (inflammation, infection, autoimmune), tumors, atrophy, or lack of stimulation from stimulating hormones.

  • Hyperfunction of the gland: Often results from overstimulation by other hormones or autoantibodies, or tumor presence.

  • Hormone Receptor Resistance: Can arise from

    • Insufficient number of receptors or low receptor affinity.

    • Defective receptor structure that prevents binding or decreased intracellular responsiveness.

Normal Thyroid Function

  • Production Requirements for Thyroid Hormones (TH):

    • Iodine, iron, tyrosine, zinc, selenium, vitamins (E, B, C, and D).

    • Population Insight: The U.S. population does not receive adequate dietary iodine.

  • Inhibitors of TH Production:

    • Stress (e.g., infection, trauma, radiation)

    • Certain medications (fluoride, bromide, and chlorine compete with iodine)

    • Toxins (e.g., pesticides)

    • Metals (like mercury, cadmium, and lead)

    • Autoimmune diseases or conditions (like leaky gut)

    • Nutrient deficiencies, adrenal dysfunction.

Hormones of Thyroid Function

  • TRH (Thyrotropin-releasing hormone):

    • Synthesized and stored in the hypothalamus.

  • TSH (Thyroid-stimulating hormone):

    • Synthesized and stored in the anterior pituitary.

  • TH (Thyroid Hormones):

    • T3 (Triiodothyronine): Secreted in small amounts (7%), very potent with a shorter half-life.

    • T4 (Thyroxine): Secreted in larger amounts (93%) with a longer half-life.

    • Essential for normal TH synthesis and thyroid function.

    • RT3 (Reverse T3): An inactive hormone that can block T3 from being utilized, secreted during the body's protective/survival mode.

Thyroid Hormone Regulation

  • Regulation Mechanism:

    • Negative feedback involving:

    • Hypothalamus producing TRH

    • TRH stimulating the anterior pituitary to produce TSH

    • TSH stimulating the thyroid to release T4 and T3.

    • T4 is converted to T3 primarily in the liver and gastrointestinal tract.

    • The system is deactivated when desired hormone levels are achieved.

Converting T4 to T3

  • TSH triggers the conversion:

    • 80% occurs in the gut and liver.

    • T4 synthesis is mainly 93% while T3 is made in small amounts (7%).

    • Conversion affected by: poor liver or gut health, stress, poor nutritional intake (undereating, deficient nutrients), medications, and disorders.

Critical Thinking Questions on Thyroid Function

  1. In a healthy thyroid, TSH secretion is regulated by which mechanism?

    • Answer: Negative feedback mediated by TRH.

  2. What insights can be inferred about T4 to T3 conversion in patients with liver issues? What symptoms might present?

Functions of Thyroid Hormone

  • Primary Effect in Adults:

    • Increases Basal Metabolic Rate (BMR) by 60-100%.

  • Cell Types Impacted:

    • Mobilization and uptake of glucose (enhanced by insulin).

    • Catabolism of fats (cholesterol, lipids) and muscle proteins.

Cardiovascular and Respiratory Effects

  • Regulates respiratory rate (RR) and oxygen utilization.

  • Causes vasodilation, increasing heat production, maintaining heart rate and contractility.

Gastrointestinal and Neuromuscular Effects

  • GI Effects: Increases appetite, glucose absorption, gastrointestinal motility, and secretions.

  • Neuromuscular Effects: Regulates muscle tone.

Blood Cell Production Effects

  • Thyroid hormones influence blood cell production; low thyroid levels lead to a decreased production of erythropoietin and lower absorption of vitamins and minerals leading to anemia-related risks.

Alterations in Thyroid Function

  1. Hypothyroidism:

    • Insufficient TH (T3 and T4) synthesis/slows metabolic processes.

  2. Hyperthyroidism:

    • Excessive TH (T3 and T4) synthesis/accelerates metabolic processes.

  3. Disorders of Origin:

    • Primary Disorder: Affects TH production directly by the thyroid affecting TSH release (99% of all cases related to thyroid issues).

    • Secondary Disorder: Originates from hypothalamus or anterior pituitary affecting TSH production/direct relation to thyroid hormones.

Hypothyroidism

  • Major Cause: Hashimoto's disease (autoimmune thyroiditis).

  • Pathophysiology Details:

    • Infiltration of thyroid gland by T-cells, NK cells, and pro-inflammatory cytokines leads to thyroiditis.

    • Low TH levels lead to increased TSH production, causing stimulation and inflammation of thyroid tissue (goiter).

    • Later development leads to gland atrophy; more common in females.

  • Additional Causes:

    • Iatrogenic causes, iodine issues, medication/food interference, genetic predispositions, aging.

Hyperthyroidism

  • Major Cause: Grave’s disease (autoimmune disorder), representing 50-80% of cases.

  • Pathophysiology Highlights:

    • Autoantibodies bind to TSH receptors, overstimulating the glands and increasing TH level secretion.

    • Leads to tissue hyperplasia (goiter).

  • Other Causes: Nodular Thyroid Disease and medication excess.

Clinical Manifestations due to Thyroid Function Alterations

  • Hypothyroidism Symptoms: Low BMR leading to fatigue, bradycardia, weight gain, cold intolerance, brittle hair/nails, hyporeflexia, goiter.

  • Hyperthyroidism Symptoms: Increased BMR leading to nervousness, tachycardia, exophthalmos, weight loss, heat intolerance, and hyperreflexia.

Lab Findings for Thyroid Function

  • Primary Hypothyroidism:

    • Low T3 and T4, high TSH.

  • Secondary Hypothyroidism:

    • Low TSH, low T3 and T4.

  • Primary Hyperthyroidism:

    • High T3 and T4, low TSH.

  • Secondary Hyperthyroidism:

    • High TSH, high T3 and T4.

    • Lab changes reflect disrupted feedback mechanisms.

Diabetes Mellitus Overview

  • Definition: Characterized by relative or absolute lack of insulin or insulin resistance, leading to carbohydrate metabolism impairment and altered fat/protein metabolism.

  • Risk Factors: Include heredity, obesity, advanced age, physical inactivity, family history, and conditions affecting insulin sensitivity.

Diabetes Mellitus Classification**

  1. Type 1 DM: Autoimmune destruction of pancreatic beta cells resulting in absolute insulin deficiency.

    • Onset primarily in youth; associated with genetic/environmental triggers.

  2. Type 2 DM: Insulin resistance prevails due to lifestyle choices and genetics; mainly affects those over 40, and is often associated with obesity.

  3. Gestational Diabetes: Occurs during pregnancy, with potential normalization postpartum but risk of later Type 2 DM.

  4. Secondary Diabetes: Related to other medical conditions or medications that adversely affect blood glucose levels.

Clinical Manifestations of Diabetes Mellitus**

  • Common symptoms include the classic triad: Polydipsia, Polyuria, and Polyphagia.

  • Symptoms can vary based on the type (Type 1 or Type 2) and often include fatigue, weight fluctuations, and higher risks of infections.

Acute Complications of Diabetes Mellitus

  • Diabetic Ketoacidosis (DKA): Serious condition due to insulin deficiency, leading to hyperglycemia, ketosis, and acidosis.

    • Lab values exhibit elevated blood glucose (>300-600 mg/dL), decreased bicarbonate, and low pH levels.

  • Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS): Characterized by extreme hyperglycemia and dehydration; more common in Type 2 DM; results from inadequate insulin response, with significant risk for renal complications.

  • Hypoglycemia: Caused by insufficient food intake or overmedication; defined as blood glucose <70 mg/dL, presenting with neurological symptoms and severe fatigue.

Chronic Complications of Diabetes Mellitus

  1. Microvascular Diseases: Resulting from AGEs, leading to damage and dysfunctional capillary quality.

    • Can lead to diabetic retinopathy, nephropathy, and neuropathy.

  2. Macrovascular Diseases: Increased risk for CAD, peripheral vascular disease, and stroke due to dyslipidemia and insulin deficiency.