CC2_LEC-FINALS-1_ENDOCRINOLOGY

Page 1: Endocrine System Overview

Introduction to the Endocrine System

• Composed of different ductless glands.

• Glands secrete hormones into the bloodstream.

Methods of Hormone Secretion

• Endocrine: Direct release into the bloodstream.

• Exocrine: Release through ducts (e.g., gastrointestinal tract).

• Neurocrine: Released by nerve cells.

• Paracrine: Released into interstitial fluid, acting locally.

Hormones

• Definition: Chemical substances that send messages to other cells (chemical messengers).

• Purpose: Control activity in cells, organs, or tissues; can stimulate or inhibit functions.

Hormone Classification

Hormonal Classes:

• Amine

  • Modified amino acids (tryptophan, tyrosine).

  • Short half-life.

  • Examples: Epinephrine (from tyrosine), Melatonin (from tryptophan).

• Peptide

  • Chains of amino acids (50 or fewer).

  • Bind to membrane-bound receptors.

  • Examples: Vasopressin, Oxytocin.

• Protein

  • Longer chains of amino acids (>50).

  • Examples: ACTH, Calcitonin, Insulin, Glucagon.

• Glycoprotein

  • Conjugated with carbohydrates.

  • Examples: FSH, LH, TSH.

• Steroids

  • Lipid-based; cholesterol derivatives.

  • Can cross cell membranes when bound to carriers.

  • Examples: Cortisol, Estrogen.

• Fatty Acids

  • Small derivatives; includes arachidonic acid.

  • Examples: Eicosanoids, Leukotrienes, Prostaglandins, Thromboxanes.

Solubility and Binding

• Amine, peptide, and protein hormones are generally water-soluble, requiring peptide-bound receptors for cell penetration.

Hormone Metabolism

• Factors influencing hormone production and breakdown:

  • Alcohol Consumption:

    • Increases degradation of Testosterone.

    • Decreases protein and hormone carriers.

  • Adrenal Steroid Synthesis:

    • Enzymatic reactions influenced by adrenal hormones.

    • Malignancies can lead to hormonal imbalances and symptoms like masculinization and amenorrhea.

Hormone Elimination

• Primarily through the kidney and liver:

  • Steroid hormones: Recycled to bile salts, excreted via urine/feces.

  • Thyroid hormones: Metabolized intracellularly via deiodinase.

  • Catecholamines: Rapidly degraded in blood circulation.

  • Fatty acid derivatives: Destined for rapid metabolic inactivation.

Hormone Transport

• Two forms:

  • Free: Unbound, prone to degradation (amines, protein, peptides, glycoproteins).

  • Protein Bound: Attached to carriers (steroid hormones).

• Solubility: Water-soluble (free) vs Fat-soluble (protein-bound).

• Carrier Proteins: Fat-soluble hormones often require carrier proteins for transport.

• Micelles: Structures that package lipid-rich substances with a hydrophilic exterior.

Feedback Mechanisms

Positive Feedback Mechanism

• Increased hormone production leads to further increases.

• Example: Oxytocin secretion during childbirth.

Negative Feedback Mechanism

• Increased hormone levels result in decreased production.

• More common mechanism.

• Example: Hypothalamus-Pituitary-Thyroid axis regulation.

Primary, Secondary, and Tertiary Disorders

• Primary: Affects the main endocrine gland.

• Secondary: Affects a regulatory gland (Pituitary Gland).

• Tertiary: Impacts the main regulatory gland (Hypothalamus).

Page 2: Factors Affecting Hormone Levels

Emotional Stress

• Affects the release of glucocorticoids, catecholamines, growth hormone, and prolactin, potentially causing hormonal imbalances.

Biological Rhythms

• Diurnal: Hormones like ACTH and cortisol have peak levels at specific times (e.g., ACTH: 6-9 AM, cortisol: 8 AM).

• Nocturnal: TSH increases at night.

Food Intake/Diet

• Can suppress hormone levels (e.g., leptin, growth hormone affected by glucose levels).

Medications

• Influence on hormone levels:

  • ACE inhibitors reduce aldosterone.

  • Methimazole lowers thyroid hormones.

  • Corticosteroids increase glucose and decrease CRH.

Menstrual Cycle and Menopause

• Hormonal fluctuations across menstrual phases influence estrogen and progesterone levels.

• Hormone Replacement Therapy can mitigate risks like coronary heart disease and prostate cancer.

Endocrine Glands and Their Hormones

Hypothalamus

• Regulates pituitary gland secretions via releasing or inhibiting hormones:

  • Examples include CRH, GnRH, TRH.

Pituitary Gland

• Known as the “master gland” connected to the endocrine system.

• Hormones can be categorized into tropic (stimulating other glands) and direct (acting on tissues).

Anterior Pituitary Hormones

• Growth Hormone: Most abundant pituitary hormone; stimulates fat metabolism; major secreted during deep sleep.

Page 3: Diagnostic Tests for Hormonal Disorders

Growth Hormone Deficiency

Screening Tests

• Physical activity test evaluates serum GH levels.

Confirmatory Tests

1. Insulin Tolerance Test: Gold standard.

2. Arginine Stimulation Test: Monitoring GH over 24-hour periods.

• Diagnosis confirmed by an inability to rise above threshold levels in adults or children.

Acromegaly

Screening and Confirmatory Tests

• Somatomedin C (IGF-1): High levels indicate acromegaly.

• Glucose Suppression Test: Evaluates GH suppression after glucose intake; failure to decline indicates acromegaly.

Gonadotropins

• Important markers for fertility and menstrual disorders.

Thyroid-Stimulating Hormone (TSH)

• Regulates T3 and T4 production, vital for thyroid function assessment.

Adrenocorticotropic Hormone (ACTH)

• Controls adrenal gland function; levels vary throughout the day, being highest in the morning.

Prolactin

• Central to lactation; has wide-ranging effects on menstrual cycle and fertility statuses.

Posterior Pituitary Hormones

• Stores oxytocin and vasopressin; critical for water conservation and uterine contractions during childbirth.

Page 4: Thyroid Gland Function

Overview

• Butterfly-shaped gland near the trachea; responsible for T3 and T4 hormone regulation.

Calcitonin

• Involved in calcium regulation; lowers blood calcium levels.

T3 and T4 Production

• Functional roles include metabolic regulation; T3 is more active than T4.

• Thyroid hormones are affected by dietary iodine intake.

Causes of Hypothyroidism

• Primary: Dysfunction of the thyroid gland (e.g., Hashimoto’s Disease).

• Secondary: Pituitary gland issues affecting TSH production.

• Tertiary: Problems in the hypothalamus affecting TRH production.

Conditions Associated with Thyroid Disorders

• Hyperthyroidism: Elevated levels of T3 and T4; includes Graves’ disease and toxic adenomas.

• Hypothyroidism: Symptoms include heat intolerance, weight changes, and fatigue.

Page 5: Laboratory Assays for Thyroid Function

Thyroid Tests

A. TSH Assay

• Vital for detecting hyper/hypo-thyroid conditions; most sensitive assay.

B. T3 Resin Uptake

• Measures carrier protein activity for thyroid hormones; influenced by TBG levels.

C. Free Thyroxine Index (FT4I)

• Indirect measure of free T4 concentration.

D. Serum Calcitonin

• Utilized as a tumor marker for medullary thyroid carcinoma.

E. TRH Stimulating Test

• Assesses TRH-TSH relationship and can help confirm borderline thyroid disease.

F. Radioactive Iodine Uptake (RAIU)

• Measures thyroid gland’s ability to capture iodine; aids in diagnosing hyperthyroidism.

G. Reverse T3 (rT3)

• Inactive form of T4 hormone, increased in euthyroid sick syndrome.

H. Thyroglobulin Assay

• Monitors for recurrent thyroid cancer post-surgery.

Page 6: Adrenal Gland Overview

Structure of Adrenal Glands

• Pyramid-shaped glands above kidneys.

• Two primary sections: Cortex and Medulla.

  • Cortex: Produces aldosterone, cortisol, and adrenal androgens.

  • Medulla: Produces catecholamines (Epinephrine, Norepinephrine).

Cortisol

• Key glucocorticoid, involved in stress response; helps increase glucose.

• Elevated cortisol levels have a feedback effect on ACTH production.

Hypercortisolism

• Relevant conditions include Cushing's Disease and Syndrome.

• Symptoms: obesity, hirsutism, hypertension.

Assays for Hypercortisolism

Screening Tests

• 24-hour free cortisol test: Measures overall cortisol levels across a day.

• Dexamethasone Suppression Test: Evaluates feedback inhibition.

Aldosterone

• Regulates minerals and electrolytes; crucial for blood pressure maintenance.

Hyperaldosteronism

• Primary (Conn’s syndrome): Associated with adrenal adenoma.

• Secondary results from excessive renin production, affecting systemic electros.

Page 7: Hormonal Regulation and Tests

Congenital Adrenal Hyperplasia (CAH)

• Genetic conditions affecting steroid hormone production in adrenal glands, leading to varying levels of cortisol and adrenal androgens.

Catecholamines: Epinephrine, Norepinephrine, and Dopamine

Clinical Correlation

• Conditions like Phaeochromocytoma and Neuroblastoma associated with excess catecholamine production; crucial tests involve urine specimen assessment.

Page 8: Gonads Overview

Function of Gonads

• Testes: Produce testosterone.

• Ovaries: Produce estrogen and progesterone.

Transport Proteins

• Bind and transport sex hormones in circulation (SHBG and CBG).

Sex Steroids

• Testosterone: Key androgen hormone, regulated by FSH and LH.

• Estrogen: Arises from testosterone transformation, critical for female development.

• Progesterone: Integral for maintaining pregnancies.

Page 9: Other Hormones

Gastrointestinal and Neurotransmitter Hormones

Gastrin

• Promotes gastric acid secretion; can indicate gastrointestinal tumors.

Serotonin

• Produced by enterocytes, involved in regulation of mood and gastrointestinal functioning.

• Use in diagnostic tests (e.g., Carcinoid syndrome).

Melatonin

• Regulates sleep cycles, produced in the pineal gland, influences the body's circadian rhythm.