Endocrinology: Thyroid Hormones Overview

Thyroid Gland

• Located on the trachea, inferior to the larynx
• Largest pure endocrine gland in the body
• Consists of two lateral lobes connected by a median mass called the isthmus
• Follicular cells line large extracellular spaces called follicles and produce thyroglobulin
• Colloid within the follicles consists of thyroglobulin plus iodine; a long-term storage form of thyroid hormone (TH)
• Parafollicular (C) cells produce calcitonin and are situated between the follicles, not along their edges

Thyroid Hormone

• Major metabolic hormone of the body, affecting nearly all cells
• A combination of two amine hormones: thyroxine (T4) and triiodothyronine (T3)
• Similar to steroids, TH is lipid-soluble, enters target cells, binds to intracellular receptors, and directly activates genes
• Released from follicles controlled by thyroid-stimulating hormone (TSH)
• Transported in the bloodstream by thyroxine-binding globulins (TBGs)
• Increases basal metabolic rate (BMR)

Thyroid Hormone Effects

• Increasing basal metabolic rate (BMR)

Hypothyroid Disorders

• Myxedema (hypothyroid syndrome) includes low metabolic rate, chills, constipation, edema, lethargy, and mental sluggishness
• Lack of iodine results in goiter (enlarged thyroid)
• Severe hypothyroidism in infants is cretinism, with symptoms of mental retardation, short stature, thick tongue, and neck

Hyperthyroid Disorder

• Graves' Disease is an autoimmune hyperthyroid condition
• Antibodies target thyroid and mimic TSH, causing excessive TH release
• Symptoms include elevated metabolic rate, sweating, rapid heartbeat, anxiety, weight loss, and protruding eyeballs

Thyroid Gland: Calcitonin

• Produced by parafollicular (C) cells of the thyroid gland
• Secreted in response to elevated blood calcium (Ca²⁺) levels (hypercalcemia)
• Significance in humans (especially adults) is unclear, but functions to reduce blood calcium levels

Parathyroid Glands

• Four (or more) tiny glands embedded on the posterior thyroid
• Secretes parathyroid hormone (PTH)
• Important for calcium (Ca²⁺) homeostasis in blood
• In response to low blood calcium, parathyroid glands secrete PTH
• Stimulates osteoclasts to digest bone matrix, releasing Ca²⁺ into blood
• Increases Ca²⁺ reabsorption by kidney tubules (reduces Ca²⁺ loss in urine)
• Increases vitamin D activation (by kidneys), which functions to increase Ca²⁺ absorption in the small intestine
• Increased blood Ca²⁺ inhibits PTH release

Adrenal Glands

• Paired, pyramid-shaped glands on top of the kidneys
• Each is two functional glands: adrenal cortex (superficial) and adrenal medulla (internal)
• Many hormones produced, but general function is coping with stress

Adrenal Cortex

• Capsule, Zona glomerulosa, Zona fasciculata, Zona reticularis
• Hormones secreted: aldosterone, cortisol, and androgens
• Epinephrine and norepinephrine

Mineralocorticoids

• From zona glomerulosa
• Regulate electrolyte (mineral salt) concentration in extracellular fluids (ECF), especially Na⁺ and K⁺
• Changes in [Na⁺] cause changes in blood volume and blood pressure
• K⁺ homeostasis is critical to activity of neurons and muscle cells
• Primary mineralocorticosteroid is aldosterone
• Elevates blood volume and blood pressure by stimulating Na⁺ reabsorption and water retention by kidneys
• Also causes elimination of K⁺ triggered by high blood K⁺

Renin-Angiotensin-Aldosterone

• Controls blood pressure
• Kidney cells release the enzyme renin in response to falling blood pressure
• Renin activates blood plasma protein angiotensinogen, leading to angiotensin II formation
• Angiotensin II stimulates glomerulosa cells of adrenal cortex to release aldosterone
• Retention of Na⁺ and water by kidneys increases blood pressure

Glucocorticoids

• From zona fasciculata
• Influence energy metabolism and resist stressors
• Include homeostasis of blood glucose, and blood pressure
• Cortisol (hydrocortisone) is the primary glucocorticoid
• Cortisol levels follow a daily rhythm, peaking early morning and declining at night

Gonadocorticoids

• From zona reticularis
• Adrenal cortex produces low levels of sex hormones (estrogen & testosterone)
• Effects promote muscle mass, bone density, secondary sexual characteristics, and sex drive
• Mostly androgens, but provide primary source of estrogen for post-menopausal women
• Hypersecretion can cause masculinization and increased body hair

Adrenal Medulla

• Reacts to short-term stress as part of a "fight or flight" response of the sympathetic nervous system
• Cells are modified postganglionic sympathetic neurons that synthesize catecholamines (epinephrine & norepinephrine)
• Ratio is 80% epinephrine to 20% norepinephrine
• Effects include increased heart rate, blood pressure, blood glucose, blood flow to heart and skeletal muscles, and bronchiole dilation

Pineal Gland

• Smallest endocrine gland located in the brain
• Secretes melatonin
• Causes drowsiness and regulates day-night cycles
• Secretion peaks at night and is inhibited by bright light
• May influence daily rhythms such as body temperature, sleep, and appetite

Pancreas

• Both an exocrine and endocrine gland
• Acinar cells (exocrine): produce enzyme-rich digestive juice secreted into the small intestine via pancreatic duct
• Pancreatic islet (Langerhans): endocrine cells
  • Alpha (α) cells: produce glucagon (hyperglycemic hormone - increase blood sugar)
  • Beta (β) cells: produce insulin (hypoglycemic hormone - decrease blood sugar)

Glucagon

• Small polypeptide with potent hyperglycemic effect
• One glucagon molecule can release 100 million glucose molecules into the blood
• During low blood glucose, major target organ is the liver and causes breakdown of glycogen to glucose, glucose synthesis from lactic acid and non-carbohydrates, and glucose release from liver cells to the blood

Insulin

• Synthesized in pancreatic β cells from a larger polypeptide called proinsulin
• Effect is to reduce blood glucose, primarily after eating, by enhancing membrane transport of glucose into body cells, especially muscle and fat cells, inhibiting breakdown of glycogen to glucose, and inhibiting conversion of amino acids and fatty acids to glucose.
• Not needed for glucose uptake in liver, kidneys, and brain
• After glucose enters target cells, insulin further causes:
  1. Oxidation of glucose for ATP production.
  2. Conversion of glucose to glycogen (glycogenesis).
  3. Conversion of excess glucose to fat in adipose tissue and protein synthesis in muscle tissue
• Insulin release is triggered by multiple factors, including elevated blood glucose, blood amino acids, and fatty acids. Also by parasympathetic release of acetylcholine. conversely sympathetic nervous systems inhibit insulin release..
  • Hormonal stimuli (negative feedback) elevated levels of hyperglycemic hormones (glucagon, epinephrine, GH, TH, and glucocorticoids). These increase blood glucose.

Insulin Disorders

• Diabetes Mellitus: hyposecretion or hypoactivity of insulin
• Body cells fail to uptake glucose after food consumption, resulting in elevated blood glucose.
• Type I diabetes is autoimmune, destroying β cells of the pancreas causing insulin deficiency. Type II diabetes is associated with obesity, excess sugar consumption & lack of exercise
• Symptoms of both types include increased thirst, frequent urination, hunger, and fatigue

Other Organs

• Heart: atrial natriuretic peptide (ANP)
• Kidneys: erythropoietin (EPO)
• Skin: provitamin D
• Thymus: several peptide hormones and paracrines

Test your knowledge on the functions and roles of thyroid hormones in the body. This quiz covers various aspects of thyroid hormone action, including their impact on metabolism, blood pressure, and related conditions such as hypothyroidism and Graves' disease. Explore the relationships between different hormones and their overall effect on health.