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Thyroid & Parathyroid Hormone Physiology

Thyroid Gland – Gross Anatomy

  • Butterfly-shaped endocrine organ
    • Location: inferior to thyroid cartilage, anterior to trachea
    • Two lobes (right & left) joined by an isthmus
  • Highly vascular
    • Major vessels: superior & inferior thyroid arteries and veins
  • Unique feature: largest structure devoted entirely to endocrine activity

Thyroid Gland – Microscopic Structure

  • Encapsulated by connective tissue; filled with spherical thyroid follicles
  • Follicle lumen contains viscous, protein-rich colloid (gelatinous)
  • Two key epithelial cell types
    • Follicular cells (T-thyrocytes / cuboidal epithelium)
    • Synthesize thyroglobulin (TGB), release it into colloid
    • Combine TGB with iodide → precursors of thyroid hormones
    • Upon TSH stimulation, endocytose colloid, cleave TGB, secrete T4 & T3
    • Parafollicular (C) cells
    • Reside between follicles
    • Produce calcitonin (Ca²⁺-lowering hormone)

Thyroid Hormones – Chemistry & Forms

  • Two iodinated amine hormones derived from tyrosine
    • Tetraiodothyronine (T4, thyroxine)
    • \approx 90\% of total secretion
    • Four iodine atoms
    • Triiodothyronine (T3)
    • \approx 10\% of total secretion
    • Three iodine atoms; biologically more potent
  • Visualization:
    • T_4: 4 iodines attached to two tyrosine rings
    • T_3: 3 iodines (one removed by deiodinase)

Transport in Blood

  • Lipid-soluble → require carrier proteins
    • Major carrier: thyroxine-binding globulin (TBG)
  • Fractions
    • Bound hormone (majority) – inactive while bound
    • Free T4 / T3 (small % checked clinically) – able to exit capillaries & bind receptors

Peripheral Conversion

  • Within target cells: T4 \xrightarrow{\text{deiodinase}} T3 + I^-
  • Ensures active hormone at site of action

Mechanism of Action (Genomic)

  • Lipid-soluble → diffuse through plasma & nuclear membranes
  • Bind nuclear thyroid-hormone receptors → hormone-receptor complex binds DNA
  • Alters transcription → changes protein synthesis → long-lasting metabolic effects

Physiological Actions of Thyroid Hormone

  • Basal Metabolic Rate (BMR) ↑
    • Stimulates O₂ consumption & ATP hydrolysis
    • Generates heat → calorigenic effect (body-temperature regulation)
  • Fuels
    • ↑ Glucose uptake & oxidation
    • ↑ Lipolysis & fatty-acid oxidation
  • Synergism with catecholamines
    • Up-regulates \beta-adrenergic receptors → potentiates epinephrine & norepinephrine → ↑ sympathetic tone
  • Growth & Development
    • Essential for fetal/childhood brain maturation & skeletal growth
  • Clinical relevance
    • Hypothyroidism → fatigue, cold intolerance, growth retardation
    • Hyperthyroidism → heat intolerance, weight loss, tachycardia

Iodine & Goiter – Real-World Example

  • Public-health measure: iodizing table salt prevents iodine-deficiency goiter (thyroid enlargement)
  • Countries lacking iodized salt show higher prevalence of goiter & developmental delay

Hypothalamic–Pituitary–Thyroid (HPT) Axis

  • Stimuli for ↑ TH demand
    • Low plasma T3/T4, ↓ metabolic rate, cold exposure, pregnancy, any ATP-demanding state
  • Sequence
    1. Hypothalamus releases TRH (thyrotropin-releasing hormone) into hypophyseal portal blood
    2. Anterior pituitary thyrotrophs secrete TSH (thyroid-stimulating hormone)
    3. TSH acts on follicular cells → ↑ iodide uptake, thyroglobulin iodination, endocytosis, T3/T4 release
    4. T3/T4 reach body cells → metabolic effects
  • Negative feedback
    • High circulating T3/T4 inhibit both TRH & TSH secretion

Calcitonin (From C Cells)

  • Stimulus: ↑ blood Ca²⁺
  • Actions (bone & kidney)
    • Inhibits osteoclast-mediated bone resorption → ↓ Ca²⁺ release
    • ↑ Ca²⁺ deposition into bone matrix
    • ↑ renal Ca²⁺ excretion, ↓ reabsorption
  • Outcome: lower plasma Ca²⁺ toward homeostasis

Parathyroid Glands – Anatomy & Histology

  • Four rice-sized glands embedded posteriorly in thyroid (superior & inferior pairs)
  • Chief (principal) cells produce parathyroid hormone (PTH)

Parathyroid Hormone (PTH)

  • Most important regulator of serum Ca²⁺, Mg²⁺, PO₄³⁻
  • Stimulus: ↓ blood Ca²⁺
  • Actions
    • Bone: stimulates osteoclasts → ↑ bone resorption → Ca²⁺ & PO₄³⁻ released
    • Kidney:
    • ↑ Ca²⁺ & Mg²⁺ reabsorption
    • ↑ PO₄³⁻ excretion (phosphaturia)
    • Activates 1-alpha-hydroxylase → converts vitamin D to calcitriol
    • Gut (indirect via calcitriol): ↑ absorption of Ca²⁺, Mg²⁺, PO₄³⁻
  • Outcome: raises plasma Ca²⁺; feedback inhibits further PTH secretion

Calcium Homeostasis – Dual Hormone Feedback Loops

  • High Ca²⁺ → Calcitonin pathway
    • \uparrow [Ca^{2+}]_{plasma} \Rightarrow Thyroid C cells → Calcitonin → ↓ osteoclast activity → ↓ Ca²⁺ → negative feedback
  • Low Ca²⁺ → PTH pathway
    • \downarrow [Ca^{2+}]_{plasma} \Rightarrow Parathyroid chief cells → PTH → ↑ osteoclasts, ↑ renal reabsorption, ↑ calcitriol → ↑ Ca²⁺ → negative feedback

Integrated Summary Table (quick reference)

  • Thyroid hormones (T3/T4)
    • Source: follicular cells
    • Targets: nearly all cells
    • Key effects: ↑ BMR, heat, sympathetic sensitivity, growth
  • Calcitonin
    • Source: parafollicular (C) cells
    • Key effect: ↓ plasma Ca²⁺
  • Parathyroid hormone (PTH)
    • Source: parathyroid glands
    • Key effect: ↑ plasma Ca²⁺, ↓ plasma PO₄³⁻, ↑ calcitriol

Ethical / Practical Implications & Connections

  • Mandatory salt iodization = inexpensive public-health strategy preventing cognitive impairment
  • Endocrine evaluations (free T4/T3) critical in prenatal care, pediatric growth assessments, metabolic disorders
  • Pharmacologic manipulation (levothyroxine, calcitonin analogs, PTH analogs) rooted in pathways outlined above