Thyroid
On this page 5 sections
Steps of T3 and T4
| Step | Process Name | Description |
| 1 | Iodide Trapping (Uptake) | Active transport of iodide ions (I-) from the bloodstream into the thyroid follicular cell via the Na+/I- symporter (NIS). |
| 2 | Oxidation of Iodide | Iodide (I-) is oxidized to active iodine (I^0 or I_2) at the apical membrane, catalyzed by the enzyme Thyroid Peroxidase (TPO). |
| 3 | Organification (Iodination) | Active iodine is attached to tyrosine residues on the protein thyroglobulin (Tg) to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). |
| 4 | Coupling Reaction | TPO links iodinated tyrosines together: • {DIT} + {DIT} - {Thyroxine } (T_4) • {MIT} + {DIT} - {Triiodothyronine } (T_3) |
| 5 | Storage | Formed thyroid hormones (T_3 and T_4) remain stored in the follicular lumen attached to thyroglobulin as a gelatinous mass called colloid. |
| 6 | Endocytosis & Proteolysis | Under TSH stimulation, follicular cells engulf colloid via pinocytosis. Lysosomes then fuse with these vesicles and enzymatically cleave T_3 and T_4 from thyroglobulin. |
| 7 | Secretion & Recycling | Free T_3 and T_4 are released into the bloodstream. Uncoupled MIT and DIT are deiodinated by thyroid deiodinase to recycle iodine back into the cell. |
- TPO is involved in oxidation, organification and coupling.
- T4 is produced in greater quantity; T3 is more potent (approximately 3–4 times).
- Pregnancy/estrogen increases TBG and total T3/T4, while free hormone generally remains normal. Liver failure may decrease TBG and total hormone while free hormone remains normal.
- TRH (hypothalamus) → TSH (anterior pituitary) → thyroid T3/T4. T3/T4 exert negative feedback on TRH and TSH. Chronic TSH elevation can cause thyroid hypertrophy/goiter.
Graves disease: IgG thyroid-stimulating immunoglobulins (TSI) activate the TSH receptor. Hashimoto thyroiditis is associated with anti-TPO antibodies.
PTU, propranolol, amiodarone and steroids as inhibitors of peripheral T4-to-T3 conversion.
| Thyroid state | Typical findings | Typical lab pattern / cause |
| Primary hypothyroidism | Weight gain, cold intolerance, lethargy, reduced metabolic rate and cardiac output | TSH high, free T4 low; Hashimoto, thyroid surgery or iodine deficiency |
| Primary hyperthyroidism | Weight loss, heat intolerance/sweating, tremor, tachycardia and increased metabolic rate | TSH low, T3/T4 high; Graves disease or toxic nodules |
| Secondary hypothyroidism | Hypothyroid features due to pituitary failure | TSH low or inappropriately normal with low thyroid hormone |
| High-TBG state | Often clinically euthyroid | Total T4 elevated, free T4 normal; e.g., pregnancy/estrogen |
Actions of thyroid hormone
- Supports normal growth, bone maturation and epiphyseal fusion; acts synergistically with GH/IGF.
- Perinatal deficiency can cause irreversible neurodevelopmental impairment; neonatal screening is important.
- Increases basal metabolic rate, oxygen consumption and Na⁺/K⁺-ATPase in most tissues.
- Increases GI glucose absorption, glycogenolysis, gluconeogenesis, glucose oxidation and lipolysis; overall protein catabolism can increase.
- Increases heart rate, stroke volume and cardiac output; up-regulates cardiac β-adrenergic responsiveness.
Dental considerations and emergencies
- Uncontrolled hyperthyroidism: defer elective care; avoid epinephrine-containing local anesthetic/retraction cord because stress or exogenous epinephrine may precipitate thyroid storm. Use stress reduction and good pain control.
- Hypothyroidism: controlled patients can generally receive routine care; use sedatives/opioids cautiously because of increased sensitivity to CNS depressants.
- PTU/methimazole can cause leukopenia; CBC consideration before invasive procedures. Thyroid replacement can interact with warfarin and certain antibiotics.
- Thyroid storm: fever, tachycardia, agitation, sweating/tremor and possible arrhythmia. Stop procedure, call emergency services, provide oxygen/cooling and arrange immediate hospital transfer; do not give epinephrine.
- Myxedema coma: severe bradycardia, hypotension, hypothermia and altered consciousness. Stop treatment, call emergency services, provide oxygen, keep warm and transfer.
- Iodine effects: Wolff–Chaikoff = excess iodine temporarily inhibits thyroid hormone synthesis. Jod–Basedow = iodine exposure precipitates hyperthyroidism in susceptible tissue.
Calcium
About 40% of total serum calcium is protein-bound and inactive; the free ionized fraction is biologically active. The remainder is ultrafilterable/complexed.
Serum calcium balance depends on intestinal absorption, renal excretion and bone remodeling.
PTH is the major regulator. It is synthesized by parathyroid chief cells and released when serum ionized Ca²⁺ falls (reduced activation of the calcium-sensing receptor).
Mild hypomagnesemia may stimulate PTH; severe hypomagnesemia can suppress PTH and produce hypoparathyroid-like features.
PTH uses cAMP signaling.
| Target | PTH action | Net result |
| Bone | Increases bone resorption indirectly through osteoblast/osteoclast signaling | Releases calcium and phosphate into ECF |
| Kidney — proximal tubule | Decreases phosphate reabsorption (phosphaturia) | Serum phosphate falls; less phosphate complexes with calcium |
| Kidney — distal tubule | Increases calcium reabsorption | Serum calcium rises |
| Kidney | Increases 1α-hydroxylase activity → active vitamin D (1,25-dihydroxycholecalciferol/calcitriol) | Increases intestinal calcium absorption |
| Intestine (via calcitriol) | Increases calcium absorption | Supports rise in serum calcium |
Net PTH effect: Raises serum calcium and lowers serum phosphate.
| Condition | PTH | Serum Ca²⁺ | Serum phosphate | Clue |
| Primary hyperparathyroidism | ↑ | ↑ | ↓ | Often parathyroid adenoma; urinary phosphate and urinary cAMP increased |
| Humoral hypercalcemia of malignancy | ↓ | ↑ | ↓ | PTH-related peptide (PTHrP) from tumour; native PTH suppressed |
| Hypoparathyroidism | ↓ | ↓ | ↑ | After thyroid surgery or congenital; tetany/hypocalcemia |
| Pseudohypoparathyroidism | ↑ | ↓ | ↑ | End-organ resistance; defective Gs signaling; not corrected by exogenous PTH |
| Chronic renal failure / secondary hyperparathyroidism | ↑ | ↓ | ↑ | Reduced GFR → phosphate retention and reduced calcium; renal osteodystrophy/osteomalacia |
| Familial hypocalciuric hypercalcemia | Normal or ↑ | ↑ | Often normal | Inactivating calcium-sensing receptor mutation; autosomal dominant; urinary calcium reduced |
Vitamin D and calcitonin
Vitamin D increases both serum calcium and phosphate.
Calcitonin is released by thyroid parafollicular (C) cells when calcium is high; it inhibits osteoclasts and favours calcium deposition in bone.
Dental link: Loss of lamina dura is highlighted as a classic radiographic clue for primary hyperparathyroidism.