Pathophysiology

Pathophysiology

I-19. Pathogenesis of hyperthyroidism and its symptoms

甲状腺機能亢進症の発症機序と症状

Thyroid Hormone Physiology

  • Axis: TRH (hypothalamus) → TSH (pituitary) → T4 + T3 (thyroid).
  • Thyroid hormones act intracellularly on gene expression: ↑O₂ consumption, ↑basal metabolic rate, ↑ATP turnover, ↑cell respiration → excess heat → ↑skin blood flow → sweating. Iodine required for synthesis.

Types of Hyperthyroidism

  • Primary → ↑T3/T4, ↓TSH:
    • Graves disease — autoantibodies chronically stimulate TSH receptors.
    • Neonatal transient thyrotoxicosis (maternal Graves IgG crossing placenta).
    • Toxic (thyroid-producing) adenoma.
    • Postpartum thyroiditis (transient); exogenous thyroid hormone intake.
  • Secondary → ↑T4/T3, ↑TSH → goiter: TSH-producing pituitary adenoma.

Graves–Basedow Disease

  • Hyperthyroidism (↑T3/T4, ↓TSH); women 30–40 yrs; genetic predisposition + trigger (virus, stress).
  • TSH-receptor-stimulating autoantibody (often anti-TPO).
  • Merseburg triad: diffuse goiter, ophthalmopathy, tachycardia.
  • Ophthalmopathy (exophthalmos — outward eye bulging) and dermopathy (myxedema = edema + skin thickening) occur only in Graves.
  • Treatment: thyrostatic agents, β-blocker, surgery.

Organ Effects of Hyperthyroidism

(“As if always exercising”)

  • Cardiovascular: tachycardia, ↑SV/CO, ↑contractility (↑myocardial Ca²⁺), cardiac hypertrophy.
  • Vascular: ↓TPR (endothelial vasorelaxation, ↑NO) → systolic hypertension (↑systolic/diastolic/pulse pressure).
  • Nervous: irritability, restlessness, tremor, psychosis/depression, cognitive disturbance; myopathy (weakness, pain), osteoporosis (50–60%, ↑osteoclasts); ophthalmopathy (autoimmune orbital inflammation, glycosaminoglycan deposition, edema → exophthalmos, eye pain, conjunctivitis).
  • Skin: sweaty, red, warm (SYM cholinergic activation); myxedema only in Graves.
  • GI: weight loss despite ↑intake (↑BMR); ↑GI motility → malabsorption/diarrhea; liver damage (necrosis, fibrosis).
  • Renal: ↑RBF/GFR (↑CO, ↑NO vasorelaxation). Blood: ↑volume (T3 → ↑EPO). Metabolism: ↓total cholesterol/LDL, chronic hyperglycemia.

Thyrotoxic Crisis (acute hyperthyroidism)

  • Acute T4/T3 surge from acute stress (infection).
  • Symptoms: hyperthermia (↑BMR), GI overactivation (diarrhea), acute liver failure, restlessness, tachycardia, hypertension, circulatory shock; severe GI–CNS–cardiovascular symptoms (often in untreated patients).
  • Treatment: β-blocker, high-dose iodine infusion, glucocorticoids.

一問一答

▶What is the Merseburg triad of Graves disease?

Diffuse goiter, ophthalmopathy (exophthalmos), and tachycardia.

▶How do primary and secondary hyperthyroidism differ in hormone levels?

Primary: ↑T3/T4 with ↓TSH. Secondary: ↑T4/T3 with ↑TSH (TSH-producing pituitary adenoma) → goiter.

▶What are the metabolic actions of thyroid hormones?

Acting intracellularly on gene expression, they increase O2 consumption, basal metabolic rate, ATP turnover, and cell respiration → excess heat → ↑skin blood flow and sweating; iodine is required for synthesis.

▶What is the pathomechanism of Graves–Basedow disease?

A TSH-receptor-stimulating autoantibody chronically stimulates the thyroid → ↑T3/T4, ↓TSH; typically in women 30–40 yrs with genetic predisposition plus a trigger (virus, stress).

▶What are the causes of primary hyperthyroidism?

Graves disease, neonatal transient thyrotoxicosis (maternal Graves IgG), toxic adenoma, postpartum thyroiditis, and exogenous thyroid hormone intake.

▶Which features occur only in Graves disease (not other hyperthyroidism)?

Ophthalmopathy (exophthalmos — outward eye bulging) and dermopathy (pretibial myxedema = edema + skin thickening).

▶What is the treatment of Graves disease?

Thyrostatic agents, a β-blocker, and surgery.

▶What are the cardiovascular effects of hyperthyroidism?

Tachycardia, ↑stroke volume/cardiac output, ↑contractility (↑myocardial Ca2+), and cardiac hypertrophy.

▶Why does hyperthyroidism cause systolic hypertension?

↓TPR from endothelial vasorelaxation (↑NO) combined with ↑cardiac output raises systolic, diastolic, and pulse pressure — predominantly systolic hypertension.

▶What are the nervous system and musculoskeletal effects of hyperthyroidism?

Irritability, restlessness, tremor, psychosis/depression, cognitive disturbance; myopathy (weakness, pain); and osteoporosis (50–60%, from ↑osteoclasts).

▶What is the mechanism of Graves ophthalmopathy?

Autoimmune orbital inflammation with glycosaminoglycan deposition and edema → exophthalmos, eye pain, and conjunctivitis.

▶Why do hyperthyroid patients have warm, sweaty, red skin?

Sympathetic cholinergic activation increases sweating, and heat dissipation from ↑BMR increases skin blood flow.

▶What are the GI effects of hyperthyroidism?

Weight loss despite increased intake (↑BMR), increased GI motility → malabsorption/diarrhea, and liver damage (necrosis, fibrosis).

▶What are the renal, hematologic, and metabolic effects of hyperthyroidism?

↑Renal blood flow/GFR (↑CO, ↑NO); ↑blood volume (T3 → ↑EPO); and ↓total cholesterol/LDL with chronic hyperglycemia.

▶What is a thyrotoxic crisis and what triggers it?

An acute surge of T4/T3, usually triggered by acute stress (e.g., infection), often in untreated patients.

▶What are the symptoms of thyrotoxic crisis?

Hyperthermia (↑BMR), GI overactivation (diarrhea), acute liver failure, restlessness, tachycardia, hypertension, and circulatory shock.

▶What is the treatment of thyrotoxic crisis?

β-blocker, high-dose iodine infusion, and glucocorticoids.

▶What is the thyroid hormone axis?

TRH (hypothalamus) → TSH (pituitary) → T4 + T3 (thyroid).

▶Why does hyperthyroidism cause weight loss with increased appetite?

The markedly increased basal metabolic rate burns more energy than intake provides, so patients lose weight despite eating more.

▶What causes neonatal transient thyrotoxicosis?

Maternal Graves IgG (TSH-receptor-stimulating antibodies) crossing the placenta.