Thyroid Disorders for Step 2: Hyperthyroidism vs. Hypothyroidism Made Easy
Keywords: thyroid disorders step 2, hyperthyroidism vs hypothyroidism, thyroid labs step 2, thyroid hormone regulation, USMLE thyroid disease
1. Big-Picture Physiology
- Hypothalamic-Pituitary-Thyroid (HPT) Axis: TRH → TSH → T₄/T₃
Step 1 tie-in: negative feedback loops & G-protein–coupled TSH receptor signaling. - Peripheral conversion: 80% of circulating T₃ comes from 5′-deiodination of T₄—blocked by PTU, β-blockers, and steroids.
Step 1 tie-in: 5′-deiodinase requires selenium, a classic micronutrient biochemistry fact.
2. Clinical Comparison at a Glance
| Feature | Hyperthyroidism | Hypothyroidism |
|---|---|---|
| Metabolic rate | ↑ Heat intolerance, weight loss | ↓ Cold intolerance, weight gain |
| Cardiac | Tachyarrhythmias, high-output heart failure | Bradycardia, pericardial effusion |
| Neuro | Tremor, hyperreflexia | Delayed reflexes, cognitive “fog” |
| Skin/Hair | Warm, moist skin; fine hair | Dry skin; coarse hair; alopecia |
| Labs | ↓ TSH (primary), ↑ Free T₄/T₃ | ↑ TSH (primary), ↓ Free T₄ |
| Antibodies | TSH-R-stim Ig (Graves) | Anti-TPO, anti-TG (Hashimoto) |
| Unique clues | Ophthalmopathy, pretibial myxedema | Non-pitting myxedema, ↑ cholesterol |
3. Labs & Interpretation
Start with TSH.
- Low TSH + high Free T₄ → primary hyperthyroidism.
- High TSH + low Free T₄ → primary hypothyroidism.
Reflex Testing:
- Measure Free T₃ when Free T₄ is borderline.
- Check thyroid antibodies (TSH-R-stim, TPO, Tg) for autoimmune clues.
Radioactive Iodine Uptake (RAIU):
- Diffuse uptake → Graves.
- Patchy or focal → toxic adenoma or multinodular goiter.
Step 1 tie-in: RAIU exploits the Na⁺/I⁻ symporter—same transporter targeted by perchlorate & thiocyanate.
4. Etiologies You Must Differentiate
Hyperthyroidism
| Cause | Hallmark | Key Management |
|---|---|---|
| Graves disease | Diffuse goiter, ophthalmopathy | ATDs, RAI, or surgery; steroids for eye disease |
| Toxic multinodular goiter | Heterogeneous RAIU | RAI or surgery |
| Toxic adenoma | Solitary hot nodule | RAI or lobectomy |
| Thyroid storm | Fever, delirium, tachyarrhythmia | PTU + iodine (1 hr later) + β-blocker + steroids |
Hypothyroidism
- Hashimoto thyroiditis: autoimmune destruction; ↑ risk of B-cell lymphoma.
Step 1 tie-in: HLA-DR5 association. - Subacute (de Quervain) thyroiditis: post-viral, painful gland, elevated ESR; self-limited.
- Post-partum thyroiditis: transient hyper → hypo → recovery.
- Congenital (cretinism): thyroid dysgenesis (most common in U.S.).
- Iatrogenic: surgery, RAI, amiodarone, lithium.
5. Treatment Algorithms
Hyperthyroidism
- Symptom control: Non-selective β-blockers (propranolol) for tachycardia and tremor.
- Disease-specific therapy:
- Antithyroid drugs (ATDs): Methimazole first-line except in first-trimester pregnancy or thyroid storm (use PTU).
- Radioactive iodine ablation (I-131): Contraindicated in pregnancy; give steroid prophylaxis if mild Graves orbitopathy present.
- Surgery: Large goiter, suspicion of cancer, or if RAI/ATDs contraindicated.
- Pregnancy pearls (2024 ATA update): Treat overt hyperthyroidism; target maternal T₄ just above upper normal to minimize fetal hypothyroidism; shared decision-making emphasized.
Pharm integration: Methimazole inhibits thyroid peroxidase (TPO); PTU additionally blocks peripheral T₄ → T₃ conversion.
Hypothyroidism
- Levothyroxine (T₄) replacement: Weight-based dosing ≈ 1.6 µg/kg/day; adjust every 6–8 weeks.
- Post-thyroidectomy dosing: Algorithms can improve initial dose accuracy vs. simple weight-based formulas.
- Pregnancy: Increase LT₄ dose by ~25–30 % as early as week 5; keep TSH < 2.5 mIU/L in first trimester.
Pharm integration: LT₄ has a 7-day half-life; steady state in ~6 weeks—classic pharm kinetics test favorite.
6. High-Yield Clinical Pearls
- Don’t miss subclinical disease. TSH > 10 mIU/L warrants treatment even if Free T₄ is normal.
- Amiodarone can cause both hyper (type II destructive thyroiditis) and hypo (iodine overload).
- “Thyrotoxic periodic paralysis”: Asian male, hypokalemia, weakness—treat hyperthyroidism and give β-blockers.
- Myxedema coma: Elderly woman in winter; give IV LT₄ + hydrocortisone.
- Check cortisol before starting LT₄ if adrenal insufficiency is suspected—avoid precipitating adrenal crisis.
7. Quick Practice Question
A 28-year-old woman in her eighth week of pregnancy presents with palpitations and weight loss. TSH is undetectable, Free T₄ is elevated, and she has mild proptosis. Which treatment is most appropriate?
Answer: Propylthiouracil (PTU) — first-trimester choice due to methimazole teratogenicity. Switch to methimazole in the second trimester to avoid hepatotoxicity.
8. Takeaways for Readers
- Search intent: Whether you Googled “hyperthyroidism vs hypothyroidism” or “how to interpret thyroid labs,” this post covers the full pathway—from TSH physiology to medication dosing.
- Actionable steps: Start with TSH, confirm with Free T₄, then match etiology to therapy.
- Exam relevance: Expect integrated questions that weave biochemistry, immunology, and pharmacology—exactly as modeled above.
Key Stats (Great for Shelf “Fun Facts”)
- Prevalence: ~5% hypothyroidism; ~1% hyperthyroidism in U.S. adults
- Most common cause worldwide: iodine deficiency; in U.S.: autoimmune thyroiditis.
Final Word
Mastering thyroid disease is about pattern recognition plus mechanistic understanding. Anchor each symptom to physiology, pair each lab derangement with its pathogenesis, and the management algorithms will feel intuitive—both on exam day and in the clinic.
Integration is the secret sauce: the same Na⁺/I⁻ symporter that fuels RAI therapy is inhibited by perchlorate in Step 1 biochem questions.
Happy studying, and remember: if the question stem gives you heat intolerance and tremor, think “TSH low, Free T₄ high” before you blink!
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