Hypothyroidism: Clinical Pharmacology
Diagnosis, dosing, thyroid-stimulating hormone targets, and emergencies
Primary vs. Central Hypothyroidism
Feature Primary Hypothyroidism Central Hypothyroidism
Cause Thyroid gland failure (Hashimoto's, ablation, lithium) Pituitary / hypothalamic disease
TSH Elevated Low, normal, or mildly elevated
Free T4 Low Low
Monitor with TSH Free T4 (upper half of range)
TSH target 0.5–2.5 mIU/L (standard adult) Not used — free T4 is endpoint
Thyroid-Stimulating Hormone Targets by Context
Standard
Adult Replacement
  • TSH: 0.5–2.5 mIU/L
  • Dose: ~1.6 mcg/kg/day
  • Recheck no sooner than 6 weeks
Elderly >65
Less Aggressive Target
  • TSH: 1.0–4.0 mIU/L
  • Start 12.5–25 mcg, titrate slowly
  • TRUST trial: no benefit in mild subclinical
Pregnancy
Trimester-Specific
  • 1st trimester: TSH <2.5 mIU/L
  • 2nd/3rd trimester: TSH <3.0 mIU/L
  • Increase dose 25–30% immediately on positive test
Myxedema Coma: Emergency Protocol
Recognition
Clinical Features
  • Depressed consciousness, hypothermia
  • Hypoventilation, bradycardia
  • Hyponatremia, hypoglycemia
  • Precipitant: infection, cold, opioids, non-adherence
  • Mortality 20–50% despite treatment
Treatment
IV Protocol
  • IV levothyroxine: 300–500 mcg load, then 50–100 mcg/day
  • +/− IV liothyronine (debated; arrhythmia risk)
  • IV hydrocortisone empirically — adrenal insufficiency co-occurs
  • Give glucocorticoid before or with thyroid hormone
  • Treat precipitating illness
6-Week Rule — Universal

After any levothyroxine dose initiation or change, thyroid-stimulating hormone must not be rechecked sooner than 6 weeks. The 6–7 day half-life requires 4–5 half-lives to reach steady state. Earlier measurements capture non-equilibrium values and lead to inappropriate dose adjustments.