Hypothyroidism: Diagnosis, Levothyroxine Dosing & Special Cases

Most hypothyroidism is autoimmune and straightforward to treat—if you read the labs in context and adjust slowly. This guide covers diagnosis, when to treat subclinical disease, and safe levothyroxine (LT4) dosing with high-yield special situations.

Who to Test

• Symptoms: fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, heavy menses.
• Risk groups: autoimmune disease, goiter, neck irradiation, thyroid surgery, lithium/amiodarone use, pregnancy/planning, abnormal lipids, infertility.

Core Labs & Interpretation

• TSH is the best screening test in stable outpatients without pituitary disease.
• Overt hypothyroidism: TSH ↑ and free T4 ↓ → treat.
• Subclinical hypothyroidism: TSH ↑ with normal free T4. Consider symptoms, TPO antibodies, pregnancy plans, and cardiovascular risk.
• Central (secondary) hypothyroidism: low/normal TSH with low free T4 (pituitary disease) → treat and evaluate pituitary/adrenal axis.
• TPO antibodies: positive in autoimmune thyroiditis; predict progression in subclinical disease.

When to Treat Subclinical Hypothyroidism

• Generally treat if TSH ≥10 mIU/L.
• Consider treatment if TSH 4.5–9.9 with symptoms, positive TPO Ab, goiter, atherosclerotic/CVD risk, infertility, or pregnancy/plans for conception.
• Repeat labs in 6–12 weeks before committing, if mild/asymptomatic and antibodies negative.

Levothyroxine (LT4) — Dosing & Titration

• Full replacement for healthy adults <60 without heart disease: ~1.6 µg/kg/day (use lean/ideal body weight in obesity).
• Elderly or CAD: start low (e.g., 12.5–25 µg/day) and titrate every 6–8 weeks.
• Subclinical: start 25–75 µg/day, titrate to target TSH.
• Central hypothyroidism: dose to keep free T4 in the upper half of normal (TSH is unreliable).
• Myxedema coma (ICU): IV LT4 ± liothyronine per specialty protocols; treat precipitating cause and give stress-dose steroids until AI is excluded.

Absorption Rules (don’t skip these)

• Take LT4 on an empty stomach with water, ideally 30–60 minutes before breakfast or ≥3–4 hours after last meal at bedtime.
• Separate by 4 hours from iron, calcium, magnesium, PPIs, bile-acid binders, sucralfate, and phosphate binders.
• Be consistent with brand/formulation; consider soft-gel/liquid if absorption issues or on PPIs.

Monitoring & Targets

• Re-check TSH (or free T4 in central) 6–8 weeks after any dose change.
• Once stable, check every 6–12 months or sooner if symptoms, pregnancy, weight change, or new meds.
• TSH goal commonly mid-normal (≈0.5–2.5 mIU/L) in nonpregnant adults; individualize by age/comorbidity.

Pregnancy & Preconception

• Increase LT4 dose by ~20–30% as soon as pregnancy is confirmed (often +2 extra doses/week), then check TSH/FT4 every 4 weeks in first half of pregnancy.
• Trimester-specific TSH targets (roughly): 1st 0.1–2.5, 2nd 0.2–3.0, 3rd 0.3–3.0 mIU/L (use local ranges).
• TPO-positive women with subclinical disease are often treated to lower miscarriage and progression risk—follow obstetric endocrine guidance.

Drugs That Disturb Thyroid Function

• Amiodarone (hypo or hyper), lithium (hypo), interferons, TKIs, immune checkpoint inhibitors (thyroiditis).
• Enzyme inducers (phenytoin, carbamazepine) may increase LT4 requirements.

Persistent Symptoms Despite “Normal” TSH

• Check adherence/absorption, interactions, sleep, depression, anemia, vitamin D/B12, OSA, and other endocrine causes.
• Routine T3 (liothyronine) add-on is not standard; consider only in carefully selected, well-counseled patients with specialist input.

When to Refer

• Pregnancy, central hypothyroidism, refractory symptoms, major absorption issues, cardiac disease with titration difficulty, or complex drug interactions.

Patient FAQs

“Can I drink coffee with my pill?” Coffee reduces absorption if taken together—separate by at least 60 minutes or take LT4 at bedtime on an empty stomach.

“Will I take thyroid hormone forever?” Usually for autoimmune hypothyroidism; exceptions include transient thyroiditis or reversible causes.

References & Notes

Practical approach: confirm pattern (overt, subclinical, central), treat when thresholds met, dose LT4 by weight/risks, enforce absorption rules, and titrate slowly with 6–8 week checks. Local protocols vary—follow institutional guidance. Educational only.