Management of Hypothyroidism

Classification (for treatment purposes)

1. Drug of Choice: Levothyroxine (L-T4)

• Available tablet strengths: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, and 300 mcg
• Average replacement dose: 1.6 mcg/kg/day (adults)
• Effectiveness: Improvement in symptoms often takes weeks; TSH should be measured 6-8 weeks after initiation or dose change

• Goldman-Cecil Medicine, TREATMENT - Overt Hypothyroidism
• Textbook of Family Medicine 9e, p. 1022
• Lippincott Illustrated Reviews: Pharmacology, Clinical Application 23.2

2. Overt Hypothyroidism

• Start at the weight-based dose (1.6 mcg/kg) in otherwise healthy adults
• In elderly patients or those with coronary artery disease, start at a low dose (25-50 mcg/day) and titrate slowly to avoid precipitating angina or arrhythmia
• Aging decreases the L-thyroxine requirement (reduced tissue demand)
• Monitoring goal: Normalize serum TSH to the laboratory reference range
• Recheck TSH no earlier than 5-6 weeks after starting or changing the dose (time to steady state)
• Once stable, TSH can be rechecked annually

3. Subclinical Hypothyroidism

• Goldman-Cecil Medicine, Subclinical Hypothyroidism section

4. Administration - Critical Points

• Stick to the same brand/formulation where possible - bioavailability varies between formulations
• If formulation is switched, recheck TSH at 6 weeks

5. Secondary (Central) Hypothyroidism

• Caused by pituitary failure (TSH low/normal with low FT4)
• Cannot use TSH to monitor - use free T4 instead (target mid-normal FT4 range)
• Treat with levothyroxine at the same weight-based dose
• Must rule out and treat concurrent adrenal insufficiency first before starting T4 (giving T4 without steroids can precipitate an adrenal crisis)

6. Myxedema Coma (Emergency)

1. IV levothyroxine loading dose: 200-300 mcg IV, then 1.6 mcg/kg IV every 24 hours
2. IV T3 (liothyronine): 5-10 mcg every 8-12 hours - added because T4 to T3 conversion may be impaired; continue until clinical improvement
3. Hydrocortisone 100 mg IV every 6 hours - mandatory before or alongside T4, to cover possible concurrent adrenal insufficiency
4. Supportive care: Passive rewarming only for hypothermia (active rewarming causes vasodilation and hypotension), ventilatory support, fluids, treat precipitating cause

• Goldman-Cecil Medicine, Myxedema Coma section

7. Hypothyroidism in Pregnancy

• Required dose may increase by 25-50% depending on residual thyroid reserve
• Women with no thyroid reserve (post-thyroidectomy): may need up to 33-50% dose increase
• Women with Hashimoto thyroiditis (partial reserve): 25% increase often sufficient
• Increase dose as soon as pregnancy is confirmed - undetected hypothyroidism in early pregnancy is linked to impaired fetal neurological development
• Practical approach: increase from 7 tablets/week to 9 tablets/week (add one tablet on two days)
• TSH target during gestation: <2.5 mIU/L
• Recheck TSH every 4 weeks until mid-gestation
• Goldman-Cecil Medicine, Pregnancy section; Creasy & Resnik's Maternal-Fetal Medicine

8. Hashimoto Thyroiditis (Most Common Cause in Developed Countries)

• Autoimmune destruction of the thyroid gland; TPO antibodies are the primary marker
• Once hypothyroidism is confirmed (elevated TSH, low/normal FT4, positive TPO Ab), start levothyroxine at 1.6 mcg/kg/day
• Monitor TSH annually once stable
• Titer of TPO/anti-Tg antibodies predicts progression of thyroid failure

9. Monitoring Summary

Clinical Image: Levothyroxine Treatment Effect

Recent Literature

• Levothyroxine (T4) monotherapy is the standard of care
• Dose: 1.6 mcg/kg/day; start low in elderly/cardiac patients
• Take on an empty stomach; separate from interfering medications by hours
• Monitor TSH at 6 weeks post-change; annually when stable
• Pregnancy requires prompt dose increase and TSH target <2.5 mIU/L
• Myxedema coma needs IV T4 + IV T3 + hydrocortisone + supportive care

Clinical Guidelines for Screening Hypothyroidism in Pregnancy

Key Guideline Sources

1. Universal vs. Targeted Screening - The Core Debate

• Universal screening protocols identify more thyroid dysfunction, but they primarily identify subclinical hypothyroidism (SCH), and LT4 treatment of SCH has not clearly demonstrated improved pregnancy or offspring outcomes in large RCTs.
• Both ATA and ACOG recommend against universal thyroid screening in pregnancy based on lack of demonstrated benefit in RCT data.
• However, targeted screening may miss 18%-89% of pregnant persons with thyroid dysfunction - a widely acknowledged limitation.
• Some European societies and experts argue that thyroid function screening is a cost-effective strategy meeting WHO criteria for screening programs; a universal screen-and-treat program has been shown to decrease adverse perinatal outcomes in low-risk populations (Negro et al.).
• Creasy & Resnik's Maternal-Fetal Medicine, Screening section, p. 1502
• Harrison's Principles of Internal Medicine 22E, 2025

2. Recommended Approach: Verbal Risk Screening + Targeted TSH Testing

1. Verbally screen all reproductive-age persons planning pregnancy or in early gestation for high-risk factors
2. If risk factors present → targeted TSH testing

3. High-Risk Factors Warranting TSH Screening (Box 61.1)

• Women with type 1 diabetes (33% prevalence of thyroid dysfunction; 3-fold increased risk of postpartum thyroid dysfunction)
• Women taking lithium therapy (35% prevalence)
• Women with infertility (12% prevalence)
• Women with depression (10-12% prevalence)
• Women ≥50 years
• Berek & Novak's Gynecology, Recommendations for Testing and Treatment, p. 1982

4. Screening Algorithm

5. Trimester-Specific TSH Reference Ranges

• TSH is lower than normal in the first trimester due to hCG cross-reactivity with the TSH receptor
• Total T4 and T3 are ~1.5x higher throughout pregnancy (estrogen increases TBG)
• Free T4 progressively decreases into the third trimester, often falling below the nonpregnant lower reference cutoff
• Harrison's Principles of Internal Medicine 22E, Thyroid Function in Pregnancy

6. Diagnosis Subtypes and Their Criteria in Pregnancy

7. Treatment Thresholds Based on Screening Results

• Berek & Novak's Gynecology, p. 1982

8. Monitoring Frequency After Screening

• Euthyroid women with TPO antibodies: TSH each trimester
• Women started on LT4 during pregnancy: recheck thyroid function within 30-40 days, then every 4-6 weeks
• Known hypothyroid women on LT4 before pregnancy: increase dose by 25-50% at conception (add two extra tablets per week); recheck TSH at 3 weeks; monitor every 4 weeks until mid-gestation
• TSH target throughout gestation: <2.5 mIU/L
• After delivery: reduce LT4 dose back to pre-pregnancy level

9. Preconception Counselling

• Women with known hypothyroidism should have TSH <2.5 mIU/L before conception
• Dose escalation of 30-60% is anticipated in the first trimester for those with no residual thyroid reserve (e.g., post-thyroidectomy)
• Undetected hypothyroidism in early pregnancy is linked to impaired fetal neurological development - hence the urgency of increasing LT4 as soon as pregnancy is confirmed

Summary: Who to Screen and How

All pregnant women / women planning pregnancy
        ↓
Verbal risk factor assessment
        ↓
1+ risk factor present?
   YES → Serum TSH (first prenatal visit / preconception)
    NO → No routine screening (ATA/ACOG)
           (European societies may argue for universal screening)
        ↓
TSH elevated (above trimester-specific upper limit)?
   YES → Check FT4 + TPO antibodies
       → Classify (overt / subclinical / isolated / autoimmunity)
       → Treat or monitor per thresholds above
    NO → Reassure; recheck if new risk factors develop