Hypothyroidism

Definition

Epidemiology

• 1-2% of women in the US are affected by overt hypothyroidism
• Subclinical hypothyroidism affects 4-10% of the general population
• Subclinical hypothyroidism in pregnancy: 5-8%
• Higher incidence in women (attributed to higher prevalence of autoimmune disease)
• Older age groups carry higher risk
• No specific racial/ethnic predilection

Classification & Causes

Primary Hypothyroidism (intrinsic gland failure - ~99% of cases)

Secondary (Central) Hypothyroidism (~1%)

• Pituitary failure (low or absent TSH with low FT4)
• Hypothalamic dysfunction (TRH deficiency)

Transient Hypothyroidism

• Silent/postpartum thyroiditis
• Subacute thyroiditis (3-6 months of hypothyroidism, usually self-limiting)
• After withdrawal of supraphysiologic T4

Hashimoto's Thyroiditis (Most Common Cause in Developed World)

• Autoimmune - anti-TPO antibodies (primary) and anti-thyroglobulin antibodies attack thyroidal stroma causing progressive fibrosis
• Female:male ratio 10-14:1; usually diagnosed in the fifth decade
• Diagnosis: elevated TSH + low/low-normal FT4 + positive TPO antibodies
• Progressive - as fibrosis advances, less T4 is produced and replacement becomes necessary

Clinical Features

Diagnosis

Treatment

Levothyroxine (LT4) - Treatment of Choice

• Adults <60 y/o without cardiac disease: start 50-100 µg/day
• Full replacement dose: 1.6 µg/kg/day (typically 100-150 µg/day)
• Post-Graves' treatment: lower doses usually sufficient (75-125 µg/day) due to residual autonomous function
• Take 30-60 minutes before breakfast (or at bedtime) to optimize absorption

• Recheck TSH 6-8 weeks after starting or changing dose
• Target: TSH in the lower half of the normal reference range
• Adjust in 12.5-25 µg increments
• Once stable: annual TSH checks

• Suppressed TSH (from overtreatment) → risk of atrial fibrillation and reduced bone density
• Malabsorption states (celiac disease, H. pylori gastritis, small bowel surgery) increase LT4 requirements
• Drug interactions: bile acid sequestrants, ferrous sulfate, calcium carbonate, PPIs reduce absorption
• Oral estrogen and SERMs increase LT4 requirements

• Treat if TSH >10 mIU/L
• Consider treatment if TSH 5.1-10 mIU/L with symptoms
• Typical dose: 50-75 µg/day

T4 + T3 Combination Therapy

• ~10-15% of patients have persistent symptoms despite normal TSH on LT4 monotherapy
• Combination LT4 + liothyronine (T3) has been investigated - not proven superior in prospective studies
• The American Thyroid Association does not recommend combination therapy for routine treatment
• Desiccated thyroid extract (thyroid USP) is not recommended due to nonphysiologic T3:T4 ratio
• T3 (liothyronine) monotherapy is not suitable for long-term replacement (short half-life requires 3-4 doses/day, causes T3 fluctuations)

Myxedema Coma

1. Airway - protect airway, ventilatory support; monitor for alkalosis
2. Fluids - 0.9% NS or D5/NS if hypoglycemic; avoid hypotonic fluids
3. Thyroid hormone replacement:
   • IV T4 loading dose: 200-400 µg IV (lower for small patients, CAD, arrhythmia history)
   • Subsequent daily replacement: 1.6 µg/kg/day PO (75% of this dose if IV)
4. Hydrocortisone 100 mg IV q8h (concurrent adrenal insufficiency must be covered)
5. Hyponatremia - fluid restriction; if Na <120 mEq/L, consider 3% saline 50-100 mL boluses
6. Passive rewarming - regular blankets; heating blankets require IV preloading and BP monitoring
7. Treat precipitating illness (especially infections)
8. ICU admission required

Special Populations

Pregnancy

• All pregnant patients with elevated TSH should be treated with levothyroxine
• Hypothyroidism in pregnancy is associated with adverse fetal neurodevelopmental outcomes
• LT4 requirements typically increase ~30% during pregnancy
• TSH target: lower half of trimester-specific reference range

Congenital Hypothyroidism

• 1 in 2000-4000 newborns; neonatal screening is standard in industrialized countries
• Permanent in majority; may be transient if maternal TSH-R blocking antibodies present
• Causes: thyroid dysgenesis (65%), dyshormonogenesis (30%), TSH-R antibody mediated (5%)
• Early treatment is critical to prevent cretinism (intellectual disability, growth failure)

Elderly

• Higher background risk for hypothyroidism
• Start LT4 at lower doses (25-50 µg/day); titrate more slowly due to cardiac risk

Key Takeaways

• Most common cause worldwide: iodine deficiency; developed world: Hashimoto's thyroiditis
• Best initial test: serum TSH
• Treatment of choice: levothyroxine (LT4) monotherapy, 1.6 µg/kg/day
• Monitor: TSH at 6-8 weeks post-initiation, then annually once stable
• Overtreatment risk: atrial fibrillation and osteoporosis from TSH suppression
• Myxedema coma: medical emergency requiring ICU care, IV T4, and hydrocortisone