What is hypothyroidism?

Hypothyroidism: Definition, Diagnosis, and Management

Hypothyroidism is a condition characterized by underactive thyroid function resulting in deficient production of thyroid hormones, primarily affecting metabolism and multiple body systems, with symptoms ranging from mild to life-threatening if left untreated. 1, 2

Definition and Etiology

Hypothyroidism is classified as:

• Primary hypothyroidism (95% of cases): Results from thyroid gland dysfunction

  • Most common causes:
    • Hashimoto's disease (chronic autoimmune thyroiditis) - most frequent cause in industrialized nations 1
    • Iodine deficiency - most common cause worldwide 1
    • Other causes: subacute thyroiditis, radioactive iodine therapy, thyroidectomy 1

• Secondary/Central hypothyroidism (5% of cases): Results from hypothalamic or pituitary dysfunction 3

• Subclinical hypothyroidism: Elevated TSH with normal free T4 levels 4

Epidemiology

• Affects approximately 5% of the general population with another 5% undiagnosed 5
• Higher prevalence among females and older individuals 6
• Clinical hypothyroidism affects 1 in 300 people in the United States 6

Clinical Presentation

Common Symptoms

• Fatigue and lethargy
• Cold intolerance
• Weight gain
• Dry skin (xeroderma)
• Constipation
• Voice changes
• Hair loss
• Muscle cramps 1, 2

Advanced Symptoms

• Intellectual slowness
• Insomnia
• Voice changes
• Progressive symptoms can lead to myxedema and myxedema coma (medical emergency) 1, 7

Special Populations

• Pregnant women: Untreated maternal hypothyroidism increases risk of preeclampsia and low birth weight 1
• Infants: Untreated congenital hypothyroidism can lead to cretinism (growth failure, mental retardation, neuropsychologic defects) 1
• Elderly: May present with more subtle or atypical symptoms 4

Diagnosis

Laboratory Testing

1. Initial screening: TSH testing using monoclonal antibodies 1
2. Confirmatory testing: TSH and Free T4 or Free Thyroxine Index (FTI) 1, 4

Diagnostic Criteria

• Overt hypothyroidism: Elevated TSH with low free T4 4, 6
• Subclinical hypothyroidism: Elevated TSH with normal free T4 4, 3

Treatment

Levothyroxine (T4) Replacement

• Standard treatment: Oral levothyroxine monotherapy 4, 6
• Initial dosing:
  • General population: 1.5-1.8 mcg/kg/day 6
  • Patients >60 years or with ischemic heart disease: Lower starting dose (12.5-50 mcg/day) 6
  • Pregnant women: Increase weekly dosage by 30% (one extra dose twice weekly) 6

Monitoring

• Check thyroid function tests (TSH, free T4) every 4-6 weeks during dose adjustments 4
• Once stable, monitor every 3-6 months initially, then every 6-12 months 4
• Target TSH in normal range (0.45-4.12 mU/L), with mid-normal range (1.0-2.5 mIU/L) for reproductive-age women 4

Special Considerations

• Adding T3 (triiodothyronine) is not recommended, even in patients with persistent symptoms and normal TSH levels 6
• Subclinical hypothyroidism treatment is recommended when:
  • TSH >10 mIU/L 6, 3
  • Patient is pregnant or planning pregnancy 3
  • Patient has symptoms, infertility, goiter, or positive anti-TPO antibodies 3
  • Treatment should be avoided in patients >85 years with TSH ≤10 mIU/L 3

Complications of Untreated Hypothyroidism

• Cardiovascular disease and increased mortality 5
• In pregnancy: preeclampsia, preterm delivery, heart failure, miscarriage 1
• In infants: congenital cretinism, growth failure, mental retardation 1
• Severe cases: myxedema coma (medical emergency) 1, 2

Common Pitfalls in Management

• Undertreatment: Can lead to persistent symptoms and complications
• Overtreatment: Common in clinical practice; increases risk of atrial fibrillation and osteoporosis 3
• Medication interactions: Various medications can interfere with levothyroxine absorption
• Poor compliance: Consider in patients with persistently elevated TSH despite adequate replacement dose 3
• Failure to recognize central hypothyroidism: Evaluate other pituitary hormones, especially hypothalamic-pituitary-adrenal axis, as hypocortisolism needs correction before starting thyroid hormone replacement 3

Early recognition and appropriate treatment of hypothyroidism is essential to prevent complications and improve quality of life for affected individuals.