What causes hypothyroidism?

Causes of Hypothyroidism

The most common cause of hypothyroidism in industrialized nations is Hashimoto's thyroiditis (chronic autoimmune thyroiditis), while worldwide, iodine deficiency remains the leading cause. 1, 2

Primary Causes of Hypothyroidism

Autoimmune Causes

• Hashimoto's thyroiditis: Accounts for approximately 90% of adult hypothyroidism in iodine-sufficient areas 3
  • Characterized by lymphocytic infiltration and gradual thyroid destruction
  • More common in women aged 20-60 years 3
  • Involves autoimmune destruction through various mechanisms:
    • Antibody-dependent cytotoxicity
    • T lymphocyte cytotoxicity
    • Thyroid stimulation blocking antibodies (TSBAb)

Iodine-Related Causes

• Iodine deficiency: Most common cause worldwide 1, 2
• Iodine excess: Paradoxically can also cause hypothyroidism 1

Iatrogenic Causes

• Post-surgical hypothyroidism: Following thyroidectomy 1, 2
• Radiation-induced:
  • Radioactive iodine therapy for hyperthyroidism 1, 2
  • External beam radiation to head and neck 1

Inflammatory Causes

• Subacute thyroiditis: Can lead to transient or permanent hypothyroidism 2
• Silent (painless) thyroiditis: Often in postpartum period 3

Medication-Induced

• Amiodarone: Contains high iodine content that can disrupt thyroid function 1
• Lithium: Inhibits thyroid hormone release 1
• Immune checkpoint inhibitors: Newer cause of autoimmune thyroiditis 4

Congenital Causes

• Thyroid dysgenesis or agenesis: Absent or underdeveloped thyroid gland 5
• Congenital enzymatic defects: Affecting thyroid hormone synthesis 5

Risk Factors

• Female sex: Women are more commonly affected than men 1
• Advancing age: Risk increases with age 1
• White race: Higher prevalence in white populations 1
• Family history of thyroid disease: Genetic predisposition 1
• Other autoimmune conditions: Type 1 diabetes, Down syndrome 1
• Previous hyperthyroidism: Often due to ablation therapy 1

Diagnostic Approach

The diagnosis of hypothyroidism is primarily biochemical:

• Elevated TSH with low free T4 indicates overt primary hypothyroidism 2
• Elevated TSH with normal free T4 indicates subclinical hypothyroidism 2

Imaging studies have no role in determining the cause of hypothyroidism, as noted by the American College of Radiology 1. All causes of hypothyroidism will have decreased radioiodine uptake, making imaging unhelpful for differential diagnosis.

Treatment Considerations

Levothyroxine (T4) is the standard treatment for hypothyroidism regardless of cause 5, 6:

• Starting dose typically 1.6 μg/kg/day in adults with overt hypothyroidism 6
• Goal is to normalize TSH levels (typically 0.4-4.5 mIU/L) 2
• Monitor TSH and free T4 levels 6-8 weeks after starting therapy or changing doses 2

Important Clinical Pitfalls

• Missed diagnosis: Symptoms of hypothyroidism are non-specific and can overlap with other conditions 7, 4
• Overtreatment: Excessive thyroid hormone replacement can lead to iatrogenic hyperthyroidism with risks of cardiac arrhythmias and bone mineral density loss 2
• Unrecognized adrenal insufficiency: Patients with adrenal insufficiency require corticosteroid treatment before starting thyroid hormone replacement to prevent adrenal crisis 2
• Transient hypothyroidism: Common in postpartum period and post-thyrotoxic phase of silent thyroiditis; may resolve spontaneously 3

Understanding the specific cause of hypothyroidism is important for prognosis and management, though the mainstay of treatment remains thyroid hormone replacement regardless of etiology.