What causes subclinical hypothyroidism?

Causes of Subclinical Hypothyroidism

Subclinical hypothyroidism is most commonly caused by autoimmune (Hashimoto's) thyroiditis, which accounts for up to 85% of cases in areas with adequate iodine intake. 1, 2

Definition and Prevalence

• Subclinical hypothyroidism is defined as an elevated thyroid-stimulating hormone (TSH) level with normal free thyroxine (T4) and triiodothyronine (T3) levels 1
• Affects approximately 4-8.5% of the adult population without known thyroid disease 3
• Prevalence increases with age, affecting up to 20% of women over 60 years 3
• More common in women than men, with men over 65 years approaching similar prevalence in some studies 3
• Approximately 75% of patients with elevated TSH have values lower than 10 mIU/L 3

Primary Causes

• Autoimmune thyroiditis (Hashimoto's): The most common cause in iodine-sufficient regions 2
• Previous hyperthyroidism: History of treated Graves' disease or other hyperthyroid conditions 3
• Type 1 diabetes mellitus: Increases risk due to autoimmune association 3
• Family history of thyroid disease: Genetic predisposition plays a significant role 3
• Previous head and neck cancer treated with radiation: Radiation exposure damages thyroid tissue 3
• Medications: Certain drugs can cause thyroid dysfunction:
  • Amiodarone (iodine-containing antiarrhythmic) 3
  • Immune checkpoint inhibitors 2
  • Other thyroid-affecting medications 2

Risk Factors for Progression

• Approximately 2-5% of patients with subclinical hypothyroidism progress to overt hypothyroidism annually 4
• Progression risk is proportional to baseline TSH concentration 3
• Presence of thyroid peroxidase (TPO) antibodies significantly increases progression risk (4.3% vs 2.6% per year in antibody-negative individuals) 5
• Higher initial TSH levels (>10 mIU/L) carry greater risk of progression 5

Important Considerations

• 30-60% of high TSH levels normalize spontaneously on repeat testing, highlighting the importance of confirming the diagnosis before initiating treatment 5, 6
• TSH levels naturally rise with age, which may lead to overdiagnosis in elderly populations 1
• Prevalence of subclinical hypothyroidism is one-third lower in Black individuals compared to whites 3
• Lower prevalence is observed in populations with iodine deficiency 3

Clinical Implications

• Untreated subclinical hypothyroidism may be associated with:
  • Cardiac dysfunction and adverse cardiac events 3
  • Elevated total and LDL cholesterol 3
  • Systemic and neuropsychiatric symptoms in some patients 3
  • Progression to overt hypothyroidism 3
  • Potential adverse pregnancy outcomes in women planning pregnancy 5

Treatment Considerations

• Treatment is generally recommended for:
  • Patients with TSH >10 mIU/L regardless of symptoms 5, 4
  • Pregnant women or those planning pregnancy 4
  • Symptomatic patients with TSH between 4.5-10 mIU/L 4, 1
  • Patients with goiter or positive TPO antibodies 4
• Treatment may be unnecessary for:
  • Asymptomatic patients with TSH <10 mIU/L 7, 1
  • Elderly patients (>85 years) with mild TSH elevation 4

Monitoring Approach

• Repeat thyroid function tests in 3-6 months for untreated patients 5
• Annual monitoring for those with stable subclinical hypothyroidism 5