What is subclinical hypothyroidism?

Subclinical Hypothyroidism: Definition, Diagnosis, and Management

Subclinical hypothyroidism is defined as an elevated thyroid stimulating hormone (TSH) level above the normal reference range with normal free thyroxine (FT4) and triiodothyronine (T3) levels, representing an early stage of thyroid dysfunction that requires careful evaluation and selective treatment based on risk factors and TSH levels.1

Definition and Prevalence

• Subclinical hypothyroidism is characterized by serum TSH concentration above the statistically defined upper limit of the reference range (typically 4.5 mIU/L) when serum free T4 concentration remains within its reference range.2
• It affects approximately 4-8.5% of the general population without known thyroid disease, with prevalence increasing with age.2
• Women are more commonly affected, with up to 20% of women over 60 years having subclinical hypothyroidism.1
• The prevalence in blacks is about one-third that in whites, and it's also lower in some iodine-deficient populations.2

Diagnostic Considerations

• The normal reference range for TSH is generally considered to be 0.45-4.5 mIU/L, though some experts suggest a lower upper limit of 2.5 mIU/L.1, 2
• Other causes of elevated TSH must be excluded, including:
  • Recent adjustments in levothyroxine dosage2
  • Recovery from severe illness or destructive thyroiditis2
  • Untreated primary adrenal insufficiency2
  • Recombinant human TSH injections2
  • Laboratory interference from heterophilic antibodies2

Risk Factors and Progression

• Risk factors include female gender, older age, family history of thyroid disease, previous hyperthyroidism, type 1 diabetes mellitus, and previous head and neck radiation treatment.1
• Approximately 2-5% of patients with subclinical hypothyroidism progress to overt hypothyroidism each year.3
• The rate of progression is proportional to baseline TSH concentration and is higher in individuals with antithyroid antibodies.2
• In about 5% of cases, TSH levels normalize spontaneously after one year of follow-up.2

Clinical Significance and Health Consequences

• Subclinical hypothyroidism is often categorized based on TSH levels:
  • Mild: TSH between 4.5-10 mIU/L4
  • Severe: TSH >10 mIU/L4
• Potential consequences include:
  • Cardiac dysfunction and possible increased risk of cardiovascular events2, 1
  • Elevated total and LDL cholesterol levels2, 1
  • Systemic hypothyroid symptoms and neuropsychiatric symptoms in some patients2, 1
  • Increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease, particularly in younger patients5
  • Cognitive impairment and altered mood in middle-aged patients5

Treatment Considerations

• Treatment is recommended for all patients with TSH >10 mIU/L and for pregnant women or those planning pregnancy regardless of TSH level.3, 5
• For patients with mild subclinical hypothyroidism (TSH 4.5-10 mIU/L), treatment decisions should consider:
  • Age (treatment may be more beneficial in younger patients <65-70 years)6
  • Presence of symptoms consistent with hypothyroidism5
  • Presence of thyroid antibodies (especially TPO antibodies)7
  • Presence of cardiovascular risk factors or established cardiovascular disease6
  • Presence of goiter7
  • Fertility concerns7
• Treatment may be less beneficial or potentially harmful in elderly patients (>65-70 years), with risk of iatrogenic thyrotoxicosis.5, 6

Monitoring

• In untreated patients with subclinical hypothyroidism, regular monitoring of thyroid function is recommended to detect progression to overt hypothyroidism.3
• In treated patients, TSH should be maintained in the target range of 0.5-2.0 mIU/L.3
• If TSH remains elevated despite apparently adequate levothyroxine dosage, consider poor compliance, malabsorption, or drug interactions.3

Treatment Pitfalls

• Over-replacement with levothyroxine is common and associated with increased risk of atrial fibrillation and osteoporosis.3
• Levothyroxine therapy should be initiated at lower doses in elderly patients, those with coronary artery disease, and those with long-standing severe hypothyroidism.3
• Treatment of subclinical hypothyroidism in patients >85 years with TSH up to 10 mIU/L should generally be avoided.3