What is subclinical hypothyroidism?

Subclinical Hypothyroidism: Definition, Diagnosis, and Clinical Significance

Subclinical hypothyroidism is defined as an elevated thyroid stimulating hormone (TSH) level above the normal reference range (0.45-4.5 mIU/L) with normal free thyroxine (FT4) and triiodothyronine (T3) levels. 1

Epidemiology and Risk Factors

• Subclinical hypothyroidism affects approximately 4-8.5% of the general population without known thyroid disease, with higher prevalence in women, especially those over 60 years old, where it can reach up to 20% 1
• It is more common in women than men, in whites than blacks, and its prevalence increases with age 2
• Risk factors include age, female gender, family history of thyroid disease, previous hyperthyroidism, type 1 diabetes mellitus, previous head and neck radiation treatment, and presence of antithyroid antibodies 1

Diagnostic Criteria

• Elevated TSH (typically 4.5-10 mIU/L) with normal free T4 and T3 levels 2, 1
• Patients with symptoms of thyroid dysfunction or history of thyroid disease/treatment are excluded from this definition 2
• Other conditions that can cause temporary TSH elevation should be excluded, including:
  • Recent adjustments in levothyroxine dosage
  • Recovery from severe illness
  • Recovery from thyroiditis
  • Untreated adrenal insufficiency
  • Laboratory interference from heterophilic antibodies 1
• Medications like dopamine, glucocorticoids, and dobutamine can affect TSH values 1

Natural History and Progression

• Approximately 2-5% of patients with subclinical hypothyroidism progress to overt hypothyroidism each year 1, 3
• Higher risk of progression is associated with:
  • Higher baseline TSH levels (especially >10 mIU/L)
  • Presence of antithyroid antibodies 1, 4
• Many patients with mild TSH elevation (between 4.5-10 mIU/L) may not progress to overt disease 5

Potential Health Consequences

• Cardiac dysfunction: Subtle decreases in myocardial contractility may be detected by echocardiography 2
• Cardiovascular risk: Possible association with aortic atherosclerosis and myocardial infarction, though evidence is inconsistent 2, 1
• Lipid abnormalities: Elevation in total and LDL cholesterol levels 2, 1
• Neuropsychiatric symptoms: May experience cognitive and mood disturbances 2, 1
• Obstetric complications: Associated with poor obstetric outcomes and poor cognitive development in children 2
• Quality of life: Evidence for decreased quality of life is inconsistent 2

Clinical Significance and Monitoring

• Subclinical hypothyroidism is often discovered during routine screening 2
• Clinicians should be aware of subtle signs of thyroid dysfunction, particularly among high-risk individuals 2
• People at higher risk include the elderly, post-partum women, those with high levels of radiation exposure, and patients with Down syndrome 2
• Evaluating hypothyroid symptoms in patients with Down syndrome is challenging as some symptoms overlap with typical findings in Down syndrome 2

Common Pitfalls and Caveats

• TSH can be temporarily elevated during recovery from non-thyroidal illness, leading to false diagnosis 1
• Laboratory interference from heterophilic antibodies can cause falsely elevated TSH 1
• A single elevated TSH measurement should be confirmed with repeat testing before diagnosing subclinical hypothyroidism 5
• Not all patients with subclinical hypothyroidism will progress to overt disease; approximately 80% of patients with subclinical hypothyroidism have TSH levels less than 10 mIU/L 5
• Over-treatment with levothyroxine can lead to increased risk of atrial fibrillation and osteoporosis 3