What can cause elevated Thyroid-Stimulating Hormone (TSH) levels?

Causes of Elevated TSH Levels

Hashimoto's thyroiditis is the leading cause of elevated TSH in iodine-sufficient areas, characterized by lymphocyte infiltration of the thyroid gland and elevated antibodies against thyroid peroxidase and thyroglobulin. 1

Primary Causes of Elevated TSH

• Subclinical hypothyroidism: Defined as an elevated TSH (typically above 4.5 mIU/L) with normal free T4 levels, representing early thyroid dysfunction 2
• Overt hypothyroidism: Characterized by elevated TSH with low free T4 levels, requiring prompt medical attention 1
• Hashimoto's thyroiditis: The most common cause of primary hypothyroidism in iodine-sufficient regions 1
• Iodine deficiency: A significant cause of thyroid dysfunction globally, particularly in areas with low dietary iodine intake 1
• Previous treatment for hyperthyroidism: Radioactive iodine therapy, surgery, or antithyroid medications can lead to hypothyroidism 1
• Inadequate thyroid hormone replacement: Affecting approximately 20% of patients taking thyroid medications 1

Transient and Secondary Causes

• Recovery from severe illness: TSH can transiently increase during recovery from acute nonthyroidal illness 2, 3
• Recovery from destructive thyroiditis: Including postviral subacute thyroiditis and postpartum thyroiditis 2
• Untreated primary adrenal insufficiency: Can cause elevated TSH levels that normalize with glucocorticoid replacement 2
• Recent adjustments in levothyroxine dosage: Particularly in poorly compliant patients before reaching steady state 2
• Hospitalization: Approximately 4.2% of elderly hospitalized patients may experience transient TSH elevations during acute illness 3

Laboratory and Technical Considerations

• Heterophilic antibodies: Can cause falsely elevated TSH in some assays 2
• Bioinactive TSH molecules: In rare cases of central hypothyroidism (usually hypothalamic), TSH may be mildly elevated but biologically inactive 2, 4
• Recombinant human TSH injections: Used in thyroid cancer management can cause temporary TSH elevation 2
• Laboratory reference ranges: The normal TSH range is typically defined as 0.45 to 4.5 mIU/L, though some experts suggest 2.5 mIU/L as a more appropriate upper limit 2, 1

Demographic and Risk Factors

• Age: The prevalence of subclinical hypothyroidism increases with age, affecting up to 20% of women over 60 years 1
• Sex: Women are more likely to develop hypothyroidism than men 1
• Ethnicity: The prevalence of hypothyroidism is lower in Black individuals, approximately one-third the rate seen in whites 1
• Autoimmune conditions: Type 1 diabetes mellitus is associated with increased risk of autoimmune thyroid disease 1
• Family history: Genetic predisposition increases the risk of developing thyroid disorders 1
• Radiation exposure: Previous head and neck cancer treated with radiation can damage thyroid tissue 1

Clinical Implications and Monitoring

• Progression risk: The risk of progression from subclinical to overt hypothyroidism is estimated at 2-5% annually, with higher risk in patients with higher baseline TSH and positive antithyroid antibodies 1
• Cardiovascular effects: Untreated hypothyroidism may lead to cardiac dysfunction and adverse cardiac endpoints 1
• Lipid abnormalities: Elevation in total and LDL cholesterol can occur in patients with hypothyroidism 1
• Pregnancy considerations: Hypothyroidism may be associated with adverse pregnancy outcomes, requiring regular monitoring 1, 5

Special Considerations and Pitfalls

• Transient elevations: Approximately 5% of elevated TSH levels return to normal after 1 year without treatment 1
• Secondary hyperthyroidism: In rare cases, elevated TSH with elevated peripheral thyroid hormones may indicate thyroid hormone resistance or TSH-secreting pituitary adenoma 6
• Overdiagnosis risk: Widespread screening can result in harms due to labeling, false-positive results, and overtreatment 2
• Elderly patients: Screening for thyroid disorders among elderly patients with acute illnesses is not warranted as TSH elevations may be transient 3

Remember that TSH levels should be interpreted in the context of clinical presentation and other thyroid function tests, as isolated TSH elevations may be transient or due to laboratory factors rather than true thyroid dysfunction 2, 3.