What are the causes of a low Thyroid-Stimulating Hormone (TSH) level?

Causes of Low TSH Levels

A low Thyroid-Stimulating Hormone (TSH) level (below 0.45 mIU/L) is most commonly caused by hyperthyroidism, but can also result from non-thyroidal illnesses, certain medications, laboratory errors, and other conditions. 1

Primary Causes of Low TSH

1. Thyroid Disorders

• Overt Hyperthyroidism: Characterized by low TSH with elevated free T4 and/or T3 levels 2
• Subclinical Hyperthyroidism: Low TSH (0.1-0.4 mIU/L) with normal free T4 and T3 levels, affecting approximately 2% of the population 1
• Graves' Disease: The most common cause of persistent hyperthyroidism, characterized by:
  • Low or undetectable TSH
  • Elevated T4/T3
  • Increased radioactive iodine uptake
  • Positive anti-TSH receptor antibodies 1, 3
• Thyroiditis: Causes transient hyperthyroidism with decreased radioactive iodine uptake and negative anti-TSH receptor antibodies 1

2. Medication-Induced Low TSH

• Dopamine: Directly suppresses TSH secretion 1
• Glucocorticoids: Can decrease TSH levels, particularly at higher doses 1
• Dobutamine: May decrease TSH levels 1
• Excessive Levothyroxine: Overtreatment with thyroid hormone replacement can cause TSH suppression 1

3. Non-Thyroidal Conditions

• Pregnancy: Normal pregnancy may be associated with lower TSH values 1
• Non-thyroidal illnesses: Severe systemic illnesses can temporarily suppress TSH 1
• Gestational Hyperthyroidism: Human choriogonadotropin (hCG) can cross-react with TSH receptors, causing transient hyperthyroidism during pregnancy 4
• Trophoblastic Tumors: Rare tumors secreting hCG can cause hyperthyroidism through TSH receptor stimulation 4

4. Laboratory and Technical Factors

• Laboratory Errors: Different assay methods can yield different results, with some methods potentially showing falsely undetectable TSH levels 5
• Heterophile Antibodies: Can interfere with immunoassays, causing falsely low TSH readings

Clinical Approach to Low TSH

When encountering a low TSH level, consider:

1. Confirm the result: Repeat testing is often necessary before making a diagnosis or treatment decision, especially for mildly suppressed TSH (0.1-0.4 mIU/L) 2, 6

2. Measure free T4 and possibly free T3: Essential to distinguish between subclinical and overt hyperthyroidism 1

3. Review medications: Assess if the patient is taking medications known to suppress TSH 1

4. Consider clinical context: Pregnancy, severe illness, or recent hospitalization can affect TSH levels 1

5. Consider alternative testing methods: If results are inconsistent with clinical presentation, consider using a different assay method 5

Important Caveats

• A single low TSH measurement should not immediately lead to a diagnosis of hyperthyroidism without confirmation and clinical correlation 6

• TSH levels can fluctuate, and transient abnormalities may resolve without intervention 6

• The degree of TSH suppression can provide diagnostic clues:

  • Mildly suppressed (0.1-0.4 mIU/L): Often subclinical or non-thyroidal causes
  • Severely suppressed (<0.1 mIU/L): More likely to represent true hyperthyroidism 2

• Genetic factors can influence TSH receptor function:

  • Activating mutations can cause non-autoimmune hyperthyroidism 4
  • Inactivating mutations can cause TSH resistance 4

• Laboratory methods matter: If clinical presentation doesn't match a very low or undetectable TSH result, consider measuring TSH using an alternative method 5