What is considered subclinical hyperthyroidism?

Definition of Subclinical Hyperthyroidism

Subclinical hyperthyroidism is defined as a serum TSH concentration below 0.45 mIU/L (the lower limit of the normal reference range) with normal free T4 and T3 concentrations within their reference ranges. 1

Biochemical Criteria

• TSH must be below the lower limit of normal (typically <0.45 mIU/L) while free T4 and T3 remain within normal reference ranges 1
• The normal TSH reference range is defined as 0.45 to 4.5 mIU/L 1

Severity Classification

Subclinical hyperthyroidism is further stratified into two grades based on the degree of TSH suppression:

• Grade I (Mild): TSH 0.1-0.45 mIU/L with normal free T4 and T3 2, 3
• Grade II (Severe): TSH <0.1 mIU/L with normal free T4 and T3 2, 3

This classification has important clinical implications, as patients with TSH <0.1 mIU/L have a 3-fold increased risk of atrial fibrillation over 10 years and up to 3-fold increased cardiovascular mortality compared to those with mild suppression 2

Essential Exclusion Criteria

Before confirming the diagnosis, other causes of low TSH with normal thyroid hormones must be excluded 1:

• Delayed pituitary recovery following treatment for hyperthyroidism 1
• Normal pregnancy (physiologic TSH suppression) 1
• Nonthyroidal illness (euthyroid sick syndrome) - though undetectable TSH (<0.01 mIU/L) is rare unless glucocorticoids or dopamine are being administered 1
• Medications: dopamine, glucocorticoids (especially high doses), and possibly dobutamine 1
• Pituitary or hypothalamic failure - though in these cases FT4 is typically also subnormal, not normal 1

Key Diagnostic Distinction

In subclinical hyperthyroidism, when FT4 is normal, it is typically in the high-normal range, which contrasts with nonthyroidal illness where FT4 is usually in the low-normal range 1. This distinction helps differentiate true subclinical hyperthyroidism from other causes of TSH suppression.

Confirmation Required

Because TSH can be transiently suppressed, the diagnosis should be confirmed by repeating TSH, free T4, and free T3 measurements 2, 4:

• If TSH is 0.1-0.45 mIU/L: repeat in 3 months 2
• If TSH is <0.1 mIU/L: repeat in 4 weeks 2
• If cardiac problems are present: repeat within 2 weeks 2