Is the patient experiencing subclinical hyperthyroidism?

Diagnosing Subclinical Hyperthyroidism

Your patient has subclinical hyperthyroidism if their serum TSH is below 0.45 mIU/L (or below your laboratory's lower reference limit) with normal free T4 and T3 levels. 1

Biochemical Diagnostic Criteria

The diagnosis requires all three of the following laboratory findings 2, 1:

• TSH below the lower limit of normal (typically <0.45 mIU/L, though some labs use <0.4 mIU/L) 2, 1
• Normal free T4 (within reference range, typically in the high-normal range) 1
• Normal T3 or free T3 (within reference range) 2, 1

Severity Classification

Once diagnosed, subclinical hyperthyroidism should be classified into two grades based on TSH level 3, 1:

• Grade I (Mild): TSH 0.1-0.45 mIU/L 3
• Grade II (Severe): TSH <0.1 mIU/L 3

This distinction is clinically critical because 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 3, 1.

Essential Exclusion Criteria Before Confirming Diagnosis

You must rule out other causes of low TSH with normal thyroid hormones before confirming subclinical hyperthyroidism 1, 4:

Medications that suppress TSH 2, 3, 1:

• Dopamine
• Glucocorticoids
• Dobutamine
• Excessive levothyroxine (iatrogenic/factitial hyperthyroidism) 4

Physiologic and pathologic conditions 1, 4:

• Nonthyroidal illness (euthyroid sick syndrome) - key distinguishing feature: FT4 is typically in the low-normal range in nonthyroidal illness versus high-normal range in subclinical hyperthyroidism 1
• Normal pregnancy (first trimester) 4
• Delayed pituitary recovery 1
• Central hypothyroidism (pituitary or hypothalamic failure) 2, 1

Confirmation Testing Protocol

A single abnormal TSH is insufficient for diagnosis - confirmation requires repeat testing 2, 3:

If initial TSH is 0.1-0.45 mIU/L 2, 3:

• Repeat TSH, free T4, and free T3 (or total T3) within 3 months for stable patients 2, 3
• Repeat within 2 weeks if patient has atrial fibrillation, cardiac disease, or other serious medical conditions 2, 3

If initial TSH is <0.1 mIU/L 2, 3:

• Repeat TSH, free T4, and free T3 (or total T3) within 4 weeks 2, 3
• Consider earlier testing if signs of cardiac disease, atrial fibrillation, or other arrhythmias are present 2, 3

Key Diagnostic Pitfall

Transient TSH suppression is common - many patients will have spontaneous normalization of TSH over time 3. This is why confirmation testing at appropriate intervals is mandatory before labeling a patient with subclinical hyperthyroidism and considering treatment 2, 4.

Additional Evaluation After Confirmation

Once subclinical hyperthyroidism is confirmed, determine the etiology with thyroid scintigraphy with radioactive iodine uptake to distinguish between 3:

• Graves' disease
• Toxic nodular goiter
• Destructive thyroiditis

Screen for complications with 3:

• ECG to detect atrial fibrillation or other arrhythmias
• Cardiac function evaluation, especially in patients with hypertension or known cardiac disease

Special Precaution

Patients with nodular goiter and low TSH may develop overt hyperthyroidism when exposed to excess iodine (such as radiographic contrast agents), requiring special consideration 2, 3.