Evaluation of Hyperthyroidism with Subcentimeter Thyroid Nodule
Yes, measure both TSH and free T4 (and free T3 if TSH is suppressed) when evaluating hyperthyroidism with a subcentimeter thyroid nodule, as autonomously functioning thyroid nodules (AFTNs) can cause hyperthyroidism regardless of size, and there is no volume threshold below which hyperthyroidism can be excluded. 1
Initial Thyroid Function Testing
Measure TSH as the primary screening test for suspected hyperthyroidism, as it has sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 2
If TSH is suppressed (<0.1-0.4 mIU/L), measure both free T4 and free T3 to confirm hyperthyroidism and characterize the pattern of hormone elevation 3
Free T4 and free T3 measurements distinguish between overt hyperthyroidism (elevated thyroid hormones) and subclinical hyperthyroidism (normal thyroid hormones with suppressed TSH) 2
Why T3 Measurement Is Critical in Nodular Disease
Isolated T3 elevation (T3 toxicosis) occurs more commonly in nodular thyroid disease, making free T3 measurement essential when evaluating hyperthyroidism with thyroid nodules 4
Hyperthyroidism can rarely present with normal or low T4 levels but elevated T3, particularly in autonomously functioning nodules 4
Measuring only TSH and T4 may miss T3 toxicosis, which would result in inadequate diagnosis and treatment 4
Size Does Not Predict Function
There is no correlation between AFTN volume and TSH levels (r² = 0.044), meaning even subcentimeter nodules can cause significant thyroid dysfunction 1
No volume threshold exists below which an AFTN is always associated with normal TSH, so small nodules (<1 cm) can still demonstrate subclinical or overt hyperthyroidism 1
A normal TSH level does not preclude the presence of an AFTN, emphasizing the importance of functional assessment regardless of nodule size 1
Role of Thyroid Scintigraphy
Reserve thyroid scintigraphy for patients with suppressed TSH levels to determine if the nodule is hyperfunctioning 5
Only 2.8% of patients with normal or elevated TSH have a hyperfunctioning nodule, making scintigraphy unnecessary when TSH is not suppressed 5
When TSH is low, 86% of patients with thyroid nodules have hyperfunctioning nodules, warranting scintigraphy to guide management 5
Scintigraphy avoids unnecessary scans in 91% of patients with thyroid nodules by limiting use to those with suppressed TSH 5
Follow-up Testing for Autonomously Functioning Nodules
For patients with AFTNs treated with thermal ablation, measure TSH, free T3, and free T4 at each follow-up until normal thyroid function is restored 6
Thyroid function tests should be conducted at 3,6, and 12 months during the first year after ablation, then every 6 months once TSH control is achieved 6
For patients with elevated thyroid antibodies before ablation, thorough thyroid function assessment is necessary to prevent post-ablation hyperthyroidism or hypothyroidism 6
Common Pitfalls to Avoid
Never assume a subcentimeter nodule cannot cause hyperthyroidism based on size alone, as functional status is independent of nodule volume 1
Do not rely on TSH and free T4 alone in nodular thyroid disease—always include free T3 to detect T3 toxicosis 4
Avoid treating based on elevated total T4 alone without confirming elevated free T4 and suppressed TSH, as increased binding proteins can elevate total T4 without true hyperthyroidism 3
Do not perform scintigraphy when TSH is normal or elevated, as this leads to unnecessary testing with minimal diagnostic yield 5