Functional assessment of thyroid nodules
When a lump is found in the thyroid, a scan showing whether it takes up iodine-like tracer more or less than the rest of the gland tells doctors whether it is a low-risk overactive nodule that rarely needs a biopsy, or a quiet 'cold' nodule that does.
Overview
Thyroid nodules are extremely common, and the central triage question once one is found and the patient's TSH is checked is not usually 'is this cancer' outright, but 'does this nodule need a biopsy'. Thyroid scintigraphy, using either iodine-123 or Tc-99m-pertechnetate, answers a narrower but very useful part of that question: whether the nodule is functioning autonomously (a 'hot' nodule, taking up more tracer than surrounding tissue) or non-functioning ('cold', taking up less). Guidelines converge on scintigraphy being indicated specifically when serum TSH is low or low-normal, because a hyperfunctioning nodule found in that setting is very unlikely to be malignant - reported negative predictive value for malignancy in hot nodules is around 96-99% - and can often avoid fine-needle aspiration biopsy altogether, going instead toward treatment of the underlying autonomy (radioactive iodine or surgery) if symptomatic.
ACR appropriateness criteria correspondingly rate thyroid scintigraphy (I-123 uptake, or I-131/Tc-99m-pertechnetate) as usually not appropriate for an initial, euthyroid, palpable nodule where ultrasound is the right first test, but usually appropriate once thyrotoxicosis is present, reflecting that the scan's value lies in explaining biochemical hyperthyroidism found alongside a nodule, or a multinodular goitre, rather than in routinely characterising every palpable lump. The 2019 EANM/SNMMI radioiodine uptake and scintigraphy guideline notes that different national guidelines disagree on exactly which TSH threshold or nodule size should trigger a scan, reflecting genuine practice variation between US, German and pan-European recommendations.
Because the great majority of thyroid cancers are 'cold' on scintigraphy, but the great majority of cold nodules are in turn benign (up to 80-90%), a cold result is not itself diagnostic and simply routes the nodule onward to ultrasound risk stratification (such as ACR TI-RADS) and, if indicated by size and sonographic features, fine-needle aspiration cytology - the scan narrows the population needing biopsy rather than replacing biopsy. In iodine-avid nodules with indeterminate cytology, adjunct molecular or metabolic imaging (Tc-99m-sestamibi or FDG PET) has been explored to further refine malignancy risk, but is not part of routine first-line assessment.
State of the art
- The EANM practice guideline/SNMMI procedure standard for radioiodine uptake and thyroid scintigraphy (2019) sets the current joint acquisition and interpretation standard, and explicitly tabulates how ATA, German, and AACE/AME/ETA guidelines differ on scanning thresholds.
- ACR appropriateness criteria rate ultrasound as usually appropriate for essentially every thyroid nodule scenario, and reserve thyroid scintigraphy for scenarios with confirmed or suspected thyrotoxicosis, where it is usually appropriate.
- A hyperfunctioning ('hot') nodule carries a well-established 96-99% negative predictive value for malignancy, a figure robust enough that current risk-stratification systems such as ACR TI-RADS are understood to apply primarily to nodules not already known to be autonomously functioning.
Thyroid nodules are found on ultrasound in a large proportion of the adult population (commonly cited at up to half of adults by sensitive imaging), the great majority are benign, and only a small minority prove malignant on biopsy, making appropriate triage - rather than universal biopsy - the central clinical challenge.
Ultrasound first; thyroid scintigraphy is not indicated at this stage per ACR appropriateness criteria.
Tc-99m-pertechnetate or I-123 thyroid scintigraphy to determine whether the nodule is autonomously functioning ('hot', very low malignancy risk, usually no biopsy needed) or non-functioning ('cold', routed to ultrasound risk stratification and possible biopsy).
Scintigraphy to identify hypofunctioning ('cold') areas within the goitre that specifically warrant fine-needle aspiration, since function cannot be inferred from ultrasound risk features alone.
Subtypes & biomarkers
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Open problems and what is being done
National guidelines disagree on the TSH level and nodule size that should trigger scintigraphy, so practice varies meaningfully between the US, Germany and other European guidance, without a single internationally harmonised threshold.
A 'cold' scan result has low specificity for malignancy (most cold nodules are benign), so scintigraphy narrows rather than replaces the ultrasound-and-biopsy pathway, and cannot be used alone to reassure a patient a nodule is benign.
Adjunct techniques (Tc-99m-sestamibi washout imaging, FDG PET) for indeterminate-cytology cold nodules are used in some centres to help decide on diagnostic surgery, but are not yet standard first-line practice.
Trials
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