A thyroid nodule is a small lump or growth in the thyroid gland. Nodules are very common: up to 6 in 10 adults have one, and only about 1 to 5 in every 100 nodules are cancer [2]. TI-RADS is a score that the radiologist gives from the appearance of the nodule on ultrasound; the higher the number, the higher the chance of cancer, but even at TI-RADS 4 most nodules are benign [1, 2]. Whether a biopsy is needed or ultrasound follow-up is enough depends on the TI-RADS level and the size of the nodule together [1].
Key points
- Thyroid nodules are very common, and most are not cancer [2, 6].
- TI-RADS runs from 1 to 5: 1 and 2 mean benign or not suspicious; 5 means the highest suspicion. But TI-RADS is not a diagnosis; it only shows which nodules need further tests [1, 2].
- Size matters too: in the American system, a TI-RADS 4 nodule is biopsied from 1.5 cm and a TI-RADS 5 nodule from 1 cm upwards; smaller nodules are followed up [1].
- The biopsy result is reported in 6 Bethesda categories: Bethesda 2 means benign and Bethesda 6 means cancer [4].
- "Indeterminate" results (Bethesda 3 and 4) are common, about 2 to 3 in every 10 biopsies; the next step is a repeat biopsy, a genetic test or surgery to make the diagnosis [5, 2].
- Even if a nodule is cancer, most thyroid cancers have a very good outcome with treatment [6, 7].
What is a thyroid nodule? Is a thyroid nodule dangerous?
The thyroid is a butterfly-shaped gland in the front of the neck that makes thyroid hormone. A nodule is a lump or growth in this gland; it may be solid, filled with fluid (a cyst), or both [1].
Thyroid nodules are very common. Only a few are found by feeling the neck (about 5 in 100 women and 1 in 100 men), but ultrasound shows nodules in a large share of people [3]; up to 6 in 10 adults have one or more nodules [2]. Many nodules are found by chance, on scans done for other reasons [5].
Most nodules are not cancer. Of every 100 nodules found in the general population, usually only 1 to 5 are cancer [2]. This chance depends on age, sex, past radiation to the neck and family history [3]. A small number of nodules grow large enough to press on structures in the neck, or make extra hormone; each happens in about 1 in 20 nodules [5].
(full-size image, opens in a new tab)What is TI-RADS? Scoring a nodule on thyroid ultrasound
TI-RADS is a scoring method that the radiologist uses to estimate, from the ultrasound appearance of a nodule, how likely it is to be cancer, so that it is clear which nodules need a biopsy and which need only follow-up [1]. In the most widely used system (that of the American College of Radiology), five features of the nodule are assessed and each gets 0 to 3 points; the total sets the TI-RADS level [1]. The terms in brackets in the table below are the ones usually written in ultrasound reports.
| Feature | Lower risk | Higher risk |
|---|---|---|
| Make-up of the nodule (composition) | Cystic or almost completely cystic, or spongiform: 0 points [1] | Mixed cystic and solid: 1 point; solid or almost completely solid: 2 points [1] |
| How bright the nodule looks on the image (echogenicity) | Anechoic, like fluid: 0 points; same brightness as or brighter than thyroid tissue (isoechoic or hyperechoic): 1 point [1] | Darker than the thyroid (hypoechoic): 2 points; very dark (very hypoechoic): 3 points [1] |
| Shape | Wider than it is tall (wider-than-tall): 0 points [1] | Taller than it is wide (taller-than-wide): 3 points [1] |
| Edge (margin) | Smooth or ill-defined: 0 points [1] | Lobulated or irregular: 2 points; spreading outside the thyroid (extrathyroidal extension): 3 points [1] |
| Bright spots, including calcifications (echogenic foci) | None, or large comet-tail artefacts: 0 points [1] | Macrocalcifications: 1; calcification around the edge of the nodule (rim): 2; tiny bright spots (punctate echogenic foci): 3 points [1] |
One option is chosen from each row, except for echogenic foci, where the points of all types present are added together [1].
TI-RADS 3, TI-RADS 4 and TI-RADS 5: what do they mean and when does a suspicious nodule need a biopsy?
| Level | Total points | Meaning | Biopsy if the nodule is | Ultrasound follow-up if the nodule is |
|---|---|---|---|---|
| TI-RADS 1 (TR1) | 0 | Benign | Not needed | Not needed [1] |
| TI-RADS 2 (TR2) | 2 | Not suspicious | Not needed | Not needed [1] |
| TI-RADS 3 (TR3) | 3 | Mildly suspicious | 2.5 cm or larger | 1.5 cm or larger [1] |
| TI-RADS 4 (TR4) | 4 to 6 | Moderately suspicious | 1.5 cm or larger | 1 cm or larger [1] |
| TI-RADS 5 (TR5) | 7 or more | Highly suspicious | 1 cm or larger | 0.5 cm or larger [1] |
The European guideline and the American Thyroid Association use slightly different sizes [2, 3]. Your doctor makes the final decision, taking your situation into account.
What do TI-RADS 1 and TI-RADS 2 mean? The nodule is benign or not suspicious and does not need a biopsy [1]. For example, a simple cyst (filled with fluid) scores zero points [1].
What does TI-RADS 3 mean? The nodule is mildly suspicious. In the European system, only 2 to 4 in every 100 nodules in this category are cancer [2]. A biopsy is needed only for large nodules (2.5 cm or more in the American system) [1].
What does TI-RADS 4 mean? The nodule is moderately suspicious. In the European system, 6 to 17 in every 100 nodules in this category are cancer; in other words, most TI-RADS 4 nodules are also benign [2]. In the American system, a biopsy is done from 1.5 cm upwards [1]; a smaller nodule is followed up with ultrasound, and the European guideline suggests a repeat ultrasound after one year [2].
What does TI-RADS 5 mean? The nodule is highly suspicious. In the European system, about 3 to 9 in every 10 nodules in this category are cancer [2]. A biopsy is done from 1 cm upwards [1]. The European guideline follows a smaller nodule with ultrasound every 6 to 12 months, unless a lymph node in the neck looks suspicious, the nodule may have grown outside the thyroid, or it lies close to the windpipe or the voice nerve; in that case a biopsy is advised [2].
There are several TI-RADS systems, such as the American and the European systems, and none has always been better than the others [2]. The numbers do not mean exactly the same thing in every system, and sometimes category 4 is written with a letter (such as 4a or 4b). So read your ultrasound result together with your own doctor.
Thyroid nodule with calcification: is it dangerous?
Calcification means deposits of calcium, which show up on ultrasound as bright spots. The type matters [1]:
- Tiny bright spots ("microcalcifications" or punctate echogenic foci in reports): these score the most points (3 points) and in the European system are one of the features of high suspicion [1, 2].
- Calcification around the edge of the nodule (rim or peripheral): 2 points [1].
- Coarse calcification (macrocalcification): 1 point [1].
Calcification on its own does not mean cancer; its points are added to those of the nodule's other features to give the TI-RADS level [1].
Needle biopsy (FNA) and Bethesda results 1 to 6
First of all, the doctor orders a TSH blood test (the hormone that stimulates the thyroid) [2, 3]. If TSH is low, a thyroid scan is done to see whether the nodule is "hot" (overactive); hot nodules are rarely cancer and are not biopsied [2].
If a biopsy is needed, a thin needle is passed through the skin into the thyroid to remove a little tissue from the nodule [6]. A pathologist reports the result in one of the 6 Bethesda categories, and each category carries a known chance of cancer [4].
| Category | Name | Chance of cancer | Usual next step |
|---|---|---|---|
| Bethesda 1 | Nondiagnostic | About 1 in 8 [4] | Repeat biopsy [2, 4] |
| Bethesda 2 | Benign | About 1 in 25 [4] | Ultrasound follow-up; in the European guideline usually after 3 to 5 years [2, 4] |
| Bethesda 3 | Atypia of undetermined significance (AUS) | About 1 in 5 [4] | Repeat biopsy; sometimes a genetic test, follow-up or surgery [2, 4] |
| Bethesda 4 | Follicular neoplasm | About 1 in 3 [4] | Usually surgery to make the diagnosis (removal of half of the thyroid); sometimes a genetic test [2, 4] |
| Bethesda 5 | Suspicious for cancer | About 3 in 4 [4] | Usually surgery [2, 4] |
| Bethesda 6 | Malignant (cancer) | Almost all [4] | Surgery; for some very small cancers, regular monitoring [2, 4] |
The decision is always made taking the ultrasound, the size of the nodule and your situation into account.
Bethesda 3 and 4: what does an "indeterminate" result mean and what happens next?
About 2 to 3 in every 10 thyroid biopsies give an "indeterminate" result [5]; this means the cells are neither completely normal nor clearly cancer. Most of these nodules are not cancer either: about 1 in 5 people with Bethesda 3 and about 1 in 3 with Bethesda 4 have cancer [4].
- Repeat biopsy: for Bethesda 3, the European guideline suggests repeating the biopsy [2].
- A genetic (molecular) test on the sample: helps the decision when the result is indeterminate [5, 2].
- Regular monitoring: if a Bethesda 3 result comes back again, regular monitoring is one of the options [2].
- Surgery to make the diagnosis: removal of half of the thyroid so that the whole nodule can be examined under the microscope; for Bethesda 4, surgery is usually offered [2, 4].
When is surgery needed, and when is follow-up enough?
- Benign nodule (Bethesda 2): usually ultrasound follow-up only; the European guideline suggests an ultrasound after 3 to 5 years, but if the nodule looks highly suspicious on ultrasound (TI-RADS 5), the biopsy is repeated [2].
- A benign nodule that presses on structures in the neck: surgery, or heat treatment through the skin (destroying the nodule with a needle) instead of surgery [2].
- A nodule that grows during follow-up: the American Thyroid Association counts a nodule as having grown if at least two of its measurements increase by a fifth (and by at least 2 mm), or its volume increases by more than half [3]. In that case your doctor decides whether to repeat the biopsy.
- Suspicious for cancer or cancer (Bethesda 5 and 6): usually surgery. For nodules of 5 to 10 mm without suspicious lymph nodes and with no risk of growth outside the thyroid, regular monitoring or minimally invasive treatments (such as heat treatment through the skin) are also possible [2]. On monitoring very small cancers, see Active surveillance for papillary microcarcinoma.
If the biopsy shows cancer, know that most thyroid cancers can be cured [6]: Is thyroid cancer curable?
When should I see a doctor?
Most thyroid nodules cause no symptoms. Tell your doctor promptly about these:
- A new lump in the neck, or a nodule that is getting bigger [6, 3]
- Hoarseness that does not go away [6]
- Difficulty or pain when swallowing [6]
- Difficulty breathing [6]
If you had radiation to the head and neck as a child or thyroid cancer runs in your family, tell your doctor this too, because the chance of cancer in a nodule is higher [3, 6].
Severe shortness of breath or being unable to swallow needs urgent care; call your local emergency number.
Frequently asked questions
What does a "malignant" thyroid nodule mean?
Malignant means cancer, and benign means not cancer. Most thyroid nodules are benign [2]. Even if a nodule is cancer, most thyroid cancers have a very good outcome with treatment [7]. See Is thyroid cancer curable? and What is the difference between a benign and a malignant tumour?
My small nodule is TI-RADS 5 (for example 6 mm); does it need a biopsy?
Usually not. In the American system, a TI-RADS 5 nodule is biopsied from 1 cm upwards and followed up from 0.5 cm upwards [1]. For a highly suspicious nodule smaller than 1 cm, the European guideline suggests an ultrasound every 6 to 12 months and advises a biopsy when a lymph node in the neck looks suspicious, the nodule may have grown outside the thyroid, or it lies close to the windpipe or the voice nerve [2].
Is a thyroid cyst dangerous?
Do I need a thyroid ultrasound as a check-up?
If you have no symptoms, no; the US Preventive Services Task Force recommends against screening for thyroid cancer in adults without symptoms, because the harms of finding and treating harmless cancers outweigh the benefit [7]. If you feel a lump in your neck or have one of the symptoms above, see a doctor.
What is a "hot" nodule?
A hot (overactive) nodule makes thyroid hormone itself and shows up more strongly than the rest of the gland on a thyroid scan. When the TSH level in the blood is low, a scan is done to find these nodules. Hot nodules are rarely cancer and are not biopsied [2].
Does Bethesda 3 mean I have cancer?
Can a thyroid biopsy make cancer spread?
A thin-needle biopsy is the main way to diagnose a suspicious nodule [6, 2]. Read more about this worry: Does a biopsy make cancer spread?
TI-RADS, Bethesda and decision-making criteria (for physicians)
For physicians
ACR TI-RADS (2017). Points: composition (cystic or spongiform 0, mixed 1, solid 2), echogenicity (anechoic 0, hyper- or isoechoic 1, hypoechoic 2, very hypoechoic 3), shape (wider-than-tall 0, taller-than-wide 3), margin (smooth or ill-defined 0, lobulated or irregular 2, extrathyroidal extension 3) and echogenic foci (none or large comet-tail 0, macrocalcifications 1, peripheral calcifications 2, punctate echogenic foci 3; all present are added). TR1 (0 points) and TR2 (2 points): no FNA; TR3 (3): FNA from 2.5 cm and follow-up from 1.5 cm; TR4 (4 to 6): FNA from 1.5 cm and follow-up from 1 cm; TR5 (7 or more): FNA from 1 cm and follow-up from 0.5 cm [1].
EU-TIRADS (ETA 2023). Risk of malignancy: EU-TIRADS 2 0%; 3 (iso- or hyperechoic without high-suspicion features) 2% to 4%; 4 (mildly hypoechoic without high-suspicion features) 6% to 17%; 5 (at least one of: irregular shape, irregular margins, microcalcifications, marked hypoechogenicity) 26% to 87%. FNA thresholds: more than 20, 15 and 10 mm for categories 3, 4 and 5. Follow-up of nodules not biopsied: EU-TIRADS 2 over 10 mm and EU-TIRADS 3 between 10 and 20 mm every 3 to 5 years; 5 to 10 mm, no further evaluation; EU-TIRADS 4 under 15 mm after 1 year; EU-TIRADS 5 under 10 mm every 6 to 12 months. For EU-TIRADS 5 nodules of 5 to 10 mm, FNA is recommended if there are suspicious lymph nodes, a risk of extrathyroidal extension or a worrisome location (e.g. close to the trachea or the recurrent laryngeal nerve). No system has been consistently superior, and in Europe EU-TIRADS is preferred [2].
ATA 2015. Nodule prevalence 19% to 68% on high-resolution ultrasound and about 5% in women and 1% in men by palpation; cancer in 7% to 15% of nodules depending on age, sex, radiation history and family history. Patterns: high suspicion (risk >70% to 90%; FNA from 1 cm), intermediate suspicion (10% to 20%; from 1 cm), low suspicion (5% to 10%; from 1.5 cm), very low suspicion (<3%; from 2 cm or observation), benign (<1%; no FNA). Measure TSH at the initial evaluation and perform radionuclide scanning if TSH is low. Growth: a 20% increase in at least two dimensions with a minimum of 2 mm, or more than 50% in volume [3].
Bethesda 2023 (mean risk of malignancy and range). I nondiagnostic 13% (5 to 20); II benign 4% (2 to 7); III AUS 22% (13 to 30); IV follicular neoplasm 30% (23 to 34); V suspicious for malignancy 74% (67 to 83); VI malignant 97% (97 to 100). In the third edition, each category has a single name, and AUS is simplified into two subgroups based on risk and molecular profile [4]. Indeterminate cytology accounts for about 20% to 30% of all FNAs, and molecular testing is indicated only in selected cases, such as indeterminate cytology [5].
ETA 2023 recommendations by cytology. Bethesda I: repeat FNA; if still nondiagnostic, core needle biopsy (CNB), or molecular testing in EU-TIRADS 4 and 5; then follow-up or surgery. Bethesda II: in EU-TIRADS 3 and 4, re-evaluation after 3 to 5 years, and in EU-TIRADS 5, repeat FNA. Bethesda III: repeat FNA regardless of EU-TIRADS category; if Bethesda III again, re-evaluation within 1 year, molecular testing or surgery for EU-TIRADS 3, and surgery or active surveillance (with molecular testing if available) for EU-TIRADS 4 and 5. Bethesda IV: offer surgery and molecular testing. Bethesda V and VI: recommend surgery; for 5 to 10 mm nodules without suspicious lymph nodes or risk of extrathyroidal extension, active surveillance or minimally invasive treatment (MIT) may be considered. Hyperfunctioning nodules are rarely malignant and are not biopsied; scintigraphy when TSH is low. Consider calcitonin for nodules scheduled for surgery or MIT and for indeterminate cytology or suspicious ultrasound features, and measure it with a personal or family history of medullary cancer or MEN2 (cut-offs >30 pg/mL in women and >34 pg/mL in men). Thermal ablation (TA) is an alternative to surgery for symptomatic solid benign nodules [2].
Screening. The USPSTF (2017, grade D) recommends against screening for thyroid cancer in asymptomatic adults [7].
Related cancer types
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References
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