Thyroid Uptake and Scan (Thyroid Scintigraphy)

1. Overview

Thyroid scintigraphy and the radioactive iodine uptake (RAIU) test are functional nuclear-medicine studies that image the distribution of trapping/organifying tissue in the thyroid and quantify how avidly the gland concentrates iodine or its analogue. Unlike ultrasound, which shows anatomy, scintigraphy shows function — which tissue is autonomously working, which is suppressed, and how much iodine the gland handles.

The dominant clinical role is the evaluation of thyrotoxicosis with a suppressed thyroid-stimulating hormone (TSH): distinguishing hyperthyroidism driven by intrinsic gland overactivity (Graves disease, toxic nodular goitre, toxic adenoma) from thyroiditis and other low-uptake causes. This distinction changes management directly — it separates patients who benefit from antithyroid drugs or radioiodine therapy from those managed symptomatically [1,2].

Secondary roles include characterising the functional status of a thyroid nodule (hot vs cold), confirming or excluding a discordant/autonomous nodule, evaluating retrosternal (substernal) goitre, and calculating the RAIU needed for dosimetry-based ¹³¹I therapy planning [1,3]. Nuclear medicine contributes the one piece of information that laboratory tests and anatomical imaging cannot: regional and whole-gland thyroid function.

2. Core Concepts & Pathophysiology

Thyroid follicular cells actively transport iodide via the sodium–iodide symporter (NIS), then organify it into thyroglobulin. Radioiodine (¹²³I, ¹³¹I) is trapped and organified, mirroring true iodine handling. ⁹⁹ᵐTc-pertechnetate is trapped by NIS but not organified, so it reflects trapping only — a clinically important difference in the rare discordant nodule (pertechnetate-warm but radioiodine-cold), where trapping without organification can mask malignancy [1].

TSH from the pituitary drives NIS activity. In autonomous tissue (Graves, adenoma, toxic nodules), function is TSH-independent, so uptake is high or focally increased despite a suppressed serum TSH. In destructive thyroiditis, follicular cells are damaged and leak preformed hormone; trapping fails and uptake is low. This inverse relationship between serum thyroid hormone and radiotracer uptake is the diagnostic engine of the study.

3. Clinical Indications

Established - Thyrotoxicosis with suppressed TSH: differentiate high-uptake (Graves, toxic multinodular goitre [TMNG], toxic adenoma) from low-uptake states (thyroiditis, exogenous/factitious thyroxine, iodine-induced, struma ovarii) [1,2]. - Functional characterisation of a palpable or scintigraphically evident nodule in a thyrotoxic patient (hot vs cold). - RAIU measurement for ¹³¹I therapy dose calculation [3]. - Evaluation of retrosternal goitre extent and function (¹²³I preferred for mediastinal imaging).

Selected / conditional - Congenital hypothyroidism (aetiology: agenesis, ectopia, dyshormonogenesis) — ⁹⁹ᵐTc or ¹²³I. - Ectopic thyroid tissue (lingual thyroid, struma ovarii). - Assessment of an autonomously functioning nodule causing subclinical hyperthyroidism.

Emerging / selected - ⁹⁹ᵐTc-sestamibi (visual and washout index) or ¹⁸F-FDG PET/CT to risk-stratify cytologically indeterminate hypofunctioning nodules — included in the EANM/SNMMI guideline but used mainly in European centres [1]. - ⁹⁹ᵐTc-sestamibi to separate type 1 from type 2 amiodarone-induced thyrotoxicosis [1]. - Quantitative SPECT/CT (single-photon emission computed tomography/CT) uptake measurement (research/early clinical use).

Unlikely to help - Euthyroid patients with a normal TSH and a thyroid nodule in iodine-sufficient regions — scintigraphy rarely changes management; ultrasound and, when indicated, fine-needle aspiration (FNA) are preferred (ATA 2015) [5]. In iodine-deficient regions autonomous nodules are common despite a normal TSH, and European practice uses scintigraphy more liberally (e.g. TSH <1.0–1.5 mU/L or nodules >10 mm) [1]. - Differentiated thyroid cancer surveillance, which uses whole-body ¹²³I/¹³¹I imaging and thyroglobulin rather than the uptake-and-scan protocol.

4. Radiopharmaceuticals

Administered activities (adult, per the European Association of Nuclear Medicine [EANM] / Society of Nuclear Medicine and Molecular Imaging [SNMMI]): ⁹⁹ᵐTc-pertechnetate 74–111 MBq (2–3 mCi); ¹²³I for scanning 7.4–14.8 MBq (0.2–0.4 mCi); ¹³¹I for uptake only 0.15–0.37 MBq (4–10 µCi); ⁹⁹ᵐTc-sestamibi 185–370 MBq [1]. Values are protocol- and equipment-dependent.

5. Radiation Dosimetry

Diagnostic thyroid scintigraphy and uptake testing are low-dose procedures.

• ⁹⁹ᵐTc-pertechnetate (74–111 MBq): effective dose ≈ 1–1.5 mSv (0.013 mSv/MBq) — the lowest of the routine options, and part of why it is first-line.
• ¹²³I (7.4–14.8 MBq): effective dose ≈1.5–3 mSv (0.20 mSv/MBq; uptake-dependent), with a favourable thyroid absorbed dose for imaging.
• ¹³¹I: even the small activities used for uptake testing deliver a comparatively high thyroid absorbed dose per unit activity because of the energetic β⁻ emission and long half-life; this is why ¹²³I or ⁹⁹ᵐTc are preferred whenever imaging is required, and ¹³¹I is reserved for uptake/dosimetry or therapy.

For context, natural background radiation is roughly 2–3 mSv per year. In children, use weight-based activity and the lowest activity consistent with a diagnostic result (as-low-as-reasonably-achievable principle) [1,6].

6. Patient Selection & Preparation

• History: thyroid symptoms, prior thyroid surgery/radioiodine, family history, and — critically — recent iodine exposure and interfering drugs.
• Required labs: TSH and free thyroid hormones; the study is interpreted against biochemical status. A suppressed TSH is the usual trigger.
• Medication and iodine interference (withhold before RAIU/scan) [1]:

• Fasting: not required by the EANM/SNMMI guideline (patients may eat and drink) [1]; some centres request a short fast before oral radioiodine capsules (institution-dependent); not required for intravenous (IV) pertechnetate.
• Pregnancy: radioiodine is contraindicated in pregnancy (crosses placenta; fetal thyroid concentrates iodine after ~10–12 weeks). Exclude pregnancy before administration [1,2].
• Breastfeeding: diagnostic ¹²³I and ⁹⁹ᵐTc require temporary interruption of breastfeeding per local rules; ¹³¹I (diagnostic or therapeutic) requires cessation of breastfeeding for that child.
• Consent & radiation safety: explain the low diagnostic dose; advise avoiding pregnancy for a defined interval after therapeutic (not diagnostic) radioiodine.
• Renal/hepatic/marrow status rarely affects the diagnostic study.

7. Imaging & RAIU Protocol (chronological)

RAIU test 1. Administer oral ¹²³I (or a small ¹³¹I capsule) with a counted standard. 2. Measure neck counts with a probe/gamma camera at 4–6 h and 24 h (with later time points when the effective half-life is needed for dosimetry) against the standard and thigh background [1]. 3. RAIU (%) = (neck counts − thigh counts)/(standard counts − room background) × 100 [1].

Thyroid scan - ⁹⁹ᵐTc-pertechnetate: IV injection; image at 15–20 minutes. - ¹²³I: oral; image at 2–6 h, with 24 h delayed imaging when needed (retrosternal/ectopic tissue). - Positioning: supine, neck extended. - Acquisition: pinhole or high-resolution parallel-hole collimator (low-energy for ⁹⁹ᵐTc/¹²³I; high-energy for ¹³¹I); anterior view, with oblique views and/or SPECT(/CT) on indication; 128×128 or 256×256 matrix, zoom 1.5–2; ~100–200k counts or 5–10 min per view [1,6]. - Markers (sternal notch, palpable nodule) aid localisation. - Quantitation: pertechnetate thyroid uptake (TcTU, %) or RAIU (%). SPECT/CT is used selectively for retrosternal extent or ambiguous nodule localisation. - Post-procedure: routine hydration; no restrictions after diagnostic doses beyond standard advice.

8. Normal Findings

• Homogeneous tracer distribution across both lobes, butterfly shape, pyramidal lobe occasionally seen.
• With pertechnetate, physiological salivary gland, oral, gastric and (background) blood-pool activity is normal.
• Normal RAIU (region- and diet-dependent; must be locally validated): roughly 3–16% at 6 h and 8–25% at 24 h; values >25% suggest hyperfunction in iodine-sufficient regions [1,4].
• Normal TcTU has traditionally been quoted as ~1–4%, but recent population studies report lower normal ranges (~0.2–2%); it is strongly institution- and method-dependent and falls with age — use locally derived ranges [1].

9. Interpretation

Sequence: correlate TSH/thyroid hormones → assess overall uptake (high/normal/low) → assess distribution (diffuse/focal/patchy) → localise any nodule’s function → quantify (RAIU/TcTU).

• Hot (functioning) nodule: overwhelmingly benign — malignancy is rare; autonomously functioning nodules carry a very high negative predictive value for cancer [1].
• Cold (non-functioning) nodule: non-specific; a minority are malignant, so a cold nodule warrants ultrasound-guided FNA per risk stratification, not reassurance [2,5].
• Discordant nodule: pertechnetate-warm but radioiodine-cold (very rare; organification defect) — treat as cold; image with ¹²³I when an organification defect is suspected, e.g. a pertechnetate-hot nodule that is clinically or sonographically suspicious [1].
• RAIU quantifies function for ¹³¹I dosimetry: high uptake favours effective therapy; very low uptake predicts poor radioiodine response [3].

10. Differential Diagnosis

• Graves vs TMNG: diffuse homogeneous high uptake vs heterogeneous patchy uptake with hot/cold foci.
• Graves vs subacute (de Quervain) thyroiditis: both thyrotoxic, but uptake is high in Graves and near-absent in thyroiditis (painful gland, raised inflammatory markers) — the pivotal distinction [2].
• Toxic adenoma vs Graves: single hot focus with suppressed background vs uniform gland.
• Low-uptake thyrotoxicosis: thyroiditis vs exogenous thyroxine vs iodine-induced vs struma ovarii (pelvic uptake on whole-body imaging) — history and thyroglobulin help.

11. Pitfalls & Artefacts

False-positive (apparent abnormality) - Salivary/oesophageal pertechnetate activity mimicking ectopic or nodal uptake — recognise by physiological location; an oral water swallow clears the oesophagus. - Prominent pyramidal lobe misread as a nodule.

False-negative / suppressed uptake - Recent iodinated contrast, amiodarone, or dietary iodine load causing spuriously low uptake — a common error; take an iodine history [1]. - Antithyroid drugs or thyroid hormone not withheld → suppressed or diffusely reduced uptake.

Physiological variants - Hemiagenesis mimicking a hot nodule with a suppressed contralateral lobe (ultrasound resolves). - Asymmetric lobes; thymic uptake in children.

Technical - Wrong collimator/energy window for ¹³¹I → scatter and poor resolution. - Patient motion, incorrect neck marker, or background region-of-interest (ROI) errors distorting quantitation. - Visual comparison with salivary activity and thyroid-to-background ratios are only rough approximations; validated TcTU/RAIU methodology is preferred [1].

12. Reporting Guidance

Checklist: indication and TSH/hormone status; radiopharmaceutical, activity, route, imaging time; iodine/medication history; gland size, position, contour; distribution (diffuse/focal/patchy); each nodule’s function (hot/cold/discordant); quantitation (RAIU %/TcTU % with local reference range); retrosternal extent if relevant; overall impression tying pattern to biochemistry.

Conclusion approach: state the functional diagnosis and its management relevance, not just the image description.

Sample conclusion (illustrative, not patient-specific): > “Diffusely increased homogeneous ⁹⁹ᵐTc-pertechnetate uptake with an elevated thyroid uptake fraction, in the setting of suppressed TSH — consistent with Graves disease. No discrete cold nodule identified.”

13. Clinical Management Impact

The scan/RAIU steers therapy: Graves and toxic nodular disease (high uptake) are candidates for antithyroid drugs, ¹³¹I therapy, or surgery, whereas thyroiditis (low uptake) is managed with beta-blockers/anti-inflammatories and observation — radioiodine would be ineffective and inappropriate [2]. RAIU also underpins ¹³¹I activity calculation and predicts therapeutic response [3]. Identifying a cold nodule redirects the patient to ultrasound/FNA.

14. Comparison with Alternatives

• Ultrasound: superior for anatomy, nodule morphology, and FNA guidance; gives no functional data. Complementary, not a substitute [2].
• Laboratory (TSH, free T4/T3, TSH-receptor antibody [TRAb], thyroglobulin, inflammatory markers): TRAb positivity can confirm Graves without scintigraphy in a straightforward diffuse goitre; scintigraphy is decisive when TRAb is negative/equivocal or nodular disease is present [2].
• Cross-sectional CT/magnetic resonance imaging (MRI): anatomical retrosternal mapping; iodinated CT contrast blocks subsequent radioiodine studies for several weeks — sequence carefully.
• FNA biopsy: definitive for cytology of cold nodules; scintigraphy triages which nodules need it [5].
• Competing radiopharmaceuticals: ¹²³I over ¹³¹I for diagnostic imaging (lower dose, better images); pertechnetate for speed and availability.

15. Special Situations

• Paediatric/congenital hypothyroidism: ⁹⁹ᵐTc or ¹²³I to distinguish agenesis, ectopia, dyshormonogenesis; do not delay treatment for imaging.
• Pregnancy: radioiodine contraindicated; defer or use alternatives.
• Breastfeeding: interrupt/cease per isotope rules.
• Post-therapy: persistent uptake after ¹³¹I may indicate incomplete ablation; reassess with biochemistry.
• Prior iodine load/contrast: delay the study until washout intervals have elapsed.
• Incidental focal uptake on other studies warrants correlation.

16. Recent Advances

• Quantitative SPECT/CT absolute uptake measurement, aiming to improve reproducibility of thyroid uptake (research/early clinical use).
• ⁹⁹ᵐTc-sestamibi washout indices for indeterminate-nodule risk stratification (guideline-described; cut-offs must be validated locally) [1].
• Artificial-intelligence (AI)-assisted pattern classification and gland segmentation for uptake quantitation (research stage).
• Harmonised EANM/SNMMI (2019) methodology standardising RAIU and scintigraphy practice [1].

17. High-Yield Numbers

18. Reporting Pearls

1. Always interpret uptake against the current TSH — the scan without biochemistry is uninterpretable.
2. A suppressed-TSH thyrotoxic patient with low uptake means thyroiditis or an iodine/exogenous cause, not hyperthyroidism.
3. Take an explicit iodine and drug history before blaming the gland for low uptake.
4. Call a pertechnetate-warm/radioiodine-cold nodule discordant and manage as cold.
5. Localise nodule function with markers; state which nodule is hot vs cold.
6. Report retrosternal extent and add ¹²³I 24 h/SPECT-CT views when the goitre dips substernally.
7. Give quantitation with the local reference range, not a textbook one.
8. A hot nodule is reassuring against malignancy; a cold nodule is non-specific and needs ultrasound/FNA triage.

19. Common Examination Traps

1. Assuming pertechnetate and radioiodine are interchangeable — pertechnetate does not organify (discordant-nodule trap).
2. Reading low uptake as “normal” in a thyrotoxic patient — it points to thyroiditis/exogenous cause.
3. Forgetting that recent CT contrast suppresses uptake for weeks.
4. Believing a cold nodule is usually cancer — most are benign, but it still needs FNA.
5. Believing a hot nodule needs FNA — it rarely does.
6. Confusing Graves (diffuse) with TMNG (patchy) uptake.
7. Giving diagnostic radioiodine in pregnancy — always contraindicated.
8. Quoting a single universal RAIU normal range — it varies with regional iodine intake.
9. Mistaking physiological salivary/oesophageal pertechnetate activity for pathology.

20. One-Minute Review

• Scintigraphy/RAIU show thyroid function, complementing ultrasound (anatomy).
• Chief role: work up suppressed-TSH thyrotoxicosis.
• High diffuse uptake = Graves; patchy = TMNG; focal hot = toxic adenoma; low = thyroiditis/exogenous/iodine.
• ⁹⁹ᵐTc-pertechnetate: trapping only, fast, cheap; ¹²³I: trapping + organification, best for nodules/retrosternal.
• Adult doses: pertechnetate 74–111 MBq; ¹²³I 7.4–14.8 MBq.
• RAIU ~3–16% (6 h), ~8–25% (24 h); >25% suggests hyperfunction (locally validated).
• Withhold interfering iodine/drugs; contrast blocks uptake for 1–2 months.
• Hot nodule ≈ benign; cold nodule → FNA; discordant nodule → treat as cold.
• Radioiodine contraindicated in pregnancy; manage breastfeeding by isotope.
• RAIU also drives ¹³¹I therapy dosimetry.

21. Clinical Bottom Line

In a patient with suppressed TSH, thyroid scintigraphy and RAIU reliably separate the high-uptake hyperthyroid disorders (Graves, toxic nodular goitre, toxic adenoma) from low-uptake destructive or exogenous causes, directing radioiodine or antithyroid therapy versus supportive management. Interpretation is only valid alongside biochemistry and a careful iodine/drug history, and normal reference ranges must be locally validated.

22. Key References

1. Giovanella L, Avram AM, Iakovou I, et al. EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy. Eur J Nucl Med Mol Imaging. 2019;46(12):2514–2525. doi:10.1007/s00259-019-04472-8
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343–1421. doi:10.1089/thy.2016.0229
3. Silberstein EB, Alavi A, Balon HR, et al. The SNMMI Practice Guideline for Therapy of Thyroid Disease with ¹³¹I 3.0. J Nucl Med. 2012;53(10):1633–1651. doi:10.2967/jnumed.112.105148
4. Iqbal A, Rehman A. Thyroid Uptake and Scan (archived). In: StatPearls. Treasure Island (FL): StatPearls Publishing. NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK555978/
5. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133. doi:10.1089/thy.2015.0020
6. ACR–ACNM–SNMMI–SPR Practice Parameter for Thyroid Scintigraphy and Uptake Measurements (revised 2024, Resolution 16). American College of Radiology. https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards

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