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Radionuclide therapy

¹³¹I for hyperthyroidism

Source: EANM 2023 / ATA 2016 / SNMMI 2012 / EUGOGO 2021 · confirm locally
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Educational aid — verify against EANM/SNMMI/ATA/NCCN, the drug label and local protocol. Session-only.
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Before planning therapy

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On the day of treatment

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After treatment & follow-up

Background & evidence

Oral sodium [¹³¹I]iodide is trapped by follicular cells through the sodium–iodide symporter. Its β-particles (mean tissue range 0.4 mm, T½ 8.02 days) destroy hyperfunctioning tissue over weeks to months. It is a definitive, usually outpatient, alternative to long-term antithyroid drugs or surgery. In Graves' disease the aim is now ablation, meaning hypothyroidism and then replacement. In toxic nodular disease the aim is to remove hyperthyroidism, ideally keeping normal function.

Indications & contraindications

Indications

  • Graves' disease, first line when antithyroid drugs are contraindicated or not tolerated, surgical risk is high (heart failure, pulmonary hypertension, laryngeal nerve palsy), hyperthyroidism relapses after drugs or surgery, the patient is elderly with comorbidity, or no high-volume thyroid surgeon is available (EANM 2023)
  • Graves' disease as an elective first-line choice in patients >10 years with a small-to-medium goitre and inactive or mild GO (EANM 2023); ATA 2016 treats RAI, drugs and surgery as equally acceptable if there is no GO
  • Toxic adenoma (Plummer disease) and toxic multinodular goitre without suspicion of cancer, especially in older or comorbid patients or after previous neck surgery or irradiation (EANM 2023; ATA 2016)
  • Persistent or recurrent hyperthyroidism after a previous ¹³¹I treatment (ATA 2016)

Contraindications

  • Absolute: pregnancy; breastfeeding (stop ≥6 weeks before RAI and do not resume for that child); suspected or confirmed thyroid cancer; age ≤5 years (EANM 2023)
  • Active moderate-to-severe or sight-threatening Graves' orbitopathy: ATA recommends against RAI, ETA 2018 calls it a contraindication, and EUGOGO advises antithyroid drugs until GO treatment is complete. EANM lists it as relative; if RAI is unavoidable it advises IV methylprednisolone cover (0.5 g weekly for 6 weeks, then 0.25 g weekly for 6 weeks)
  • Relative: age 5–10 years (delay if possible); very large goitre (≥80 g) or compressive symptoms; low RAIU; pregnancy planned within ~6 months
  • Inability to follow radiation-safety precautions: choose another treatment (ATA 2016); consider inpatient treatment for incontinence (EANM 2023)
Activity, dosing & administration
SettingTarget absorbed dose (EANM 2023)Fixed activityCalculated activity
Graves' disease, ablative (EANM preferred aim)200–300 Gy370–555 MBq (10–15 mCi), more if the gland is >40 mL (EANM); ATA: mean 370–555 MBq to render hypothyroidEANM: 8 (200 Gy) or 12 (300 Gy) MBq × mass (g) ÷ 24-h RAIU. ATA: 50–200 µCi/g ÷ 24-h RAIU; >150 µCi/g (5.55 MBq/g) needed for hypothyroidism. SNMMI: 3–8 MBq/g
Graves' disease, functional (euthyroid aim; milder disease, patient preference)100–150 GyNo guideline valueEANM: 6 MBq × g ÷ 24-h RAIU for 150 Gy; more retreatment and later hypothyroidism still likely
Toxic adenoma (dose to nodule)300–400 Gy370–740 MBq (EANM); ATA ~370–740 MBq (10–20 mCi); SNMMI example 550 MBq for a 1.5–3 cm noduleEANM: 12 (300 Gy) or 16 (400 Gy) MBq × nodule mass ÷ 24-h RAIU, with uptake corrected for the nodule fraction. ATA: 150–200 µCi/g (5.55–7.4 MBq/g) corrected for 24-h RAIU
Toxic multinodular goitre150–300 Gy to nodules; 100–150 Gy to the whole gland if nodule mass cannot be measured370–740 MBq (EANM)EANM: 6 (150 Gy) to 12 (300 Gy) MBq × g ÷ 24-h RAIU. ATA: 150–200 µCi/g (5.55–7.4 MBq/g) corrected for 24-h RAIU; usually more than for Graves'
Graves' disease in children and adolescentsAblation; ≥300 Gy if dosimetry is used200–800 MBq reported15 MBq/g (ultrasound mass); EANM recommends dosimetry where available
Full dosimetry (EANM SOP)Any of the aboveNot applicableA (MBq) = M (g) × D (Gy) ÷ [2.808 × ∫RIU(t)dt (days)]. With mono-exponential kinetics this is the Marinelli form A ≈ 24.7 × M × D ÷ (RIUmax % × Teff days)
  • EANM early-uptake rule assumes an effective half-life of 5.5 days. Worked example: 35 g gland, 24-h RAIU 65%, 200 Gy → 8 × 35 ÷ 0.65 ≈ 430 MBq.
  • If no uptake is measured, EANM gives 9, 12 and 18 MBq per gram for about 150, 200 and 300 Gy. This assumes about half the activity decays in the gland.
  • EANM does not recommend fixed activity without adjustment for mass and kinetics: 555 MBq is more than twice what a 20 g Graves' gland needs. It also notes that no trial has shown fixed activity to be inferior. ATA 2016 regards fixed and calculated activity as equally effective, and full dosimetry is seldom used in the US.
  • Mass by ultrasound: ellipsoid A × B × C ÷ 2 per lobe or nodule (cm, g). Compare with scintigraphy so the measured volume matches the functioning tissue. Planar scintigraphy is reliable only above ~20 g.
  • Among individualised methods, the Marinelli formula gave the smallest deviation of achieved from intended dose in toxic multinodular goitre (Hammes 2018).
  • Dose–response in Graves': 150, 200 and 300 Gy cure hyperthyroidism in about 74%, 81% and 88%, with euthyroidism in 38%, 35% and 29% (EANM, from Taprogge 2021). Large glands with fast turnover fail more often.
  • Units: 1 mCi = 37 MBq; 150 µCi/g = 5.55 MBq/g.
Key trials & evidence
Trial / studyPopulationResultReference
Dose–response meta-analysis15 studies, 2303 Graves' patients with dosimetryNon-hyperthyroid outcome OR 1.11 per 10 Gy; highest euthyroid rate 38% at 128 Gy; euthyroidism more likely at 120–180 GyTaprogge, Thyroid 2021
RAI ± prednisone vs methimazole (RCT)443 Graves' patients with slight or no GOGO appeared or worsened in 15% after RAI (persistent in 5%), 0% after RAI + prednisone and 3% on methimazoleBartalena, NEJM 1998
TT96 (RCT)313 newly diagnosed Graves': ¹³¹I vs 18 months of drugs, early T4 in bothNew or worse ophthalmopathy 38.7% vs 21.3% (P <0.001); smokers had the highest riskTräisk, JCEM 2009
Low-dose prednisone cohort111 RAI-treated patients with mild or no GO~0.2 mg/kg for 6 weeks as effective as 0.3–0.5 mg/kg; no GO progression in either group, less weight gainLai, JCEM 2010
Adjunctive antithyroid drugs (meta-analysis)14 RCTs, 1306 patientsDrugs in the week around RAI: failure RR 1.28 (1.07–1.52); hypothyroidism RR 0.68 (0.53–0.87)Walter, BMJ 2007
Dosimetric therapy of toxic nodulesSingle or few measurable nodules, 300–400 GyHyperthyroidism eliminated in 85–100%; hypothyroidism 10–20%EANM 2023 (summary)
Long-term toxic adenoma follow-up684 patients after RAIHypothyroidism 7.6% at 1 year, 28% at 5, 46% at 10 and 60% at 20 yearsATA 2016 (summary)
Cooperative Thyrotoxicosis Therapy Follow-up Study18 805 RAI-treated US/UK patients (94% Graves')Solid cancer mortality RR 1.06 per 100 mGy stomach dose; estimated 19–32 excess deaths per 1000 over a lifetimeKitahara, JAMA Intern Med 2019
Toxicity & its management
  • Transient worsening of thyrotoxicosis in about 10%, mostly in poorly controlled disease. Painful radiation thyroiditis is uncommon (about 1% EANM; 1–5% SNMMI): use paracetamol or an NSAID. Steroids are rarely needed and should not be given before RAI.
  • Thyroid storm is rare but life-threatening. Treat with antithyroid drugs, inorganic iodide, β-blocker, corticosteroid and antipyretics, and prevent it by pretreating high-risk patients.
  • Neck swelling or compression can occur with large goitres. Patients must report tightness, stridor or breathlessness at once (ATA 2016).
  • Hypothyroidism is the intended outcome in Graves' disease. After nodular disease it accrues with time: about 20–60% depending on disease, extranodular suppression and follow-up (EANM).
  • Graves' orbitopathy: new or worse in 15% (Bartalena 1998) to 38.7% (Träisk 2009). Risk factors: smoking, high TRAb (ATA example: >8.8 IU/L, assay-specific), severe hyperthyroidism, active GO and uncontrolled post-RAI hypothyroidism.
  • Steroid prophylaxis. ATA 2016: prednisone 0.4–0.5 mg/kg/day from 1–3 days after RAI for 1 month, then tapered over 2 months; about 0.2 mg/kg/day for 6 weeks may suffice. EUGOGO 2021: 0.3–0.5 mg/kg tapered over 3 months if high risk, 0.1–0.2 mg/kg over 6 weeks if low risk. No steroid cover is needed for long-standing inactive GO without risk factors.
  • Sialadenitis, dry mouth and taste change are mainly seen with activities ≥1000 MBq (EANM).
  • Graves'-type hyperthyroidism after RAI for nodular goitre: 2.7–4.1% (EANM) or up to 4% (ATA), more often when TPO antibodies are positive. It responds to further RAI.
  • Cancer and fertility: EANM and SNMMI find no convincing excess cancer or infertility. A large cohort found a modest dose-related rise in solid cancer mortality (Kitahara 2019), so use the lowest activity that achieves the aim.
Radiation protection & discharge
  • Therapy must be justified and optimised under Directive 2013/59/Euratom in the EU and national law elsewhere. Some countries require inpatient treatment above set activities. Follow local release criteria (EANM 2023).
  • Named example, US: NRC 10 CFR 35.75 allows release when no other person is likely to receive >5 mSv, when the activity at release is ≤1.22 GBq (33 mCi), or when the dose rate is <0.07 mSv/h at 1 m. The NRC discourages release to hotels (SNMMI 2012).
  • Named example, EU: public exposure must not exceed 1 mSv per year. Patients are told to increase distance and reduce contact time, especially with children and pregnant or breastfeeding women (EANM 2023).
  • Give written advice before release. If the patient cannot follow it, choose another treatment (ATA 2016). Provide a card or letter stating the nuclide, activity and date, as travel radiation monitors may detect it (SNMMI 2012).
  • Typical home hygiene (SNMMI 2012): flush twice, wash hands, men sit to urinate, wash dishes before sharing, and avoid prolonged public transport in the first 24 h. Separate laundry or disposable plates are not needed.
  • Pregnancy test within 24–72 h depending on the guideline. Stop breastfeeding ≥6 weeks before RAI (3 months is more reliable) and do not resume for that child. Delay conception ≥4–6 months (women) or 3–4 months (men).
  • Use a capsule where possible to limit contamination. Plan inpatient care for incontinent patients so excreta can be handled safely (EANM 2023).

References

  1. Campennì A, Avram AM, Verburg FA, Iakovou I, Hänscheid H, de Keizer B, et al. The EANM guideline on radioiodine therapy of benign thyroid disease. Eur J Nucl Med Mol Imaging. 2023;50(11):3324-48. doi:10.1007/s00259-023-06274-5
  2. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-421. doi:10.1089/thy.2016.0229
  3. Silberstein EB, Alavi A, Balon HR, Clarke SEM, Divgi C, Gelfand MJ, et al. The SNMMI practice guideline for therapy of thyroid disease with 131I 3.0. J Nucl Med. 2012;53(10):1633-51. doi:10.2967/jnumed.112.105148
  4. Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021;185(4):G43-67.
  5. Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association guideline for the management of Graves' hyperthyroidism. Eur Thyroid J. 2018;7(4):167-86. doi:10.1159/000490384
  6. Hänscheid H, Canzi C, Eschner W, Flux G, Luster M, Strigari L, et al. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases. Eur J Nucl Med Mol Imaging. 2013;40(7):1126-34.
  7. Taprogge J, Gape PMD, Carnegie-Peake L, Murray I, Gear JI, Leek F, et al. A systematic review and meta-analysis of the relationship between the radiation absorbed dose to the thyroid and response in patients treated with radioiodine for Graves' disease. Thyroid. 2021;31(12):1829-38. doi:10.1089/thy.2021.0302
  8. Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell'Unto E, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med. 1998;338(2):73-8. doi:10.1056/NEJM199801083380201
  9. Träisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, et al. Thyroid-associated ophthalmopathy after treatment for Graves' hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab. 2009;94(10):3700-7. doi:10.1210/jc.2009-0747
  10. Lai A, Sassi L, Compri E, Marino F, Sivelli P, Piantanida E, et al. Lower dose prednisone prevents radioiodine-associated exacerbation of initially mild or absent Graves' orbitopathy: a retrospective cohort study. J Clin Endocrinol Metab. 2010;95(3):1333-7. doi:10.1210/jc.2009-2130
  11. Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514. doi:10.1136/bmj.39114.670150.BE
  12. Kitahara CM, Berrington de Gonzalez A, Bouville A, Brill AB, Doody MM, Melo DR, et al. Association of radioactive iodine treatment with cancer mortality in patients with hyperthyroidism. JAMA Intern Med. 2019;179(8):1034-42. doi:10.1001/jamainternmed.2019.0981
  13. Hammes J, van Heek L, Hohberg M, Reifegerst M, Stockter S, Dietlein M, et al. Impact of different approaches to calculation of treatment activities on achieved doses in radioiodine therapy of benign thyroid diseases. EJNMMI Phys. 2018;5(1):32.
  14. Szumowski P, Mojsak M, Abdelrazek S, Sykała M, Amelian-Fiłonowicz A, Jurgilewicz D, et al. Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy. Endocrine. 2016;54(3):751-6.
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