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Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018

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Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 I Love What I do, i.e. Nuclear Medicine … RADIOACTIVE IODINE THERAPY FOR No other relevant disclosures HYERTHYROIDISM Mark Tulchinsky, MD, FACNM, CCD or conflicts of interest Professor of Radiology and Medicine Division of Nuclear Medicine Penn State University Hospital Radioactive Iodine (RAI) Learning Objectives Administration for Graves’ • Treatment Options Disease: Birthplace of • Medications Radiotheranostics • Surgery Saul Hertz, M.D. • 131I Treatment (RAIT) (April 20, 1905 – July 28, 1950) • The first to study RAI in an • Graves’ Disease w/o Orbitopathy animal model of hyperthyroidism • Graves’ Disease with Orbitopathy • March 31st, 1941, at the age of 35 y, administered • Toxic Adenoma the first RAI treatment • Multinodular Toxic Goiter (RAIT) to a patient with Grave’s disease • Intermittent (recurrent) Thyroiditis • The first to use RAI uptake to inform RAIT, i.e. • Amiodarone Thyrotoxicosis radiotheranostic principle Therapeutic Options for Productive Conditions Amenable to RAIT Hyperthyroidism Condition Etiology • Antithyroid Drug therapy (ATDT) Graves’ disease (~80%) TSH-R-Ab stimulation of thyrocyte Symptomatic control with beta blockers Toxic Multinodular Goiter mutation → TSH-R-Ab activation → Toxic Adenoma autonomous function Thioureas, aka Thionamides, Anti- Hashimoto’s Thyroiditis in autoimmune disease - a variety of Thyroid Drugs (ATD’s) productive phase (“Hashi- cell- and antibody-mediated toxicosis”, overlaps Graves’) immune processes Corticosteroids Intermittent/recurrent Thyroiditis* Unknown Stable Iodine (SSKI, etc.) Amiodarone thyroiditis Multifactorial Rituximab *RAIT in recovery phase, prevents recurrences • Radioactive Iodine Treatment (RAIT) Abbreviations: TSH-R-Ab = thyroid stimulating hormone Alone or with adjuncts (steroids ± other DT) receptor autoantibobdy, RAIT = RAI treatment • Surgery Mark Tulchinsky, MD, FACNM, CCD 1 Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 Hyperthyroidism Drug Therapy Hyperthyroidism Drug Therapy Thioureas: Propylthiouracil (PTU) & Methimazole (MZ) Propylthiouracil (PTU) & Methimazole (MZ) •PTUATD’s & MZ divert oxidizedPTU iodide & MZ away from thyroglobulin, effectively ceasing thyroid Major Minor hormone biosynthesis Rare (0.2%–0.5%) Common (1%–5%) ATD’s do NOT Agranulocytosis Urticaria or other rash block I- trapping Inhibition of hormone synthesis depletes Very rare (<0.1%) Arthralgia existing stores of iodinated thyroglobulin as Thrombocytopenia Fever the protein is hydrolyzed and hormone Aplastic anemia Transient granulocytopenia released, depleting thyroid hormone stores Vasculitis, lupus-like syndrome Uncommon (<1%) Hypoglycemia (anti-insulin Ab) (MZ) Gastrointestinal upset • ATD’s bind intrathyroidal iodide and Cholestatic hepatitis (MZ) Abnormalities of taste and smell facilitate its clearance from the thyroid, Fulminant hepatitis (PTU) Arthritis depleting thyroid iodine content Hypoprothrombinemia (PTU) • PTU inhibits peripheral T4 to T3 conversion X = the site of biochemical block by thioureas Disadvantages of RAIT When Compared to Long-term ATDT: Realizations of 1990’s and 2000’s • RAI may induce or worsen Graves’ Orbitopathy (GO) in 15-33% • RAIT practice not standardized with erratic clinical & biochemical outcomes Euthyroid goal (Eu-RAIT) The Thyrotoxicosis Therapy Follow-up Study, multiple, fixed or calculated SMALL activities assembled in 1961, comprises 35,000 subjects Hypothyroid goal (Ablation) treated for hyperthyroidism at over 20 medical Fixed activity (15 mCi), over & under treat a lot centers in the US and 1 in the UK between 1946 Radiation dose to thyroid, prolonged dosimetry and 1964. This is the largest group of Activity per g of thyroid, simple & fewest failures hyperthyroid patients that has been followed up for subsequent cancer and other health outcomes. Thyrotoxicosis Therapy Follow-up Study 1946-1964 Typical Approach to GD in the USA: First Decade of 21st Century • ATD ± beta blocker for 1-2 years • Stop therapy to check for remission • If no remission or patient recurs after short remission → RAIT or Surgery • Eu-RAIT used in early days, ablation became dominant after 2005 study that showed mortality advantage* • No standardization of hypo-RAIT technique, approaches vary widely * Franklyn JA, Sheppard MC, Maisonneuve P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA. 2005;294:71-80. Mark Tulchinsky, MD, FACNM, CCD 2 Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 RAIT n=102 pts MMI n=114 pts Abbreviation: MMI = Methimazole Between 1995 and 2013, Brazil (Campinas & São Paulo): What NM Docs Should Know? Reviewed • Be proactive in confronting GO concerns Post RAIT Hypothyroidism→ minimize Practice RAIT that has predictable outcome 15 mCi Guide referring about timing for TH replacement Selective steroid prophylaxis • Be proactive in improving symptoms before, during, and after RAIT Worsened Unchanged Pre-treat with ATDT, beta blockers RAITImproved group MZ group • Good practice – offer consultation service Villagelin, D. et al. Outcomes in Relapsed Graves' Disease Patients Following • Best practice – offer to consult and manage Radioiodine or Prolonged Low Dose of patients after RAIT Methimazole Treatment. Thyroid 2015. DOI: 10.1089/thy.2015.0195 Pre-RAIT Work-Up: Educate Patients (and Referring 99m − 131 TcO4 Scan + 24-Hr I Uptake Doctors) About RAIT at Consultation Document Etiology Chin • Minimized dietary (LID) and medical Iodine • Go over radiation precautions, pt. should come for RAIT unescorted, etc. • Assure pts. – they will leave the facility SSN Anterior Dominant Cold Nodule? Anterior - generally feeling the same as on arrival 99m - Document Benign Cause! TcO4 Thyroid Uptake = 2.45% (Normal 0.36-1.6%) • Review meds, provide guidance (monitor HR for beta blocker adjustments, etc.) • Explain RAIT comes as a capsule (pediatric Measure Uptake: cap. or liquid, if swallowing difficulties) • It doesn’t cause nausea – but expectation RAO LAO ±4 Hr. & 24 Hr. and/or nervousness sure could! Mild (Early) Graves’ Disease 24-Hr 131I uptake = 43% Mark Tulchinsky, MD, FACNM, CCD 3 Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 RAIT for Thyrotoxicosis HYPERTHYROIDISM: General Considerations TREATMENT GOAL • Absolute contraindication – Pregnancy and • RAIT Goals other*, document pregnancy test results Euthyroidism – futile in Graves’ & hypothetically may increase carcinogenic risk – not recommended • Treating a very toxic patient may result in Ablation – predictable, time-saver for pts & dead cells thyroid storm – pretreat with MZ (4-6 wks.) don’t turn cancerous – recommended (1) • Stop ATD’s for 2 d. (48 hrs), start uptake • Approach to Ablation day 3, measure uptake, scan & RAIT day 4 Fixed dose (15 mCi) – simple, but not as predictable • Beta-blocker can be continued, HR guided Radiation dose (cGy) based – multiday dosimetry makes • Re-starting ATDT post-RAIT, optional it impractical, simplified is same as below • Iodine (lithium) loading post-RAIT is Delivered activity per g of thyroid, normalized to 24hr uptake – simple, practical and rational optional, practiced rarely 1. Bahn RS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management *Contraindications: pregnancy, lactation, known or suspected thyroid guidelines of the American Thyroid Association and American Association of Clinical cancer, individuals unable to comply with radiation safety guidelines. Endocrinologists. Endocr Pract 2011;17:456-520. Relationship between thyroid radiation dose and Grave’s Disease RAIT: hypothyroidism rate in patients who were <18 years old mCi/g of Thyroid @ 24 hrs. • Most give 0.12-0.20 mCi of 131I/g of thyroid, normalized to 24 hr. uptake • Ablation activity (AA) coefficient at PSU is 0.24 mCi/g (developed empirically) • AA = (gland weight in g x 0.24 mCi/g) / 24 hr. uptake fraction (i.e. 0.5 for 50% uptake) • Gland weight: cannot palpate it for sure – 30 g; can palpate, but cannot see it – 40 g; can see it when pt. walks in – ≥ 60 g • “Fudge Factor” – give more to pts. who are older, on anti-thyroid meds, MNG, severe HT, Scott A. Rivkees, et al. Influence of iodine-131 dose on the outcome of hyperthyroidism rapid 131I turnover, larger glands in children. Pediatrics 2003;111:745-749. Response to 131I Therapy in Graves’: 0.24 mCi per gm of Thyroid Treatment Complications: Early (PSU Experience) • Typically None • Thyroiditis (sore throat) is the most common 1:40 Occurs 1-3 days post therapy Rarely needs medication Responds well to NSAIDs 25 75 300 Mark Tulchinsky, MD, FACNM, CCD 4 Optimal 131I Therapy of Thyrotoxicosis SNMMI Annual Meeting, 6/26/2018 Treatment Complications: Early Late Complication of RAIT • Exacerbation of thyrotoxicosis (~1%) Rare in ATD-pretreated, self limited • Ageusia – water swish/swallow after RAI Increase/start β-blockers and ± ATD’s • Very Rare complications – • Thyroid storm (0.3%) – ATD pretreatment Sialadenitis/Xerostomia diminishes risk • Hypoparathyroidism is extremely rare Key manifestation is fever • Hyperparathyroidism (parathyroid 131 Mean time to onset 6 days adenoma) – questionable relation to I Treatment of the thyroid storm: • There is no evidence of increased Thermoregulation, physiologic support secondary primary malignancy incidence Iodine (30 drops of SSKI a day) • No evidence of congenital defects PTU (900-1200 mg a day) Avoid conception for 6-12 months β-adrenergic blockade (propranolol,
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