Background Long-term follow-up after radioactive iodine therapy (RIT) for Graves’ disease and toxic thyroid autonomy is incompletely addressed by current guidelines. We retrospectively analyzed the clinical course of 1233 out of 1728 consecutive Graves’ disease (n = 536) and thyroid autonomy (n = 1192) patients after dosimetry-guided RIT to optimize follow-up. Methods Patients were referred between 1990 and 2018; follow-up was monitored according to available electronic registers with medical reports, including autopsies from 9 hospitals and 10 residential care homes. Results In total, 495/1728 cases were censored because of incomplete 6-month follow-up data. The conversion rates to hypothyroidism in Graves’ disease and different forms of thyroid autonomy can be deconvoluted into two follow-up periods: first year after RIT and afterward. The conversion rate in Graves’ disease was significantly higher than that in all thyroid autonomy subgroups during the first year but almost identical afterwards. Thyroxine substitution started between 10 and 7900 days after RIT at thyroid stimulating hormone between 0.11 and 177 µU/ml. Conclusions We advise earlier (2–3 weeks) first follow-up checks after RIT in all Graves’ disease patients and thyroid autonomy under antithyroid drugs (ATD) and re-checks every 2–4 weeks until conversion to hypothyroidism during the first year. The first check in thyroid autonomy without ATD should be after 3–4 weeks with re-checks every 4–6 weeks. After 1 year, both groups can be re-checked every 4–6 months over the next 5 years. The success rate of RIT in thyroid autonomyincreases with age but the history of RIT is rapidly lost during follow-up.

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