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Background  It is known that Hashimoto’s thyroiditis (HT) may progress to Graves’ disease (GD) and that this phenomenon may be more frequent in the patients with Down syndrome (DS).    Aims  To shed light on the relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity.    Patients and Methods  We reconstructed the conversion process from HT to GD in 12 DS children. All the data recorded at HT diagnosis and throughout the time interval from entry to GD presentation were retrospectively taken from patients’ files, as well as those recorded at GD diagnosis and during the subsequent evolution.  From GD diagnosis all patients underwent methimazole treatment, at a dose that was adjusted on the basis of clinical findings and thyroid tests.    Results  Time interval between HT and GD was not different in the seven patients who received during that time a L-thyroxine (L-T4) treatment than in those who were not treated. After methimazole onset all patients exhibited a prolonged remission of hyperthyroidism. In 8/12 patients this treatment is still being continued 2–7 years after its initiation. The mean methimazole dosage needed to maintain euthyroidism in these eight patients was 0.12 ± 0.02 mg/kg/day.  In the remaining four patients methimazole was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0–2.1 years after its withdrawal. These patients developed, 0.1–0.3 years after methimazole withdrawal, a picture of overt hypothyroidism and needed treatment with L-T4, that is now being continued.  No patients needed non-pharmacological therapies.    Conclusions  1) DS children might be incline to manifest over time a phenotypic metamorphosis from HT to GD and to subsequently fluctuate from hyperthyroidism to hypothyroidism; 2) in DS GD may have a mild biochemical and clinical course.

Metamorphic thyroid autoimmunity in Down Syndrome: from Hashimoto’s thyroiditis to Graves’ disease and beyond