Metamorphic Thyroid Autoimmunity in Down Syndrome: From Hashimoto’s Thyroiditis to Graves’ Disease and Beyond

Background: During the last years, it has been sporadically reported that Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) may follow one another in the same individuals, due to a sequential phenotypic conversion from GD to HT or vice versa.Objective and hypotheses: To shed further light on the specific relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity. Method: We have reconstructed the conversion process from HT to GD in a selected population consisting of 12 DS individuals aged between 3.0 and 13.5 years at HT diagnosis and between 4.1 and 19.9 years at GD diagnosis. All the patients underwent a treatment with methimazole (MMI), at a dose that was periodically adjusted on the basis of clinical findings and thyroid function tests. Results: After MMI treatment onset all patients exhibited, at varying time intervals, a prolonged clinical and biochemical remission of hyperthyroidism. In eight/12 patients this treatment is still being continued 2–7 years after its initiation.The mean MMI dosage needed to maintain euthyroidism in these eight patients was 0.12G0.02 mg/kg per day. In the remaining four patients MMI was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0–2.1 years after its withdrawal. All these four patients developed, from 0.1–0.3 years after MMI withdrawal, a biochemical picture of overt hypothyroidism and needed treatment with LT4 , that is now being continued since 2.0–2.1 years. No patients needed non-pharmacological therapies, such as surgery or radioiodine ablation. Conclusion: i) DS children may be incline to manifest over time a phenotypic metamorphosis from HT to GD; ii) A share of GD children with DS may subsequently fluctuate from hyperthyroidism to hypothyroidism; iii) In DS HT presentation is absolutely peculiar; iv) in DS GD is characterized by a mild biochemical and clinical course.