Hyperthyroidism Can Precipitate Peak‐Dose Levodopa‐Induced Dyskinesia in Parkinson's Disease

Thyroid dysfunction may modulate Parkinson's disease (PD) symptoms; however, its relationship with levodopa-induced dyskinesia (LID) remains unclear.1, 2 We report a patient in whom hyperthyroidism precipitated peak-dose LID despite no prior history of dyskinesia. A 68-year-old Japanese woman with no thyroid disease developed right resting tremor at age 66 and was diagnosed with clinically established PD according to the International Parkinson and Movement Disorder Society (MDS) criteria. Treatment with levodopa/benserazide (100/25 mg twice daily) and a ropinirole patch (8 mg/day) kept symptoms slight-to-mild for 1.5 years. When off periods appeared, the levodopa/benserazide dose was increased to 100/25 mg three times daily. Two days later, she developed fatigue, fever, and pain with tenderness over the right thyroid lobe, accompanied by sweating, palpitations, and dyskinesia emerging after each levodopa dose, which she had never experienced before (Video 1A). Ten days later, laboratory testing (Table 1) and ultrasonography confirmed subacute thyroiditis. Prednisolone alleviated systemic symptoms but not dyskinesia. To evaluate the nature of the movements, an intravenous levodopa challenge (10-minute infusion of 71 mg) was performed. Before infusion, her MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score was 48, with a serum levodopa level of 3.3 ng/mL. After infusion, the score improved to 29, but generalized choreiform dyskinesia appeared (Video 1B) with a serum levodopa level of 2978.6 ng/mL, confirming peak-dose LID. Withdrawal of ropinirole alleviated dyskinesia, but restless legs syndrome (RLS) and early-morning off symptoms subsequently worsened. Restarting the ropinirole and reducing levodopa/benserazide to 75/18.75 mg three times daily controlled both RLS and off symptoms without troublesome dyskinesia. Three months after the onset of thyroiditis, inflammation resolved, laboratory values normalized (Table 1), and prednisolone was discontinued. Dyskinesia completely disappeared, but her off symptoms gradually worsened. Two months later (5 months after thyroiditis onset), another levodopa challenge was performed. Before infusion, her MDS-UPDRS III score was 45 (serum levodopa 14.2 ng/mL); after infusion, the score improved to 31 without dyskinesia (serum levodopa 1264.3 ng/mL; Video 1C). Increasing levodopa/benserazide to 100/25 mg three times daily with ropinirole (8 mg/day) improved off periods, and dyskinesia did not recur. The key finding of this case is that hyperthyroidism precipitated peak-dose LID in a PD patient without prior dyskinesia. Only one prior case has been reported.3 In that case, a 66-year-old woman developed chorea and off periods during hyperthyroidism, both resolving with antithyroid therapy. However, because chorea occurred simultaneously with moderate parkinsonism, it was unclear whether it truly represented peak-dose LID. Because hyperthyroidism can itself cause hyperkinesia, including chorea,1 careful distinction from peak-dose LID is essential and justified the serial levodopa challenges. In our patient, serial levodopa challenges during and after thyroiditis demonstrated that during thyroiditis, choreiform movements emerged in parallel with rising levodopa levels and motor improvement, whereas after the resolution of thyroiditis, equivalent motor improvement occurred without dyskinesia. These findings indicate typical peak-dose LID rather than hyperthyroidism-induced chorea. The complete disappearance of dyskinesia after normalization of thyroid function suggests hyperthyroidism played a decisive role independent of PD progression. The mechanism remains unclear, but striatal dopaminergic receptor hypersensitivity,4 along with genetic, body weight, sex, and immune/inflammatory factors may contribute.2, 5 In summary, our findings provide the first clear evidence that hyperthyroidism can precipitate peak-dose LID in PD. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. S.T.: 1A, 1B, 1C, 2A. H.S.: 1B, 1C, 2B. T.N.: 1B, 1C, 2B. N.A.: 2B. H.S: 1B, 1C, 2B. Ethical Compliance Statement: This study did not require approval by an institutional review board, as it describes a single clinical case and was conducted in accordance with the principles of the Declaration of Helsinki. Verbal and written informed consent were obtained from the patient for publication of this case study and the accompanying video material. The consent form explicitly stated that the patient understood that their medical information and still or video images related to the conditions of hyperthyroidism, Parkinson's disease, and dyskinesia might be published in academic journals, including online access, and could be viewed by healthcare professionals and the general public. The patient also understood that all personally identifiable information would be removed and that the consent could be withdrawn at any time. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work and the authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the previous 12 months: ST has received honoraria and travel expenses from AbbVie GK. for speaking at meetings, and grants from PDR Pharma Inc. NA has received honoraria for lecturing from Mitsubishi Tanabe Pharma, Biogen, Eisai, Alexion, Eli Lilly, Kowa, Novartis, and Argenx, as well as research grants from the Japan Agency for Medical Research and Development (AMED) and the Grants-in-Aid for Scientific Research. He has also served as a consultant for Ono Pharma and Biogen. HS has received honoraria and travel expenses from Kyowa Kirin Co., Ltd., Eisai Co., Ltd., Sumitomo Pharma Co., Ltd., Medtronic Japan Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiyo Pharma Co., Ltd., AbbVie GK., InSightec Japan Co., Ltd., and consultation fee from e-Projection K.K. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.