Hashimoto's Encephalopathy Co-Occurring with Graves' Disease in a Paediatric Patient: Efficacy of Early Plasma Exchange

By Yan Wang, Peisen Ruan, Hehe Chen

Affiliations

1. Paediatric Intensive Care Unit, Women and Children’s Hospital of Ningbo University, Ningbo, China

doi: 10.29271/jcpsp.2025.06.805

Sir,

Hashimoto's encephalopathy (HE) is a rare autoimmune disorder characterised by a spectrum of neurological manifestations, including cognitive impairment, altered consciousness, seizures, ataxia, and stroke-like symptoms.¹ Due to its non-specific and complex clinical presentation, HE is frequently misdiagnosed or overlooked, particularly in paediatric patients. The management of HE involves glucocorticoid therapy alongside thyroid function optimisation. In cases refractory to corticosteroids, immunosuppressive agents or intravenous immunoglobulin may be considered. Therapeutic plasma exchange (TPE), classified as a Class II indication for HE, has demonstrated favourable outcomes in treatment- resistant or recurrent cases. Yet, its optimal timing in children remains unclear.²

The authors report a 12-year male who was admitted with fever, persistent convulsions, and altered mental status. Over the preceding six months, the patient had experienced weight loss, personality changes, and memory decline.

Physical examination revealed thyroid gland enlargement. Thyroid function tests showed markedly elevated levels of free thyroxine (FT4) at 6.05 ng/dL and free triiodothyronine (FT3) at 14.0 pg/mL. Anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) were both >1000 IU/mL, while thyrotropin receptor antibodies (TRAb) were 21.99 IU/L, indicating significantly elevated anti-thyroid auto-antibodies. Thyroid ultrasound demonstrated thyroid enlargement with heterogeneous echotexture and increased vascularity. Brain MRI revealed abnormal signal intensities in the right temporo- parieto-occipital lobe, right dorsal thalamus, and right insular cortex (Figure 1). Cerebrospinal fluid analysis, including high- throughput genetic testing and specific anti-neuronal antibody assays, ruled out infectious encephalitis and other autoimmune encephalopathies. MRI and MRA excluded vascular and neoplastic aetiologies. Based on the 2016 diagnostic criteria for HE,³ the patient was diagnosed with HE coexisting with Graves' disease.

In addition to glucocorticoid and anti-thyroid medications, the patient underwent TPE within 48 hours of admission. Following three consecutive TPE sessions, the patient's symptoms improved rapidly, and thyroid function normalised (Figure 2). Although anti-thyroid antibody levels decreased initially and then rebounded to a sustained level (Figure 3), clinical symptoms continued to improve, leading to discharge after approximately 20 days. Glucocorticoids were gradually tapered and discontinued after three months. Follow-up evaluations showed no significant abnormalities in thyroid function or neurological status, with gradual resolution of MRI lesions (Figure  4).

Figure  1:  Initial cranial MRI results on the 6^th day of admission: Swelling in the right temporo-parieto-occipital lobe, right dorsal thalamus, and insular cortex. (A1) High signal on DWI. (A 2-4) Long signal shadows on T1-weighted imaging and T2-enhanced imaging (indicated by arrows).

Figure 2: Trends in free tri-iodothyronine (FT3) and serum free thyroxine (FT4) levels.

Figure 3: Trends in anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TGAb) levels.

Figure 4: Brain MRI results 5 months after discharge: In the right temporoparietal cortical region, (C1) DWI signal is no longer high, (C2 and 4) T1-weighted imaging and T2-enhanced imaging showing long signal shadows, (C3) FLAIR showing high signal. The lesion has significantly resolved (indicated by arrows).
 

In paediatric patients, HE often presents with seizures as the initial symptom and is more likely to result in neurological sequelae compared to adults.⁴ The application of adult diagnostic criteria to children lacks sensitivity, underscoring the need for heightened awareness of HE in paediatric populations. The pathophysiology of HE remains unclear, although the presence of elevated anti-thyroid autoantibodies and the efficacy of immunosuppressive treatments support an autoimmune mechanism. However, the role of anti-thyroid antibodies as diagnostic markers versus pathogenic agents remains controversial. In this case, the fluctuation of thyroid antibodies during treatment appears to support their role as diagnostic markers rather than pathogenic factors. TPE is typically reserved for HE patients intolerant to steroid side effects or unresponsive to steroid therapy, with limited reports of its use in children. In addition to conventional therapy, early initiation of TPE in this case led to rapid symptom resolution and sustained clinical improvement. Follow-up imaging demonstrated gradual resolution of MRI lesions, with no significant neurological sequelae observed to date. Given that TPE can remove circulating thyroid hormones, serum-binding proteins, and potentially inflammatory mediators released during critical states, early initiation of TPE in paediatric HE cases may help prevent adverse outcomes. Further studies are needed to establish optimal treatment protocols and to elucidate the precise role of anti-thyroid  antibodies  in  the  pathogenesis  of  HE.

FUNDING:
This work was supported by Ningbo Medical and Health Brand Discipline (PPXK2024-06), Medical and Health Technology Plan Projects of Zhejiang (2023RC085, 2023KY1117, and 2025KY273), Ningbo Health Technology Plan Project (2023Y23, 2024Y15), Ningbo Public Welfare Science and Technology Project (2024S145), Zhejiang Province Traditional Chinese Medicine Science and Technology Project (2025ZL122), Ningbo Clinical Research Centre for Children's Health and Diseases (2019A21002), and Ningbo Key Discipline of Paediatrics (2022-B17). The Innovation Project of Distinguished Medical Team in Ningbo (2022020405).
 

COMPETING   INTEREST:
The  authors  declared  no  conflict  of  interest.

AUTHORS’  CONTRIBUTION:
YW: Designed the study, analysed the data, and drafted the manuscript.
PR: Revised the manuscript critically.
HC: Supervised the study.
All authors approved the final version of the manuscript to be published.
 

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