Serum thyroid-stimulating hormone and anti-thyroglobulin antibody are independently associated with lesions in spinal cord in central nervous system demyelinating diseases

Abstract

Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR] = 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.

Figure 1. Changes in levels of TSH, TG-Ab, and TPO-Ab after ivMP administration in nine paired patients (a, b, c): changes of TSH; (d, e, f): changes of TG-Ab; (g, h, i): changes of TPO-Ab.

Figure 2. Frequency of abnormal thyroid parameters among NMO, TM, and MS patients at their first attack.

(a) In 96 patients, higher numbers of NMO and TM samples had abnormal levels of TSH, TG-Ab and TPO-Ab than MS samples (p<0.0001). (b) The 96 patients were divided into those with (n = 58) and without myelitis (n = 38). TSH, TG-Ab and TPO-Ab levels in patients with myelitis were significantly different to patients without myelitis. (c) Of 52 MS patients, greater numbers with myelitis showed abnormal TSH (p<0.0001) levels compared with those without myelitis.

Figure 3. Level of thyroid parameters among different groups at the first attack.

(a) In total patients (n = 96) and NMO (n = 19) and TM (n = 48) subgroups, TSH levels were not significantly different between AQP4 antibody positive or negative patients (p>0.05). In total patients (n = 96) and MS subgroup (n = 52), TSH levels were significantly different between patients with and without myelitis (p<0.05). (b) In total patients and of NMO and TM subgroups, TG-Ab levels were not significantly different between AQP4 antibody positive or negative patients (p>0.05). In total patients, TG-Ab levels were significantly different between patients with and without myelitis (p = 0.034). (c) In total patients, AQP4 antibody positive patients had higher TPO-Ab levels than AQP4 antibody negative patients (p = 0.007). Patients with myelitis had higher TPO-Ab levels than patients without myelitis (p = 0.021). Ab: AQP4 antibody; MY: myelitis; +: positive; -: negative; red dashed line: normal range.

Figure 4. MRI of spinal cord and thyroid parameters of representative cases.

A: MRI shows longitudinal extensive lesion in the cervical and thoracic cord (C3-T1) at the first attack; B: At the second attack, T2-weighed spinal MRI shows a lesion extending from C1 to T1; C: Immunofluorescence staining shows serum antibodies bind to the cytoplasmic membranes of follicular cells (short arrow) and thyroid microsoma (dot arrow); (a): Changes of TSH in myelitis attack and remission; (b): Changes of TG-Ab in myelitis attack and remission; (c): (a): Changes of TPO-Ab in myelitis attack and remission.