Graves’ disease in a patient with Down syndrome: a shift from hyperthyroidism to hypothyroidism

Down syndrome (DS) is associated with an increased risk of multisystemic dysfunction, namely endocrine abnormalities. Thyroid dysfunction is the most common endocrinological disorder, and it can manifest as either hypothyroidism or hyperthyroidism. A 16-year-old patient with DS developed hyperthyroidism after a lifetime of alternating between subclinical hypothyroidism and euthyroidism. He presented new onset weight loss, agitation and diarrhoea. Laboratory studies were compatible with hyperthyroidism. Thyroid receptor antibodies (TRAbs) were positive, antithyroid peroxidase antibodies and thyroglobulin antibodies were negative. Antithyroid medication (methimazole) was prescribed and, despite therapy adjustments, laboratory evaluation revealed new onset hypothyroidism with persistently positive TRAbs. He experienced weight gain and remained in a hypothyroid state even with withdrawal of methimazole and administration of levothyroxine. This case illustrates an example of Graves’ disease with coexisting stimulating and inhibiting TRAbs that led to a shift from hyperthyroidism to hypothyroidism, a rare condition in patients with DS.

Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker

The prognosis of malignant gliomas such as glioblastoma multiforme (GBM) has remained poor due to limited therapeutic strategies. Thus, it is pivotal to determine prognostic factors for gliomas. Thyroid Receptor Interacting Protein 13 (TRIP13) was found to be overexpressed in several solid tumors, but its role and clinical significance in gliomas is still unclear. Here, we conducted a comprehensive expression analysis of TRIP13 to determine the prognostic values. Gene expression profiles of the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and GSE16011 dataset showed increased TRIP13 expression in advanced stage and worse prognosis in IDH-wild type lower-grade glioma. We performed RT-PCR and Western blot to validate TRIP13 mRNA expression and protein levels in GBM cell lines. TRIP13 co-expressed genes via database screening were regulated by essential cancer-related upstream regulators (such as TP53 and FOXM1). Then, TCGA analysis revealed that more TRIP13 promoter hypomethylation was observed in GBM than in low-grade glioma. We also inferred that the upregulated TRIP13 levels in gliomas could be regulated by dysfunction of miR-29 in gliomas patient cohorts. Moreover, TRIP13-expressing tumors not only had higher aneuploidy but also tended to reduce the ratio of CD8+/Treg, which led to a worse survival outcome. Overall, these findings demonstrate that TRIP13 has with multiple functions in gliomas, and they may be crucial for therapeutic potential.

Surgery for Grave’s Disease

Graves’ disease (GD) is the commonest cause of hyperthyroidism followed by toxic nodular goitre. Patients presenting as goitre with clinical features of hyperthyroidism are to be carefully evaluated with biochemically with thyroid stimulating hormone (TSH), free thyroxine (fT4) and radionuclide scan (Technitium-99/Iodine-123). Those with GD also have raised thyroid receptor stimulating antibody levels. Patients are simultaneously evaluated for eye disease and managed accordingly. Initial treatment is rendering patient euthyroid using anti thyroid drugs (ATD) and if remission does not occur either continue medical therapy or proceed for definitive therapy by radioactive iodine ablation (RAI) or surgery. In last decades there is ample literature preferring surgery as preferred definitive therapy. Surgery in thyroid disease has become safer with development of many intra-operative adjuncts but it should be performed by high volume thyroid surgeon. The procedure of choice is near total or total thyroidectomy as it avoids recurrences. Patients who are not eligible or willing for surgery can be managed with RAI.

The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves’ disease

Background: The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines. Methods: A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease. Results: A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease ( p < 0.001). Under anti-thyroid drugs treatment, thyroid-stimulating immunoglobulin value decreased gradually. A total of 21 patients had positive thyroid-stimulating immunoglobulin at the end of treatment. According to clinical fate of patients with Graves’ disease after withdrawal of anti-thyroid drugs, thyroid-stimulating immunoglobulin value and positivity in patients with relapse were significantly higher than that reported in patients with remission ( p = 0.001, p < 0.001). After adjustment for age, gender, initial thyroid receptor antibody, initial thyroid-stimulating immunoglobulin, and thyroid receptor antibody at the end of treatment, the odds ratio of positive thyroid-stimulating immunoglobulin for the risk of relapse was 33.271 (95% confidence interval: 4.741–233.458, p < 0.001) and odds ratio of quantitative thyroid-stimulating immunoglobulin was 1.009 (95% confidence interval: 1.002–1.015, p < 0.001). Conclusion: Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves’ disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE

We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4mg/kg), Sob (5mg/kg) or Sob-AM2 (5mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.HighlightsThyroid hormone, the thyromimetic Sob and its CNS penetrating prodrug, Sob-AM2, reduce disease severity, reduce myelin and axonal degeneration and protect oligodendrocytes in EAE.The benefits of Sob and Sob-AM2 may be via direct protective effects on oligodendrocytes and reduction in activity of microglia/macrophages.