The role of thyroid hormone nuclear receptors in the heart: evidence from pharmacological approaches

This review evaluates the hypothesis that the cardiac effects of amiodarone can be explained—at least partly—by the induction of a local ‘hypothyroid-like condition’ in the heart. Evidence supporting the hypothesis comprises the observation that amiodarone exerts an inhibitory effect on the binding of T3 to thyroid hormone receptors (TR) alpha-1 and beta-1 in vitro, and on the expression of particular T3-dependent genes in vivo. In the heart, amiodarone decreases heart rate and alpha myosin heavy chain expression (mediated via TR alpha-1), and increases sarcoplasmic reticulum calcium-activated ATPase and beta myosin heavy chain expression (mediated via TR beta-1). Recent data show a significant similarity in expression profiles of 8,435 genes in the heart of hypothyroid and amiodarone-treated animals, although similarities do not always exist in transcripts of ion channel genes. Induction of a hypothyroid cardiac phenotype by amiodarone may be advantageous by decreasing energy demands and increasing energy availability

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition

Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients

CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. CONCLUSIONS: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients

Thyroid function, autoimmunity and nodules in hematological malignancies

Objective Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one.Materials and methods We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests.Results A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls.Conclusion In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls. Arch Endocrinol Metab. 2015;59(3):236-4

Graves' disease is associated with a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells

Introduction Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms. Herein we assessed the expression and function of galectin-1 and galectin-9 (Gal-1, Gal-9) in dendritic cells (DCs) from patients with AITD. Materials and Methods Peripheral blood samples from 25 patients with Graves’ disease (GD), 11 Hashimoto’s thyroiditis (HT), and 24 healthy subjects were studied. Thyroid tissue samples from 44 patients with AITD and 22 patients with goiter were also analyzed. Expression and function of Gal-1 and Gal-9 was assessed by quantitative RT-PCR, immunofluorescence and flow cytometry. Results A diminished expression of Gal-9, but not of Gal-1, by peripheral blood DCs was observed in GD patients, mainly in those with Graves´ ophthalmopathy, and a significant negative association between disease severity and Gal-9 expression was detected. In addition, the mRNA levels of Gal-9 and its ligand TIM-3 were increased in thyroid tissue from AITD patients and its expression was associated with the levels of Th1/Th12/Th17 cytokines. Immunofluorescence studies proved that intrathyroidal Gal-9 expression was confined to DCs and macrophages. Finally, in vitro functional assays showed that exogenous Gal-9 had a suppressive effect on the release of Th1/Th2/Th17 cytokines by DC/lymphocyte autologous co-cultures from both AITD patients and healthy controls. Conclusions The altered pattern of expression of Gal-9 in peripheral blood DCs from GD patients, its correlation with disease severity as well as its ability to suppress cytokine release suggest that Gal-9 could be involved in the pathogenesis of AITDThis work was supported by grants from the Fondo de Investigaciones Sanitarias (FISS) PI10/ 02521 and S2010/BMD-2328 TIRONET (Comunidad de Madrid), Spain (to MM) and the Fondo de Cooperación Internacional en Ciencia y Tecnología (FONCICYT) 95395, European Union-México (to RGA