Pre-operative use of Lugol’s iodine in a case with toxic adenomatous goiter

Euthyroid state is considered a requisite before planning a thyroid surgery. Before such a surgery, pharmacotherapy can be used for managing a hyperthyroid state. It warrants a long-term treatment with pharmacotherapy agents like imidazole class (carbimazole, methimazole) or propylthiouracil. In cases with large goiters, with pressure symptoms like dyspnoea, dysphagia, dysphonia; a surgeon would prefer a pharmacotherapy with a quicker action than the established agents. Lugol’s iodine was used pre-operatively before the advent of newer agents. In rural areas, where patients present with large goiters, hyperthyroid states due to lack of awareness and availability of the modern pharmacotherapy, Lugol’s iodine can be a rescue pre-operative therapy to make such a patient euthyroid and to decrease the vascularity of the goiter, which facilitates a safer thyroid surgery.

Hyperthyroidism in Takotsubo syndrome: prevalence, clinical features and long-term outcomes

Background Takotsubo syndrome (TTS) is an increasingly recognized form of transient left ventricular dysfunction, often completely reversible. The exact pathogenesis is not fully understood, but central role of adrenergic dysfunction has been widely accepted. A possible link between hyperthyroidism and TTS has been hypothesized, since thyroid and adrenergic systems are in closely connection. Nevertheless, clinical study to define the association between hyperthyroidism and TTS is still lacking. Purpose This study aimed to assess prevalence, clinical features and long-term outcomes of hyperthyroidism at presentation in TTS patients. Methods Overall, 590 TTS patients from 23 centers were included in this prospective registry. Thyroid profile was available for 314 patients at time of TTS admission. Patients in hypothyroid state (n=32) according to TSH value were excluded. The remaining 282 patients were divided in normal thyroid state and hyperthyroid state according to TSH value, respectively 240 (85%) and 42 (15%) patients. Results The median age was 73±10 and the female rate was 93%. TTS related to physical trigger was mostly detected in hyperthyroidism patients (52% vs 30%, respectively in hyperthyroid state and normal thyroid state; p=0.005); while, TTS related to emotional trigger was less common (19%, vs 38%, respectively in hyperthyroid state and normal thyroid state; p=0.016). In TTS unprovoked by a stress factor, there was no statistical difference in thyroid state (29% vs 31%, respectively in hyperthyroid state and normal thyroid state; p=0.690). Follow-up rate was 95% and follow-up length was 41±36 months. At long-term follow-up, mortality rate was 39% and 20% in hyperthyroidism and normal thyroid state, respectively (p=0.008; Figure 1) and adverse event rates (the composite of all-cause death, myocardial infarction and stroke) were 39% and 24% in hyperthyroid state and normal thyroid state, respectively (p=0.034). At multivariable analysis, hyperthyroidism resulted as a strong predictor of mortality (OR 3.82, 95% CI: 1.71–8.50; p=0.001) and of adverse event rates (OR 2.18, 95% CI: 1.19–3.98; p=0.011). Conclusion Hyperthyroidism at presentation is relatively common in TTS patients and associated with physical triggers and unfavorable long-term prognosis. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

Thyroid hormones critically modulate body homeostasis and haemostasis by regulating energy and metabolism. Previous studies have focused on individual pathways or proteins that are affected by increases in thyroid hormone levels, while an overall plasma proteomic signature of this increased level is lacking. Herein, an integrated untargeted proteomic approach with network analysis was used to identify changes in circulating proteins in the plasma proteome between hyperthyroid and euthyroid states. Plasma from 10 age-matched subjects at baseline (hyperthyroid) and post treatment with carbimazole (euthyroid) was compared by difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization time of flight (MALDI TOF) mass spectrometry (MS). A total of 20 proteins were identified with significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two states (12 increased and 8 decreased in abundance in the hyperthyroid state). Twelve protein spots corresponding to ten unique proteins were significantly more abundant in the hyperthyroid state compared with the euthyroid state. These increased proteins were haptoglobin (HP), hemopexin (HPX), clusterin (CLU), apolipoprotein L1 (APOL1), alpha-1-B glycoprotein (A1BG), fibrinogen gamma chain (FGG), Ig alpha-1 chain C region (IGHA1), complement C6 (C6), leucine rich alpha 2 glycoprotein (LRG1), and carboxypeptidase N catalytic chain (CPN1). Eight protein spots corresponding to six unique proteins were significantly decreased in abundance in the hyperthyroid samples compared with euthyroid samples. These decreased proteins were apolipoprotein A1 (APOA1), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), plasminogen (PLG), alpha-1 antitrypsin (SERPINA1), fibrinogen beta chain (FGB), and complement C1r subcomponent (C1R). The differentially abundant proteins were investigated by ingenuity pathway analysis (IPA). The network pathway identified related to infectious disease, inflammatory disease, organismal injury and abnormalities, and the connectivity map focused around two central nodes, namely the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. The plasma proteome of patients with hyperthyroidism revealed differences in the abundance of proteins involved in acute phase response signaling, and development of a hypercoagulable and hypofibrinolytic state. Our findings enhance our existing knowledge of the altered proteins and associated biochemical pathways in hyperthyroidism.

Changes in serum hepcidin according to thyrometabolic status in patients with Graves’ disease

Introduction Hepcidin is an acute-phase protein and a key regulator of iron homeostasis. Anaemia frequently occurs in patients with thyroid dysfunction, and hepcidin may be a potential link. Objectives Prospective assessment of hepcidin serum concentration and other parameters related to Fe homeostasis in hyperthyroid patients in the course of GD at diagnosis and during remission. Patients and Methods Out of the 70 patients recruited, 42 (32 women, 10 men), aged 42.5 ± 15.1 years, met the inclusion criteria. Clinical and biochemical assessment, including hepcidin measurement by ELISA, was performed at baseline (T0) and after restoration of euthyroidism (T1). Results Hepcidin concentration at T0 in the 24 patients who completed the study was significantly higher than the value during euthyroidism (28.7 (8.1–39.4) ng/mL vs 7.9 (4.3–12.9) ng/mL, P < 0.001). Hepcidin level was most significantly correlated with ferritin (rho = 0.723) in women at T0. In both men (377 (171–411) vs 165 (84–237) ng/mL, P = 0.001) and women (84 (23–104) vs 35 (16–64) ng/mL, P = 0.001), a significant decrease in ferritin level was demonstrated following therapy. A significant (P < 0.001) increase in mean corpuscular volume (MCV) (83.5 (82.5–87.1) vs 89.5 (88.8–90.0) fL) and mean concentration of haemoglobin (MCH) (29.0 (28.0–29.4) vs 30.4 (29.5–31.1) pg) was observed. Conclusions Hepcidin and ferritin decrease significantly during the transition from a hyperthyroid state to euthyroidism in patients with GD. The observed changes occur in parallel to iron homeostasis fluctuations. During the transition from the hyperthyroid state to euthyroidism, the improvement of haematological status is reflected mainly by the increase in MCV and MCH.

Graves' Disease and Diabetes Mellitus

Thyroid hormones play an important role in the metabolic propesses. Its disturbances will involve several organs, consequently. A 5 year old girl with Graves' diseases, after several weeks of treatment with propylthiouracil (PTV), developed thyrotoxicosis crisis and diabetes mellitus with ketoacidosis; a condition which is usually fatal. Treatment toward the hyperthyroid state overcome the diabetic stage, eventually. This report is an example of an endocrinological interaction in a hyperthyroid patient. Therefore, the diabetogenic effect of hyperthyroxinemia should not be overlooked.

Value of Apoptotic, Antiapoptotic, and Cell Proliferation Markers in the Treatment of Graves’ Disease

To better understand the genesis of autoimmunity in Graves’ disease (GD), it is essential to study the mechanism of apoptosis and cell proliferation in thyroid cells and intrathyroidal lymphocytic infiltrate of GD patients. Methods. A cross sectional, observational study performed by evaluating histopathological samples of thyroidectomy products from GD patients using immunohistochemistry. New histological sections were prepared for immunohistochemical analysis with markers of cell proliferation, antiproliferation, apoptosis, and antiapoptosis. Results. Patients with GD who underwent radioiodine therapy (RIT) had a lower lymphocytic expression level of p27Kip1, and those who took beta-blockers had higher expression levels of BID (BH3-interacting domain) and a lower Ki-67 expression level in thyrocytes than those who did not. The association of a shorter diagnostic time with a lower expression level of MCL-1 in thyroid cells suggests that the hyperthyroid state was related to a lower antiapoptotic effect on thyrocytes. In comparison to patients with GD not using antithyroid drugs (ATD), we found a lower expression level of BID in lymphocytes for those who used ATD. Conclusion. In GD, the hyperthyroid state was associated with a lower antiapoptotic effect on thyroid cells. RIT, beta-blockers, and thionamide act by stimulating apoptosis of thyrocytes by intrathyroidal lymphocytes.