Prophylactic Central Neck Lymph Node Dissection Adds No Short-Term Benefit to Total Thyroidectomy for Differentiated Thyroid Cancer.

Background and Objectives: To answer the research question: "Is prophylactic central neck lymph node dissection (pCNLD) beneficial among differentiated thyroid carcinoma (DTC) patients?" Materials and Methods: This was a retrospective cohort study enrolling DTC patients treated at the University Hospital Kaspela, Bulgaria, from 30 January 2019 to October 2021. The predictor variable was presence of pCNLD (total thyroidectomy with vs. without pCNLD). The main outcome variables were postoperative complications (i.e., vocal cord paralysis, hypoparathyroidism, postoperative bleeding, and adjacent organ injury) and recurrence parameters. Appropriate statistics were computed with the significant level at p ≤ 0.05. Results: During the study period, 300 DTC patients (59.7% with pCNLD; 79.3% females) with an average age of 52 ± 2.8 years were treated. The mean follow-up period of the entire cohort was 45.8 ± 19.1 months. On bivariate analyses, TT with pCNLD, when compared to TT alone, required longer surgical time (mean difference: 9.4 min), caused nearly similar complications (except transient hypothyroidism: p = 0.04; relative risk, 1.32; 95% confidence interval, 1.0 to 1.73), and no significantly different recurrence events, time to recurrence, and recurrent sites. The benefit-risk analyses using the number needed to treat and to harm (NNT; NNH) also confirmed that TT plus pCNLD was not very beneficial in DTC management. Conclusion: The results of this study refute the benefit of pCNLD in DTC patient care with TT. Further well-designed studies in a larger cohort with a longer follow-up period are required to confirm this conclusion.

A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa.

Introduction: Although a considerable body of knowledge has been accumulated regarding the early diagnosis and treatment of oral squamous cell carcinoma (OSCC), its survival rates have not improved over the last decades. Thus, deciphering the molecular mechanisms governing oral cancer will support the development of even better diagnostic and therapeutic strategies. Previous studies have linked aberrantly expressed microRNAs (miRNAs) with the development of OSCC. Methods: We combined bioinformatical and molecular methods to identify miRNAs with possible clinical significance as biomarkers in OSCC. A set of 10 miRNAs were selected via an in silico approach by analysing the 3'untranslated regions (3'UTRs) of cancer-related mRNAs such as FLRT2, NTRK3, and SLC8A1, TFCP2L1 and etc. RT-qPCR was used to compare the expression of in silico identified miRNAs in OSCC and normal tissues (n=32). Results: Among the screened miRNAs, miR-21-5p (p < 0.0001), miR-93-5p (p < 0.0197), miR-146b-5p (p <0.0012), miR-155-5p (p < 0.0001), miR-182-5p (p < 0.0001) were significantly overexpressed, whereas miR-133b (p < 0.05) was significantly downregulated in OSCC tissues, a scenario confirmed in two additional OSCC validation cohorts: Regina Elena National Cancer Institute (IRE cohort, N=74) and The Cancer Genome Atlas Data Portal (TCGA cohort, N=354). Initial stage tumors (T1, T2) expressed significantly higher levels of miR-133b (p < 0.0004) compared to more advanced ones (T3, T4). Also, we identified miR-93-5p (p < 0.0003), miR-133b (p < 0.0017) and miR-155-5p (p < 0.0004) as correlated with HPV-induced OSCC. The high expression of these 6 miRNAs as a signature predicted shorter disease-free survival (DFS) and could efficiently distinguish OSCC cases from healthy controls with areas under the curve (AUC) of 0.91 with sensitivity and specificity of 0.98 and 0.6, respectively. Further target identification analysis revealed enrichment of genes involved in FOXO, longevity, glycan biosynthesis and p53 cancer-related signaling pathways. Also, the selected targets were underexpressed in OSCC tissues and showed clinical significance related to overall survival (OS) and DFS. Discussion: Our results demonstrate that a novel panel consisting of miR-21-5p, miR-93-5p, miR-133b, miR-146b-5p, miR-155-5p and miR-182-5p could be used as OSCC-specific molecular signature with diagnostic and prognostic significance related to OS and DFS.

Serum selenium concentration in patients with autoimmune thyroid disease.

Abstract.

Weight Gain after Treatment of Thyroid Dysfunction and Thyroid Surgery.

Thyroid surgery is generally recommended for malignant conditions and for some benign thyroid disorders. Many patients report weight gain after thyroidectomy especially during the first months following surgery. Studies on patients with Graves' disease treated either with antithyroid drugs or radioiodine confirm that these patients frequently gain weight after restoration of thyroid function. Other studies have also shown that there is considerable weight gain after thyroidectomy for both nodular goiter and thyroid cancer. Transient hypothyroidism during the postoperative period is often thought to be associated with weight gain after thyroidectomy. The role of a number of adipocytokines and their interaction with the thyroid function has been investigated in the pathogenesis of weight changes. Levothyroxine replacement or suppressive therapy after thyroidectomy has a different impact on the metabolic parameters independent of TSH levels. The long-term effects of the impaired T3/T4 ratio are not fully understood as there are no sensitive markers to assess the biological response of target organs and tissues. Future studies are needed to identify such parameters, provide new considerations for the treatment of patients after total thyroidectomy, and help determine individual target hormone levels to ensure a sustained euthyroid state.

Vitamin D and Autoimmune Thyroid Diseases - a Review.

The essential biological action of vitamin D is regulation of calcium and phosphorus metabolism and preserving bone health. In recent years there have been reports about the extraskeletal actions of vitamin D and its role in the regulation of immune system. Vitamin D supplementation appears to reduce the incidence of cardiovascular diseases, cancer, and infections and be able to reduce all-cause mortality. Deficiency of vitamin D has been found to correlate with the increased incidence of autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Autoimmune thyroid diseases (AITD), including Graves' disease, Hashimoto's thyroiditis are relatively common autoimmune disorders affecting more than 5% of general population. It has been shown that vitamin D receptors (VDR) and 1-alpha hydroxylase are expressed in papillary thyroid cancer and normal thyroid tissue, suggesting local synthesis of 1,25(OH)2D in the thyroid. While VDR gene polymorphism has been found in much research to be associated with AITDs, very few studies have examined the impact of vitamin D deficiency on the incidence of AITDs in humans with conflicting results. This review focuses on the association between vitamin D and autoimmune thyroid diseases and summarizes the results of vitamin D supplementation studies in patients with AITD.

Serum Levels of Incretin Hormones - GLP-1 and GIP in Patients with Type 1 Diabetes Mellitus.

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.

Risk Factors for Postpartum Thyroid Dysfunction in Euthyroid Women Prior to Pregnancy.

BACKGROUND: Thyroid dysfunction is common during the postpartum and the predisposing factors for its development are considered specific for the population studied. The aim of this study was to evaluate the risk factors for the occurrence of postpartum thyroid dysfunction (PPTD) in euthyroid women prior to pregnancy. MATERIALS AND METHODS: Forty-five women with PPTD and 55 age-matched euthyroid postpartum women from Plovdiv, Bulgaria were included in the study. TSH, FT4, FT3, TPOAb, TgAb, TRAb were measured and ultrasound evaluation of the thyroid was performed in the first trimester of pregnancy and during the postpartum. RESULTS: The study found higher risk of developing PPTD in women with family history of thyroid disease (OR 4.42; 95% CI 1.87,10.43), smokers (OR 4.01; 95% CI 1.72,9.35), personal history of autoimmune thyroid disease (OR 5.37; 95% CI 1.15,28.53), positive TPOAb (OR 18.12; 95% CI 4.93,66.65) and thyroid US hypoechogenicity during early pregnancy (OR 6.39; 95% CI 2.53,16.12) and those who needed levothyroxine during pregnancy (OR 3.69; 95% CI 1.28,10.61). BMI before pregnancy was significantly lower in women with PPTD than in euthyroid postpartum women (22.80±0.55 vs 26.25±0.97, p=0.013). The multivariate logistic regression analysis identified as most important independent risk factors for PPTD occurrence the TPOAb positivity during early pregnancy, family history of thyroid disease, smoking and lower BMI before pregnancy. CONCLUSION: Our data suggest that in the population studied several factors are associated with an increased risk of PPTD and screening for thyroid disorders among those women can be beneficial.

Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

Postpartum thyroid dysfunction in women with autoimmune thyroiditis.

INTRODUCTION: Autoimmune thyroiditis (AIT) is a predisposing factor for developing postpartum thyroid dysfunction (PPTD). AIM: To study the characteristics of PPTD in women with AIT. METHODS: Thirty-eight women with pre-existing AIT were included in the study. Thyroid-stimulating hormone, free triiodthyronine, free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies were measured and ultrasound evaluation of the thyroid gland was performed in the first trimester of pregnancy and during the first year following delivery. RESULTS: Thyroid dysfunction was recognized in 68.4% of the patients - 28.9% presented with hypothyroidism and 39.5 % with thyrotoxicosis. The immunological and morphological parameters did not differ between euthyroid women and those with thyroid dysfunction. At the end of the postpartum period restoration of euthyroid state (being on the treatment before pregnancy) was observed in 15.4% of patients with PPTD, while 84.6% required increase of the levothyroxine dose. The analysis found a significantly lower volume of the thyroid gland, shorter duration of the disease, a lower dose of levothyroxine before and during gestation in patients with impaired thyroid function at the end of the postpartum period. CONCLUSION: The risk of PPTD in women with AIT predating pregnancy is higher among women with preserved thyroid functional capacity motivating a thorough assessment of thyroid hormone levels and close follow-up of those women during the postpartum period.

Postpartum thyroiditis.

Postpartum thyroiditis (PPT) is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery or abortion. It is the most common thyroid disease in the postpartum period with incidence between 5 and 9%. In essence, it is an autoimmune inflammation of the thyroid, caused by changes in humoral and cell-mediated immune response. It has a characteristic biphasic course with an episode of transient thyrotoxicosis followed by transient or permanent hypothyroidism. Of all predisposing factors positive titers of thyroid peroxidase antibodies have the greatest importance. In some of the affected patients the disease course is marked by expressed hormonal disorders causing significant subjective symptoms. This underlines the need for early identification of risk groups aimed at prophylaxis and adequate treatment of thyroid dysfunction in the postpartum period. The frequency of PPT varies between analyses and studies on risk factors do not establish reliable predictive models for progression of the disease. This is due to the different methodology of research and the involvement of a number of genetic and non-genetic factors in different geographic regions. That is why implementation of mass screening programs is now controversial. The discrepancy in the opinions of researchers makes it necessary to have studies of the problem in performed in every clinical center in which the possible risk specific to the region and the population covered might be defined prognostically. The results of these studies can be used to introduce targeted and cost-effective screening for early detection of risk patients and prevention of morbidity and complications of PPT.

Cases of interferon-alpha and interferon-beta-induced thyroiditis.

Interferons are currently the major treatment modality for several malignant and non-malignant diseases such as chronic hepatitis C and B, multiple sclerosis, hematological malignancies, malignant melanoma, renal cell carcinoma, etc. Thyroid disorders develop in some of the interferon-treated patients with the incidence ranging from 1% to 35%. These complications may often result in dose reduction or discontinuation of interferon therapy. Interferon induced thyroid disorders can be classified as autoimmune and non-autoimmune thyroiditis. There are many studies on the development of thyroid dysfunction in interferon-alpha treated patients with chronic hepatitis C and in patients with multiple sclerosis treated with interferon-beta. There is a dearth of information about the incidence and characteristics of thyroid abnormalities in patients with hematological malignancies receiving interferon-alpha. A number of genetic determinants are discussed as causes for thyroid impairment (sex, age, ethnic group, genes involved in the thyroid immune regulation), as well as non-genetic factors (related to the underlying disease--hepatitis C virus; multiple sclerosis; therapeutic regimens of interferon administration, iodine concentration in the environment, presence of thyroid autoantibodies at the start of treatment, etc.). In this article we summarize the relevant data about the frequency and characteristics of thyroid disorders in patients treated with interferons, the risk factors and the mechanisms for their development and the peculiarities of the course, detection and treatment of these complications. The review of the literature motivates studying the thyroid function of specific groups of patients receiving interferon in order to clarify the influence of the factors drug and disease on the thyroid gland. Early detection and adequate treatment of thyroid dysfunction in these patients is important to avoid complications that may compromise treatment.

Early hypothyroidism after subtotal thyroidectomy in patients with Graves' disease--the role of the preoperative conservative treatment and hormonal status.

AIM: The aim of the present study was to evaluate the role of the preoperative antithyroid drug treatment and hormonal status in the development of early postoperative hypothyroidism after subtotal thyroidectomy in patients with Graves' disease. MATERIAL AND METHODS: Eighty-five patients with Graves' disease (males : females ratio 1:5.54, age range 19 to 64, 37.52 +/- 1.09 yrs) who had previously undergone surgical treatment were enrolled in the study. All patients underwent bilateral subtotal thyroidectomy with the amount of remnant tissue of 2-3 g for each lobe (total 4-6 g). Development of early (within one year after the operation) postoperative hypothyroidism was analyzed regarding the type of the antithyroid drug, preoperative dose, duration of the preoperative medical treatment, FT3, FT4, FT3/FT4 and hTSH. RESULTS: Forty six percent of all examined patients (54.12%) were euthyroid and 39 (45.88%/)--hypothyroid. Postoperative hypothyroidism was developed by 33.33% of the patients that had received preoperatively propylthiouracil compared with 50.82% of those treated with methymazol (p > 0.05). The duration of the preoperative treatment was 38.36 +/- 3.53 months for the hypothyroid patients and 30.11 +/- 2.34 months for the euthyroid patients (p < 0.05). Postoperative hypothyroidism developed in 58.70% of the patients with preoperatively suppressed thyroid-stimulating hormone (hTSH) and in 33.33% of those with normalized values of hTSH (p < 0.05). No statistically significant between-group difference was found in the preoperative dose of antithyroid agent, mean values of free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4, thyrotropic hormone (TSH). CONCLUSIONS: Longer preoperative antithyroid drug treatment and suppression of hTSH in the preoperative period correlated with higher risk of hypothyroidism after subtotal thyroidectomy. The type and the preoperative dose of the antithyroid agent, as well as the mean values of thyroid hormones before the operation have no prognostic significance for postoperative thyroid hypofunction.