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Open access

Qing Zhu, Jianbin Su, Xueqin Wang, Mengjie Tang, Yingying Gao, and Dongmei Zhang

Graves’ disease (GD), an organ-specific autoimmune disease, is the most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and sTNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no significant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD group. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was positively correlated with complement C3. Multiple linear regression analysis suggests that serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. According to the median value of FT3 level, GD patients were further divided into a high FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group were significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play an important role in anti-inflammatory and immune response in GD.

Open access

Xichang Wang, Xiaochun Teng, Chenyan Li, Yushu Li, Jing Li, Weiping Teng, Zhongyan Shan, and Yaxin Lai

Objective

To conduct a questionnaire survey of the current clinical practice for overt hyperthyroidism in China.

Methods

An online questionnaire survey was conducted in July 2020. The two questionnaires covered 35 and 8 questions about non-pregnancy and pregnancy clinical practice for overt hyperthyroidism, respectively.

Results

One thousand, two hundred fifty-six physicians participated. Chief physicians and associate chief physicians accounted for 58.6% of the participants. Approximately 95.2% of the respondents chose the thyrotropin receptor antibody (TRAb) test to clarify the etiology of thyrotoxicosis, while only 27.0% of them chose radioactive iodine uptake (RAIU). In terms of treatment for non-pregnant patients, anti-thyroid drugs (ATDs) were the first choice, and most of the clinicians chose methimazole. Compared with clinicians in recent studies, Chinese physicians used serum TRAb to diagnose Graves’ disease more commonly, and there were obviously more physicians preferring ATDs. For maternal hyperthyroidism, most physicians preferred propylthiouracil administration before or during the first trimester, which is consistent with the 2016 American Thyroid Association (ATA) guidelines. In terms of the initial ATD dose, monitoring the treatment process, indications for ATD withdrawal and treatment of special cases, the preferences of Chinese physicians were generally consistent with the guidelines.

Conclusion

Chinese physicians can generally follow the ATA guidelines for the diagnosis and treatment of hyperthyroidism. Moreover, there are small differences from foreign studies or the guidelines with respect to particular problems. These findings provide evidence for future clinical research in China.

Open access

Chenjia Tang, Yanting Dong, Lusi Lu, and Nan Zhang

Objective

This study was designed to explore the relationships between the clinical characteristics and outcomes of patients with subacute thyroiditis (SAT).

Design

This is a single-center retrospective study.

Patients

Eighty-nine patients with SAT who were hospitalized in the Sir Run Run Shaw Hospital in Zhejiang, China, from October 2014 to September 2020 were included.

Methods

The Mann–Whitney U-test, chi-square test, and Cox regression analysis were conducted to identify the relationships between clinical characteristics and outcomes. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff levels of C-reactive protein (CRP) and thyroid-stimulating hormone (TSH).

Results

The hypothyroidism and recurrence rates were 15.7 and 16.9%, respectively. CRP (≥72.0 mg/L), TSH (<0.02 mIU/L), and free triiodothyronine (fT3) (≥4.10 pg/mL) were associated with hypothyroidism. The cutoff level was 97.80 mg/L for CRP (area under the curve (AUC), 0.717, P = 0.014; sensitivity, 57.1%; specificity, 84.0%) and 0.10 mIU/L for TSH (AUC, 0.752, P = 0.004; sensitivity, 100%; specificity, 46.0%) by ROC curve analysis for hypothyroidism. The factors under study were not associated with recurrence.

Conclusion

CRP and TSH were risk factors for hypothyroidism in SAT. Thyroid functions should be monitored closely for the early detection of hypothyroidism, especially in patients with CRP levels of more than 97.80 mg/L and TSH levels of less than 0.10 mIU/L.

Open access

Chun-feng Lu, Wang-shu Liu, Xiao-qin Ge, Feng Xu, Jian-bin Su, Xue-qin Wang, and Yan Wang

Background

Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.

Methods

A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.

Results

Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.

Conclusions

Our results demonstrated that serum ADA levels were closely associated with GD.

Open access

Dimitra Argyro Vassiliadi, Ioannis Ilias, Maria Pratikaki, Edison Jahaj, Alice G Vassiliou, Maria Detsika, Kleio Ampelakiotou, Marina Koulenti, Konstantinos N Manolopoulos, Stamatis Tsipilis, Evdokia Gavrielatou, Aristidis Diamantopoulos, Alexandros Zacharis, Nicolaos Athanasiou, Stylianos Orfanos, Anastasia Kotanidou, Stylianos Tsagarakis, and Ioanna Dimopoulou

Objective

Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients.

Design

Cohort observational study.

Methods

We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism.

Results

A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of negative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare.

Conclusions

NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients.

Open access

Jiayang Lin, Peizhen Zhang, Yan Huang, Xueyun Wei, Dan Guo, Jianfang Liu, Deying Liu, Yajuan Deng, Bingyan Xu, Chensihan Huang, Xiaoyu Yang, Yan Lu, Lijing Jia, and Huijie Zhang

Background:

Glycoprotein non-metastatic protein B (Gpnmb) has been identified as a new cytokine secreted by hepatocyte that plays an important role in balancing lipid homeostasis and development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Gpnmb and hyperthyroid in humans.

Methods:

We measured serum Gpnmb in 180 hyperthyroid patients and 82 healthy subjects that were recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months.

Results:

Hyperthyroid subjects had higher levels of circulating Gpnmb than healthy controls (47.8 ± 10.1 ng/mL vs 31.0 ± 4.9 ng/mL, P < 0.001). Subjects with higher levels of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating Gpnmb. After thionamide treatment, levels of circulating Gpnmb in hyperthyroid subjects remarkably declined with significant improvement of thyroid function (P < 0.001). Furthermore, the change of circulating Gpnmb levels was significantly associated with basal metabolic rate (BMR) and thyroid hormones, including free T3 and free T4, adjusting for age, gender, smoking and BMI before thionamide treatment. In multivariable logistic regression analyses, circulating Gpnmb was significantly associated with risks of hyperthyroidism (OR (95% CI): 1.44 (1.20–1.74), P < 0.001), adjusted for age, gender, BMI, fasting glucose, HOMA-IR, LDL-cholesterol, ALT and AST.

Conclusions:

These findings indicate that circulating Gpnmb concentrations are independently associated with hyperthyroid, suggesting that circulating Gpnmb may be a predictor of risk for hyperthyroidism and can be used for therapeutic monitoring.

Open access

Nannan Bian, Xiaomeng Sun, Biao Zhou, Lin Zhang, Qiu Wang, Yu An, Xiaohui Li, Yinhui Li, Jia Liu, Hua Meng, and Guang Wang

Objective

Bariatric surgery has become the most effective treatment for morbid obesity. Increasing evidence showed that bariatric surgery can alleviate insulin resistance and influence thyroid function. This study aimed to investigate the relationship between changes in thyroid function and adipose tissue insulin resistance (adipo-IR) after bariatric surgery.

Methods

A total of 287 non-diabetic participants with regular thyroid function were recruited and divided into the lean, overweight and obese groups. Among them, 50 morbidly obese patients submitted to bariatric surgery.

Results

The obese group had a higher level of adipo-IR, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), FT3/free thyroxine (FT4) and metabolism disorders than the lean and overweight groups. BMI was correlated with TSH, FT3, FT3/FT4 and adipo-IR (r = 0.309, 0.315, 0.322 and 0.651, respectively, all P < 0.001). Adipo-IR was significantly correlated with TSH (r = 0.402, P < 0.001), FT3 (r = 0.309, P < 0.001), and FT3/FT4 (r = 0.228, P < 0.05). Bariatric surgery resulted in a sharp decline in BMI, adipo-IR, TSH, FT3 and FT3/FT4 levels, meanwhile, metabolic disorders improved. The decrease in BMI after bariatric surgery was significantly correlated with reductions in adipo-IR (r = 0.577, P < 0.001) and TSH (r = 0.401, P = 0.005). Interestingly, the fasting blood glucose, fasting insulin, adipo-IR and TSH in the higher TSH group decreased more remarkably than in the lower TSH group.

Conclusion

Obese individuals with higher TSH levels had an obvious metabolic improvement after bariatric surgery.

Open access

Salman Razvi, Sanaa Mrabeti, and Markus Luster

The current standard of care for hypothyroidism is levothyroxine (LT4) monotherapy to reduce levels of thyrotropin (thyroid-stimulating hormone, TSH) within its reference range and amelioration of any symptoms. A substantial minority continues to report hypothyroid-like symptoms despite optimized TSH, however. These symptoms are not specific to thyroid dysfunction and are frequent among the euthyroid population, creating a therapeutic dilemma for the treating clinician as well as the patient. We present a concise, narrative review of the clinical research and evidence-based guidance on the management of this challenging population. The clinician may endeavor to ensure that the serum TSH is within the target range. However, the symptomatic patient may turn to alternative non-evidence-based therapies in the hope of obtaining relief. Accordingly, it is important for the clinician to check for conditions unrelated to the thyroid that could account for the ongoing symptoms such as other autoimmune conditions, anemia or mental health disorders. Systematic and thorough investigation of the potential causes of persistent symptoms while receiving LT4 therapy will resolve the problem for most patients. There may be some patients that may benefit from additional treatment with liothyronine (LT3), although it is unclear as yet as to which patient group may benefit the most from combined LT4 + LT3 therapy. In the future, personalized treatment with LT4 + LT3 may be of benefit for some patients with persistent symptoms of hypothyroidism such as those with polymorphisms in the deiodinase enzyme 2 (DIO2). For now, this remains a subject for research.

Open access

Stine Linding Andersen, Louise Knøsgaard, Aase Handberg, Peter Vestergaard, and Stig Andersen

Objective

A high activity of the deiodinase type 2 has been proposed in overweight, obese, and smoking pregnant women as reflected by a high triiodothyronine (T3)/thyroxine (T4) ratio. We speculated how maternal adiposity and smoking would associate with different thyroid function tests in the early pregnancy.

Design

Cross-sectional study within the North Denmark Region Pregnancy Cohort.

Methods

Maternal thyroid-stimulating hormone (TSH), total T4 (TT4), total T3 (TT3), free T4 (fT4), and free T3 (fT3) were measured in stored blood samples (median gestational week 10) by an automatic immunoassay. Results were linked to nationwide registers, and live-birth pregnancies were included. The associations between maternal adiposity (overweight or obese), smoking, and log-transformed TSH, fT3/fT4 ratio, and TT3/TT4 ratio were assessed using multivariate linear regression and reported as adjusted exponentiated β coefficient (aβ) with 95% CI. The adjusted model included maternal age, parity, origin, week of blood sampling, and diabetes.

Results

Altogether 5529 pregnant women were included, and 40% were classified with adiposity, whereas 10% were smoking. Maternal adiposity was associated with higher TSH (aβ 1.13 (95% CI 1.08–1.20)), whereas maternal smoking was associated with lower TSH in the early pregnancy (0.875 (0.806–0.950)). Considering the T3/T4 ratio, both maternal adiposity (fT3/fT4 ratio: 1.06 (1.05–1.07); TT3/TT4 ratio: 1.07 (1.06–1.08)) and smoking (fT3/fT4 ratio: 1.07 (1.06–1.09); TT3/TT4 ratio: 1.10 (1.09–1.12)) were associated with a higher ratio.

Conclusions

In a large cohort of Danish pregnant women, adiposity and smoking showed opposite associations with maternal TSH. On the other hand, both conditions were associated with a higher T3/T4 ratio in early pregnancy, which may reflect altered deiodinase activity.

Open access

Paraskevi Kazakou, Stavroula A Paschou, Theodora Psaltopoulou, Maria Gavriatopoulou, Eleni Korompoki, Katerina Stefanaki, Fotini Kanouta, Georgia N Kassi, Meletios-Athanasios Dimopoulos, and Asimina Mitrakou

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.