Thyroid Function in Molar Pregnancies

Introduction: Molar pregnancies represent a significant burden of disease on the spectrum of gestational trophoblastic diseases. Vaginal bleeding being the most common occasionally, molar pregnancy is complicated by hyperthyroidism, which may require treatment. Aims: To determine thyroid function test and association of hyperthyroidism among the cases of molar pregnancy. Methods: This is a hospital-based cross-sectional study conducted in the department of Obstetrics and Gynecology, Nepalgunj Medical College and Teaching Hospital, Kohalpur. Sixty cases of molar pregnancy were included during the study period from February 2020 to January 2021.Patients having history of known thyroid disorders were excluded. Results: Prevalence of molar pregnancy in our study was 5.4 per thousand pregnancies in our hospital. Molar pregnancy and hyperthyroidism, both were common in the age group of 21-35 years. Hyperthyroidism was present in 10% patients. Enlarged thyroid was seen in 3.3%, tremor was present in 3.3%, and palpitation in 21.5%. Five (8.3%) patients with hyperthyroidism were underweight. Majority of patients with hyperthyroidism, beta humanchorionic gonadotrophhin level was more than three lakhs and it was mostly associated with complete hydatidiform mole compared to partial hydatidiform mole. Thyroid storm was not experienced in any of the patients. Conclusion: The rate of molar pregnancy is high. Hyperthyroidism in molar pregnancy is not uncommon. High levels of human chorionic gonadotropin, complete hydatiform mole are directly associated with hyperthyroidism. Awareness of this condition is important for diagnosis and treatment to prevent life threatening complications.

The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients

BackgroundBoth lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission.ResultsA total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001).ConclusionTSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.

Hyperthyroidism in Graves’ disease causes sleep disorders related to sympathetic hypertonia

Context It is well known that Graves’ disease (GD) causes sleep disorders (SD). However, the characteristics and associated factors of SD and its clinical course post-hyperthyroidism normalization remain unclear. Objective To clarify the characteristics and associated factors of subjective SD and its clinical course after GD treatment. Design, setting, and study participants From November 2017 to October 2020, we enrolled 72 participants (22 newly diagnosed with GD with untreated hyperthyroidism, 20 previously diagnosed with GD with normal thyroid function, and 30 normal controls) with no other underlying sleep disorder-related diseases. We compared the groups at enrollment and conducted prospective observations after 12 months of treatment on participants with newly diagnosed GD. Main outcome measures Differences and changes in the Pittsburgh Sleep Quality Index (PSQI) global and component sleep quality scores. Results PSQI global sleep quality scores (p = 0.036) and sleep disturbance scores (p = 0.011) were significantly different among the three groups, and were highest in the untreated hyperthyroidism group. Multiple regression analysis demonstrated that free thyroxine level, which was positively correlated with sympathetic tone (ST) as evaluated by pulse rate and urinary total metanephrines, was associated with poorer PSQI global sleep quality scores independently of other factors (p = 0.006). Prospective observation showed that PSQI global sleep quality scores (p = 0.018) and sleep disturbance scores (p = 0.011) significantly improved with thyroid function normalization and ST attenuation. Conclusions Hyperthyroidism caused by GD augmented ST and exacerbated subjective SD. Normalization of hyperthyroidism caused by GD improved subjective SD.

A Novel Nomogram for Predicting the Risk of Premature Delivery Based on the Thyroid Function in Pregnant Women

BackgroundMaternal thyroid dysfunction and autoantibodies were associated with preterm delivery. However, recommendations for cutoff values of thyroperoxidase antibody (TPOAb) positivity and thyroid-stimulating homone (TSH) associated with premature delivery are lacking.ObjectiveTo identify the pregnancy-specific cutoff values for TPOAb positivity and TSH associated with preterm delivery. To develop a nomogram for the risk prediction of premature delivery based on maternal thyroid function in singleton pregnant women without pre-pregnancy complications.MethodsThis study included data from the International Peace Maternity and Child Care Health Hospital (IPMCH) in Shanghai, China, between January 2013 and December 2016. Added data between September 2019 and November 2019 as the test cohort. Youden’s index calculated the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration. Univariate and multivariable logistic regression analysis were used to screen the risk factors of premature delivery. The nomogram was developed according to the regression coefficient of relevant variables. Discrimination and calibration of the model were assessed using the C-index, Hosmer-Lemeshow test, calibration curve and decision curve analysis.Results45,467 pregnant women were divided into the training and validation cohorts according to the ratio of 7: 3. The testing cohort included 727 participants. The pregnancy-specific cutoff values associated with the risk of premature delivery during the first trimester were 5.14 IU/mL for TPOAb positivity and 1.33 mU/L for TSH concentration. Multivariable logistic regression analysis showed that maternal age, history of premature delivery, elevated TSH concentration and TPOAb positivity in the early pregnancy, preeclampsia and gestational diabetes mellitus were risk factors of premature delivery. The C-index was 0.62 of the nomogram. Hosmer-Lemeshow test showed that the Chi-square value was 2.64 (P = 0.955 > 0.05). Decision curve analysis showed a positive net benefit. The calibration curves of three cohorts were shown to be in good agreement.ConclusionsWe identified the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration associated with preterm delivery in singleton pregnant women without pre-pregnancy complications. We developed a nomogram to predict the occurrence of premature delivery based on thyroid function and other risk factors as a clinical decision-making tool.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down’s Syndrome

IntroductionThyroid dysfunctions are one of the most common abnormalities coexisting in children with Down’s syndrome (DS) and have been reported in up to 54% of cases.Aim of the StudyThe purposes of this retrospective study were to investigate the course of subclinical hypothyroidism in children with DS, to evaluate the thyroid function of these subjects in relation to the risk of developing overt thyroid disease and autoimmunity, and to identify clinical and biochemical characteristics of patients prescribed L-T4 therapy in children and adolescents with DS and SH.Material and MethodsThe records of DS patients referred to the Endocrinology Outpatient Clinic between 2010 and 2015 for screening of thyroid function were observed till the end of 2019 June and analyzed retrospectively. The children diagnosed with congenital hypothyroidism, acute lymphoblastic leukemia, and seizures and treated with drugs that may have interfered with thyroid function like lithium, antiepileptic, or iodinated drugs and glucocorticoids were excluded from the study.ResultsThe data of 77 DS patients were collected, evaluated, and analyzed. The study group consisted of 73 patients (32 girls and 41 boys with the mean age at baseline of 3.0 ± 4.5 years). A total of 63/73 (87%) children were diagnosed with SH. The 16/63 (25.4%) patients were followed-up without the treatment (group SH-T0), and therapy with levothyroxine (L-T4) was introduced in 47/63 (74.6%) SH children with a mean dosage of 1.8 ± 1.0 μg/kg/day (group SH-T1). Thyroxine supplementation did not improve growth expressed as ΔhSDS (0.1 ± 1.3, ranged −2.1 to 3.8 in SH-T0 vs. 0.0 ± 0.7, ranged −1.7 to 1.4 in SH-T1, p = 0.96) and ΔBMI Z-score (0.3 ± 0.9, ranged −0.9 to 2.6 in SH-T0 vs. 0.3 ± 1.1, ranged −2.1 to 2.9 in SH-T1, p = 0.65). Positive anti-TPO and anti-TG antibodies were detected in 7/63 (11.1%) DS cases.ConclusionsSH is the most frequent presentation of thyroid gland dysfunction in DS children. A small percentage of patients develop an overt hypothyroidism, particularly in females with mostly positive titer of antithyroid autoantibodies.

The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China

Background The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. Methods A case–control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. Results Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose–response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). Conclusions Perchlorate can increase the risk of PTC in a non-linear dose–response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. OBJECTIVE To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non–English-language studies were excluded. DATA EXTRACTION Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. RESULTS The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations &gt;150 mg/dL [&gt;8.3 mmol/L] and BG concentrations &lt;50 mg/dL [&lt;2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] &lt;4.2 μg/dL [&lt;54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration &lt;18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of &lt;9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. LIMITATIONS These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. CONCLUSIONS We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.

Non-thyroidal illness syndrome predicts outcome in adult critically ill patients: a systematic review and meta-analysis

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of nonthyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients in 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% confidence interval (CI), 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in TSH levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (OR = 2.21, 95% CI 1.64.- 2.97, I2 = 65% p < 0.01) The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.