Thyroid Hormone Replacement Dosing after Bariatric Surgery in Patients with Primary Hypothyroidism And Severe Obesity: Tehran Obesity Treatment Study.

Background: Obesity and hypothyroidism are common medical conditions that are associated with each other. Bariatric surgery (BS) is a common approach used to achieve substantial weight loss in obese patients. However, there is limited evidence regarding the need for postsurgery levothyroxine (LT4) dose adjustment in patients with hypothyroidism undergoing BS. Methods: This was a three-year prospective cohort study assessing postsurgery LT4 requirements with attention to body composition changes. The current study included 1030 patients with hypothyroidism, who underwent sleeve gastrectomy (SG) (n = 707, 88.3% women) or one anastomosis gastric bypass (OAGB) (n = 323, 92% women). Patients were followed for 36 months after surgery. A bioelectrical impedance analyzer was used for body composition assessment. LT4 requirements were assessed by generalized estimating equation (GEE) methods adjusted for weight as a time-varying covariate. Results: During the follow-up, TSH (mIU/L) and T4 (ng/dL) measurements did not significantly change in the OAGB group over time. However, in the SG group, TSH measurement decreased over time (ptrend = <0.001). In the third year of the follow-up, 56.1% and 33.3% of patients in the SG and OAGB groups experienced LT4 (µg/day) dose reduction, while 24.4% and 9.1% of the participants experienced LT4 dose increments, respectively. GEE analysis showed a significant increase in the LT4/fat mass (FM) (µg/kg) ratio after 36 months of follow-up compared with the baseline in both the SG [1.8 (1.5-2.2) to 2.7 (2.0-3.5), ptrend = 0.039)] and OAGB [1.7 (1.4-2.2) to 3.2 (2.7-4.8), ptrend = <0.001)] groups. Moreover, patients who underwent OAGB experienced greater LT4/FM (µg/kg) dose adjustments compared to those undergoing SG (pbetween = 0.060). In both groups, after the first year, the increase in LT4/FM (µg/kg) plateaued (pinteraction = 0.009). Conclusion: Most hypothyroid patients experienced either a reduction or no change in LT4 (µg/day) dosage after 36 months in both surgical groups. The LT4/FM (µg/kg) was significantly increased in patients undergoing either SG or OAGB with greater alterations in the latter. Further studies on larger populations and with longer duration of follow-up are needed to confirm our results.

Subclinical Hypothyroidism and Thyroid Autoimmunity in Pregnancy: To Treat or Not to Treat.

Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L.

The Effect of Apalutamide on Thyroid Function in Prostate Cancer Patients.

Context: Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied. Objective: The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients. Methods: We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed. Results: Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels. Conclusion: APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT.

Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

PURPOSE: This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. METHODS: A clinical review. RESULTS: Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. CONCLUSION: Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy.

OBJECTIVE: To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. METHOD: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. RESULTS: There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p = 0.004 and OR 6.15, 95% CI 1.21-36.0, p = 0.033, respectively). CONCLUSIONS: Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2402-2406, 2023.

The Effectiveness of Thyroid Hormone Replacement Therapy on Heart Failure and Low-Triiodothyronine Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis evaluating the role of thyroid hormone therapy in patients with heart failure and low-triiodothyronine syndrome. METHODS: The electronic databases PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine disc were systematically searched to identify eligible studies published before November 27, 2021. The mean difference was pooled for randomized controlled trials using a random-effects model. RESULTS: The meta-analysis showed that thyroid hormone treatment improved the left ventricular ejection fraction (weighted mean difference [WMD] 5.61, 95% confidence interval [CI]: 4.38 to 6.85, I2 = 63.12%, P < 0.01). The cardiac output improved with thyroid hormone therapy (WMD 0.65, 95% CI: 0.42 to 0.89, I2 = 84.28%, P < 0.01). The early-to-late diastolic transmitral flow velocity in the thyroid hormone group was also improved compared to the control group (WMD 0.29, 95% CI: 0.15 to 0.42, I2 = 95.08%, P < 0.01). The left ventricular diastolic dysfunction was decreased with thyroid hormone treatment (WMD -5.17, 95% CI: -7.47 to -2.88, I2 = 90.18%, P < 0.01). The brain natriuretic peptide decreased with thyroid hormone treatment (standardized mean difference -1.49, 95% CI: -2.15 to -0.84, I2 = 90.18%, P < 0.01). Noradrenaline decreased with thyroid hormone therapy (WMD -349.86, 95% CI: -401.05 to -298.67, I2 = 0%, P < 0.01). Free triiodothyronine increased with thyroid hormone treatment (standardized mean difference 2.18, 95% CI: 0.75 to 2.60, I2 = 98.20%, P < 0.01). CONCLUSION: This meta-analysis showed that thyroid hormone replacement therapy was effective in patients with heart failure and low-triiodothyronine syndrome.

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent. AIM: To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy. METHODS: Our cohort's data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years. RESULTS: Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1. Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303). CONCLUSION: Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

Risk factors for thyroid hormone replacement therapy after hemithyroidectomy and development of a predictive nomogram.

PURPOSE: Hemithyroidectomy is a valid operation to retain functional contralateral thyroid lobe that is indicated for a variety of thyroid diseases. This study aimed at determination of the risk factors for thyroid hormone replacement following hemithyroidectomy and to develop a predictive nomogram. METHODS: Data of patients treated by hemithyroidectomy for benign thyroid disease between January 2015 and January 2020 were retrospectively analyzed. Baseline characteristics, surgery-related variables, and preoperative and postoperative thyroid function of patients were collected from the case records and compared between patients with postoperative euthyroidism and patients with postoperative hypothyroidism. Postoperative euthyroidism patients without thyroid hormone replacement were compared to those who developed postoperative hypothyroidism with thyroid hormone replacement. The factors associated with thyroid hormone replacement were used to construct a binomial logistic-regression model and visualized as a predictive nomogram to evaluate the risk of thyroid hormone replacement following hemithyroidectomy. RESULTS: Of the 378 patients (74% female) included in the study, 110 (29.1%) developed postoperative hypothyroidism. Preoperative serum thyroid-stimulating hormone (TSH) > 2.172 µIU/mL was identified as an independent risk factor for postoperative hypothyroidism (odds ratio [OR] = 8.02; 95% confidence interval [CI]: 4.87-13.20; P < 0.001). Of 110 patients with postoperative hypothyroidism, 56 (50.9%) received thyroid hormone replacement. Unilateral thyroid nodule and preoperative serum TSH > 2.172 µIU/mL were independent predictors of postoperative thyroid hormone replacement (P = 0.01, and P < 0.001, respectively). Temporary subclinical hypothyroidism occurred in 12 patients; all 12 reverted to euthyroid state without thyroid hormone replacement. The discriminative effect of the binomial regression model was proved reliable by the Hosmer-Lemeshow goodness-of-fit test (P = 0.503), and predictive ability of the nomogram was satisfactory with a C-index of 0.833. CONCLUSIONS: Hypothyroidism is common after hemithyroidectomy, and almost half of the patients will need thyroid hormone replacement. Elevated preoperative serum TSH level and unilateral thyroid nodule were independent predictors of thyroid hormone replacement following hemithyroidectomy. The predictive nomogram could be a useful tool for clinical practice.

Takotsubo Cardiomyopathy in the Setting of Myxedema Coma.

Myxedema coma and its treatment are potent physical stressors that likely predispose patients to develop Takotsubo cardiomyopathy (TCM). We postulate a multifactorial pathophysiology for TCM that includes a mechanism involving catecholamine-induced potentiation of cardiac adrenoreceptors during thyroid hormone replacement in the setting of severe hypothyroidism. Furthermore, TCM can be difficult to anticipate when presenting as a complication of another diagnosis. In this case report, we aim to improve awareness of TCM as a consequence of extreme hypothyroid states.

High-dose radiation exposure and hypothyroidism: aetiology, prevention and replacement therapy.

Without any doubt, high dose radiation exposure can induce hypothyroidism. However, there are open questions related to the mechanisms of its induction, corresponding dose thresholds and possible countermeasures. Therefore, this review addresses the aetiology, prevention and therapy of radiation induced hypothyroidism. External beam radiotherapy with several 10 Gy to the head and neck region and radioiodine therapy with several 100 Gy thyroid absorbed dose can destroy the thyroid gland and can induce autoantibodies against thyroid tissue. According to recent literature, clinical hypothyroidism is observed at threshold doses of ∼10 Gy after external beam radiotherapy and of ∼50 Gy after radioiodine therapy, children being more sensitive than adults. In children and adolescents exposed by the Chernobyl accident with mean thyroid absorbed doses of 500-800 mGy, subclinical hypothyroidism has been detected in 3%-6% of the cases with significant correlation to thyroid absorbed doses above 2.5 Gy. In case of nuclear emergencies, iodine thyroid blocking (ITB) is the method of choice to keep thyroid absorbed doses low. Large doses of stable iodine affect two different steps of internalization of radioiodine (transport and organification); perchlorate affecting the transport only may be an alternative to iodine. Administered before radioiodine incorporation, the effect of 100 mg iodide or more is still about 90% after 1 days, 80% after 2 days, and 50% or less after 3 days. If administered (too) late after exposure to radioiodine, the theoretically expected protective effect of ITB is about 50% after 6 h, 25% after 12 h, and about 6% after 24 h. In case of repeated or continuous exposure, repeated administration of 50 mg of iodide daily is indicated. If radiation-induced hypothyroidism cannot be avoided, thyroid hormone replacement therapy with individualized dosing and regular monitoring in order to maintain thyroid-stimulating hormone levels within the normal range ensures normal life expectancy.

Evaluation of Thyroid Hormone Replacement Dosing in Morbidly Obese Hypothyroid Patients after Bariatric Surgery-Induced Weight Loss.

The most frequent endocrine disease in obese patients is hypothyroidism. To date, there are no clear data regarding what happens to the dose of levothyroxine (LT4) after bariatric surgery (BS). The objective of the present study was to evaluate thyroid hormone replacement dose in morbidly obese hypothyroid patients after BS-induced weight loss. We explore the best type of measured or estimated body weight for LT4 dosing. We performed an observational study evaluating patients with morbid obesity and hypothyroidism who underwent BS. We included 48 patients (three men). In morbidly obese hypothyroid patients 12 months after BS-induced weight loss, the total LT4 dose or the LT4 dose/kg ideal body weight did not change, while there was a significant increase in LT4 dose/body surface area, LT4 dose/kg weight, LT4 dose/kg adjusted body weight, LT4 dose/kg body fat, and LT4 dose/kg lean body weight. There were no differences in LT4 dose and its variation between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). The present study strongly suggests that LT4 dosing in obese hypothyroid patients can be individually adapted more precisely if it is based on ideal body weight.

Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.

AIMS: Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene. METHODS AND RESULTS: A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190). CONCLUSION: Homozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.

Prediction of Thyroid Hormone Replacement Following Thyroid Lobectomy: A Long-term Retrospective Study.

OBJECTIVE: Following thyroid lobectomy, patients are at risk for hypothyroidism. This study sought to determine the incidence of postlobectomy thyroid hormone replacement as well as predictive risk factors to better counsel patients. STUDY DESIGN: Retrospective cohort study. SETTING: Patients aged 18 to 75 years treated in a single academic institution who underwent thyroid lobectomy from October 2006 to September 2017. METHODS: Patients were followed for an average of 73 months. Demographic data, body mass index, size of removed and remnant lobe, preoperative thyroid-stimulating hormone (TSH) level, final thyroid pathology, and presence of thyroiditis were collected and analyzed. Risk factors were evaluated with chi-square analyses, t tests, logistic regression, and Kaplan-Meier analysis. RESULTS: Of the 478 patients reviewed, 369 were included in the analysis, 30% of whom eventually required thyroid hormone replacement. More than 39% started therapy >12 months postoperatively, with 90% treated within 36 months. Patient age ≥50 years and preoperative TSH ≥2.5 mIU/L were associated with odds ratios of 2.034 and 3.827, respectively, for thyroid hormone replacement. Malignancy on final pathology demonstrated an odds ratio of 7.76 for hormone replacement. Sex, body mass index, volume of resected and remaining lobes, and weight of resected lobe were not significant predictors. CONCLUSION: Nearly a third of patients may ultimately require thyroid hormone replacement. Age at the time of surgery, preoperative TSH, and final pathology are strong, clinically relevant predictors of the need for future thyroid hormone replacement. After lobectomy, patients should have long-term thyroid function follow-up to monitor for delayed hypothyroidism.

Patient satisfaction and quality of life in hypothyroidism: An online survey by the british thyroid foundation.

OBJECTIVE: Dissatisfaction with treatment and impaired quality of life (QOL) are reported among people with treated hypothyroidism. We aimed to gain insight into this. DESIGN AND PATIENTS: We conducted an online survey of individuals with self-reported hypothyroidism. RESULTS: Nine hundred sixty-nine responses were analysed. Dissatisfaction with treatment was common (77.6%), and overall QOL scores were low. Patient satisfaction did not correlate with type of thyroid hormone treatment, but treatment with combination levothyroxine (L-T4) and liothyronine (L-T3) or with desiccated thyroid extract (DTE) was associated with significantly better reported QOL than L-T4 or L-T3 monotherapies (P < .001); however, multivariate analysis inclusive of other clinical parameters failed to confirm an association between type of thyroid hormone treatment and QOL or satisfaction. Multivariate analysis showed positive correlations between satisfaction and age (P = .026), male gender (P = .011), being under the care of a thyroid specialist (P < .001), family doctor (GP) prescribing DTE or L-T4 + L-T3 or L-T3 (P < .001) and being well informed about hypothyroidism (P < .001); negative correlations were observed between satisfaction and negative experiences with L-T4 (P < .001) and expectations for more support from the GP (P < .001), for L-T4 to resolve all symptoms (P = .004), and to be referred to a thyroid specialist (P < .001). For QOL, positive correlations were with male gender (P = .011) and duration of hypothyroidism (P = .002); negative correlations were with age (P = .027), visiting the GP more than 3 times before diagnosis (P < .001), sourcing DTE or L-T3 independently (P = .014), negative experiences with L-T4 (P = .013), having expectations for L-T4 to resolve all symptoms (P < .001) and of more support from the GP (P = .006). CONCLUSIONS: Multiple parameters including prior healthcare experiences and expectations influence satisfaction with hypothyroidism treatment and QOL. Focusing on enhancing the patient experience and clarifying expectations at diagnosis may improve satisfaction and QOL.

The effect of oral triiodothyronine supplementation on lactate and pyruvate after paediatric cardiac surgery.

OBJECTIVE: To determine if triiodothyronine alters lactate, glucose, and pyruvate metabolism, and if serum pyruvate concentration could serve as a predictor of low cardiac output syndrome in children after cardiopulmonary bypass procedures. METHODS: This study was ancillary to the Oral Triiodothyronine for Infants and Children undergoing Cardiopulmonary bypass (OTICC) trial. Serum pyruvate was measured in the first 48 patients and lactate and glucose were measured in all 208 patients enrolled in the OTICC study on the induction of anaesthesia, 1 and 24 hours post-aortic cross-clamp removal. Patients were also defined as having low cardiac output syndrome according to the OTICC trial protocol. RESULT: Amongst the designated patient population for pyruvate analysis, 22 received placebo, and 26 received triiodothyronine (T3). Lactate concentrations were nearly 20 times greater than pyruvate. Lactate and pyruvate levels were not significantly different between T3 and placebo group. Glucose levels were significantly higher in the placebo group mainly at 24-hour post-cross-clamp removal. Additionally, lactate and glucose levels peaked at 1-hour post-cross-clamp removal in low cardiac output syndrome and non-low cardiac output syndrome patients, but subsequently decreased at a slower rate in low cardiac output syndrome. Lactate and pyruvate concentrations correlated with glucose only prior to surgery. CONCLUSION: Thyroid supplementation does not alter systemic lactate/pyruvate metabolism after cardiopulmonary bypass and reperfusion. Pyruvate levels are not useful for predicting low cardiac output syndrome. Increased blood glucose may be regarded as a response to hypermetabolic stress, seen mostly in patients with low cardiac output syndrome.

Does hypothyroidism increase the risk of breast cancer: evidence from a meta-analysis.

PURPOSE: At present, the relationship between hypothyroidism and the risk of breast cancer is still inconclusive. This meta-analysis was used to systematically assess the relationship between hypothyroidism and breast cancer risk, and to assess whether thyroid hormone replacement therapy can increase breast cancer risk. METHODS: The relevant articles about hypothyroidism and the risk of breast cancer were obtained on the electronic database platform. Relevant data were extracted, and odd ratios (OR) with corresponding 95% confidence intervals (CI) were merged using Stata SE 12.0 software. RESULTS: A total of 19 related studies were included in the meta-analysis, including 6 cohort studies and 13 case-control studies. The results show that hypothyroidism was not related to the risk of breast cancer (odd ratios = 0.90, 95% CI 0.77-1.03). In the European subgroup, we observed that patients with hypothyroidism have a lower risk of breast cancer(odd ratios = 0.93, 95% CI 0.88-0.99). Furthermore, no significant correlation was observed between thyroid hormone replacement therapy and the risk of breast cancer. (odd ratios = 0.87, 95% CI 0.65-1.09). CONCLUSION: Hypothyroidism may reduce the risk of breast cancer in the European population, and no significant correlation was observed between hypothyroidism and breast cancer risk in non-European populations. Due to the limited number of studies included, more large-scale, high-quality, long-term prospective cohort studies are needed.

Design of the Optimal Trial of Combination Therapy.

Patients who take levothyroxine monotherapy to treat hypothyroidism frequently experience residual symptoms despite TSH testing at target levels. Trials have been conducted to evaluate the potential benefit of combination therapy with levothyroxine and liothyronine, though results have not consistently demonstrated benefit. In addition to randomization, placebo-control, and masking, four additional design choices to consider include the study population, dosing strategy for levothyroxine and liothyronine, primary and secondary outcome selection, and statistical power. A thoughtful design that considers these features will increase the likelihood that a combination trial will be considered definitive and finally resolve the important question of whether combination therapy with levothyroxine and liothyronine is a better thyroid replacement strategy than levothyroxine monotherapy.

Management of Subclinical and Overt Hypothyroidism Following Hemithyroidectomy in Children and Adolescents: A Pilot Study.

Background: To reduce surgical complications and avoid lifelong thyroid hormone replacement, hemithyroidectomy is preferred in children and adolescents with benign nodular thyroid disease. However, hypothyroidism following hemithyroidectomy may occur, and postoperative thyroid hormone replacement for hypothyroidism following hemithyroidectomy is usually administered without a full understanding of the clinical characteristics of hypothyroidism. Methods: To investigate the incidence and risk factors of hypothyroidism after hemithyroidectomy in children and adolescents, and to identify whether postoperative thyroid hormone replacement is necessary, a retrospective review of 43 patients under 18 years of age who underwent hemithyroidectomy from January 2009 to October 2016 was conducted. All hypothyroid patients were retrospectively analyzed to determine the incidence and predisposing factor(s) of postoperative hypothyroidism. All patients were measured regarding age, sex, serum thyrotropin (TSH), anti-thyroid antibody, and histological evidence of lymphocytic infiltration. Hypothyroid patients were measured for symptoms, timing of diagnosis, and thyroid hormone replacement. Results: The mean age at the time of surgery was 13.65 ± 3.04 years. Of the cohort, 34 patients were female (79.07%), and the mean follow-up time was 28 ± 9 months. Hypothyroidism was diagnosed in 11 of the 43 patients. The mean postoperative TSH level was 7.17 ± 2.13 µIU/ml. The mean preoperative TSH level was 3.11 ± 0.59 µIU/ml in hypothyroid patients compared with 1.92 ± 0.72 µIU/ml in euthyroid patients (P < 0.05). A preoperative TSH level >2.2 µIU/l and lymphocytic infiltration graded 3 or 4 were found to be independent risk factors for the development of hypothyroidism. There were no significant differences between groups in terms of patient age or sex. Conclusions: In the pediatric and adolescent population, patients with elevated preoperative TSH levels or the presence of lymphocytic infiltration may increase the risk of risk of hypothyroidism. In our study, postoperative levothyroxine (L-T4) treatment was necessary in 16.28% of cases after hemithyroidectomy. Patients with mild postoperative hypothyroidism should be followed up, without the need for immediate L-T4 replacement, so as to expect patients to recover spontaneously.

Oral Triiodothyronine Supplementation Decreases Low Cardiac Output Syndrome After Pediatric Cardiac Surgery.

The oral triiodothyronine for infants and children undergoing cardiopulmonary bypass (OTICC) trial showed that Triiodothyronine (T3) supplementation improved hemodynamic and clinical outcome parameters. We tested the validity of low cardiac output syndrome (LCOS), derived using clinical parameters and laboratory data, by comparing the LCOS diagnosis with objective parameters commonly measured in a cardiac intensive care unit (CCU) setting. OTICC, a randomized, placebo-controlled trial included children younger than 3 years with an Aristotle score between 6 and 9. We used the existing trial data set to compare the LCOS diagnosis with echocardiographic hemodynamic parameters. Additionally, we determined if LCOS, prospectively assigned during a clinical trial, served as an early predictor of clinical outcomes. All LCOS subjects at 6 and 12 h after cross-clamp release later showed significantly lower pulse pressure, stroke volume and cardiac output, and higher systemic vascular resistance. These LCOS patients also had significantly longer time to extubation (TTE) and higher mortality rate. LCOS incidence was significantly lower in the T3 treatment group [n = 86 vs. 66, respectively, p < 0.001; OR (95% CI) 0.43 (0.36-0.52)] particularly at 6 h. Also, LCOS patients in the placebo group had significantly lower FT3 serum levels over time. These analyses confirm that early clinically defined LCOS successfully predicts cardiac dysfunction determined later by objective hemodynamic echocardiographic parameters. Furthermore, early LCOS significantly impacts TTE and mortality. Finally, the data support prior clinical trial data, showing that oral T3 supplementation decreases early LCOS in concordance with reducing TTE.