Thyroxine Treatment Research Articles

Draft of the federal clinical recommendations for diagnosisi and treatment of amiodarone-induced thyroid dysfunction

Amiodarone is an antiarrhythmic drug that is commonly used for treatment of various supraventricular and ventricular arrhythmias. Amiodarone and its main active metabolite desethylamiodarone have a direct dose-dependent cytotoxic effect on thyroid follicular cells. Consequently, some patients receiving amiodarone may develop thyroid dysfunction: amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). The diagnosis, classification, and treatment of amiodarone-induced thyroid dysfunction remain to be a challenge to all clinicians deal with this problem. This draft of clinical recommendations was developed by a group of specialists experienced in the diagnosis and treatment of amiodarone-induced thyroid dysfunction. AIH does not require amiodarone withdrawal. Thyroxine treatment is recommended for all patients with manifest AIH, subclinical forms of AIH do not always need its prescription. There are two main types of amiodarone-induced thyrotoxicosis: AIT type 1 (is a hyperthyroidism that develops due to excessive iodine intake in autonomous thyroid nodules or latent Graves ‘ disease) and AIT type 2 (develops due to destructive thyroiditis because of the cytotoxic effect of amiodarone). In addition, there is a mixed form, which has features of both types of AIT. Autonomous AIT 1 is characterized by the presence of one or more «hot» nodules in the thyroid. Elevated TSH receptor antibodies or typical clinical manifestations confirm the diagnosis of diffuse toxic goiter and, consequently, AIT1. Colour-flow Doppler sonography (CFDS) is proposed as the basic method of differential diagnosis of AIT 1 and AIT 2. CFDS «pattern 0», usually indicates AIT 2, the presence of «patterns I-III» mostly typical for AIT 1. The thyreostatics are recommended for AIT 1, oral glucocorticoids for AIT 2 and their combination for a mixed AIT. Emergency thyroidectomy should be applied to patients with deteriorating cardiovascular pathology and ineffective drug therapy. In the absence of clinical suspicion on thyroid dysfunction, thyroid hormones assessment should be done 3 months after the start of amiodarone treatment, thereafter every 6 months.

QOL-54. HEIGHT, WEIGHT AND CARDIOVASCULAR EFFECTS OF STIMULANTS ON CHILDREN WITH BRAIN TUMOR

INTRODUCTIONChildren with brain tumors may develop inattention, slow processing, and hypersomnia. Stimulant medications improve these problems but their effect on growth, heart rate, and blood pressure are inadequately explored.METHODSWe retrospectively studied children with brain tumors treated at our institution that had data available for one-year pre and two year post stimulant treatment. Tumor location, gender, radiation treatment (RT), age at RT, drug type, and hormone therapy were variables of interest.RESULTSWe identified 65 children (35 males) that fulfilled eligibility criteria. Focal RT was utilized in 58; 11 additionally received whole brain RT. Thirty were treated for hypersomnia and inattention, 8 for hypersomnia alone, and rest for inattention. Modafinil was the first drug in 18 (27.7%) and methylphenidate in the others. Forty-seven (72.3%), 40 (61.5%) and 49 (75.4%) were on thyroxine, cortisone and growth hormone respectively. There was no difference in pre and post stimulant BMI, heart rate, and blood pressure. There was also no difference between modafinil and methylphenidate groups. Rate of increase in height slowed on stimulants (p=0.0096). Thyroxine treatment correlated with increase in BMI after stimulants (p=0.0434). Younger age (p=0.0003) and higher BMI (p=0.0063) pre stimulants correlated with increased heart rate on stimulants, while higher age at RT (0.0159) correlated with elevated systolic BP on stimulants. No association of studied variables was found with height and diastolic BP.CONCLUSIONStimulants are well tolerated by children with brain tumors that are appropriately managed for endocrine deficiencies but may reduce the trajectory of height attainment.

Hypothyroidism Induces Interleukin-1-Dependent Autophagy Mechanism as a Key Mediator of Hippocampal Neuronal Apoptosis and Cognitive Decline in Postnatal Rats.

Thyroid hormone (TH) is essential for brain development, and hypothyroidism induces cognitive deficits in children and young adults. However, the participating mechanisms remain less explored. Here, we examined the molecular mechanism, hypothesizing the involvement of a deregulated autophagy and apoptosis pathway in hippocampal neurons that regulate cognitive functions. Therefore, we used a rat model of developmental hypothyroidism, generated through methimazole treatment from gestation until young adulthood. We detected that methimazole stimulated the autophagy mechanism, characterized by increased LC3B-II, Beclin-1, ATG7, and ATG5-12 conjugate and decreased p-mTOR/mTOR and p-ULK1/ULK1 autophagy regulators in the hippocampus of developing and young adult rats. This methimazole-induced hippocampal autophagy could be inhibited by thyroxine treatment. Subsequently, probing the upstream mediators of autophagy revealed an increased hippocampal neuroinflammation, marked by upregulated interleukin (IL)-1alpha and beta and activated microglial marker, Iba1, promoting neuronal IL-1 receptor-1 expression. Hence, IL-1R-antagonist (IL-1Ra), which reduced hippocampal neuronal IL-1R1, also inhibited the enhanced autophagy in hypothyroid rats. We then linked these events with hypothyroidism-induced apoptosis and loss of hippocampal neurons, where we observed that like thyroxine, IL-1Ra and autophagy inhibitor, 3-methyladenine, reduced the cleaved caspase-3 and TUNEL-stained apoptotic neurons and enhanced Nissl-stained neuronal count in methimazole-treated rats. We further related these molecular results with cognition through Y-maze and passive avoidance tests, demonstrating an IL-1Ra and 3-methyladenine-mediated improvement in learning-memory performances of the hypothyroid rats. Taken together, our study enlightens the critical role of neuroinflammation-dependent autophagy mechanism in TH-regulated hippocampal functions, disrupted in developmental hypothyroidism.

Height, weight, and cardiovascular effects of stimulants on children with brain tumors.

Children with brain tumors may develop inattention, slow processing, and hypersomnia. Stimulant medications improve these problems, but their effect on growth, heart rate, and blood pressure (BP) are inadequately explored. We retrospectively studied children with brain tumors treated at our institution that had data available for 1year pre and 2years on stimulant treatment. Tumor location, gender, radiation treatment (RT), age at RT, drug type, and hormone therapy were variables of interest. We identified 65 children (35 males) that fulfilled eligibility criteria. Focal RT was utilized in 58; 11 additionally had whole brain RT; and seven received no RT. Thirty were treated for hypersomnia and inattention, eight for hypersomnia alone, and rest for inattention. Modafinil was the first drug in 18 (27.7%), and methylphenidate in the others. Forty-seven (72.3%), 45 (69.2%), and 49 (75.4%) were on thyroxine, cortisone, and growth hormones, respectively. There was no difference in pre- and post-stimulant body mass index (BMI), heart rate, and BP. There was also no difference between modafinil and methylphenidate groups. Rate of height acquisition slowed on stimulants (P=.0096). Thyroxine treatment correlated with increase in BMI after stimulants (P=.04). Younger age (P=.0003) and higher prestimulant BMI (P=.0063) correlated with increased heart rate on stimulants, while higher age at RT (P=.016) correlated with elevated systolic BP on stimulants. No associations were found with height acquisition and diastolic BP. Stimulants are well tolerated by children with brain tumors that are appropriately managed for endocrine deficiencies, but may reduce the trajectory of height attainment.

Effect of thyroxine treatment on pregnancy outcomes in infertile Japanese women with TSH levels between 2.5 μIU/mL and the upper reference limit: a retrospective study.

Recent randomized controlled studies have revealed that levothyroxine (LT4) treatment improves pregnancy outcomes only in infertile women with subclinical hypothyroidism who have thyroid autoantibodies (TAs), but not for those with high TSH levels within the normal range who have TAs. Here, we retrospectively investigated pregnancy outcomes in infertile Japanese women with 2.5 μIU/mL ≤ TSH < upper reference limit (URL). Between 2012 and 2018, 286 patients diagnosed with infertility were followed for more than 1 year at our institution. Among them, we included 106 patients with 2.5 μIU/mL ≤ TSH < URL. We divided these patients into four groups based on the combination of TA positivity and LT4 treatment status to assess the effects of LT4 treatment considering TA positivity on the incidence of pregnancy or miscarriage. In this study, we did not find any significant differences in the rates of pregnancy or miscarriage among the four groups (p = 0.81 and 0.52, respectively). In addition, logistic regression analysis showed that age and history of miscarriage were associated with the incidence of pregnancy, but presence of TAs and LT4 treatment status were not and that no variables examined were associated with the incidence of miscarriage. In summary, we were not able to demonstrate the benefit of LT4 treatment for pregnancy outcomes in Japanese euthyroid infertile women with 2.5 μIU/mL ≤ TSH < URL regardless of TA status in this study.

Thyroxine Treatment During the Perinatal Stage Prevents the Alterations in the ObRb-STAT3 Leptin Signaling Pathway Caused by Congenital Hypothyroidism.

Thyroid hormone deficiency during crucial stages of development causes congenital hypothyroidism. This syndrome alters hypothalamic pathways involved in long-term bodyweight regulation as ObRb-STAT3 leptin signaling pathway, which is associated with metabolic syndrome. This study aimed to determine if thyroxine treatment during pregnancy and lactation in hypothyroid mothers avoids, in the congenital hypothyroid offspring, the alterations in metabolic programming related to metabolic syndrome and the ObRb-STAT3 leptin signaling pathway in hypothalamus. Twenty-four virgin female Wistar rats were divided into euthyroid, hypothyroid, and hypothyroid with thyroxine treatment (20 μg/kg/day T4 since pregnancy until lactation). The bodyweight and energy intake, insulin resistance, glucose tolerance, metabolic and hormonal parameters were determined in offspring at 28 weeks after birth. Then, the rats were euthanized to obtain adipose tissue reserves and hypothalamus to measure the expression of ObRb, STAT3, pSTAT3, and SOCS3. Congenital hypothyroidism presented metabolic syndrome such as insulin resistance, glucose tolerance, dyslipidemias, an increase in cardiovascular risk (Castelli I males:166.67%, females: 173.56%; Castelli II males: 375.51%, females: 546.67%), and hypothalamic leptin resistance (SOCS3, Males: 10.96%, females: 25.85%). Meanwhile, the thyroxine treatment in the mothers during pregnancy and lactation prevents the metabolic disturbance. In conclusion, thyroxine treatment during the critical perinatal stage for metabolic programming prevents congenital hypothyroidism-caused metabolic syndrome and hypothalamic leptin resistance.

CD5L Constitutes a Novel Biomarker for Integrated Hepatic Thyroid Hormone Action

Background: Pathological conditions of the thyroid hormone (TH) system are routinely diagnosed by using serum concentrations of thyrotropin (TSH), which is sufficient in most cases. However, in certain conditions, such as resistance to TH due to mutations in THRB (RTHb) or TSH-releasing pituitary adenoma (TSHoma), TSH may be insufficient for a correct diagnosis, even in combination with serum TH concentrations. Likewise, under TH replacement therapy, these parameters can be misleading and do not always allow optimal treatment. Hence, additional biomarkers to assess challenging clinical conditions would be highly beneficial. Methods: Data from untargeted multi-omics analyses of plasma samples from experimental thyrotoxicosis in human and mouse were exploited to identify proteins that might represent possible biomarkers of TH function. Subsequent mouse studies were used to identify the tissue of origin and the involvement of the two different TH receptors (TR). For in-depth characterization of the underlying cellular mechanisms, primary mouse cells were used. Results: The analysis of the plasma proteome data sets revealed 16 plasma proteins that were concordantly differentially abundant under thyroxine treatment compared with euthyroid controls across the two species. These originated predominantly from liver, spleen, and bone. Independent studies in a clinical cohort and different mouse models identified CD5L as the most robust putative biomarker under different serum TH states and treatment periods. In vitro studies revealed that CD5L originates from proinflammatory M1 macrophages, which are similar to liver-residing Kupffer cells, and is regulated by an indirect mechanism requiring the secretion of a yet unknown factor from hepatocytes. In agreement with the role of TRα1 in immune cells and the TRβ-dependent hepatocyte-derived signaling, the in vivo regulation of Cd5l expression depended on both TR isoforms. Conclusion: Our results identify several novel targets of TH action in serum, with CD5L as the most robust marker. Although further studies will be needed to validate the specificity of these targets, CD5L seems to be a promising candidate to assess TH action in hepatocyte-macrophage crosstalk.

Sfrp4 Expression in Thyroxine Treated Calvarial Cells: A Novel Target

Evidence suggests alterations of thyroid hormone levels can disrupt normal craniofacial development. Most data suggest the major targets of thyroid hormones to be the Htra1/Igf1 pathway. Recent discovery by our group suggests involvement of targets of the WNT pathway, specifically overexpression of antagonist Sfrp4 in the presence of excess thyroid hormone. Here we aimed to model these interactions in vitro to determine if thyroid hormone directly drives Sfrp4 expression in cells relevant to craniofacial development. Affymetrix transcriptional profiling found Sfrp4 to be overexpressed in cranial suture derived cells stimulated with thyroxine in vitro. Bioinformatics interrogation of the SFRP4 promoter identified multiple putative binding sites for thyroid hormone receptors. Experimentation with several cell lines demonstrated that thyroxine treatment induced Sfrp4 expression. However, protein levels did not correlate with induction of gene expression, demonstrating that Sfrp4 mRNA and protein levels are not tightly coupled. Transcriptional and protein analyses demonstrate thyroid hormone receptor binding to the proximal promoter of the target gene Sfrp4. Interestingly functional analysis of stem cells, fibroblasts, or primary culture cells after thyroxine stimulation for alkaline phosphatase activity shows only pre‐osteoblasts are pushed to become positive after thyroid hormone stimulation, suggesting cell type susceptibility. Finally, we added recombinant SFRP4 to pre‐osteoblasts in combination with thyroxine treatment and observed a significant decrease in alkaline phosphatase positivity, suggesting SFRP4 may be a key regulatory molecule that prevents thyroxine driven osteogenesis. The implications for this relationship indicate SFRP4 as a potential diagnostic or therapeutic target for hyperostotic craniofacial disorders.Support or Funding InformationThe authors would like to thank Xing Ming Shi for isolation of the bone marrow mesenchymal cells. The following funding sources were used for this study a grant from the Cleft Palate Foundation, NIH/NIDCR R03DE023350A, 5T32DE017551, and F31DE026684, NIH/NCATS UL1 TR000062, NIH/NIGM P30GM103331, GM103342 and GM103499, and MUSC’s Office of the Vice President for Research.

Follow-up of infants born to mothers with autoinmune thyroid disease. What should not be screened?

IntroductionThyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graveś disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful. Patients and methodA prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013–December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns. ResultsA total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graveś disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia. ConclusionsExperience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48 h of life in newborns of mothers with autoimmune hypothyroidism.

Evaluation of Reproductive Outcome in Infertile Hypothyroid Women on Thyroxine Therapy.

Introduction:Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine until the preconception serum TSH level is <2.5 mU/l.[1] However, insufficient evidence exist to determine if thyroxine therapy improves fertility in subclinical hypothyroid women who are trying to conceive naturally.Objectives:The objective is to study the effect of thyroxine therapy on reproductive outcome in infertile women with clinical and subclinical hypothyroidism (SCH).Materials and Methods:The study is a descriptive cohort study with 72 subjects. Women between 20 and 40 years of age with primary or secondary infertility with hypothyroidism were studied and thyroid profile including free T3, T4, TSH, and thyroid antibodies were done. Thyroxine was given to clinical, subclinical hypothyroid subjects depending on TSH levels such that serum TSH levels are maintained < 2.5 mU/L. Serial thyroid function test was done every 6 weeks until the optimal levels were reached. Once normal TSH levels were reached subjects were followed up for 6 months. Reproductive outcome was analyzed in two groups. Group A included hypothyroid infertile women who conceived and Group B included those who did not conceive following thyroxine therapy.Results:Thirty-eight out of 72 subjects (54%) conceived during thyroxine treatment (Group A) of which 4 cases had miscarriage. Maximum infertile women in Group A (20/38) conceived between 6 and 12 months (52.6%) of thyroxine therapy. Significant decrease was observed in mean TSH levels over a period of 6 months (P < 0.001). The infertility period until pregnancy in Group A reduced significantly from 5.2 ± 1.8 years to 0.5 ± 0.8 years after thyroxine treatment (P = 0.001).Conclusion:Thyroxine therapy enhances fertility in infertile women with clinical and SCH.

Incretin levels in patients with hypothyroidism and the evaluation of incretin levels alterations with treatment

Abstract Background Incretin hormones may influence the effects of thyroid hormones on insulin secretion, insulin resistance, and glucose metabolism. Thyroid hormones regulate insulin secretion, and the risk of diabetes was found to be associated with thyroid hormones. Objectives To determine whether incretin hormones influence the effects of thyroid hormones on insulin resistance and glucose metabolism. Methods A total of 26 patients were included in 2 groups consisting of 13 patients with hypothyroidism and 13 healthy controls. Levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP) levels were measured in 0, 30, 60, 90, and 120th min during the oral glucose tolerance test in the control group and before and after thyroxine treatment in the hypothyroid group. Results In the hypothyroid group, waist circumference decreased after the euthyroid state was achieved (P = 0.026). No statistically significant differences were detected in the GLP-1 and GIP levels at baseline and 30, 60, 90, and 120 min between the hypothyroidism and control groups or after ensuring the euthyroid state in patients with hypothyroidism. Peak GLP-1 levels were observed at 30 min in the control group, whereas peak GLP-1 and GIP levels were detected at 90 min in the hypothyroidism group. After achieving the euthyroid state, peak GLP-1 and GIP levels were detected at 30 min as well. Conclusion In patients with hypothyroidism, the incretin hormones, especially the peak response of the incretin system, are significantly affected. Significant changes were observed in the incretin system by correcting hypothyroidism.

Thyroxine Alleviates Energy Failure, Prevents Myocardial Cell Apoptosis, and Protects against Doxorubicin-Induced Cardiac Injury and Cardiac Dysfunction via the LKB1/AMPK/mTOR Axis in Mice.

Background Previous studies have demonstrated that energy failure is closely associated with cardiac injury. Doxorubicin (DOX) is a commonly used clinical chemotherapy drug that can mediate cardiac injury through a variety of mechanisms. Thyroxine is well known to play a critical role in energy generation; thus, this study is aimed at investigating whether thyroxine can attenuate DOX-induced cardiac injury by regulating energy generation. Methods First, the effect of DOX on adenosine diphosphate (ADP) and adenosine triphosphate (ATP) ratios in mice was assessed. In addition, thyroxine was given to mice before they were treated with DOX to investigate the effects of thyroxine on DOX-induced cardiac injury. Furthermore, to determine whether the liver kinase b1 (LKB1)/adenosine 5′-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) axis mediated the effect of thyroxine on DOX-induced cardiac injury, thyroxine was given to DOX-treated LKB1 knockout (KO) mice. Results DOX treatment time- and dose-dependently increased the ADP/ATP ratio. Thyroxine treatment also reduced lactate dehydrogenase (LDH) and creatine kinase myocardial band (CK-MB) levels in both serum and heart tissue and alleviated cardiac dysfunction in DOX-treated mice. Furthermore, thyroxine reversed DOX-induced reductions in LKB1 and AMPK phosphorylation; mitochondrial complex I, III, and IV activity; and mitochondrial swelling and reversed DOX-induced increases in mTOR pathway phosphorylation and myocardial cell apoptosis. These effects of thyroxine on DOX-treated mice were significantly attenuated by LKB1 KO. Conclusions Thyroxine alleviates energy failure, reduces myocardial cell apoptosis, and protects against DOX-induced cardiac injury via the LKB1/AMPK/mTOR axis in mice. Thyroxine may be a new agent for the clinical prevention of cardiac injury in tumor patients undergoing chemotherapy with DOX.

Physician Perception and Patient Input Are Important Influences in the Treatment of Hypothyroidism

Physician Perception and Patient Input Are Important Influences in the Treatment of Hypothyroidism

Impact of Laparoscopic Sleeve Gastrectomy on Obese Patients with Subclinical Hypothyroidism.

Background: This study aims to evaluate the incidence of subclinical hypothyroidism (SCH) among studied obese patients. The effects of laparoscopic sleeve gastrectomy (LSG) and loss of weight on thyroid hormones level and the impact of adding thyroxine treatment is described. Patients and Methods: Obese patients undergoing LSG at the university hospital between June 2016 and January 2018 were included. Weight loss and changes in body mass index (BMI), serum thyroid stimulating hormone (TSH), and FT4 were evaluated. SCH patients were randomly divided into group "A" received thyroxine treatment and group "B" received no treatment. Results: There were 554 patients studied (mean age 41 ± 12 years); the mean preoperative BMI, serum TSH, and FT4 were 45 ± 6.8 kg/m2, 3.91 ± 1 μU/mL, and 1.32 ± 1 ng, respectively. Incidence of SCH was 12.9%. Significant post-LSG decrease in BMI (30.8 ± 4.6 kg/m2) was associated with significant decrease in serum TSH (1.99 ± 1.1 μU/mL) in all patients; changes were more prominent in SCH group and in patients with higher BMI. SCH patients had normalization of mean serum TSH at 12 months post-LSG. Results of groups "A" and "B" were not significantly different. Conclusion: The incidence of SCH was 12.9%. The significant decrease in BMI was associated with a significant decrease in serum TSH after LSG; this was more evident in SCH and in patients with higher BMI. Complete resolution of SCH occurred at 12 months post-LSG. Adding thyroxine treatment in obese SCH patients did not improve outcome and should be reserved to specific clinical and laboratory indications.

Prevalence and clinical correlates of subclinical hypothyroidism in first-episode drug-naive patients with major depressive disorder in a large sample of Chinese

BackgroundThe coexistence of subclinical hypothyroidism (SCH) and depression has been intensively examined in the patients receiving thyroxine or antidepressant treatment. This study aimed to investigate the prevalence and clinical correlates of severe SCH in Chinese first-episode drug naïve patients with major depressive disorder (MDD). MethodsUsing a cross-sectional design, we recruited a total of 1706 MDD patients. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD). Severity of anxiety and psychiatric symptoms were evaluated by the Hamilton Anxiety Rating Scale (HAMA) and the Positive and Negative Syndrome Scale (PANSS), respectively. Serum thyroid function parameters were measured by a chemiluminescence immunoassay. Based on the serum thyroid stimulating hormone (TSH) level, SCH was further divided into mild (TSH < 10 mIU/L) and severe SCH (TSH ≥ 10 mIU/L). ResultsMore patients with severe SCH had severe anxiety, psychotic symptoms, suicide attempts (all p < 0.001), compared with those without severe SCH. Logistic regression showed that suicide attempts and psychiatric symptoms were associated with severe SCH (both p < 0.001). Multiple linear regression showed that age (p < 0.05), BMI (p < 0.001), HAMD score (p < 0.001), HAMA score (p < 0.001), PANSS positive subscore (p = 0.001) and CGI score (p = 0.001) were associated with TSH levels. ConclusionOur findings suggest that suicide attempts and psychiatric symptoms may be associated with severe SCH. Moreover, severe anxiety, depressive and psychotic symptoms, as well as older age and higher BMI are possibly related to elevated TSH levels.

Quantifying energy expenditure in childhood: utility in managing pediatric metabolic disorders

ABSTRACTBackgroundEnergy expenditure prediction equations are used to estimate energy intake based on general population measures. However, when using equations to compare with a disease cohort with known metabolic abnormalities, it is important to derive one's own equations based on measurement conditions matching the disease cohort.ObjectiveWe aimed to use newly developed prediction equations based on a healthy pediatric population to describe and predict resting energy expenditure (REE) in a cohort of pediatric patients with thyroid disorders.MethodsBody composition was measured by DXA and REE was assessed by indirect calorimetry in 201 healthy participants. A prediction equation for REE was derived in 100 healthy participants using multiple linear regression and z scores were calculated. The equation was validated in 101 healthy participants. This method was applied to participants with resistance to thyroid hormone (RTH) disorders, due to mutations in either thyroid hormone receptor β or α (β: female n = 17, male n = 9; α: female n = 1, male n = 1), with deviation of REE in patients compared with the healthy population presented by the difference in z scores.ResultsThe prediction equation for REE = 0.061 * Lean soft tissue (kg) − 0.138 * Sex (0 male, 1 female) + 2.41 (R2 = 0.816). The mean ± SD of the residuals is −0.02 ± 0.44 kJ/min. Mean ± SD REE z scores for RTHβ patients are −0.02 ± 1.26. z Scores of −1.69 and −2.05 were recorded in male (n = 1) and female ( n = 1) RTHα patients.ConclusionsWe have described methodology whereby differences in REE between patients with a metabolic disorder and healthy participants can be expressed as a z score. This approach also enables change in REE after a clinical intervention (e.g., thyroxine treatment of RTHα) to be monitored.

Seguimiento del hijo de madre con patología tiroidea autoinmune. ¿Qué no debemos cribar?

IntroductionThyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graveś disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful. Patients and methodA prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013-December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns. ResultsA total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graveś disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia. ConclusionsExperience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48h of life in newborns of mothers with autoimmune hypothyroidism.

Effect of thyroxine and carbimazole treatments on basal and histamine stimulated gastric acid secretion in the common African Toad (Bufo regularis).

Effect of thyroxine and carbimazole treatments on basal and histamine stimulated gastric acid secretion in the common African Toad (Bufo regularis).

Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study.

BackgroundImprovement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking.ObjectivesTo evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60).AnimalsForty client‐owned dogs with hypothyroidism and 20 clinically healthy dogs.MethodsProspective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60.ResultsHypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P = .04, P = .002, and P = .003, respectively) and E‐point‐to‐septal separation normalized to body weight (EPSSn) and trans‐mitral E wave velocity (E max; P < .001 and P = .025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P < .001, P = .004, P = .002, and P = .009, respectively) and significantly decreased left ventricular end‐diastolic volume index, and normalized systolic diameter and EPSSn (P = .03, P = .03, and P = .001, respectively) were found.Conclusions and Clinical ImportanceHypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs.

Severe hypothyroidism presenting as reversible proteinuria: two case reports

BackgroundHypothyroidism is a common medical disorder which results in many metabolic effects, such as dyslipidemia, hypertension, accelerated atherosclerosis, and coronary artery disease. Hypothyroidism affects the renal physiology by affecting the renal blood flow, vascular resistance, and sodium handling. Recent studies have shown hypothyroidism is associated with decreased estimated renal function and proteinuria. Rhabdomyolysis and acute renal insufficiency have also been described in association with hypothyroidism. The severity of the proteinuria was directly proportional to thyroid-stimulating hormone levels. Currently, there is a lack of evidence on the reversibility of proteinuria in hypothyroidism. This is the first report in the literature, to the best of our knowledge, demonstrating the reversibility of proteinuria associated with hypothyroidism, with treatment.Case presentationHere we describe two cases, a 72-year-old Sinhalese man and a 47-year-old Tamil woman, from Sri Lanka, presenting with overt hypothyroidism; they were found to have elevated creatinine, proteinuria, and elevated creatinine kinase levels. Due to lack of active sediment in urine analysis, these patients were observed after the initiation of thyroxine therapy. They were investigated in the adult-onset proteinuria pathway, excluding common reasons for proteinuria. Both patients responded to treatment: their serum creatinine, creatinine kinase, and urine protein levels reverted to physiological levels within 6 months of treatment with thyroxine, and with normalization of thyroid-stimulating hormone.ConclusionHypothyroidism can present as renal insufficiency, proteinuria, and can mimic rhabdomyolysis. Prompt initiation of thyroxine treatment and control of thyroid-stimulating hormone levels could reverse these changes.