Management of Hypothyroidism and Hypothyroxinemia During Pregnancy.

OBJECTIVE: To review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period. METHODS: A literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature. RESULTS: During pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy. CONCLUSION: The diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.

Thyroid hormone deficiency during zebrafish development impairs central nervous system myelination.

Thyroid hormones are messengers that bind to specific nuclear receptors and regulate a wide range of physiological processes in the early stages of vertebrate embryonic development, including neurodevelopment and myelogenesis. We here tested the effects of reduced T3 availability upon the myelination process by treating zebrafish embryos with low concentrations of iopanoic acid (IOP) to block T4 to T3 conversion. Black Gold II staining showed that T3 deficiency reduced the myelin density in the forebrain, midbrain, hindbrain and the spinal cord at 3 and 7 dpf. These observations were confirmed in 3 dpf mbp:egfp transgenic zebrafish, showing that the administration of IOP reduced the fluorescent signal in the brain. T3 rescue treatment restored brain myelination and reversed the changes in myelin-related gene expression induced by IOP exposure. NG2 immunostaining revealed that T3 deficiency reduced the amount of oligodendrocyte precursor cells in 3 dpf IOP-treated larvae. Altogether, the present results show that inhibition of T4 to T3 conversion results in hypomyelination, suggesting that THs are part of the key signaling molecules that control the timing of oligodendrocyte differentiation and myelin synthesis from very early stages of brain development.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome.

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

The Interactive Effect of Prepregnancy Overweight/Obesity and Isolated Maternal Hypothyroxinemia on Macrosomia.

CONTEXT: Prepregnancy overweight/obesity (OWO) and isolated maternal hypothyroxinemia (IMH) may increase the risk of macrosomia, but little is known about their potential combined effect on macrosomia. OBJECTIVE: The aim of this study was to assess whether prepregnancy OWO and first-trimester IMH have a synergistic effect on the risk of macrosomia. METHODS: A large prospective cohort study in a Chinese population from January 2016 to December 2018 in a tertiary care center. In total, 34 930 pregnant women were included. The main outcome measure was macrosomia. RESULTS: A total of 34 930 participants comprising IMH and euthyroid cases was included in this study. Prepregnancy OWO and first-trimester IMH were independently associated with an increased risk of macrosomia (adjusted odds ratio [OR] 2.48, 95% CI 2.22, 2.78, and adjusted OR 1.65, 95% CI 1.34, 2.01, respectively). The coexistence of prepregnancy OWO and IMH was associated with macrosomia, with an adjusted OR of 5.26 (95% CI 3.9, 7.0) compared with pregnant women without either condition. The additive interaction between prepregnancy OWO and IMH was found to be significant with regard to macrosomia. CONCLUSION: Prepregnancy OWO and IMH in the first trimester may synergistically increase the risk of macrosomia.

Thyroid Hormone Deficiency Suppresses Fetal Pituitary-Adrenal Function Near Term: Implications for the Control of Fetal Maturation and Parturition.

Background: The fetal hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the control of parturition and maturation of organ systems in preparation for birth. In hypothyroid fetuses, gestational length may be prolonged and maturational processes delayed. The extent to which the effects of thyroid hormone deficiency in utero on the timing of fetal maturation and parturition are mediated by changes to the structure and function of the fetal HPA axis is unknown. Methods: In twin sheep pregnancies where one fetus was thyroidectomized and the other sham-operated, this study investigated the effect of hypothyroidism on circulating concentrations of adrenocorticotrophic hormone (ACTH) and cortisol, and the structure and secretory capacity of the anterior pituitary and adrenal glands. The relative population of pituitary corticotrophs and the masses of the adrenal zones were assessed by immunohistochemical and stereological techniques. Adrenal mRNA abundances of key steroidogenic enzymes and growth factors were examined by quantitative polymerase chain reaction. Results: Hypothyroidism in utero reduced plasma concentrations of ACTH and cortisol. In thyroid-deficient fetuses, the mass of corticotrophs in the anterior pituitary gland was unexpectedly increased, while the mass of the zona fasciculata and its proportion of the adrenal gland were decreased. These structural changes were associated with lower adrenocortical mRNA abundances of insulin-like growth factor (IGF)-I and its receptor, and key steroidogenic enzymes responsible for glucocorticoid synthesis. The relative mass of the adrenal medulla and its proportion of the adrenal gland were increased by thyroid hormone deficiency in utero, without any change in expression of phenylethanolamine N-methyltransferase or the IGF system. Conclusions: Thyroid hormones are important regulators of the structure and secretory capacity of the pituitary-adrenal axis before birth. In hypothyroid fetuses, low plasma cortisol may be due to impaired adrenocortical growth and steroidogenic enzyme expression, secondary to low circulating ACTH concentration. Greater corticotroph population in the anterior pituitary gland of the hypothyroid fetus indicates compensatory cell proliferation and that there may be abnormal corticotroph capacity for ACTH synthesis and/or impaired hypothalamic input. Suppression of the development of the fetal HPA axis by thyroid hormone deficiency may contribute to the delay in fetal maturation and delivery observed in hypothyroid offspring.

Hypothyroxinemia Detected at 4 Weeks of Life in Preterm Infants Born at Less than 30 Weeks of Gestation.

OBJECTIVE: Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks. STUDY DESIGN: Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants <30 weeks of gestation. Association between FT4 at 4 weeks of life and perinatal characteristics were determined by bivariate analysis and multivariable regression. Incidence of hypothyroxinemia was determined using a gestational age adjusted definition based on in utero levels at the equivalent postmenstrual age. RESULTS: The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort. CONCLUSION: Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born <30 weeks had hypothyroxinemia at 4 weeks of life when compared with in utero levels at the equivalent postmenstrual age.

Pituitary stalk interruption syndrome: A rare case report and literature review.

RATIONALE: Pituitary stalk interruption syndrome (PSIS) is a congenital pituitary anatomical defect. It is characterized by the triad of thin or interrupted pituitary stalk, absent or ectopic posterior lobe, and hypoplastic or aplastic anterior lobe. Moreover, this condition is considered rare. PATIENT CONCERNS: A 23-year-old male patient presented with a history of short stature and hypogonadism. Laboratory assessment revealed low thyroxine, cortisol, and adrenocorticotropic hormone levels, which are consistent with adrenal insufficiency without hypoglycemia. The insulin-induced hypoglycemia tolerance test finding indicated growth hormone (GH) deficiency. Moreover, magnetic resonance imaging revealed an interrupted pituitary stalk, ectopic posterior pituitary, and hypoplastic anterior pituitary. This triad of symptoms was indicative of PSIS. DIAGNOSIS: INTERVENTIONS:: The patient was deficient in adrenaline, thyroxine, gonadal steroid, and GH. Thus, glucocorticoid replacement therapy was initiated, followed by euthyrox, androgen, and human chorionic gonadotropin treatment. Calcium tablets, calcitriol, and alendronate sodium were used for the management of osteoporosis. The patient was 164 cm tall, and his bone age was approximately 15 years old. However, owing to a poor economic condition, the family did not proceed with GH therapy. OUTCOMES: The patient did not present with adrenal or hypothyroidism crisis after receiving poly-hormonal replacement therapy. His secondary sexual characteristics began to develop. However, owing to a short treatment window period, the patient could not receive the required treatment. Hence, whether the patient would have a normal fertility function needs to be confirmed. LESSONS: PSIS is a rare disease with various clinical characteristics. During the neonatal period and infancy, the signs and symptoms of PSIS are often not evident. Therefore, diagnosis is delayed. The early detection of hormone deficiency and treatment initiation can affect both the quality of life and the prognosis of patients with PSIS. Thus, the diagnosis and treatment of this disease must be improved to help patients achieve a better quality of life and to prevent reproductive health problems.

Does Hypothyroxinemia of Preterm Neonates Persist Beyond 7 weeks of Life?

OBJECTIVES: To determine whether hypothyroxinemia in the early neonatal period normalizes by 7 wk of postnatal age. METHODS: An observational study was carried out from July 2008 through June 2010 in the neonatal and postnatal unit of Chittagong Medical College Hospital, Bangladesh. A total of 150 neonates including 100 preterm and 50 term neonates were selected by convenient sampling. Preterm neonates were stratified according to postconceptional age. By the 3rd generation two site chemiluminesent immunometric assay, free T4 (FT4) and thyroid stimulating hormone (TSH) estimations were done. Within 5-11 d, first samples were collected from all the neonates and the second samples of hypothroxinemic preterm neonates were collected within 42-50 d of birth. RESULTS: Positive correlation of FT4 was found with gestational age (p < 0.0001, n = 100, r = 0.61) in preterm neonates while significant difference was found among the gestational age subgroups (p = 0.0001). No significant differences were, however, found in TSH levels of such age groups of the preterms. Highly significant differences in FT4 and TSH levels between 1st and 2nd samples were found in subgroup analysis of the preterm neonates. In the 1st samples, TSH level correlated positively with gestational age but in the 2nd samples, significant negative correlation was observed. In all neonates with initial hypothyroxinemia, FT4 levels were found to increase to reach the normal levels by 7 wk. CONCLUSIONS: FT4 level normalizes by 7 wk of birth in preterm newborn neonates.

The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China.

OBJECTIVES: To explore the effect of isolated maternal hypothyroxinemia (IMH) during the first and second trimester of gestation on pregnancy outcomes. To explore whether levothyroxine (L-T4) treatment of women who had IMH identified in the first trimester improves pregnancy outcomes. METHODS: Women in the early pregnancy in the iodine-sufficient area (n = 3398) were recruited to this prospective cohort study (ChiCTR-TRC-12002326). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were detected. Women with IMH before 12 weeks chose to receive L-T4 or remain untreated. The L-T4 dose was adjusted to attain a normal FT4 and TSH level. Pregnancy outcomes were evaluated during follow-up. RESULTS: IMH in the first trimester was not associated with increased risk of adverse pregnancy outcome compared with controls. The incidence of macrosomia (p = 0.022) and gestational hypertension (p = 0.018) was significantly higher in IMH identified in the second trimester of gestation compared with controls. IMH identified in the second trimester of gestation was a risk factor for macrosomia [adjusted odds ratio (aOR) 1.942, 95% CI 1.076-3.503, p = 0.027] and gestational hypertension (aOR 4.203, 95% CI 1.611-10.968, p < 0.01), when body mass index in the early pregnancy was < 25 kg/m2. CONCLUSIONS: IMH in the first trimester did not increase the risk of adverse outcomes irrespective of whether women received L-T4 treatment. However, IMH identified in the second trimester was associated with increased risk of adverse pregnancy outcome. The results suggest that thyroid function follow-up during the second trimester is necessary, even if thyroid function is normal during the first trimester.

Thyroid function in neonates of women with subclinical hypothyroidism or hypothyroxinemia.

OBJECTIVE: To assess whether treatment of pregnant women with subclinical hypothyroidism or hypothyroxinemia alters neonatal TSH results. STUDY DESIGN: A planned secondary analysis of data from two multi-center randomized, double-masked, placebo-controlled thyroxine replacement trials in pregnant women with either subclinical hypothyroidism or hypothyroxinemia. Infant heel-stick specimens were obtained before discharge. We compared TSH levels between neonates born to mothers allocated to treatment or placebo within each trial and between neonates in the placebo groups. Multiples of means were generated for day-of-life-specific data. RESULTS: Neonatal TSH values were available for 573/677 (84.6%) newborns from the subclinical hypothyroidism trial and 461/526 (87.6%) newborns from the hypothyroxinemia trial. Neonatal TSH values did not differ in either trial by treatment group or between placebo groups (P > 0.05 for all comparisons). CONCLUSIONS: Neonatal TSH values did not differ with thyroid hormone replacement in pregnancies diagnosed with subclinical hypothyroidism or hypothyroxinemia.

IMPORTANCE OF ISOLATED GESTATIONAL HYPOTHYROXINEMIA IN THE DEVELOPMENT OF OBSTETRIC AND SOMATIC PATHOLOGIES.

The isolated hypothyroxinemia of pregnancy (IHP) has gained specific attention in the specialized literature during the recent years as the possible factor impeding the intellectual development of fetus and increasing the risk of complications related with pregnancy, delivery and perinatal period. Aim of the study was to define the importance of isolated hypothyroxinemia in the development of obstetric and somatic pathologies in outpatient population of pregnant females. The study of prospective design was performed at the base of "David Gagua Clinic" Ltd. Based on hospital referral we selected the pregnant patients who were diagnosed for isolated hypothyroxinemia in the 1st trimester of pregnancy by clinical-laboratory studies. 104 pregnant females with isolated hypothyroxinemia were included in the main group, and 58 pregrant females of reproductive age who were not identified to have thyroid pathology by screening studies were included in the control group,. The questionnaire used in the study process included the retrospective medical history data, demographic findings, information about premorbid background, genetic burden of somatic pathology, social-economical factors (including education level, living conditions, economic income, family environment etc.) and concomitant somatic pathology. In addition, it included the clinical and para-clinical study data and pregnancy follow-up findings. The test studies for thyroid status were performed every trimester and after one month postpartum. The software packages Microsoft Excel (2010) and SPSS/v.12 was used for statistical treatment of data. The digital data is presented by M±STD, where M is the arithmetic mean and STD is the standard deviation of arithmetic mean. To define the confidence interval for the indices and their relation, we calculated 2 and p, whose critical value was defined to be 0.05. Based on analysis of the acquired data, we found out that pregnant females with isolated hypothyroxinemia were more statistically demonstrating asthenia, dry skin, increased hair loss and fragile nails, and from somatic disorders - pregnancy-associated vomiting and anemia. From concomitant diseases, allergic disorders (18.2%), primary dysmenorrhea (27.8%), spontaneous abortions (25%) were taking the highest incidence rate and other obstetric complications (premature delivery, late delivery) were higher in the main group, though statistically significant difference was not demonstrated. It must be noted that isolated hypothyroxinemia in the studied cohort was mostly found in 1st trimester of pregnancy, whereas according to the literature data, the latter is demonstrated more frequently in the second or third trimester. The above mentioned makes us consider that the iodine deficit in the cohort of pregnant females studied by us was probably present before pregnancy as well and maybe with even higher extent. Thus, the isolated hypothyroxinemia developed in the very first trimester of pregnancy still has its negative impact on the pregnancy course and outcome, despite of applied treatment. According to performed studies and their results, for the prevention of obstetric and perinatal complications, its important to administer iodine preparations together with folic acid at pregravid stage in addition to complete elimination of diet abnormalities, plan the pregnancy in stable normothyroxinemia conditions and at positive energetic balance. In addition, its desirable to perform the repeated thyroid status evaluation in the first trimester of pregnancy and timely administration of adequate therapeutic measures in case of finding any pathology.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study.

OBJECTIVE: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. SUBJECTS AND METHODS: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. RESULTS: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). CONCLUSIONS: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study

ABSTRACT Objective: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. Subjects and methods: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. Results: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). Conclusions: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Tiroides y neurodesarrollo fetal / Thyroid hormones and fetal neurodevelopment

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Influencia de la hipotiroxinemia gestacional en el desarrollo neuropsicológico de la descendencia / Influence of gestational hypothyroxinemia on neuropsychological development of the offspring

El objetivo del presente trabajo es analizar cómo la hipotiroxinemia gestacional puede afectar al neurodesarrollo fetal, así como las posibles medidas preventivas y/o de tratamiento frente a dicha disfunción. Las hormonas tiroideas son compuestos químicos esenciales para el correcto desarrollo del cerebro y del sistema nervioso central fetal durante las primeras etapas del embarazo. Un déficit de yodo durante este periodo puede alterar los parámetros tiroideos funcionales maternos y desencadenar ciertas disfunciones como la hipotiroxinemia gestacional. Este trastorno, caracterizado por bajos niveles de tiroxina libre con niveles normales de hormona estimulante de la tiroides, causa errores de migración neuronal en el cerebro fetal en desarrollo y alteraciones en la citoarquitectura de la corteza y el hipocampo. Debido a ello, se observa un peor desarrollo cognitivo y psicomotor en la descendencia, además de un aumento en las probabilidades de padecer ciertas enfermedades psiquiátricas. A pesar de que el deterioro mental no suele ser tan severo como el de los niños cuyas madres padecen otra disfunción tiroidea gestacional, el número de embarazadas afectadas suele ser mayor. Por ello, se debe asegurar un suministro adecuado de yodo a todas las embarazadas con el objetivo de disminuir la hipotiroxinemia. La administración de levotiroxina, forma sintética de la tiroxina, desde el primer trimestre hasta el final del embarazo en el tratamiento de dicho trastorno parece disminuir el riesgo de retraso cognitivo y psicomotor de la descendencia, aunque los estudios sobre su efectividad aún son escasos y poco concluyentes (AU)

The present study analyzes how gestational hypothyroxinemia can affect fetal neurodevelopment, as well as the preventive and/or treatment measures against this dysfunction. Thyroid hormones, which are iodinated amino acids, are essential chemical compounds for the right fetal brain and central nervous system development during early stages of pregnancy. An iodine deficiency during this period may alter maternal functional thyroid parameters and trigger certain dysfunctions such as maternal hypothyroxinemia, which has a varied etiology. This disorder, which is characterized by low levels of free thyroxine combined with normal levels of thyroid stimulating hormone, causes neuronal migration mistakes in the developing fetal brain and alterations in the cortex and hippocampus cytoarchitecture. Due to this, a worse cognitive and psychomotor development in the offspring and an increase in the probabilities of suffering certain psychiatric diseases are observed. Although mental impairment is not usually as severe as that of children whose mothers have other thyroid dysfunction during pregnancy, the number of affected people is usually higher. This is why an adequate iodine supply should be ensured to all pregnant women in order to reduce hypothyroxinemia. Levothyroxine administration, a synthetic form of thyroxine, from the first trimester to the end of pregnancy in the treatment of this disorder seems to reduce the risk of cognitive and psychomotor delay of the offspring, although studies of its effectiveness are still scarce and inconclusive (AU)

The impact of isolated maternal hypothyroxinaemia on the incidence of large-for-gestational-age infants: the Ma'anshan Birth Cohort study.

OBJECTIVE: The purpose of this study was to investigate whether isolated maternal hypothyroxinaemia (IMH) is associated with risks of small/large-for-gestational-age (SGA/LGA) infants. DESIGN: Population-based prospective cohort study. SETTING: Ma'anshan Maternal and Child Health (MCH) clinics, China. POPULATION: Pregnant women with singleton births (n = 3178). METHODS: Descriptive statistics were calculated for the demographic characteristics of the mothers and their newborns. Linear regression was applied to estimate the association between thyroid hormone levels and birthweight. Logistic regression was performed to calculate the association between IMH and SGA/LGA. MAIN OUTCOME MEASURES: Outcomes included SGA/LGA. RESULTS: The prevalence of IMH, defined as a free thyroxine value (FT4) lower than the 2.5th percentile with normal thyroid stimulating hormone, was 2.5% (78/3080) and 2.5% (74/2999) in the first and second trimesters, respectively. Additionally, 306 (9.6%) and 524 (16.5%) infants were defined as SGA and LGA, respectively. No evidence supported the notion that IMH is associated with an increased risk for SGA in either the first [odds ratio (OR): 1.762, 95% confidence interval (CI): 0.759-4.089] or the second (OR: 0.763, 95% CI: 0.231-2.516) trimester. However, an increased risk of LGA was observed among IMH women in the second trimester (OR: 2.088, 95% CI: 1.193-3.654). Maternal TPO-Ab positivity in the second trimester increased the risk of SGA (OR: 2.094, 95% CI: 1.333-3.290). CONCLUSION: This study provides evidence that IMH is associated with LGA. FUNDING: This work was supported by the National Natural Science Foundation of China (No. 81330068). TWEETABLE ABSTRACT: Isolated maternal hypothyroxinaemia may increase the risk of large-for-gestational-age infants.

Cornelia de lange syndrome with thyroid agenesis of an indonesian patient.

Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities. The prevalence ranges from 1:100,000 to as high as 1:10,000. Most cases (50-60%) were carried mutation in NIPBL gene. To our knowledge this is the first CdLs Indonesian case that reported with molecular analysis study. We present an 11 months old female Indonesian patient with classic CdLs with congenital hypothyroid. Genetics studies were performed in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Thyroid studies (T3, T4, TSH and thyroid scan) were performed. Low level of T3 and T4, and high level of TSH were observed. Thyroid agenesis was found in thyroid scan examination. We detected thyroid agenesis which has been never reported in CdLs patients. We could not find any mutation in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Further genetics examinations were necessary whether there is mutation in other locus.