Low Thyroxine Concentrations Research Articles

Thyroid Function During the Fetal and Neonatal Periods.

Thyroid hormones are essential during infancy and childhood for growth and brain development. The formation and maturation of the newborn's hypothalamic-pituitary-thyroid axis begin in utero with fetal dependence on maternal thyroid hormones early in the pregnancy. As the fetal thyroid gland begins to produce thyroid hormones in the second trimester, the reliance decreases and remains at lower levels until birth. After birth, the detachment from the placenta and the change in thermal environment lead to a rapid increase in circulating thyroid-stimulating hormone in the neonate within hours, resulting in subsequent increases in thyroxine and triiodothyronine concentrations. Preterm infants may have lower thyroxine concentrations because of an immature hypothalamic-pituitary-thyroid axis at the time of birth and premature discontinuation of transference of maternal thyroid hormones. Similarly, infants with critical illness unrelated to the thyroid gland may have lower thyroxine levels. Infants born to mothers with Graves' disease are at risk for hypothyroidism and hyperthyroidism, which is related to the placental transfer of maternal autoantibodies, as well as antithyroid medications. An understanding of the normal embryology and physiology of the fetal and neonatal thyroid will help in evaluating a newborn for thyroid disorders.

Nationwide Evaluation of Congenital Hypothyroidism Screening during Neonatal Extracorporeal Membrane Oxygenation

Background: Thyroid hormone concentrations may deviate from normal values during critical illness. This condition is known as nonthyroidal illness syndrome (NTIS), and it can influence the results of screening for congenital hypothyroidism (CH) during neonatal extracorporeal membrane oxygenation (ECMO). Objectives: To determine the incidence of aberrant CH screening results in ECMO-treated neonates, to identify possible determinants, and to follow up patients with abnormal thyroid hormone concentrations. Methods: In this retrospective cohort study, we included 168 ECMO-treated neonates admitted from 2004 to 2014 and screened by protocol and divided them into the following 3 groups: group 1 (screened during ECMO, n = 107), group 2 (screened shortly before ECMO, n = 26), and group 3 (screened shortly after ECMO, n = 35). Results: CH screening results were aberrant in 67.3% (72/107) of the neonates screened during ECMO, in 73.1% (19/26) of the neonates screened before ECMO, and in 31.4% (11/35) of the neonates screened after ECMO (p < 0.001). Of the neonates with an aberrant screening result, all but 2 (i.e. 98%) had a low thyroxine concentration with a normal thyrotropin concentration at screening, as is seen in NTIS. None was diagnosed with CH. Mortality did not significantly differ between neonates with an aberrant screening result (32.4%) and neonates with a normal screening result (22.7%; p = 0.18). Screening before ECMO (OR 5.92; 95% CI 1.93-18.20), screening during ECMO (OR 4.49; 95% CI 1.98-10.19), and a higher Pediatric Logistic Organ Dysfunction-2 score (OR 1.31; 95% CI 1.04-1.66) were associated with an aberrant screening result. Conclusions: Aberrant CH screening results were found in most ECMO-treated neonates screened before or during ECMO, which is likely due to NTIS. Follow-up of thyroid hormone concentrations is best started after recovery from critical illness. Our results suggest that thyroxine therapy is not required during ECMO.

Congenital hypothyroidism – what's new?

Abstract Congenital hypothyroidism (CHT) represents an anatomical, biochemical and clinical spectrum with associated implications in terms of management and outcome. At one end of the spectrum of primary thyroid dysfunction is the child with thyroid agenesis and no significant endogenous thyroid function. This baby will require full thyroxine replacement. At the other end of the spectrum is the baby with a subtle increase in thyroid-stimulating hormone (TSH) levels, a normally sited thyroid gland and significant associated endogenous thyroid hormone generation. This baby will require a smaller dose of thyroxine supplementation to normalise TSH concentrations. The TSH ‘threshold’ that warrants intervention is unknown, although local thyroid hormone ‘normal ranges’ may be derived from adults and hence may not be representative of thyroid hormone levels in healthy neonates. The outlook for treated babies with CHT is excellent but there may still be subtle, long-term consequences of relatively low thyroxine concentrations in utero despite prompt diagnosis and treatment.

Overweight increases risk of first trimester hypothyroxinaemia in iodine‐deficient pregnant women

Hypothyroxinaemia early in pregnancy may impair fetal brain development. Increased body weight has been associated with low thyroxine concentrations in non-pregnant women. In pregnant women, morbid maternal obesity is a risk factor for thyroid dysfunction. But whether lesser degrees of overweight that are much more common could be a risk factor for hypothyroxinaemia in pregnancy is unclear. The objective of this study was to investigate if overweight increases risk for thyroid dysfunction, and specifically hypothyroxinaemia, in iodine-deficient pregnant women. We performed a cross-sectional study at first hospital visit among healthy Thai pregnant women. We measured weight and height, urinary iodine concentration (UIC), serum thyroid hormones and thyroglobulin. Pre-pregnancy weight and relevant dietary factors were determined by questionnaire, and body mass index (BMI) was used to classify weight status. Among 514 women (mean gestational age, 11 weeks) with a median UIC of 111 μg dL(-1) , indicating mild iodine deficiency, 12% had low free thyroxine (fT4) concentrations: 3% had overt hypothyroidism; 7% had subclinical hypothyroidism; and 8% had isolated hypothyroxinaemia. Based on pre-pregnancy BMI, 26% of women were overweight or obese. In a multiple regression model, BMI was a negative predictor of fT4 (β = -0.20, P < 0.001). Compared to normal weight women, the prevalence ratio (95% CI) of a low fT4 in overweight women was 3.64 (2.08-6.37) (P < 0.01). Iodine-deficient pregnant Thai women who are overweight have a 3.6-fold higher risk of hypothyroxinaemia in the first trimester compared to normal weight women. Targeted screening should consider overweight a potential risk factor for thyroid dysfunction in pregnant women in iodine-deficient areas.

A Novel Monocarboxylate Transporter 8 Gene Mutation as a Cause of Severe Neonatal Hypotonia and Developmental Delay

Monocarboxylate transporter 8 acts as a specific cell membrane transporter for thyroxine and especially triiodothyronine into target cells. It is expressed in brain neurons and in many other tissues. The monocarboxylate transporter 8 gene resides on chromosome Xq13.2. An 11-month-old male infant was referred because of severe hypotonia from early life and global developmental delay. Thyroid-function tests showed normal thyrotropin levels and the characteristic for the disorder, including high serum triiodothyronine and low thyroxine concentrations. Molecular analysis of the monocarboxylate transporter 8 gene showed that the patient was hemizygous for a novel missense mutation P537L. This case highlights the importance of determining thyroid hormone levels, especially triiodothyronine, in infants with severe neonatal hypotonia.

A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels

Thyroglobulin abnormality is a rare cause of congenital hypothyroidism and only a limited number of mutations in the thyroglobulin gene have been reported. We analyzed the thyroglobulin gene in a patient with congenital goitrous hypothyroidism. This girl was identified with hyperthyrotropinemia in a neonatal mass-screening test. The patient had goiter, and her body weight gain was poor. Distal femoral epiphysis was absent on roentgenography. Her serum thyroxine level was low; however, her triiodothyronine level was high. Autoantibodies against triiodothyronine, thyroid peroxidase, and thyroglobulin were all negative. Her serum thyroglobulin level was undetectable. The thyroglobulin gene from the genomic DNA of the patient was analyzed by direct sequencing. Two novel heterozygous missense mutations, Cys1897Tyr (exon 31) and Arg2336Gln (exon 40), were found in the patient. The former mutation was derived from her mother, suggesting a compound heterozygous state. Normal triiodothyronine and low thyroxine concentrations are often observed in patients with thyroglobulin gene mutations. We considered that some patients with thyroglobulin abnormality might have high triiodothyronine levels. In cases of congenital goitrous hypothyroidism with normal-to-high triiodothyronine levels and low serum thyroglobulin levels, thyroglobulin abnormality should be considered.

Abnormal cognitive function in treated congenital hypopituitarism

Aims: To assess cognitive function in school age children with congenital pituitary hormone deficiency (PHD). Methods: Ten children with PHD (aged 6.0–15.6 years, mean 11.5 years) and sibling controls (aged...

Developmental toxicity of in ovo exposure to polychlorinated biphenyls: II. Effects of maternal or paternal exposure on second-generation nestling american kestrels.

The development of second-generation nestling American kestrels (Falco sparverius) was altered by in ovo exposure of only one parent to polychlorinated biphenyls (PCBs). Polychlorinated biphenyls appear to alter nestling development through both maternally and paternally mediated effects. In 1998, F0 parent kestrels consumed approximately 5 to 7 microg total PCBs/g bird/d (Aroclors 1248:1254: 1260) for approximately 100 d prior to eggs hatching; these eggs, containing total PCB concentrations of 34.1 microg/g, produced 13 F1 offspring, which were then paired in 1999 with unexposed kestrels to examine developmental effects of maternal or paternal in ovo PCB exposure. Using a toxicokinetics model, eggs from the maternally exposed group had predicted PCB levels of 0.03 to 0.34 microg/g, with enriched higher chlorinated congeners. Polychlorinated biphenyl concentrations in eggs of all generations have recently been found in eggs and nestlings of free-ranging eagles. Consistent with the first generation, maternally exposed F2 females generally were larger, had altered growth rates, and delayed maximal growth and fledging compared with control females. Maternally exposed F2 males were heavier but had shorter bones, grew more quickly and earlier, and fledged 2 d later than control males. In the maternally exposed group, concentrations of plasma triiodothyronine were elevated in F2 females but suppressed in F2 males. Paternally exposed F2 hatchlings of both sexes were comparable in size to controls with the exception of having longer tarsi bones, but subsequently showed slower, delayed growth (both sexes) and fledging (females) and lower thyroxine concentrations (males). The alterations in thyroid hormones in the F2 generation are discussed in light of the enrichment of higher chlorinated PCB congeners and hydroxylated PCB congeners. The developmental changes in the kestrel nestlings are likely a function of several possible mechanisms involving maternal PCB deposition, parental behavior, and neurobehavioral and endocrine-thyroid function in nestlings.

Menstrual cycle irregularity in bulimia nervosa: Associated factors and changes with treatment

Objectives: This study determined the clinical and nutritional variables associated with menstrual disturbance in women with bulimia nervosa (BN). Methods: Eighty-two women with DSM-IV BN underwent psychiatric, nutritional and menstrual related assessments prior to an outpatient treatment programme and at 12 months follow-up. Results: Forty-five percent reported a current irregular menstrual cycle. A high frequency of vomiting, low thyroxine concentrations and low dietary fat intake were independently associated with irregular menses at pretreatment. At 12 months follow-up, 30.5% reported irregular menstrual cycles. A greater difference between past maximum and minimum body weight, smoking and depression were associated with menstrual irregularity at 12 months follow-up. Of those with irregular menstrual cycles at pretreatment, 56.8% became regular at 12 months follow-up. Conclusion: Menstrual irregularity in BN is associated with indices of nutritional restriction that are not reflected by low body weight or energy intake. Depression, cigarette smoking and fluctuations in body weight may act as metabolic stresses that contribute to the perpetuation of menstrual disturbances.

Iodine and hypothyroidism in neonates with congenital heart disease

AIMTo evaluate the influence of the intravenous injection of iodine during cardiac catheterisation, and of topical iodine antiseptics during surgical procedures, on thyroid function in full term neonates.METHODSTwenty one full...

Neonatal screening for congenital hypothyroidism by measurement of plasma thyroxine and thyroid stimulating hormone concentrations.

Neonatal screening for congenital hypothyroidism was introduced in the City of Birmingham in 1980 by measuring concentrations of both thyroid stimulating hormone and thyroxine in plasma. Over two years 30 108 babies were tested. Thirty one babies were recalled because of thyroid stimulating hormone concentrations greater than 40 mU/l, of whom 12 were treated with replacement thyroxine. Six babies were found to have low thyroxine concentrations because of reduced thyroxine binding globulin and five raised thyroxine values because of increased thyroxine binding globulin. As a result of this study screening was continued with measurement of thyroid stimulating hormone only as the primary test for congenital hypothyroidism, the thyroxine value being measured only when the concentration of thyroid stimulating hormone exceeded 20 mU/l.

Measuring thyroxine and thyrotropin simultaneously in a dried blood sample on filter paper, to screen for neonatal hypothyroidism.

We have developed a highly sensitive radioimmunoassay of thyroxine and thyrotropin for mass screening for neonatal hypothyroidism. This assay involves a single disc (3 mm diameter) of dried blood on filter paper. The minimum detectable concentrations are 15 pg/tube (10 microgram/L) for thyroxine and 15 nano-int. units/tube (10 milli-int. units/L) for thyrotropin; intra- and interassay CV's are less than 15% in both assays. The high sensitivity of this method is due to use of labeled thyroxine with high specific activity (3 kCi/g) and of an anti-thyrotropin serum with high affinity (Keq = 7.8 x 10(11) L/mol). With this method, 11337 newborns were screened; a follow-up study revealed that only newborns with both high thyrotropin and low thyroxine concentrations had permanent hypothyroidism. We conclude that this method is sensitive, simple, and reliable and that the recall rate with this method is much lower than that of tests for measuring thyroxine or thyrotropin alone.

Measuring thyroxine and thyrotropin simultaneously in a dried blood sample on filter paper, to screen for neonatal hypothyroidism.

Abstract We have developed a highly sensitive radioimmunoassay of thyroxine and thyrotropin for mass screening for neonatal hypothyroidism. This assay involves a single disc (3 mm diameter) of dried blood on filter paper. The minimum detectable concentrations are 15 pg/tube (10 microgram/L) for thyroxine and 15 nano-int. units/tube (10 milli-int. units/L) for thyrotropin; intra- and interassay CV’s are &amp;lt; 15% in both assays. The high sensitivity of this method is due to use of labeled thyroxine with high specific activity (3 kCi/g) and of an anti-thyrotropin serum with high affinity (Keq = 7.8 × 10(11) L/mol). With this method, 11337 newborns were screened; a follow-up study revealed that only newborns with both high thyrotropin and low thyroxine concentrations had permanent hypothyroidism. We conclude that this method is sensitive, simple, and reliable and that the recall rate with this method is much lower than that of tests for measuring thyroxine or thyrotropin alone.

Thyroid function during postnatal development in the rat

In normal postnatal rats the following parameters of thyroid function were measured: weight, radioiodine uptake, and serum thyroxine concentration. It was found that the weight gain of the thyroid during the first month is linearly related to body weight on a log-log basis. Radioiodine uptake expressed as the percentage of the injected dose per mg of thyroid weight shows higher values in newborn rats than during the next fortnight. A second increase in values takes place during the third and fourth week and is followed by a decline to the adult values. In serum thyroxine concentration a sharp rise within the first 2 days after birth is followed by a sharp decline. A second peak is observed at the beginning of the third week. Thyroidal 131I uptake during the first 2 weeks depends on environmental temperature. The values are significantly higher at nest temperature (35°C) than at room temperature (24°C). A compensatory increase of 131I uptake in the thyroid remnant may be observed as early as 2 days after partial thyroidectomy performed during the first postnatal week. Administration of thyroxine inhibits 131I uptake in normal young rats as well as the compensatory changes in hemithyroidectomized rats. Thyroxine concentration in the blood fell significantly as early as 3 days following total thyroidectomy performed on postnatal day 5. In spite of the low thyroxine concentration body weight differences begin to be manifest only by the end of the second week. These data indicate that the thyroid-pituitary feedback is operating during the whole postnatal period and may be activated experimentally even before the physiological impact of this system becomes manifest.