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Concept: Thyroxine


Congenital hypothyroidism, usually of the primary and permanent variety, is an eminently preventable cause of growth retardation and mental handicap whose outlook has been transformed by newborn screening, usually involving the measurement of capillary TSH. Severe primary congenital hypothyroidism, due for example to athyreosis, may result in subtle cognitive, behavioural and sensori-motor deficits, but the extent to which these can be offset by optimal postnatal diagnosis and management remains uncertain. This is because the available adult follow-up data reflect the outcome of previous management in the 1970’s and 1980’s, and also because the accurate neuro-psychological assessment of children is difficult, particularly in the preschool population. There is an urgent need to develop new consensus guidelines and to ensure that the children managed according to such guidelines are systematically and prospectively assessed so that good quality outcome data become available. In this review, key recommendations in the management of congenital hypothyroidism include: screening at day 3 so that severely affected infants can begin treatment within the first 10 days of life; setting the thyrotropin (TSH) referral cut-off at 8-10 mU/L; adopting a disciplined diagnostic algorithm to evaluate referred cases, with measurement of venous free thyroxine (T4), TSH and thyroglobulin combined with dual ultrasound and radioisotope imaging; initial treatment with a T4 dose of 50 μg daily in infants weighing ≥ 2.5 kg and 15 μg/kg/day in infants weighing < 2.5 kg followed by weekly review until thyroid function is normalised; and maintenance of free T4 levels between 15-26 pmol/L and TSH between 0.5-5 mU/L thereafter to avoid both under- and overtreatment.

Concepts: Thyroid-stimulating hormone, Hypothyroidism, Hashimoto's thyroiditis, Thyroid, Thyroid hormone, Thyroxine, Newborn screening, Congenital hypothyroidism


Childhood abuse is a powerful risk factor for developing postpartum depression in adulthood, and recently it has been associated to thyroid dysfunction in postpartum depressive women. The purpose of this study was to investigated the effects of childhood abuse on thyroid status and depressive symptomatology in two hundred and thirty-six (n=236) postpartum women 24-48h after delivery. The Early-Trauma-Inventory Self-Report was used to assess the presence of childhood abuse and the Edinburgh Postpartum Depression Scale (EPDS) to evaluate depressive symptomatology (EPDS≥11). Free thyroxin (fT4) and thyroid-stimulating hormone (TSH) were measured. Thyroid dysfunction (TD) was defined as altered TSH or TSH and fT4. Socio-demographic, reproductive, and psychopathological variables were also collected. Multivariate analysis shows that childhood physical abuse increases by four times the risk for TD (OR: 3.95, 95% CI: 1.23-12.71) and five times the risk for depressive symptomatology (OR: 5.45, 95% CI: 2.17-13.66) in the earlier postpartum. Our findings suggest that women with history of childhood physical abuse are particularly at-risk for thyroid dysfunction and depressive symptomatology 24-48h after delivery. The assessment of childhood abuse in the perinatal period is important to identify women at-risk for physical and mental health problems in this period.

Concepts: Pregnancy, Childbirth, Multivariate statistics, Child abuse, Bipolar disorder, Postpartum depression, Thyroxine, Physical abuse


Objectives: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz’s disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. Method: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz’s disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland. Results: Among the 22 patients (19%) in our cohort who were found to have hypothyroidism [thyroid stimulating hormone (TSH) > 4 mIU/L], 11 patients had clinical hypothyroidism [free thyroxine (FT4) < 1 ng/dL] and 11 patients had subclinical hypothyroidism (FT4 ≥ 1 ng/dL). Serum concentrations of IgG, IgG4, circulating immune complex (CIC), and β2-microglobulin (β2-MG) were significantly higher in the hypothyroidism group compared with the remaining 92 euthyroid patients, and serum C3 concentration was significantly lower. After prednisolone treatment, TSH values had decreased significantly (p = 0.005) in this group and FT4 values had increased significantly (p = 0.047). CT images showed that the thyroid glands of patients with clinical hypothyroidism had a significantly greater volume than those of the euthyroid and other groups. Pathological analysis of one resected thyroid gland disclosed a focused lesion with infiltration of lymphocytes and IgG4-bearing plasma cells and loss of thyroid follicles. Conclusions: Thyroid lesions associated with hypothyroidism can be considered as a new disease termed IgG4-related thyroiditis. Awareness of this condition should lead to appropriate corticosteroid treatment that may prevent progression to a fibrous state.

Concepts: Immune system, Hypothyroidism, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Thyroid hormone, Triiodothyronine, Thyroxine


Abstract Background: Thyroid dysfunction is very common and is associated with neurodevelopmental impairments in preterm infants. Objectives: This study was conducted to determine the incidence and natural course of various thyroid dysfunctions and their impacts on neurodevelopmental outcomes among premature infants. Methods: A total of 177 infants were enrolled who were born at <34 weeks or whose birth weight was <1500 g and who underwent repeat thyroid function tests. We analyzed how various thyroid dysfunctions affected neurodevelopmental outcomes at 18 months of corrected age. Results: Thyroid dysfunction was noted in 88 infants. Hypothyroxinemia was observed in 23 infants, and their thyroid function was influenced by variable clinical factors. Free T4 levels were all normalized without thyroxine medication, and neurodevelopmental outcomes were not affected. In contrast, hyperthyrotropinemia was not associated with other clinical factors. Among 58 subjects who had hyperthyrotropinemia, only 31 infants showed normal thyroid-stimulating hormone (TSH) levels at follow-up tests. The remaining 27 infants had persistently high TSH levels, which significantly and poorly influenced the neurodevelopmental outcomes. Conclusions: Thyroid dysfunction is common among preterm infants. With the exception of persistent hyperthyrotropinemia, it generally does not affect neurodevelopmental outcomes. However, the beneficial effects of thyroid hormone therapy in patients with persistent hyperthyrotropinemia merits further study.

Concepts: Thyroid-stimulating hormone, Hypothyroidism, Thyroid, Thyroid hormone, Triiodothyronine, Thyroxine, Tyrosine, Thyroglobulin


PURPOSE: The role of thyroid function in biochemical markers of first trimester screening has not been assessed. The aim of the present study was to investigate if there were any relation between maternal thyroid hormones and free-beta subunit of human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels as the biochemical markers of the combined first trimester aneuploidy screening. METHODS: 375 pregnant women between 11 and 14 weeks of gestation who were offered routine first trimester prenatal aneuploidy screening and whose thyroid hormone levels (Thyroid stimulating hormone (TSH), free and total thyroxine, free and total triiodothyronine, anti thyroid peroxidase antibody) were measured were assessed. Correlation of free-β-hCG and PAPP-A with maternal thyroid hormones was analyzed. RESULTS: There was no statistically significant correlation between maternal TSH, free and total thyroxine, free and total triiodothyronine, anti-thyroid peroxidase antibodies and free-β-hCG and PAPP-A as biochemical markers of first trimester aneuploidy screening. CONCLUSION: Maternal thyroid function does not seem to affect secretion of fβ-hCG and PAPP-A.

Concepts: Pregnancy, Hormone, Thyroid, Thyroid hormone, Human chorionic gonadotropin, Triiodothyronine, Thyroxine, Thyroid peroxidase


To provide an overview of the clinical utility of thyroglobulin antibody (TgAb) measurements in the management of differentiated thyroid cancer (DTC), taking into consideration the methodological concerns associated with these measurements.

Concepts: Thyroid, Mean, Thyroxine


There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36weeks gestation. Both mothers and fathers reported on their children’s behavioral problems, between 23 and 60months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.

Concepts: Hormone, Thyroid, Thyroid hormone, Puberty, Mother, Triiodothyronine, Thyroxine, Thyroglobulin


Free thyroxine (fT4) and free triiodothyronine (fT3) tests are often ordered when not clinically warranted. Preventing laboratory overuse by reducing inappropriate fT4 and fT3 testing is one strategy to promote resource stewardship.

Concepts: Hormone, Thyroid, Thyroid hormone, Iodine, Triiodothyronine, Thyroxine, Tyrosine, Thyroglobulin


The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.

Concepts: Biology, Hormone, Thyroid, Thyroid hormone, Triiodothyronine, Thyroxine, Giant Panda, Carnivora


The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.

Concepts: Immune system, Metabolism, Energy, Hormone, Thermoregulation, Thyroid hormone, Thyroxine, Iraq War troop surge of 2007