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Non-Thyroidal Illness Syndrome in Critically Ill Children: Prognostic Value and Impact of Nutritional Management.
Jacobs, A, Derese, I, Vander Perre, S, van Puffelen, E, Verstraete, S, Pauwels, L, Verbruggen, S, Wouters, P, Langouche, L, Garcia Guerra, G, et al
Thyroid : official journal of the American Thyroid Association. 2019;(4):480-492
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Abstract
INTRODUCTION Non-thyroidal illness (NTI), which occurs with fasting and in response to illness, is characterized by thyroid hormone inactivation with low triiodothyronine (T3) and high reverse T3 (rT3), followed by suppressed thyrotropin (TSH). Withholding supplemental parenteral nutrition early in pediatric critical illness (late-PN), thus accepting low/no macronutrient intake up to day 8 in the pediatric intensive care unit (PICU), accelerated recovery compared to initiating supplemental parenteral nutrition early (early-PN). Whether NTI is harmful or beneficial in pediatric critical illness and how it is affected by a macronutrient deficit remains unclear. This study investigated the prognostic value of NTI, the impact of late-PN on NTI, and whether such impact explains or counteracts the outcome benefit of late-PN in critically ill children. METHODS This preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial quantified serum TSH, total thyroxine (T4), T3, and rT3 concentrations in 982 patients upon PICU admission versus 64 matched healthy children and in 772 propensity score-matched early-PN and late-PN patients upon admission and at day 3 or last PICU day for shorter PICU stay. Associations between thyroid hormone concentrations upon admission and outcome, as well as impact of late-PN on NTI in relation with outcome, were assessed with univariable analyses and multivariable logistic regression, linear regression, or Cox proportional hazard analysis, adjusted for baseline risk factors. RESULTS Upon PICU admission, critically ill children revealed lower TSH, T4, T3, and T3/rT3 and higher rT3 than healthy children (p < 0.0001). A more pronounced NTI upon admission, with low T4, T3, and T3/rT3 and high rT3 was associated with higher mortality and morbidity. Late-PN further reduced T4, T3, and T3/rT3 and increased rT3 (p ≤ 0.001). Statistically, the further lowering of T4 by late-PN reduced the outcome benefit (p < 0.0001), whereas the further lowering of T3/rT3 explained part of the outcome benefit of late-PN (p ≤ 0.004). This effect was greater for infants than for older children. CONCLUSION In critically ill children, the peripheral inactivation of thyroid hormone, characterized by a decrease in T3/rT3, which is further accentuated by low/no macronutrient intake, appears beneficial. In contrast, the central component of NTI attributable to suppressed TSH, evidenced by the decrease in T4, seems to be a harmful response to critical illness. Whether treating the central component with TSH releasing hormone infusion in the PICU is beneficial requires further investigation.
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Intake of Phthalate-tainted Foods and Serum Thyroid Hormones in Taiwanese Children and Adolescents.
Tsai, HJ, Wu, CF, Tsai, YC, Huang, PC, Chen, ML, Wang, SL, Chen, BH, Chen, CC, Wu, WC, Hsu, PS, et al
Scientific reports. 2016;:30589
Abstract
On April-May, 2011, phthalates, mainly Di-(2-ethylhexyl) phthalate (DEHP), were deliberately added to a variety of foodstuff as a substitute emulsifier in Taiwan. This study investigated the relationship between DEHP-tainted foodstuffs exposure and thyroid function in possibly affected children and adolescents. Two hundred fifty participants <18 years possibly exposed to DEHP were enrolled in this study between August 2012 and January 2013. Questionnaires were used to collect details on their past exposure to DEHP-tainted food items. Blood and urine samples were collected for biochemical workups to measure current exposure derived from three urinary DEHP metabolites using a creatinine excretion-based model. More than half of 250 participants were estimated to be exposed to DEHP-tainted foods found to exceed the recommend tolerable daily intake of DEHP established by the European Food Safety Authority (<50 μg/kg/day). The median daily DEHP intake (DDI) among those 250 participants was 46.52 μg/kg/day after multiple imputation. This value was ~10-fold higher than the current median DEHP intake (4.46 μg/kg/day, n = 240). Neither past nor current DEHP exposure intensity was significantly associated with serum thyroid profiles. Future studies may want to follow the long-term health effects of this food scandal in affected children and adolescents.
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The second wave of the Controlled Antenatal Thyroid Screening (CATS II) study: the cognitive assessment protocol.
Hales, C, Channon, S, Taylor, PN, Draman, MS, Muller, I, Lazarus, J, Paradice, R, Rees, A, Shillabeer, D, Gregory, JW, et al
BMC endocrine disorders. 2014;:95
Abstract
BACKGROUND Children whose mothers had low thyroid hormone levels during pregnancy have been reported to have decreased cognitive function. The reported research is part of the follow-on study of the Controlled Antenatal Thyroid Screening Study (CATS I), a randomised controlled trial which investigated the impact of treated vs. untreated low thyroid hormone level in women during pregnancy with the primary outcome being the child's IQ at age 3. No significant differences in IQ were found between the treated and untreated groups. These children are now aged between 7 and 10 years and aspects of their cognitive functioning including their IQ are being reassessed as part of CATS II. METHODS/DESIGN Cognitive assessments generate an IQ score and further tests administered will investigate long term memory function and motor coordination. The aim is to complete the assessments with 40% of the children born to mothers either in the treated or untreated low thyroid hormone groups (n = 120 per group). Also children born to mothers who had normal thyroid functioning during CATS I are being assessed for the first time (n = 240) to provide a comparison. Assessments are conducted either in the research facility or the participant's home. DISCUSSION The study is designed to assess the cognitive functioning of children born to mothers with low thyroid hormone levels and normal thyroid functioning during pregnancy. This is the largest study of its type and also is distinguishable in its longitudinal design. The research has the potential to have a significant impact on public health policy in the UK; universal screening of thyroid hormone levels in pregnancy may be the recommendation.
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Basal metabolic rate and thyroid hormones of late-middle-aged and older human subjects: the ZENITH study.
Meunier, N, Beattie, JH, Ciarapica, D, O'Connor, JM, Andriollo-Sanchez, M, Taras, A, Coudray, C, Polito, A
European journal of clinical nutrition. 2005;:S53-7
Abstract
OBJECTIVE This paper describes baseline data on basal metabolic rate (BMR), thyroid hormone levels and body composition of middle-aged and older people participating in the ZENITH project and the correlation of thyroid hormone levels with zinc status. DESIGN A multicentre prospective intervention study employing a randomised double blind design. SETTING Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France), Rome (Italy). INTERVENTIONS BMR has been measured on a subsample of 70 middle-aged volunteers (35 men and 35 women recruited in Clermont-Ferrand, France, aged 55-70 y) and 108 older volunteers (56 men and 52 women recruited in Rome, Italy, aged 70-85 y). Thyroid hormone levels were evaluated in the entire group of ZENITH volunteers (n = 387). BMR was measured by indirect calorimetry. Fat-free mass (FFM) was derived by four skinfold thicknesses using Durnin and Womersley's equations. Concentrations of thyroid hormones (total T3 and T4) were measured using a competitive immunoassay with an enhanced chemiluminescence end point. RESULTS Italian older volunteers had a significantly lower FFM than middle-aged French volunteers (-7% P < 0.01). A negative correlation between BMR and age (men, r = -0.64; women, r = -0.62; both P < 0.0001) was observed: BMR was significantly (P < 0.000001) lower in Italian elderly volunteers (4.03+/-0.46 kJ/min and 3.29+/-0.42 kJ/min for men and women, respectively) than in middle-aged French volunteers (4.84+/-0.45 kJ/min and 3.87+/-0.38 kJ/min for men and women, respectively), even after adjustment for FFM (-12%). No correlation has been observed between BMR and thyroid hormones both in French and Italian subjects. Total T4 (TT4) concentrations were lowest in middle-aged population (-10%, P < 0.0001). A moderate negative correlation has been found with TT4 and red blood cell zinc (r = -0.12, P < 0.02, slope -0.026). CONCLUSIONS The results confirm an age-related decline in BMR not entirely explained by body composition or thyroid hormones differences.