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1.
Trimester-specific reference ranges for thyroid hormones in pregnant women.
Zhang, D, Cai, K, Wang, G, Xu, S, Mao, X, Zheng, A, Liu, C, Fan, K
Medicine. 2019;(4):e14245
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Abstract
The aim of this study was to determine the trimester-specific reference range of thyroid function in Nanjing.A total of 805 pregnant women in the 1st, 2nd, and 3rd trimesters were recruited in the prospective, observational study during their routine antenatal clinic visit and 282 nonpregnant subjects served as controls. A questionnaire was completed by the subjects to record their personal health history, family history of thyroid disease, and consumption of estrogen or antithyroid drugs. Thyroid palpation was performed to exclude the thyroid goiter. Thyroid function and urine iodine were measured by chemiluminescence and arsenic cerium analysis.The trimester-specific reference ranges in Nanjing were as follows: thyroid-stimulating hormone (TSH) 0.02 to 3.78 mIU/L, free thyroxine (FT4) 13.93 to 26.49 pmol/L, total thyroxine (TT4) 103.39 to 319.43 nmol/L in the 1st trimester. TSH 0.47 to 3.89 mIU/L, FT4 12.33 to 19.33 pmol/L, TT4 92.28 to 234.88 nmol/L in the 2nd trimester. TSH 0.55 to 4.91 mIU/L, FT4 11.38 to 19.21 pmol/L, TT4 83.54 to 258.12 nmol/L in the 3rd trimester. According to the TSH reference range recommended by American Thyroid Association (ATA), the prevalence of subclinical hypothyroidism, subclinical hyperthyroidism, hyperthyroidism, hypothyroxinemia, and thyroid peroxidase antibody-positive were 12.42%, 0.50%, 0.99%, 1.61%, and 11.80%, respectively, prevalence according to the trimester-specific reference range were 1.99%, 0.25%, 1.61%, 0.37%, and 1.61%, respectively, which showed elevated hypothyroxinemia incidence and declined incidence of subclinical hypothyroidism and hyperthyroidism.Trimester-specific reference range varied from that of ATA's recommendation, influencing the diagnosis, and treatment of pregnant thyroid disorders. To detect and control these disorders properly, setting up trimester-specific reference is clinically essential.
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2.
The possible global hazard of cell phone radiation on thyroid cells and hormones: a systematic review of evidences.
Asl, JF, Larijani, B, Zakerkish, M, Rahim, F, Shirbandi, K, Akbari, R
Environmental science and pollution research international. 2019;(18):18017-18031
Abstract
The aim of this review was to investigate the effects of possible harmful waves from either cell phone use or being within the range of the cell phone from 450 to 3800 MHz on the thyroid cells and hormones. Eight electronic datasets were systematically searched using MeSH terms, including "cell phone," "mobile phone," "GSM," "radio frequency," "smartphone," "triiodothyronine," "thyroxin," "thyroid-stimulating hormone," "T3," "T4," "TSH," and "morphological" and all possible combinations, to identify relevant studies published up to Dec 2018. We also manually searched the reference lists of potentially selected studies to identify further relevant publications. About 161 relevant studies were initially found. After screening titles and abstracts, 139 studies were excluded, and finally 22 studies (comprising 7182 cases) were included in the qualitative synthesis. Of the 22 included studies, 11 studies reported changes in T3 and T4 levels (six reported a decrease in T3 levels and one reported increase in it); moreover, five found decreased T4 levels and two studies an increased level. In other 10 studies, TSH alteration was reported. Of these, two studies reported a decrease in TSH level and one reported an increase in the hormone levels, while in the remaining studies non-significant changes were reported. Finally, seven studies examined histological changes in the thyroid gland follicles and showed that the volume of these cells was reduced. Based on the evidence discussed above, the reduction in diameter of thyroid follicles is potentially linked with cell phone radiation. Exposure may negatively influence the iodine uptake in the thyroid gland or increases temperature effect on the thyroid gland. However, further research are needed in order to show that the level of TSH and thyroid hormone suppression by microwave.
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3.
Thyroid peroxidase as a dual active site enzyme: Focus on biosynthesis, hormonogenesis and thyroid disorders of autoimmunity and cancer.
Godlewska, M, Banga, PJ
Biochimie. 2019;:34-45
Abstract
Thyroid peroxidase (TPO) is the key enzyme involved in thyroid hormone synthesis. Autoantibodies to TPO (TPOAbs) are a hallmark of autoimmune thyroid disease (AITD). Here, we highlight recent progress over several years in understanding TPO biochemistry and function in various pathologies. TPO undergoes complex post-translational modifications as a dimer in endoplasmic reticulum during secretory pathway to apical membrane of thyrocytes. In silico modelling of TPO dimer has provided new information into the two enzyme active site regions and autoantigenic determinants. TPO and hydrogen peroxide generating DUOX and caveolin-1 form a complex known as thyroxisome to bring together in close proximity the components of hormone synthesis in apical membrane. Autoimmunity to TPO is characterised by autoantibodies and T cell reactivity in Hashimoto's disease and Graves' disease. TPOAbs are directed predominantly to two immunodominant determinants (IDR) termed IDR-A and IDR-B regions, with the latter antibodies more predominant in autoimmune disease. Strong genetic risk has been shown to be associated with TPOAbs for AITD development. A different antibody with unusual features of bispecificity for both TPO and thyroglobulin may play protective role in Hashimoto's disease. In the context of TPO biology in human cancer, thyroid tumor tissue and breast cancer differ in TPO expression and isoform composition. In thyroid cancer, TPO expression is decreased partly by the BRAF(V600E) mutation, with direct impact on significant hormone production. TPOAbs may play a protective role in breast cancer development. An understanding of TPO and its unique two enzymatic active sites and autoantigenic determinants continues to add new knowledge on the biochemistry and immunology of this enzyme.
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4.
Low thyroid function is not associated with an accelerated deterioration in renal function.
Meuwese, CL, van Diepen, M, Cappola, AR, Sarnak, MJ, Shlipak, MG, Bauer, DC, Fried, LP, Iacoviello, M, Vaes, B, Degryse, J, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(4):650-659
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Abstract
BACKGROUND Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. METHODS Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. RESULTS A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. CONCLUSIONS Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
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Diagnosis and treatment of hypothyroidism in the elderly.
Duntas, LH, Yen, PM
Endocrine. 2019;(1):63-69
Abstract
The global population is aging with millions of people today living into their 90 s. Thyroid disease, particularly hypothyroidism, is widespread among all age groups, and it is expected to steadily increase as the population gets older. Clinical diagnosis of hypothyroidism is challenging, as the TSH reference range needs to be evaluated according to age, while evaluation of TSH levels must also take into account body weight and other variants such as polypharmacy, comorbidities, and general health condition. Since thyroid hormone has a potent regulatory effect on cholesterol metabolism, the possibility of thyroid dysfunction should be considered in cases of unexplained dyslipidemia. Once hypothyroidism has been confirmed, treatment requires caution, frequent cardiovascular monitoring, and individualized (precision) medicine. Treatment of subclinical hypothyroidism (SCH) in the elderly should be undertaken with care, guided by age and the degree of SCH: a TSH higher than 10 mU/l seems a reasonable threshold, though it should be regularly re-evaluated, while the LT4 dose needs to be tailored, taking into account the patient's health condition and the potential presence of dyslipidemia as well as other metabolic derangements.
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Combined docosahexaenoic acid and thyroid hormone supplementation as a protocol supporting energy supply to precondition and afford protection against metabolic stress situations.
Videla, LA
IUBMB life. 2019;(9):1211-1220
Abstract
Liver preconditioning (PC) refers to the development of an enhanced tolerance to injuring stimuli. For example, the protection from ischemia-reperfusion (IR) in the liver that is obtained by previous maneuvers triggering beneficial molecular and functional changes. Recently, we have assessed the PC effects of thyroid hormone (T3; single dose of 0.1 mg/kg) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs; daily doses of 450 mg/kg for 7 days) that abrogate IR injury to the liver. This feature is also achieved by a combined T3 and the n-3 LCPUFA docosahexaenoic acid (DHA) using a reduced period of supplementation of the FA (daily doses of 300 mg/kg for 3 days) and half of the T3 dosage (0.05 mg/kg). T3 -dependent protective mechanisms include (i) the reactive oxygen species (ROS)-dependent activation of transcription factors nuclear factor-κB (NF-κB), AP-1, signal transducer and activator of transcription 3, and nuclear factor erythroid-2-related factor 2 (Nrf2) upregulating the expression of protective proteins. (ii) ROS-induced endoplasmic reticulum stress affording proper protein folding. (iii) The autophagy response to produce FAs for oxidation and ATP supply and amino acids for protein synthesis. (iv) Downregulation of inflammasome nucleotide-bonding oligomerization domain leucine-rich repeat containing family pyrin containing 3 and interleukin-1β expression to prevent inflammation. N-3 LCPUFAs induce antioxidant responses due to Nrf2 upregulation, with inflammation resolution being related to production of oxidation products and NF-κB downregulation. Energy supply to achieve liver PC is met by the combined DHA plus T3 protocol through upregulation of AMPK coupled to peroxisome proliferator-activated receptor-γ coactivator 1α signaling. In conclusion, DHA plus T3 coadministration favors hepatic bioenergetics and lipid homeostasis that is of crucial importance in acute and clinical conditions such as IR, which may be extended to long-term or chronic situations including steatosis in obesity and diabetes. © 2019 IUBMB Life, 71(9):1211-1220, 2019.
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Effects of thyroid hormone and depression on common components of central obesity.
Du, FM, Kuang, HY, Duan, BH, Liu, DN, Yu, XY
The Journal of international medical research. 2019;(7):3040-3049
Abstract
OBJECTIVE We investigated the prevalence of abnormal thyroid function and depression in centrally obese participants, and to analyze the relationship of thyroid hormones and depression with components of central obesity. METHODS We randomly selected 858 centrally obese participants and 500 non-obese controls in this study. For all participants, we measured serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), body mass index (BMI), waist–hip ratio (WHR), fasting blood glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid concentrations, and blood pressure. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale. RESULTS Centrally obese participants had a higher prevalence of hypothyroidism and depression than non-obese controls. Serum FT4 levels negatively correlated with BMI and serum TSH levels and positively correlated with BMI, WHR, total triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C). After excluding participants with hypothyroidism and hyperthyroidism, serum FT4 levels showed negative correlation and serum TSH levels showed positive correlation with BMI in the remaining centrally obese participants. CES-D scores positively correlated with BMI. CONCLUSION We found high prevalences of hypothyroidism and depression among centrally obese participants. FT4 and TSH are important in weight regulation. Depression positively correlated with obesity.
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Stimulated Thyroglobulin and Thyroglobulin Reduction Index Predict Excellent Response in Differentiated Thyroid Cancers.
Barres, B, Kelly, A, Kwiatkowski, F, Batisse-Lignier, M, Fouilhoux, G, Aubert, B, Dutheil, F, Tauveron, I, Cachin, F, Maqdasy, S
The Journal of clinical endocrinology and metabolism. 2019;(8):3462-3472
Abstract
CONTEXT Despite its good prognosis, differentiated thyroid cancer (DTC) is characterized by high rates of disease persistence and recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to individualize the active surveillance schedule. OBJECTIVE Evaluation of the ability of stimulated thyroglobulin (Tg) and Tg reduction index (TRI) to predict long-term remission in patients with DTC managed by thyroidectomy and radioactive iodine (RAI) remnant ablation. PATIENTS AND INTERVENTIONS Observational retrospective study of 1093 patients treated for DTC between 1995 and 2010. Preablation stimulated thyroglobulin (presTg) was measured under thyroid hormone withdrawal just before RAI. Recombinant human TSH-stimulated thyroglobulin (sTg) was measured at first evaluation of the initial management 6 to 12 months after RAI. TRI was calculated based on pre-Tg and sTg. RESULTS After univariate and multivariate analyses, lymph node invasion (N1, OR = 2.08; 95% CI, 1.19 to 3.64), presTg (OR = 4.04; 95% CI, 2.56 to 6.38), sTg (OR = 2.62; 95% CI, 2.05 to 3.34), and TRI (OR = 0.43; 95% CI, 0.21 to 0.88) were identified as independent prognostic factors influencing the rate of disease persistence or recurrence after the initial management. Receiver operating characteristic analysis identified presTg cutoff (<10 µg/L) to predict excellent response, with a negative predictive value of 94%, and validated for higher stages (T3/T4, N1). Furthermore, sTg <1 µg/L predicts excellent response. TRI >60% for the entire cohort and 62.5% for locally advanced disease (T3/T4, N1) was sensitive predictor for excellent response. CONCLUSION This study identifies presTg, sTg, and TRI as highly sensitive predictors of excellent response in patients with DTC and subsequently disease-free status. The cutoff of such parameters is also adapted for patients with higher tumor stages (T3/T4, N1).
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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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Bone and hormonal status 10 years post-allogeneic bone marrow transplantation.
Gubrianska, D, Machaczka, M, Hassan, M, Hägglund, H, Ljungman, P, Palmér, M
Clinical transplantation. 2019;(12):e13742
Abstract
Bone loss and endocrine dysfunction are potential late complications of allogeneic stem cell transplant (allo-SCT); however, scant information concerning the long-term effects in SCT adult patients is available. In the present study, we evaluated bone status, expressed as bone mineral density (BMD), and endocrine functions including PTH, TSH, free T4, testosterone, SHBG, FSH, LH, and IGF-1, in 20 adult leukemia patients >10 years after allo-SCT. A low BMD (Z score <-2.0) was observed in two patients; two patients had osteoporotic fractures, and two had a unilateral avascular necrosis of the femoral head. Elevated PTH was observed in 30% of patients, and 25-hydroxy vitamin D (25(OH)D) was low (<50 nmol/L) in 45% of the patients. The majority of the patients had thyroid tests within the reference range, while elevated FSH values were present in 8 of 12 males. We conclude that adult leukemia patients have relatively well-preserved BMD >10 years post-allo-SCT. Prophylactic treatment of osteoporosis should be individualized, but control of BMD is necessary for long-term follow-up. Control of PTH and vitamin D levels before and after allo-SCT is recommended, and vitamin D supplementation should be considered if indicated. Estrogen replacement therapy is a routine treatment in females, whereas gonadal function in males requires further investigation.