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Association between change in serum bicarbonate and change in thyroid hormone levels in patients receiving conventional or more frequent maintenance haemodialysis.
Molfino, A, Beck, GJ, Li, M, Lo, JC, Kaysen, GA, ,
Nephrology (Carlton, Vic.). 2019;(1):81-87
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Abstract
AIM: Correction of metabolic acidosis in patients with chronic kidney disease has been associated with improvement in thyroid function. We examined whether changes in bicarbonate were associated with changes in thyroid function in patients with end-stage renal disease receiving conventional or more frequent haemodialysis. METHODS In the Frequent Hemodialysis Network Trials, the relationship between changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine (FT4) was examined among 147 and 48 patients with endogenous thyroid function who received conventional (3×/week) or more frequent (6×/week) haemodialysis (Daily Trial) or who received conventional or more frequent nocturnal haemodialysis (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was examined to account for nutritional factors affecting both acid load and thyroid function. RESULTS Increasing dialysis frequency was associated with increased bicarbonate level. Baseline bicarbonate level was not associated with baseline FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3 and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r ≤ 0.14, P > 0.21). While, a significant correlation between change in serum bicarbonate and change in FT3 (r = 0.44, P = 0.02) was observed in the Nocturnal Trial; findings were no longer significant after adjusting for change in enPCR (r = 0.37, P = 0.08). For participants with baseline bicarbonate <23 mmol/L, no association between change in bicarbonate and change in thyroid indices were seen in the Daily Trial; for the Nocturnal Trial, findings were also not significant for change in FT3 and the association between change in bicarbonate and change in FT4 (r = 0.54, P = 0.03) was no longer significant after adjusting for enPCR (r = 0.45, P = 0.11). CONCLUSION Changes in bicarbonate were not associated with changes in thyroid hormone levels after adjusting for enPCR, as a marker of nutritional status. Future studies should examine whether improvement in acid base status improves thyroid function in haemodialysis patients with evidence of thyroid hypofunction.
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Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis.
Rao, M, Zeng, Z, Zhou, F, Wang, H, Liu, J, Wang, R, Wen, Y, Yang, Z, Su, C, Su, Z, et al
Human reproduction update. 2019;(3):344-361
Abstract
BACKGROUND Subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes such as pregnancy loss and preterm birth. However, the ability of levothyroxine (LT4) supplementation to attenuate the risks of these outcomes remains controversial. OBJECTIVE AND RATIONALE This systematic review and meta-analysis was conducted to determine the effect of LT4 supplementation on pregnancy loss rate (PLR) and preterm birth rate (PBR) among pregnant women with SCH and TAI. SEARCH METHODS A systematic literature search of the PubMed, EMBASE, Web of Science and Cochrane Controlled Trials Register databases and Clinicaltrials.gov was performed to identify all relevant English studies published up to April 2018. The following terms were used for the search: [subclinical hypothyroidism OR thyroid autoimmunity OR thyroperoxidase antibody (TPO-Ab) OR thyroglobulin antibodies (Tg-Ab)] AND (levothyroxine OR euthyrox) AND [pregnancy outcome OR miscarriage OR abortion OR pregnancy loss OR preterm birth OR premature delivery OR early labo(u)r]. The reference lists of the relevant publications were also manually searched for related studies. Published manuscripts were included if they reported data on pregnancy loss, preterm birth or both. We separately analysed the pooled effects of LT4 supplementation on PLR and PBR in women with SCH and TAI. OUTCOMES Overall, 13 eligible studies including 7970 women were included in the meta-analysis. Eight and five of these studies were randomized controlled trials (RCTs) and retrospective studies, respectively. The pooled results indicated that LT4 supplementation significantly decreased the PLR [relative risk (RR) = 0.56, 95% confidence interval (CI): 0.42-0.75, I2 = 1%, 12 studies] and PBR (RR = 0.68, 95% CI: 0.51-0.91, I2 = 21%, eight studies) in women with SCH and/or TAI. We further found that LT4 supplementation significantly decreased the risk of pregnancy loss (RR = 0.43, 95% CI: 0.26-0.72, P = 0.001, I2 = 0%) but not of preterm birth (RR = 0.67, 95% CI: 0.41-1.12, P = 0.13, I2 = 0%) in women with SCH. Furthermore, LT4 supplementation significantly decreased the risks of both pregnancy loss (RR = 0.63, 95% CI: 0.45-0.89, P = 0.009, I2 = 0%) and preterm birth (RR = 0.68 95% CI: 0.48-0.98, P = 0.04, I2 = 46%) in women with TAI. These results were consistent when only RCTs were included in the analysis. Further, in women with SCH, LT4 supplementation reduced the risk of pregnancy loss in pregnancies achieved by assisted reproduction (RR = 0.27, 95% CI: 0.14-0.52, P < 0.001, I2 = 14%) but not in naturally conceived pregnancies (RR = 0.60, 95% CI: 0.28-1.30, P = 0.13, I2 = 0%). By contrast, in women with TAI, LT4 supplementation reduced the risks of both pregnancy loss (RR = 0.61, 95% CI: 0.39-0.96, P = 0.03, I2 = 0%) and preterm birth (RR = 0.49, 95% CI: 0.30-0.79, P = 0.003, I2 = 0%) in naturally conceived pregnancies but not in pregnancies achieved by assisted reproduction (RR = 0.68, 95% CI: 0.40-1.15, P = 0.15, I2 = 0% for pregnancy loss and RR = 1.20, 95% CI: 0.68-2.13, P = 0.53, I2 not applicable for preterm birth). WIDER IMPLICATIONS This meta-analysis confirmed the beneficial effects of LT4 supplementation, namely the reduced risks of pregnancy loss and preterm birth, among pregnant women with SCH and/or TAI. The different effects of LT4 supplementation on naturally conceived pregnancies and pregnancies achieved by assisted reproduction in women with SCH and/or TAI suggest that these women should be managed separately. Due to the limited number of studies included in this meta-analysis, especially in the subgroup analysis, further large RCTs and fundamental studies are warranted to confirm the conclusions and better clarify the molecular mechanism underlying these associations.
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Slightly elevated thyrotropin levels in pregnancy in our clinical practice.
Alcázar Lázaro, V, López Del Val, T, García Lacalle, C, Torres Moreno, B, Castillo Carvajal, G, Vergara Fernández, L, Benfdil, L, Torre Carrera, C, Orizales Lago, MC, Ramos Zuñiga, L
Endocrinologia, diabetes y nutricion. 2019;(10):620-627
Abstract
OBJECTIVE The aim of this study was to assess the incidence of obstetric and neonatal complications in pregnant women with "normal" thyroid-stimulating hormone (TSH) levels in the first trimester (group A) and to compare them with those with "slightly elevated" TSH (SET) levels treated with levothyroxine (group B2) or not treated (group B1). METHODS A total of 2375 women who had been performed laboratory tests in their first trimester of pregnancy were detected at our hospital between April 2015 and August 2017. Of these, 469 patients with SET were prospectively detected and randomized to groups B1 (227) and B2 (242). They were monitored prospectively until 6 months after delivery. Data of the control group (n=1906, group A) were retrospectively reviewed. A total of 1745 women were analyzed. Variables assessed included demographic and clinical characteristics and complications of pregnancy and delivery. RESULTS A, B1, and B2 had similar clinical characteristics. There were no statistically significant differences in complications between the three groups during pregnancy, except in that natural deliveries were more common in group A as compared to group B1 (76.8% vs. 68.7%, p 0.017) and group B2 (66.3%), p<0.002). There were more induced deliveries in groups B1 (35.8%), and B2 (36.2%) than in group A (18.4%), p<0.01. Although the recommended TSH level was achieved in the second and third trimesters, no benefit could be found of treatment of SET. CONCLUSION Although there were less natural deliveries and more induced deliveries in patients with SET, treatment with levothyroxine could not reverse this situation, despite achievement of levels considered appropriate in the second and third trimester.
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Thyroid Related Quality of Life in Elderly with Subclinical Hypothyroidism and Improvement on Levothyroxine is Distinct from that in Young Patients (TSAGE).
Recker, S, Voigtländer, R, Viehmann, A, Dunschen, K, Kerp, H, Frank-Raue, K, Leidig-Bruckner, G, Graf, D, Lederbogen, S, Dietrich, JW, et al
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(9):568-574
Abstract
The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (<40 years) and older subjects (>60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with newly diagnosed, untreated subclinical hypothyroidism defined by TSH>8 mU/l. Patients were recruited throughout Germany from 2013-2016 and evaluated by clinical assessment, blood sampling and questionnaires for health related QoL and thyroid-disease thyroid-related QoL (ThyPRO) at time of diagnosis and six months after initiation of LT4 treatment. We found significantly lower QoL in both young and old patients with subclinical hypothyroidism compared to age-matched healthy individuals. Higher scores on follow-up were found in all patients irrespective of age, indicating better QoL on LT4 therapy. Analysis of the ThyPRO questionnaire showed that old patients experienced less Emotional Susceptibility, Tiredness, and Impaired Day Life on LT4, while young patients reported less Cognitive Complaints, Emotional Susceptibility, and Impaired Day Life compared to baseline assessment. Hypothyroidism with TSH concentrations>8 mU/l is associated with impairment in general and ThyPRO QoL in young and old age. Older patients benefited from LT4 therapy and remarkably show similar degree of improvement as younger patients, albeit with some thematic variation in ThyPRO QoL. Our data confirm current recommendations on initiation of LT4 substitution and suggest that this should not be withheld in elderly with TSH concentration above 8-10 mU/l.
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EMPATHY: A New Tool for Identifying the Most Suitable Thyroxine Formulation in Hypothyroid Patients.
Bellastella, G, Caputo, M, Maiorino, MI, Longo, M, Scappaticcio, L, Giugliano, D, Esposito, K
Thyroid : official journal of the American Thyroid Association. 2019;(7):928-933
Abstract
Background: Therapy of hypothyroidism is based on the administration of appropriate doses of levothyroxine (LT4). A failure to achieve the thyrotropin (TSH) target may be due to poor compliance with the LT4 therapy in about 60% of cases or to malabsorption in about 40% of cases. No tools are available for detecting malabsorption disorders before the choice of the most appropriate therapy. The aim of this study was to validate the Evaluation of Malabsorption in PATients with HYpothyroidism (EMPATHY) questionnaire and to demonstrate its usefulness in indicating the most appropriate therapy. Methods: EMPATHY consists of seven questions that allow the evaluation of several intolerances and allergies. Three hundred (100 males) newly diagnosed hypothyroid patients were enrolled and randomly assigned to complete an EMPATHY questionnaire (150 patients; group 1) or to a control group (150 patients; group 2). The choice of thyroxine formulation and dose for each group was made on the basis of the questionnaire answers or based on the history. Thyroid hormones and TSH were evaluated at enrollment and then every two months for six months; the number of the dose adjustments in the six months for each patient was recorded. Results: Of the 150 patients in each group, 21 (14%) in group 1 and 42 (28%) in group 2 (p = 0.005) needed more than two dose adjustments within six months. After six months of replacement therapy, six (4%) patients in group 1 and 17 (11%) in group 2 (p = 0.03) did not have appropriately controlled hypothyroidism (TSH ≥2.5 mIU/L). A significantly higher LT4 final dose was found in group 2 (148 ± 33 μg/day) than in group 1 (136 ± 28 μg/day; p = 0.003). Conclusions: Validation of EMPATHY provides endocrinologists with a useful tool in clinical practice, permitting a better personalization of LT4 replacement therapy, a more rapid attainment of the target TSH levels, and a decreased need for dose adjustments after initiating therapy.
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Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial.
Palui, R, Sahoo, J, Kamalanathan, S, Kar, SS, Sridharan, K, Durgia, H, Raj, H, Patil, M
Journal of endocrinological investigation. 2019;(12):1451-1458
Abstract
PURPOSE Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH). METHODOLOGY In this open label, parallel arm, randomised controlled trial, 60 patients of SCH (TSH 5.5-10 mIU/L) were randomised to either metformin group (1500 mg/day) or control group. RESULT A total of 46 patients (23 in each group) completed the study and no significant difference in serum TSH, free T4 or free T3 was found in between the 2 groups. Neither there was any significant change in serum TSH, free T4 or free T3 (pre and post 6 months) within the individual groups. However, the rate of normalisation of serum TSH in patients with negative thyroid antibody was significantly higher than patients with positive thyroid antibody (71.4% vs. 18.8%; P = 0.026) in metformin group in post hoc analysis. Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group. Four patients (17%) had mild gastrointestinal adverse effects in the metformin group. CONCLUSION We did not find any significant change in thyroid function test in patients with SCH with metformin therapy.
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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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Changes in Thyroid Replacement Therapy after Bariatric Surgery: Differences between Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy.
Julià, H, Benaiges, D, Mollà, P, Pedro-Botet, J, Villatoro, M, Fontané, L, Ramon, JM, Climent, E, Flores Le Roux, JA, Goday, A
Obesity surgery. 2019;(8):2593-2599
Abstract
INTRODUCTION Levothyroxine (LT4) requirements can presumably be modified differently after laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). The present study compared changes in LT4 dose in hypothyroid subjects undergoing LRYGB or LSG 2 years after the procedure. MATERIAL AND METHODS A 2-year follow-up observational study was conducted in a prospective cohort of obese patients who had undergone bariatric surgery and were receiving LT4. Indication for the type of surgical procedure was based on clinical criteria. Repeated measures ANOVA models were used to examine differences within and between groups. RESULTS Thirty-five consecutive patients were included for analysis: 22 LRYGB and 13 LSG. Total daily LT4 dosage decreased in the LSG group (133.7 ± 50.3 mcg/day at baseline to 104.3 ± 43.3 mcg/day at 2 years; p = 0.047) whereas it remained stable in the LRYGB group (129.5 ± 46.1 mcg/day at baseline to 125.2 ± 55.7 mcg/day at 2 years; p = 1.000). Differences between groups became significant at 24 months. Daily weight-based LT4 dose increased in the LRYGB group (1.11 ± 0.38 mcg/kg day at baseline to 1.57 ± 0.74 mcg/kg day at 2 years; p = 0.005) with no significant changes in the LSG group (1.15 ± 0.35 mcg/kg day at baseline vs 1.11 ± 0.49 mcg/kg day at 2 years; p = 1.000). CONCLUSION LRYGB and LSG showed different changes in LT4 requirements 2 years after surgery. There was an early decrease in daily total LT4 dose requirements after LSG, which suggests an early preventive reduction to be validated in future studies.
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Heterogeneity of Thyroid Function and Impact of Peripheral Thyroxine Deiodination in Centenarians and Semi-Supercentenarians: Association With Functional Status and Mortality.
Ostan, R, Monti, D, Mari, D, Arosio, B, Gentilini, D, Ferri, E, Passarino, G, De Rango, F, D'Aquila, P, Mariotti, S, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2019;(6):802-810
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Thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) were evaluated in a population of 672 well-characterized Italian subjects (age range: 52-113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian's offspring and age-matched elderly (CENT, 105+, CENTOFF, and CTRL, respectively). The results show that FT3 level and FT3/FT4 ratio decrease while FT4 and TSH increase in an age-dependent manner. In CENT/105+, higher FT4 level, and lower FT3/FT4 ratio are associated with an impaired functional status and an increased mortality. A cluster analysis identified three clusters of CENT/105+ based on their FT3, FT4, and TSH levels. Cluster 3, characterized by lower FT3 and TSH and higher FT4, shows the worst health status and the shortest survival. Thus, the age-related changes of thyroid hormones extend to the most advanced age, and CENT/105+ are highly heterogeneous regarding thyroid function. This heterogeneity is related to different health, functional and cognitive status, as well as with survival/mortality in CENT/105+. Finally, we investigated a remarkable number of CENT/105+ showing a thyroid profile suggestive of non-thyroidal illness syndrome (NTIS) (excluded from the previous analysis). NTIS CENT/105+ are characterized by a worse functional and cognitive status and an increased mortality with respect to CENT/105+ without NTIS.
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Trend of lipid and thyroid function tests in adults without overt thyroid diseases: A cohort from Tehran thyroid study.
Ahi, S, Amouzegar, A, Gharibzadeh, S, Delshad, H, Tohidi, M, Azizi, F
PloS one. 2019;(5):e0216389
Abstract
CONTEXT While the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified. OBJECTIVE To examine lipid trends based on thyroid function over a 10-year period. DESIGN This is a prospective population based cohort study. SETTING General community. PARTICIPANTS 2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded. MAIN OUTCOME MEASURES Lipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations. RESULTS In every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps <0.001) except for HDL-C, in which a decrescendo-crescendo trend was observed. The results did not change after adjusting for thyroid status, consumption of lipid lowering drugs during the follow-up period, or other variables. There were significant decreases in the prevalence of hypercholesterolemia and hypertriglyceridemia (all Ps <0.001) during the follow-up period. CONCLUSION During a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status.