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Intake of seaweed as part of a single sushi meal, iodine excretion and thyroid function in euthyroid subjects: a randomized dinner study.
Noahsen, P, Kleist, I, Larsen, HM, Andersen, S
Journal of endocrinological investigation. 2020;(4):431-438
Abstract
OBJECTIVE Globalisation has extended to the kitchen and the Asian cuisine has gained international popularity with sushi and seaweed now being widespread. We explored the possible acute adverse effects of an iodine load from a single sushi-and-seaweed meal as seaweed iodine may induce thyroid dysfunction. METHODS Nine euthyroid participants were randomized into three groups: Halibut maki roll with either (A) newly harvested Greenlandic seaweed salad, (B) no seaweed salad on the side, or (C) Japanese seaweed salad purchased at a local store. We collected spot urine and blood samples daily for a week for measurement of iodine and creatinine in urine, thyroid stimulating hormone (TSH), and estimated-free T4 (fT4) in serum. RESULTS All participants ingested the full meal and the drop-out was nil. No adverse effects were reported. Pre-meal urinary iodine excretion (UIE) was 75 µg/g. UIE rose (p < 0.001) by 385%, 59% and 43% for groups A, B, and C, peaked in the 6-h spot urine sample at 393, 120, and 109 µg/g, and was down to pre-meal values by day 2. Serum TSH rose (p = 0.012) 150% on day 2 and was down to pre-meal values by day 3. Serum fT4 remained at the same level. No adverse reactions were reported. CONCLUSION A sushi meal increased urinary iodine excretion by 40 µg/g, or 400 µg/g if a newly harvested seaweed salad was added. An ensuing rise in serum TSH was brief, and a single sushi meal with seaweed salad did not cause any adverse events.
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Higher Muscle Mass Implies Increased Free-Thyroxine to Free-Triiodothyronine Ratio in Subjects With Overweight and Obesity.
Zupo, R, Castellana, F, Sardone, R, Lampignano, L, Paradiso, S, Giagulli, VA, Triggiani, V, Di Lorenzo, L, Giannelli, G, De Pergola, G
Frontiers in endocrinology. 2020;:565065
Abstract
UNLABELLED Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT04327375.
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Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: a systematic review with meta-analysis of randomized controlled trials.
Wang, X, Zhang, Y, Tan, H, Bai, Y, Zhou, L, Fang, F, Faramand, A, Chong, W, Hai, Y
Fertility and sterility. 2020;(6):1306-1314
Abstract
OBJECTIVE To investigate whether levothyroxine is associated with improved live birth and other benefits in women with thyroid autoimmunity. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S): Women positive for thyroid peroxidase antibody. INTERVENTION(S): MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched without any language restrictions. Pooled effect sizes were calculated using random-effects models. MAIN OUTCOME MEASURE(S): The primary outcome was the incidence of live birth, miscarriage, preterm birth, clinical pregnancy, ectopic pregnancy, neonatal admission, and birth weight. The summary measures were reported as relative risk (RR) with 95% confidence interval. RESULT(S): Levothyroxine supplementation was not associated with an increased rate of live birth or a decreased risk of miscarriage. Results were similar in subgroup analyses of live birth by age, baseline thyrotropin, baseline thyroid peroxidase antibody, body mass index, and use of assisted conception. For live birth, the effect estimate lay within the futility boundary for RR of 20% and 15%, but at a 10% RR, the effect estimate lay between the futility boundary and the inferior boundary. CONCLUSION(S): High- to moderate-quality evidence demonstrated that the use of levothyroxine was not associated with improvements in clinical pregnancy outcomes among women positive for thyroid peroxidase antibody. REGISTRATION NUMBER PROSPERO CRD42019132976.
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Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Ettleson, MD, Bianco, AC
The Journal of clinical endocrinology and metabolism. 2020;(9):e3090-104
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Abstract
CONTEXT It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. EVIDENCE ACQUISITION This review is based on a collection of primary and review literature gathered from a PubMed search of "hypothyroidism," "levothyroxine," "liothyronine," and "desiccated thyroid extract," among other keywords. PubMed searches were supplemented by Google Scholar and the authors' prior knowledge of the subject. EVIDENCE SYNTHESIS In most LT4-treated patients, normalization of serum thyrotropin levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, for example, specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels. CONCLUSIONS After excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients who have persistent symptoms or metabolic abnormalities despite normalization of serum thyrotropin level. New clinical trials focused on symptomatic patients, genetic makeup, and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.
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Short-term Effect of Fresh Pomegranate Juice on Serum Cortisol and Thyroxine in Patients with type 2 Diabetes.
Banihani, SA, Makahleh, SM, El-Akawi, ZJ
Current molecular medicine. 2020;(5):355-360
Abstract
BACKGROUND The effect of pomegranate juice on type 2 diabetic conditions has been determined in various occasions. However, such an effect on cortisol and thyroxine hormones, which are major controllers of energy metabolism, is not yet revealed. OBJECTIVES In this study, we intended to measure the short-term effect of fresh pomegranate juice on serum cortisol and thyroxine in patients with type 2 diabetes. MATERIALS AND METHODS This study was a randomized clinical trial in which 89 fasted patients with type 2 diabetes were supplemented with fresh pomegranate juice at a dose of 1.5 mL kg-1. Blood specimens were then collected before and at 1 and 3 hours after juice administration. Serum cortisol and thyroxine were assessed using commercial chemiluminescent-immunoassay kits. RESULTS Serum cortisol, but not thyroxine, was significantly (P < 0.0001) lower in patients with type 2 diabetes after ingesting fresh pomegranate juice. In addition, no significant correlation (r2 = 0.00003, P = 0.9569) was observed between cortisol response to fresh pomegranate juice and the level of fasting serum glucose in the recruited patients. Moreover, no significant difference (P = 0.9118) in cortisol response to fresh pomegranate juice was found between recruited males and females. CONCLUSIONS In conclusion, fresh pomegranate juice decreased serum cortisol, 1 hour after juice ingestion, but not serum thyroxine 3 hours after juice ingestion, in patients with type 2 diabetes. In addition, cortisol response to fresh pomegranate juice was found not to be affected by patients' gender and the level of fasting serum glucose.
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Compartment syndrome of the leg after thyroid hormone withdrawal; two cases and a systematic review of the literature.
van Veelen, NM, Fischli, S, Beeres, FJP, Eisenhut, T, Babst, R, Henzen, C, Link, BC
BMC endocrine disorders. 2020;(1):80
Abstract
BACKGROUND Acute compartment syndrome is a rare complication of severe hypothyroidism. If the symptoms are not recognized promptly and treatment initiated immediately, there is a high risk of permanent damage. Only few other cases of compartment syndrome due to hypothyroidism have been published and the exact pathophysiological mechanism remains unknown. CASE PRESENTATIONS A 59 year old male developed acute compartment syndrome of his right lower leg after thyroid hormone withdrawal prior to radioiodine remnant ablation after total thyroidectomy for follicular thyroid cancer. He underwent emergency fasciotomy of all four compartments of the lower leg. The muscle tissue in the anterior and lateral compartment was necrotic and was therefore excised. The second patient was a 62 year old female with Hashimoto's thyroiditis, who developed acute compartment syndrome of both lower legs after thyroid hormone withdrawal due to non-compliance. Emergency fasciotomy of all four compartments of both legs was performed. The muscle tissue was viable in all compartments. CONCLUSION Although compartment syndrome due to hypothyroidism is uncommon, it is a complication physicians should be aware of. The majority of reported cases are caused by an acute withdrawal of thyroid hormones and not by undetected hypothyroidism. No previous case of compartment syndrome caused by an iatrogenic hormone withdrawal in preparation for radioactive iodine has been published. However, as shown in this report, it may be beneficial to inform patients of this rare complication prior to hormone withdrawal in preparation for remnant ablation after thyroidectomy.
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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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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.