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1.
Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study.
Skelin, M, Lucijanić, T, Liberati-Čizmek, AM, Klobučar, SM, Lucijanić, M, Jakupović, L, Bakula, M, Lončar, JV, Marušić, S, Matić, T, et al
Endocrine. 2018;(2):432-439
Abstract
AIM: Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. METHODS The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A-half an hour before breakfast; timing regimen B-an hour before the main meal of the day; timing regimen C-at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. RESULTS Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = -0.017 95% C.I. (-0.400-0.192); baseline vs. B = -0.325 95% C.I. (-0.562-0.023); baseline vs. C = -0.260 95% C.I. (-0.475-0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. CONCLUSION The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.
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2.
The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity.
Marzullo, P, Minocci, A, Mele, C, Fessehatsion, R, Tagliaferri, M, Pagano, L, Scacchi, M, Aimaretti, G, Sartorio, A
PloS one. 2018;(10):e0205293
Abstract
BACKGROUND Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss. METHODS We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM). RESULTS Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p<0.001 vs. baseline) and their percent changes were significantly associated (p<0.05), while no association related percent changes of REE and FFM or FM. Individually, REE decreased in 66 and increased in 34 patients irrespective of gender, BMI and body composition. Weight loss significantly impacted TSH (-6.3%), FT3 (-3.3%) and FT4 levels (3.9%; p<0.001 for all). By the study end, a significant correlation became evident between REE and FT4 (r = 0.42, p<0.001) as well as FT3 (r = 0.24, p<0.05). In stepwise multivariable regression analysis, however, neither THs nor body composition entered the regression equation for REE response to weight loss. CONCLUSIONS In severe obesity, short-term weight loss discloses a positive relationship between REE and THs.
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3.
Statistical Evaluation of Trace Metals, TSH and T4 in Blood Serum of Thyroid Disease Patients in Comparison with Controls.
Hanif, S, Ilyas, A, Shah, MH
Biological trace element research. 2018;(1):58-70
Abstract
The present study is based on the measurement of concentrations of selected trace metals (Fe, Zn, Cu, Co, Mn, Ni, Cr, Cd and Pb) and thyroid hormones (TSH and T4) in blood serum of hypothyroid and hyperthyroid patients in comparison with healthy donors/controls in order to establish the imbalances of the trace metals in diseased subjects. The serum samples were digested in HNO3-HClO4 mixture and quantification of the metals was performed by flame atomic absorption spectrometry. Average levels of Fe, Ni, Cu, Cr, Pb and TSH were found to be significantly higher (p < 0.05) in the serum of hypothyroid patients compared with other donor categories, while mean concentrations of Mn, Cd and T4 were significantly elevated in the serum of hyperthyroid patients compared with other donor groups (p < 0.05). The correlation pattern of trace metals in the serum of patient groups revealed significantly different mutual associations compared with the controls. PCA and CA pointed out the interferences of the toxic metals with essential metals in the serum of both patient groups compared with the controls. Most of the metals exhibited noticeable disparities in their concentrations based on gender, food habits and tobacco use for all donor groups. Thus, the pathogenesis of thyroid diseases is significantly affecting the essential trace and toxic metals balance in both patients groups.
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Establishment of trimester-specific reference range for thyroid hormones during pregnancy.
Nazarpour, S, Ramezani Tehrani, F, Simbar, M, Minooee, S, Rahmati, M, Mansournia, MA, Azizi, F
Clinical biochemistry. 2018;:49-54
Abstract
OBJECTIVE Physiological gestational changes are associated with alterations in thyroid function which require different biochemical interpretation from that of non-pregnant women and necessitate established pregnancy-specific reference ranges. We aimed to identify the trimester-specific ranges of thyroid markers in a healthy population of pregnant Iranian women. METHODS In this self-sequential study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4 and FT4I and first trimester reference range for TPOAb were estimated. The normal and modulus exponential-normal models were fitted by maximum likelihood using STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were determined and used as reference intervals. RESULTS Mean±SD age of participants was 26.8±5.2years. Estimated reference intervals for TSH, T4 and FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9μIU/ml; 78.01-215.19, 93.23-243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively. Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of TSH was low in the 1st trimester, and gradually increased until 2nd trimester, followed by a slight decrease onward. A decreasing trend in TSH levels was observed in higher centiles with advancing gestational age. CONCLUSION This study provides trimester-specific reference ranges for some common thyroid markers among healthy Iranian women in an iodine sufficient area, to prevent biochemical misinterpretations during pregnancy.
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5.
Effects of Levothyroxine on Pregnant Women With Subclinical Hypothyroidism, Negative for Thyroid Peroxidase Antibodies.
Nazarpour, S, Ramezani Tehrani, F, Simbar, M, Tohidi, M, Minooee, S, Rahmati, M, Azizi, F
The Journal of clinical endocrinology and metabolism. 2018;(3):926-935
Abstract
CONTEXT Currently, there is no consensus on universal thyroid screening and levothyroxine (LT4) treatment of pregnant women with subclinical hypothyroidism (SCH) who are negative for thyroid peroxidase antibody (TPOAb-). OBJECTIVE We aimed to evaluate the benefits of LT4 treatment on pregnancy outcomes in SCH-TPOAb- women. DESIGN This study was conducted within the framework of the Tehran Thyroid and Pregnancy Study. A single-blind randomized clinical trial was undertaken in pregnant women who were SCH-TPOAb-. SETTING Prenatal care centers of the Shahid Beheshti University of Medical Sciences. PATIENTS Using the thyrotropin (TSH) cut point of 2.5 mIU/L, 366 SCH-TPOAb- and 1092 euthyroid TPOAb- women were recruited. INTERVENTION SCH-TPOAb- women were randomly assigned to two groups: group A (n = 183) who were treated with LT4 and group B (n = 183) who received no treatment. A total of 1,028 euthyroid TPOAb- women served as the control group (group C). MAIN OUTCOME MEASURE The primary outcome was the rate of preterm delivery. RESULTS Using the TSH cutoff of 2.5 mIU/L, no significant difference in preterm delivery was observed between groups A and B [relative risk (RR): 0.86; 95% confidence interval (CI): 0.47 to 1.55; P = 0.61]. However, log-binomial model analysis based on a cut point of 4.0 mIU/L demonstrated a significantly lower rate of preterm delivery in LT4-treated women compared with those who received no treatment (RR: 0.38; 95% CI: 0.15 to 0.98; P = 0.04). CONCLUSIONS Despite no beneficial effect of LT4 therapy in reducing preterm delivery in SCH-TPOAb- women with a TSH cut point of 2.5 to 4 mIU/L, LT4 could precisely decrease this complication using the newly recommended cutoff ≥4.0 mIU/L.
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6.
Amiodarone induced myxedema coma: Two case reports and literature review.
Hawatmeh, A, Thawabi, M, Abuarqoub, A, Shamoon, F
Heart & lung : the journal of critical care. 2018;(4):429-431
Abstract
Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes.
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7.
Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm.
Favresse, J, Burlacu, MC, Maiter, D, Gruson, D
Endocrine reviews. 2018;(5):830-850
Abstract
Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.
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8.
Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects.
Samuels, MH, Kolobova, I, Niederhausen, M, Janowsky, JS, Schuff, KG
The Journal of clinical endocrinology and metabolism. 2018;(5):1997-2008
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Abstract
BACKGROUND The brain is a critical target organ for thyroid hormone, but it is unclear whether variations in thyroid function within and near the reference range affect quality of life, mood, or cognition. METHODS A total of 138 subjects with levothyroxine (L-T4)-treated hypothyroidism and normal thyrotropin (TSH) levels underwent measures of quality of life (36-Item Short Form Health Survey, Underactive Thyroid-Dependent Quality of Life Questionnaire), mood (Profile of Mood States, Affective Lability Scale), and cognition (executive function, memory). They were then randomly assigned to receive an unchanged, higher, or lower L-T4 dose in double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). Doses were adjusted every 6 weeks based on TSH levels. Baseline measures were reassessed at 6 months. RESULTS At the end of the study, by intention to treat, mean L-T4 doses were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 μg/kg (P < 0.001), and mean TSH levels were 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. There were minor differences in a few outcomes between the three arms, which were no longer significant after correction for multiple comparisons. Subjects could not ascertain how their L-T4 doses had been adjusted (P = 0.55) but preferred L-T4 doses they perceived to be higher (P < 0.001). CONCLUSIONS Altering L-T4 doses in hypothyroid subjects to vary TSH levels in and near the reference range does not affect quality of life, mood, or cognition. L-T4-treated subjects prefer perceived higher L-T4 doses despite a lack of objective benefit. Adjusting L-T4 doses in hypothyroid patients based on symptoms in these areas may not result in significant clinical improvement.
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9.
Treatment of refractory thyroid cancer.
Berdelou, A, Lamartina, L, Klain, M, Leboulleux, S, Schlumberger, M
Endocrine-related cancer. 2018;(4):R209-R223
Abstract
Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.
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10.
Effects of Supra-Physiological Levothyroxine Dosages on Liver Parameters, Lipids and Lipoproteins in Healthy Volunteers: A Randomized Controlled Crossover Study.
Sjouke, B, Elbers, LPB, van Zaane, B, Kastelein, JJP, Hovingh, GK, Gerdes, VEA
Scientific reports. 2017;(1):14174
Abstract
Eprotirome, a liver specific thyroid hormone agonist, was shown to induce significant increases in markers of liver injury along with a modest decrease in atherogenic lipids and lipoproteins. To get more insight into whether these effects on liver parameters were compound specific or the effect of mimicking thyrotoxicosis, we studied the effects of supra-physiological levothyroxine dosages on liver parameters, lipids and lipoproteins. We used data of a single-blinded, randomized controlled crossover trial. Herein, healthy volunteers received levothyroxine or no medication for 14 days. Thyroid hormone excess did not induce clinically relevant changes in liver parameters, while significant reductions in total cholesterol, low-density lipoprotein-cholesterol as well as apolipoprotein-B levels were observed in the intervention periods compared with the control periods. Supra-physiological thyroid hormone levels did not induce clinically relevant increases in markers of liver injury after 2 weeks of exposure, while it reduced total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B levels. This suggests that the effects of eprotirome on liver parameters in previous studies were either off-target and compound specific or due to drug-drug interaction at the level of the liver. The results of our study are relevant for the development of novel thyroid hormone agonists to reduce atherogenic lipoproteins.