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1.
Serum biotin interference: A troublemaker in hormone immunoassays.
Öncül, Ü, Eminoğlu, FT, Köse, E, Doğan, Ö, Özsu, E, Aycan, Z
Clinical biochemistry. 2022;:97-102
Abstract
OBJECTIVES Biotin therapy can affect the results of many immunoassay procedures. The present study investigates biotin's interference on 25-hydroxy vitamin D (25-OHD), parathyroidhormone (PTH) and thyroid-stimulating hormone (TSH) tests using four different assay systems and biotin neutralization. DESIGN AND METHODS Enrolled in the study were 50 children diagnosed with biotinidase deficiency (BTD) undergoing treatment with biotin (5-20 mg/day) who were subjected to a series of analyses involving 25-OHD (Roche Diagnostics assays, Beckman Coulter assays, HPLC, LC/MS-MS), TSH, PTH (Roche Diagnostics assays, Beckman Coulter assays) and biotin (LC/MS-MS), before and after biotin neutralization with Streptavidin-coated magnetic particles (SMP). RESULTS The median biotin concentration was found to be 175.2 [94.0-307.1] μg/L. There was no significant difference in the 25-OHD results before and after neutralization with the Beckman Coulter, HPLC and LC-MS/MS assays. In contrast, the median 25-OHD level was seen to decrease from 90.2 [35.9-105.3] ng/mL to 29.1 [22.6-37.6] ng/mL after neutralization with the Roche assay (p < 0.0001). While there was no statistically significant difference in the values recorded before and after neutralization in PTH analysis using Beckman assay, the median PTH levels increased from 7.8 [1.6-21.6] pg/mL to 28.2 [22.5-41.9] pg/mL after neutralization with the Roche assay (p < 0.0001). The cut-off values at which serum biotin interfered in the Roche assay PTH test, with 25-OHD levels determined as 51.4 μg/L and 62.9 μg/L, respectively. A significant increase was detected in the TSH levels analyzed with a Roche assay after neutralization (from 2.36 [1.85-3.00] mIU/L to 2.74 [1.93-3.70] mIU/L, p < 0.0001). CONCLUSIONS The PTH, 25-OHD and TSH results were found to be affected by high biotin concentrations in Roche assays, leading to a risk of misdiagnosis, although SMP neutralization can suppress any such interference efficiently.
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2.
A prospective, observational clinical trial on the impact of COVID-19-related national lockdown on thyroid hormone in young males.
Brigante, G, Spaggiari, G, Rossi, B, Granata, A, Simoni, M, Santi, D
Scientific reports. 2021;(1):7075
Abstract
Trying to manage the dramatic coronavirus disease 2019 (COVID-19) infection spread, many countries imposed national lockdown, radically changing the routinely life of humans worldwide. We hypothesized that both the pandemic per se and the consequent socio-psychological sequelae could constitute stressors for Italian population, potentially affecting the endocrine system. This study was designed to describe the effect of lockdown-related stress on the hypothalamic-pituitary-thyroid (HPT) axis in a cohort of young men. A prospective, observational clinical trial was carried out, including patients attending the male infertility outpatient clinic before and after the national lockdown for COVID-19 pandemic. The study provided a baseline visit performed before and a follow-up visit after the lockdown in 2020. During the follow-up visit, hormonal measurements, lifestyle habits and work management were recorded. Thirty-one male subjects were enrolled (mean age: 31.6 ± 6.0 years). TSH significantly decreased after lockdown (p = 0.015), whereas no significant changes were observed in the testosterone, luteinising hormone, follicle-stimulating hormone, estradiol and prolactin serum levels. No patient showed TSH serum levels above or below reference ranges, neither before nor after lockdown. Interestingly, TSH variation after lockdown was dependent on the working habit change during lockdown (p = 0.042). We described for the first time a TSH reduction after a stressful event in a prospective way, evaluating the HPT axis in the same population, before and after the national lockdown. This result reinforces the possible interconnection between psychological consequences of a stressful event and the endocrine regulation.
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3.
Thyroid Volume and Thyroid Function Parameters Are Independently Associated with Weight Status in Overweight Children.
Lass, N, Barth, A, Reinehr, T
Hormone research in paediatrics. 2020;(5):279-286
Abstract
BACKGROUND A relation between thyroid-stimulating hormone (TSH), insulin resistance - both of which are related to obesity - and thyroid volume has been suggested. Therefore, we analyzed thyroid volume and structure in relation to thyroid function parameters, weight status, and insulin resistance. METHODS This is a cross-sectional study in which weight status (BMI-SDS), thyroid function parameters (TSH, free tri-iodothyronine [fT3], and free thyroxine [fT4]), insulin resistance index (HOMA-IR), and thyroid volume (ultrasound) were determined in 617 overweight children (aged 10.4 ± 2.2 years, 50% male, BMI-SDS 2.5 ± 0.6) and in 27 normal-weight children of a similar age and gender. Furthermore, changes in thyroid volume and structure, and thyroid function parameters were analyzed in 83 obese children (51% male, mean age 10.3 ± 2.2) at baseline and at the end of a 1-year lifestyle intervention. RESULTS Overweight children had a significant greater thyroid volume (4.2 ± 1.8 vs. 4.1 ± 0.5 mL) and higher TSH (3.1 ± 1.5 vs. 2.4 ± 1.1 mU/L) and fT3 (4.4 ± 0.7 vs. 4.1 ± 0.5 pg/mL) concentrations compared to normal-weight children. In multiple linear regression analyses adjusted to multiple confounders, thyroid volume was significantly related to BMI-SDS (b coefficient 0.44 ± 0.10, r2 = 0.41) but not to any thyroid function parameter or HOMA-IR. Changes in BMI-SDS were significantly associated with changes in thyroid volume (r = 0.22). The changes in thyroid volume were not correlated to changes of any thyroid function parameter or HOMA-IR. CONCLUSIONS Thyroid volume is positively correlated to weight status in childhood obesity and the change is reversible after weight loss independently of thyroid function parameters and insulin resistance. Further studies are needed to understand why thyroid volume is increased reversibly in overweight children.
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4.
Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?
Piccardo, A, Puntoni, M, Ferrarazzo, G, Foppiani, L, Bottoni, G, Altrinetti, V, Treglia, G, Naseri, M, Dib, B, Cabria, M, et al
European journal of nuclear medicine and molecular imaging. 2018;(7):1218-1223
Abstract
PURPOSE Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.
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5.
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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6.
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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7.
Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.
Rijks, J, Penders, B, Dorenbos, E, Straetemans, S, Gerver, WJ, Vreugdenhil, A
Scientific reports. 2016;:31032
Abstract
Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.
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8.
Liquid liothyronine to obtain target TSH in differentiated thyroid cancer patients.
Trimboli, P, Centanni, M, Virili, C
Endocrine journal. 2016;(6):563-7
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Abstract
In the last ten years a liquid formulation of liothyronine (L-T3) became available. To date, no studies on its systematic use have been reported. This study is aimed at assessing the reliability of liquid L-T3 in achieving target TSH in patients with differentiated thyroid cancers (DTC). Twenty-one high risk DTC patients in whom levothyroxine treatment up to 2.0 μg/kg/day did not suppress TSH levels (i.e. >0.1 mIU/L) were selected. Maintaining the same L-T4 dose, they started to assume liquid L-T3 at an initial fixed dose of 3.55 μg (5 drops). Further adjustments of L-T3 dose were tailored according to individual assessment. Initial serum TSH ranged from 0.8 to 12.0 mIU/L, when patients assumed high dose of L-T4 alone. Following the addition of a daily single dose of 3.55 μg L-T3, the target TSH was attained in five patients (23.8%). After increasing L-T3 dose up to a mean of 7.3±3.4 μg/day all patients reached target serum TSH (<0.1 mIU/L). The mean individual L-T3 dose was significantly correlated with the body weight and was 0.11±0.04 μg/kg/day (p=0.013). Mean L-T4:L-T3 ratio was 21:1. No patients showed skewed free-T3 or free-T4 values, neither experienced discomfort nor reported adverse events. Liquid L-T3 can be useful to achieve optimal TSH suppression in high risk DTC with not suppressed TSH on L-T4 alone. This formulation allows an individual tailoring of L-T3, minimizing risks of side effects as well as of overtreatment in these clinical conditions.
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Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects.
Hoermann, R, Midgley, JE, Larisch, R, Dietrich, JW
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;(9):674-80
Abstract
The objective of the study was to evaluate the roles of central and peripheral T3 regulation. In a prospective study involving 1,796 patients, the equilibria between FT3 and TSH were compared in untreated and L-T4-treated patients with varying functional states, residual thyroid secretory capacities and magnitudes of TSH stimulation. T3 concentrations were stable over wide variations in TSH levels (from 0.2 to 7 mU/l) and endogenous T4 production in untreated patients, but unbalanced in L-T4-treated athyreotic patients where T3 correlated with exogenous T4 supply. T3 stability was related to TSH-stimulated deiodinase activity by clinical observation, as predicted by theoretical modelling. Deiodinase activity in treated patients was reduced due to both diminished responsiveness to TSH and lack of thyroidal capacity. Deiodinase activity was increased in high thyroid volume, compared to lower volumes in euthyroid patients (<5 ml, p<0.001). While deiodinase differed between euthyroid and subclinically hypothyroid patients in high volume, 26.7 nmol/s (23.6, 29.2), n=214 vs. 28.9 nmol/s (26.7, 31.5), n=20, p=0.02, it was equivalent between the 2 functional groups in low volume, 23.3 nmol/s (21.3, 26.1), n=117 vs. 24.6 nmol/s (22.2, 27.5), n=38, p=0.22. These findings suggest that the thyroid gland and peripheral tissues are integrated in the physiological process of T3 homeostasis in humans via a feed-forward TSH motif, which coordinates peripheral and central regulatory mechanisms. Regulatory and capacity deficiencies collectively impair T3 homeostasis in L-T4-treated patients.
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Association between Hyperhomocysteinemia and Thyroid Hormones in Euthyroid Diabetic Subjects.
Zhang, Y, Wang, Q, Li, Q, Lu, P
BioMed research international. 2015;:196379
Abstract
OBJECTIVES The concept now emerging is that higher thyroid-stimulating hormone (TSH) and lower thyroid hormone levels within the euthyroid range may adversely affect atherosclerosis. The present study aimed to investigate the potential associations between thyroid parameters and hyperhomocysteinaemia in a cohort of euthyroid diabetic subjects. MATERIAL AND METHODS Two hundred and seventy-three euthyroid diabetic subjects (167 males and 106 females) were consecutively recruited in this cross-sectional study. Clinical and biomedical data was collected. RESULTS TSH level was higher in females than males. Compared to normal-homocysteine group, hyperhomocysteinaemia group was more likely to be elderly, males, with longer diabetes history, and with lower diastolic blood pressure. Free thyroxine (FT4) level was lower in hyperhomocysteinaemia group than in normal-homocysteine group; however, it was not statistically significant. Adjusted for age, sex, body mass index, duration of diabetes, blood pressure, fasting glucose, total cholesterol, and triglyceride in logistic regression analyses, hyperhomocysteinaemia was significantly correlated with FT4 (P = 0.021). No significant association was found with TSH or free triiodothyronine. When analyzed in subjects with TSH < 2.5 uIU/mL separately, we got similar results. CONCLUSIONS In conclusion, we identified a relation between hyperhomocysteinemia and FT4 in a group of euthyroid diabetic patients.