Levothyroxine Dosage Is Associated with Stability of Thyroid-stimulating Hormone Values

STUDY QUESTIONDoes lower quartile normal range thyroid stimulating hormone (TSH) compared to higher quartile normal range in women without thyroid hormone substitution affect live birth rate after a complete IUI treatment series?SUMMARY ANSWERLower quartile normal range TSH, in women without thyroid hormone substitution, does not affect live birth rate after a complete intrauterine insemination treatment series compared to higher quartile normal range TSH.WHAT IS KNOWN ALREADYTSH is historically seen as the most sensitive test for thyroid function. Its distribution is right-skewed. Whether the preconceptional upper reference TSH values in subfertile women should be 2.5 or 4.5 mIU/L is under debate. Studies have shown that IUI patients treated with levothyroxine for TSH levels above 2.5 mIU/L show higher pregnancy rates. However, no adverse outcome is associated with untreated high normal TSH levels studied in first IUI cycles. Thyroid peroxidase antibodies have also impaired outcomes in some studies whereas others have shown an effect only in combination with high normal TSH levels. As a subgroup, patients with unexplained infertility showed increased levels of TSH. This article adds to the value of TSH evaluation and fertility outcome in four quartiles and in the context of a completed IUI treatment modus of a maximum of six inseminations.STUDY DESIGN, SIZE, DURATIONThis is a retrospective cohort study in 909 women undergoing 3588 IUI cycles starting treatment between the first of January 2008 and the first of March 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included at Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands, an Iodine-sufficient area. The primary endpoint was live birth. Clinical pregnancy, pregnancy loss and ongoing pregnancy were secondary endpoints. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Chi-square tests and logistic regression were used to compare groups of patients based on TSH values in four quartile TSH groups (0.3–1.21 mIU/L; 1.22–1.75 mIU/L; 1.76–2.34 mIU/L; 2.35–4.5 mIU/L) on basic characteristics and on the endpoints while adjusting for confounders.MAIN RESULTS AND THE ROLE OF CHANCEAnalysis with the natural logarithm of TSH as a continuous variable showed no association with live birth, pregnancy chance or pregnancy loss. There were no differences in any of the outcomes across the quartile TSH level ranges after regression analysis before and after adjusting for age, BMI, use of alcohol, tobacco, use or gonadotrophins, sperm count, diminished ovarian reserve, unexplained infertility and primary or secondary subfertility.The distribution of primary and secondary subfertility and smoking characteristics were remarkably different across the four groups, with proportionally the lowest prevalence of primary subfertility and the highest rate of smoking in the lowest TSH group (0.3–1.20 mIU/L).LIMITATIONS, REASONS FOR CAUTIONUnknown values of free thyroxine and thyroid peroxidase antibodies, as well as the retrospective character of the study, limit the clinical interpretability.WIDER IMPLICATIONS OF THE FINDINGSTSH in the highest quartile range (2.35–4.5 mIU/L) in subfertile women preceding IUI is not associated with a lower live birth rate or rate of clinical and ongoing pregnancy, or with loss of pregnancies, compared to subfertile women with TSH in the lower three quartile groups after complete intrauterine insemination treatment.STUDY FUNDING/COMPETING INTEREST(s)The department of Obstetrics and Gynaecology, division of Reproductive Medicine, and of Internal Medicine, division of Endocrinology provided support. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

Objective: The objective of the study was to correlate prolactin (PRL) levels with different levels of thyroid-stimulating hormone (TSH).
 Methods: The study included 221 non-pregnant females of the age group of 16–43 years. TSH and PRL were assayed. Subjects were divided into three groups based on TSH levels, namely, low, normal, and high TSH levels and results compared.
 Statistical analysis: The comparison between different groups was done using test ANOVA. Correlation between TSH and PRL was established using Pearson’s correlation test.
 Results: Five subjects in Group-1 with low TSH values (mean 0.096±0.08 μIU/ml) had PRL 9.8±6.25 ng/dl, 186 subjects in Group-2 with normal TSH values (mean 1.98±0.94 μIU/ml) had PRL 16.58±8.78 ng/dl, and in Group-3 with high TSH values (mean 6.45±3.91 μIU/ml) had PRL 26.53±15.98 ng/dl. p value for TSH is <0.001 (significant) and for PRL also is <0.001 (significant). Positive correlation has been found in overall 221 subjects between TSH and PRL with correlation coefficient r=0.239 and p=0.01 (significant).
 Conclusion: PRL levels were higher in group with high TSH values. In most previous studies (subjects with established subclinical or overt hypothyroid), PRL was found higher with higher TSH levels. This study showed strong positive association between TSH and PRL irrespective of the thyroid status.

Lower-normal TSH is associated with better metabolic risk factors: A cross-sectional study on Spanish men

Levothyroxine Liquid Solution Versus Tablet for Replacement Treatment in Hypothyroid Patients

Objective To explore the correlation of the gene polymorphism of the two single nucleotide polymorphisms(SNPs)rs1443434 and rs925489 on forkhead box El(FOXE1)with the high normal thyroid stimulating hormone(TSH)level in Chinese Han population. Methods 1 400 subjects with normal serum TSH and thyroid peroxidase antibody(TPOAb)levels were included. According to TSH or TPOAb levels, the subjects were divided into high normal TSH group(H-TSH group, n=195)and normal TSH control group(TSH control group, n=1 205)or high normal TPOAb group(H-TPOAb group, n=711)and low normal TPOAb group(L-TPOAb group, n=689), respectively. The genotypes on the two SNPs of all the subjects were performed by whole-genome genotyping chips. Results There were significant differences in rs925489 genotypic distributions and allele frequencies between H-TSH group and TSH control group(both P<0.05). The genotype TT and allele T in H-TSH group were significantly higher than those in TSH control group(89.75% vs 83.15%, 94.62% vs 91.29%). The normal TSH levels were positively associated with rs925489 genotypic distributions after adjustment for sex, age, and high density lipoprotein cholesterol(P<0.01). There were no significant differences in rs1443434 genotypic distributions and allele frequencies between two TSH groups or two TPOAb groups. Conclusion FOXE1 rs925489 gene polymorphism may be correlated with the high normal TSH level in Chinese Han population. Key words: Forkhead box El; rs925489; Polymorphism, single nucleotide; TSH

In September 1979 screening for Congenital Hypothyroidism (C.H.) was started in Greece. As the screening method Thyroid-Stimulating Hormone (TSH) determination in dried blood spots collected on the 5th day of life was chosen. To date 137,207 newborns (65% of all live births in Greece) have been screened. The distribution of TSH levels in a single estimation was as follows: < 12.5μIU/ml 87.7%, 12.5-30μIU/ml 11.4% and > 30μIU/ml 0.9%.Values > 30μIU/ml were confirmed by a second estimation from the initial card in 171 cases, which were recalled for a new blood specimen (recall rate 0.12%). Among them 97 had TSH values between 30 and 50μIU/ml and TSH estimation from a blood spot on a new card 1-3 months later showed TSH values < 12.5μIU/ml. In 41 cases with TSH values 50-80μIU/ml, serum TSH and T4 revealed 4 cases of C.H. (9.7%), while 37 cases had serum TSH and T4 values within normal limits and were considered as Transient Hyperthyrotropinemias (T.H.). Finally among 33 cases with initial TSH values > 80μIU/ml, in 29 (88%) the diagnosis of C.H. was confirmed on biochemical and clinical grounds, while 4 were considered as T.H. The overall incidence of primary C.H. in our population was 1:4,157.

Background: Patients being treated for hypothyroidism with levothyroxine are typically monitored by measuring serum thyroid stimulating hormone (TSH) and if needed, free thyroxine (FT4) concentrations. However, FT4 reference intervals (RIs) established using healthy subjects may not be applicable to patients taking synthetic thyroid hormone. Establishing method-specific FT4 RIs for patients on thyroxine replacement would be valuable. Objective: The objectives were to: 1) Compare central 95th percentile (%) ranges for serum FT4 concentrations in patients with no thyroid disease and normal TSH with ranges in patients prescribed levothyroxine with normal TSH and 2) Determine if there are differences in serum FT4 concentrations between patients taking levothyroxine with normal TSH who have had Hashimoto’s disease, thyroid lobectomy, or thyroidectomy. Methods: One year of TSH and FT4 results reported on the same day for individual patients were extracted from the electronic medical record (10/1/2017-10/1/2018, n=27,534 unique patients). Patients with TSH results outside of the RI (n=7,082), hospitalized patients (n=4,833) and pregnant patients (n=223) were excluded. Results from patients without documented thyroid disease for whom thyroid testing was ordered due to symptoms suggestive of thyroid dysfunction (no thyroid disease (NTD) patients, n=6,774; male=39% and female=61%) and those from patients taking levothyroxine for established thyroid disease (levothyroxine-treated (LT) patients, n=4,294; male=21% and female=79%) were analyzed. The LT group was subsequently divided into patients with: Hashimoto’s disease (n=150), thyroid lobectomy (n=128) and thyroidectomy (n=381). TSH (RI: 0.3-4.2 mIU/L) and FT4 (RI: 0.9-1.7 ng/dL) tests were performed on Roche Cobas 8000 immunoassays. Central 95th percentile (%) was determined using non-parametric analysis. Results: FT4 values for the NTD and LT patients had a median(interquartile range) of 1.2(1.1-1.3) ng/dL and 1.4(1.2-1.6) ng/dL, respectively. The central 95th % for FT4 was 0.9-1.6 ng/dL for NTD and 0.9-2.0 ng/dL for LT patients using the Roche FT4 assay. In LT patients with Hashimoto’s disease, thyroid lobectomy, or thyroidectomy, the median (interquartile range) FT4 values were 1.4(1.2-1.6) ng/dL, 1.5(1.3-1.7) ng/dL, and 1.6(1.4-1.8) ng/dL, respectively. The central 95th % for FT4 in LT patients was 0.8-1.9 ng/dL for Hashimoto’s disease, 0.8-2.3 ng/dL for thyroid lobectomy and 1.0-2.1 ng/dL for thyroidectomy patients. Conclusion: In levothyroxine-treated patients with normal TSH, the FT4 results are shifted higher compared to the population without thyroid disease. Awareness of this finding should prevent inadvertent changes in levothyroxine dose in patients whose TSH is at goal.

Objectives: Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability in the world. It has been shown in multiple studies that with early detection and treatment of CH normal cognitive function is attainable. The Bayley scales of infant development (BSID) have been used extensively to evaluate the developmental functioning and to assist in planning of treatment for infants with neurodevelopmental delays or disabilities. The aim of the study was to assess the neuromotor and neurocognitive development of children with CH and to correlate it with treatment initiation, duration, and normalization of thyroid stimulating hormone (TSH) post-replacement therapy. Material and Methods: This was a cross-sectional study, where children with diagnosed CH were selected from two tertiary care centers. The children aged between 18 and 42 months were called for the neurodevelopmental assessment using BSID-III. Results: A total of 53 children diagnosed with CH were enrolled. The mean age of children was 29.53 ± 8.7 months during the study. On evaluating the children, mean cognitive composite score (CS) was 102.83 ± 12.77. Mean language CS was 106.55 ± 19.47. Mean motor CS was 111.45 ± 16.4. We noticed that there was statistically significant negative correlation between time for normalization of TSH and BSID-III motor score (P = 0.03). There was no statistically significant correlation between day of initiation of treatment, initial TSH level, or dose of levothyroxine to the BSID-III (P &gt; 0.05). Conclusion: Neurodevelopmental retardation has been detected in children with CH in whom time taken for normalization of TSH was longer. Babies diagnosed with CH should be under regular follow-up for evaluation of neuromotor developmental status by a multidisciplinary team.

OBJECTIVE:&nbsp;Currently, the position of the American Thyroid Association is that hypothyroidism causes symptoms of metabolic slowing due to inadequate production of thyroid hormone by the thyroid gland; it is diagnosed by a lab result of a high thyroid stimulating hormone (TSH) level. While hypothyroidism is considered a chronic, incurable condition, the symptoms typically can be controlled by ingestion of thyroxine (T4) for life. Due to this conclusion, medical providers overall adhere to the assumption that people with normal TSH levels can not have thyroid-hormone-responsive symptoms; likewise, thyroid-hormone-responsive symptoms should not be treated with triiodothyronine T3 and are not reversible. Our objective was to examine if treatment with sustained-release (SR-T3), in patients with normal TSH values and low body temperatures, reduced symptoms consistent with low metabolic rate—and if improvement in symptoms remained even after discontinuation of the T3 treatment regimen. INTERVENTIONS:&nbsp;We report the results of 11 euthyroid outpatients with low body temperatures who took oral SR-T3 every 12 hours according to a cyclic dosing schedule designed to titrate low body temperatures to normal. The SR-T3 they took was formulated with the aim of delivering the T3 gradually over 12 hours. RESULTS:&nbsp;All of the patients in this study responded with an elevation in oral temperatures and improvement in five symptoms measured following the T3 treatment regimen. CONCLUSION:&nbsp;Patients exhibiting hypometabolism with normal TSH levels may experience a reversal of symptoms with normalization of low body temperatures on administration of a sustained-release T3 regimen such that their symptoms remain improved after the regimen has been discontinued.

To explore the association between levels of thyroid-stimulating hormone (TSH) on admission and prognosis of patients admitted to intensive care unit (ICU). The data were collected from patients who were admitted to the ICU of the Beth Israel Deaconess Medical Center in the United States from 2001 to 2012 with available TSH test records within 24 hours after the ICU admission via the Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4). Information including gender, age, ethnicity, type of admission, mechanical ventilation (MV) or renal replacement therapy (RRT) received on admission, comorbidities, and TSH test records within 24 hours after the ICU admission were collected. The sequential organ failure assessment (SOFA) score, simplified acute physiology score II (SAPS II) and the comorbidities index Elixhauser (SID30) score were calculated according to the parameters. The primary outcome was hospital mortality. Differences in baseline characteristics and prognosis were examined between patients with normal TSH levels and abnormal TSH levels which was determined according to a dichotomous variable provided by the data. Multivariable Logistic regression was used to analyze the association between TSH levels and prognosis after adjusting for confounding factors. A sensitivity analysis was conducted which categorized the study population as three groups (i.e., decreased, normal, and elevated TSH levels) using the range of 0.30-3.00 mU/L as the normal range of TSH. A total of 3 425 ICU patients were enrolled in the study, of which 2 692 (78.60%) were with normal TSH and 733 (21.40%) were with abnormal TSH. There was no statistically significant difference in gender, age, ethnicity, type of admission and the ratio of MV between the normal TSH and abnormal TSH groups. Compared with normal TSH group, the patients in abnormal TSH had a higher SOFA, SAPS II and SID30 scores as well as the ratio of RRT [SOFA score: 4 (2, 7) vs. 4 (2, 6), SAPS II score: 38.02±13.76 vs. 36.53±13.75, SID30 score: 11 (4, 22) vs. 11 (0, 20), RRT ratio: 5.32% (39/733) vs. 3.49% (94/2 692), all P < 0.05]. The hospital mortality of patients in normal TSH was significantly higher than that of those in abnormal TSH [9.82% (72/733) vs. 5.94% (160/2 692), P < 0.01]. After adjusting for confounding factors, abnormal TSH was significantly associated with hospital mortality [odds ratio (OR) = 1.71, 95% confidence interval (95%CI) was 1.24-2.35, P = 0.001]. In the sensitivity analysis in which the range of 0.30-3.00 mU/L was used as the normal range of TSH, compared with normal TSH, decreased TSH (OR = 2.36, 95%CI was 1.40-3.97, P = 0.001) and elevated TSH (OR = 1.44, 95%CI was 1.05-1.98, P = 0.023) were both significantly associated with increased hospital mortality. An abnormal level of TSH within 24 hours after admitted to ICU is an independent risk factor for hospital mortality among ICU patients.

Disclosure: T.D. Hoang: None. A.A. Patel: None. A.J. Spiro: None. N.L. Watson: None. M.K. Shakir: None. Levothyroxine monotherapy (LT4) is the standard of care for treating patients with hypothyroidism; however, a subset of patients have bothersome symptoms despite normal thyroid stimulating hormone (TSH) values. Some patients may benefit from combination thyroid hormone replacement therapy, like desiccated thyroid extract (DTE) or levothyroxine with liothyronine (LT4+LT3). Objective: To determine whether the 36-Point Thyroid Symptom Questionnaire (TSQ-36) can guide which patients should trial combination replacement therapy. Methods: We performed a post-hoc subgroup analysis of two previous randomized, double-blind, cross-over studies (total n=143) to evaluate patient symptoms on treatment with LT4, DTE, and LT4+LT3. The TSQ-36 was completed at the end of each treatment period. Patients were stratified based on their TSQ-36 score on LT4: Low Symptoms (TSQ-36: 0-12), Moderate Symptoms (TSQ-36: 13-24), High Symptoms (TSQ-36: 25-36). Mean TSQ-36 scores were compared on LT4, LT4+LT3, and DTE. Treatment-blinded preference of therapy was also stratified by TSQ-36 score on LT4.Results:In Cohort 1, the Moderate-High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (p=0.01).In Cohort 2, the High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (p&amp;lt;0.01) and on LT4+LT3 vs LT4 (p&amp;lt;0.001). The Moderate Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (p=0.02). The Low Symptoms group had significantly lower TSQ-36 scores on LT4 vs DTE (p=0.03) and LT4+LT3 (p=0.02).Patients who preferred combination therapy had significantly higher TSQ-36 scores than patients who preferred LT4. Conclusion: The TSQ-36 can be used to quantify patient symptoms and guide thyroid hormone replacement therapy. Patients on LT4, with moderate-to-severe symptoms despite normalization of TSH, should consider a trial of combination therapy. Patients with low symptoms on LT4 should generally avoid combination therapy. Presentation: Sunday, July 13, 2025

To evaluate the effectiveness of thyroid-stimulating hormone (TSH) and thyroxine (T4) measurements at neonatal screening for congenital hypothyroidism, we compared our false-negative results with those we would have obtained if we had used TSH screening alone. Between January 1989 and December 2001 745,258 newborns were screened (98.3% of total born) for congenital hypothyroidism in northeast Italy. T4 and TSH were measured simultaneously on blood spots collected after birth. Between 1989 and 1998, semi-quantitative total T4 (tT4) and TSH concentrations were measured by radiolabelled immunological assay and, from 1999 to 2001, using time-resolved fluorometer Delfia instruments (EG&G Wallac Oy, Finland) and fluoroimmunometric assay (Delfia neonatal hTSH and T4 kits). Ten neonates were missed by our screening programme (normal tT4 and TSH) and classified as false negatives; these infants were diagnosed later in life with central hypothyroidism. If we had measured TSH alone in our screening programme, we would have missed an additional 21 patients with low tT4 and normal TSH; of these, four were affected by central hypothyroidism and 17 were diagnosed within the second month of life as affected by primary hypothyroidism with delayed TSH rise. Simultaneous T4 and TSH measurements at neonatal screening can miss patients affected by central hypothyroidism. However, this screening procedure allows identification of cases of central hypothyroidism with low T4 values and those neonates affected by primary hypothyroidism with delayed TSH rise who we would have missed by using the TSH measure alone.

Objective To observe the value of thyroid stimulating hormone (TSH) combined with β-human chorionic gonadotropin (β-hCG) in the prediction of preeclampsia (PE) in the first trimester of pregnancy. Methods A retrospectively cohort analysis was performed on 368 pregnant women who had undergone early clinical examination and delivery. The patients were divided into PE group (52 cases) and control group (316 cases) according to whether PE occurred. The general data, thyroid function, β-hCG and pregnancy-associated plasma protein A (PAPP-A) were comparatively analyzed. Using the clinical diagnosis as the golden standard , the receiver operating characteristic (ROC) curves were used to compare the diagnostic value and diagnostic efficacy of those indicators for predicting adverse pregnancy outcomes. Results Univariate analysis showed that pre-pregnancy body mass index [BMI, (24.41±2.11) kg/m2], TSH [(2.79±0.83) mIU/L] and PAPP-A [(1.27±0.28) mIU/L)] levels in PE group were significantly higher than those in control group [(23.72±1.96) kg/m2, (1.99±0.53) mIU/L, (0.98±0.39) mIU/L](P=0.021, 0.000, 0.000), while β-hCG level [(3.06±1.72)×104 IU/L] was significantly lower than that in control group [(5.48±2.29)×104 IU/L](P=0.000). Multivariate logistic regression analysis showed that TSH (OR=15.423, 95% CI=12.963~59.162, P=0.000) and PAPP-A (OR=9.794, 95% CI=4.195~22.867, P=0.000) were independent risk factors for PE, while β-hCG (OR=0.889, 95% CI=0.853~0.927, P=0.000) was a protective factor of PE. ROC curves showed that the area under the curve of TSH and β-hCG (AUC=0.780, 0.788) was higher than that of PAPP-A (AUC=0.705) and pre-pregnancy BMI (AUC=0.575), the Youden index showed that the best cut-off of TSH and β-hCG were TSH≥2.21 mIU/L and β-hCG≤ 3.96×104 IU/L. The diagnostic value of TSH combined with β-hCG (AUC=0.927) was significantly higher than that of TSH or β-hCG alone. The sensitivity of TSH combined with β-hCG in predicting PE was 96.15%, which was significantly higher than that of TSH and β-hCG (χ2=3.983, 4.981; P=0.046, 0.026), while no statistical differences were found in the diagnostic accuracy (χ2=0.363, 3.160; P=0.547, 0.075). Conclusion TSH combined with β-hCG have a high value in the prediction of PE in the first trimester of pregnancy, of which the best cut-off of TSH and β-hCG are TSH≥2.21 mIU/L and β-hCG≤3.96×104 IU/L, respectively. Key words: Thyroid stimulating hormone (TSH); Human chorionic gonadotropin (hCG); Preeclampsia (PE); Eclampsia; Sensitivity; Specificity

Although levothyroxine (LT4) replacement therapy for hypothyroidism has been established as safe, inexpensive and effective, many studies from different countries reported out-of-reference range thyroid-stimulating hormone (TSH) values for the hypothyroid patients under LT4 treatment. The aim of this study was to determine TSH levels of primary hypothyroid patients under LT4 treatment and to assess self-reported compliance with daily LT4 intake in tertiary care centers in Turkey. In this cross-sectional, observational study, adult patients with primary hypothyroidism, receiving LT4 treatment for at least 6 months, were included. The patients were from 12 tertiary care centers in 9 cities of Turkey. TSH and free T4 levels were recorded from patient files and self-reported compliance with daily LT4 intake was assessed by interviewing the subjects at the last visit. A total of 1,755 subjects (46 ± 13 years; F/M: 89.9/10.1%) with primary hypothyroidism were enrolled. Of the hypothyroid subjects, 44.8% had out-of-reference range serum TSH levels. TSH values were over the reference range (TSH > 4 mIU/L) in 26.2% and were under the reference range (TSH < 0.5 mIU/L) in 18.6% of the patients. Total duration of LT4 treatment was 5.9 ± 4.7 years and mean dose was 1.2 ± 0.6 μg/kg/day. Non-compliant patients (31.1%) had higher TSH levels (6.9 ± 16 vs 3.8 ± 0.9 mIU/L, P = 0.01) compared to compliant patients. The results of this study revealed that nearly half of the hypothyroid patients had out-of-reference range serum TSH values, despite under LT4 treatment. Compliance with LT4 treatment seems to be one of the major determinants to reach the target TSH levels in hypothyroid patients.

What is a normal thyroid stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after IVF