Serum FT4 Levels Research Articles

Evaluate the hematologic parameters, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with autoimmune hypothyroidism from Amara City, Southern Iraq

Abstract Background: Thyroid diseases are affecting 3%–5% of the women general population. Autoimmune thyroid diseases such as Graves’ disease (GD) and Hashimoto’s disease were detected to be the commonest disorders affecting thyroid function. Objectives: This study is a case–control study that aimed to estimate the effect of HT on hematological parameters. Materials and Methods: A total of 100 persons (50 HT patients and 50 euthyroid groups) of both sexes aged between 15 and 50 years were included in this study during the period April 2021–April 2022. Samples of venous blood (5 mL) were obtained from the study participants and used for the estimation of serum thyroid-stimulating hormone (TSH), FT3, and FT4 levels, as well as anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG) concentration, as well as hematologic parameters. Results: The results of this study showed that HT patients had significantly higher levels of TSH as well as thyroid autoantibodies (anti-TPO and anti-TG) and significantly lower levels of FT3 and FT4. A considerable decrease was found in the hematocrit, hemoglobin, and mean corpuscular volume among HT patients, whereas no significant differences were found between the HT patients and the euthyroid group in total red blood cell count, total white blood cell count, neutrophils, lymphocytes, monocytes, basophils, platelet counts, MPV, mean distribution width, plateletcrit, and PLCR. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were significantly higher in the HT patients compared with the euthyroid group. Conclusions: The current study concluded that Hashimoto’s thyroiditis is associated with significant elevation in the serum concentrations of anti-TPO and anti-TG antibodies, high TSH levels, and decreased FT3 and FT4 levels. Hashimoto’s disease resulted in a significant decrease in the hemoglobin concentration; hence, patients with HT could be at risk to have anemia. Also, HT was associated with elevated NLR and PLR values; therefore, NLR and PLR ratios could be used as routine, inexpensive, easily accessible markers at the clinical course or the severity of autoimmune diseases that progress with chronic inflammation.

Association Between Serum Ferritin Levels in Early Pregnancy and Thyroid Function and Pregnancy Outcomes in Chinese Population.

The relationship of iron deficiency and thyroid hormone has been researched a lot among pregnant or other healthy population. However, invisible iron deficiency, namely shortage of serum ferritin (sFer) level, has been barely investigated among Chinese pregnant women. This study aimed to explore the effects of sFer status on thyroid function and pregnancy outcomes in a population-based upper first-class hospital. A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in this retrospective cohort study. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across sFer quartiles. Categorical measures were compared by Fisher exact test or chi-square test. As the sFer concentration rises, incidence of premature birth (15.8%vs 12.3% vs 9.20% vs 6.20% p = 0.016) as well as threatened miscarriage (14.8% vs 7.2% vs 8.70% vs 6.70% p = 0.021) presented a downward trend. Compared with the other sFer group, subjects of the low sFer group were older, more often to be found to have lower serum γT3 and FT4 levels in early pregnancy but not in middle pregnancy. sFer concentration in the first trimester can affect thyroid function. The correction of invisible iron deficiency with inadequate sFer status prior to pregnancy or during early pregnancy is imperative, not only to prevent anemia, but also for maintaining optimum thyroid function and normal fetal development. For clinicians, sFer status of pregnant women should be attached great importance apart from attention to iron level.

Changes of serum TSH, FT3, and FT4 levels in infants received surgical correction of congenital heart disease under cardiopulmonary bypass

ObjectiveThis study aimed to explore the fluctuations and clinical relevance of serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels in infants undergoing surgical correction for congenital heart disease (CHD) using cardiopulmonary bypass (CPB).MethodsIn a retrospective design, 58 infants who underwent CHD surgical correction under CPB between January 2021 and January 2022 at our institution were incorporated. These infants were categorized into two groups: simple CHD (n = 34) and complex CHD (n = 24). TSH, FT3, and FT4 serum concentrations were assessed at four intervals: 24 h pre-surgery (T0) and 24 h (T1), 48 h (T2), and 72 h (T3) post-surgery.ResultsThe simple CHD group displayed a significantly reduced CPB duration compared to the complex CHD group (P < 0.001). Both groups exhibited a notable decline in serum thyroid hormone concentrations at T1 compared to T0. However, from T1 to T3, an upward trend in hormone levels was observed. By T3, though the levels in both groups had risen notably from T1, they remained significantly diminished from T0 (P < 0.01). In both the simple and complex CHD cohorts, significant fluctuations in thyroid hormone levels (TSH, FT3, FT4) were noted across the different timepoints (T0, T1, T3) (P < 0.01). While no significant disparities were found between the two groups’ hormone concentrations at T0 and T1 (P > 0.05), at T2 and T3, the simple CHD group manifested higher TSH, FT3, and FT4 levels compared to the complex CHD group (P < 0.05).ConclusionsInfants undergoing CHD surgical correction under CPB experience significant declines in TSH, FT3, and FT4 serum levels. The post-surgery thyroid hormone recovery was more pronounced in infants with simple CHD compared to those with complex CHD. As such, vigilant monitoring of thyroid hormone levels during the perioperative phase is imperative, and timely intervention measures should be employed when necessary.

Relationship between Iron Deficiency and Thyroid Function: A Systematic Review and Meta-Analysis.

Objective: Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. Methods: This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "iron deficiency", "thyroid function", "thyroid disease", "thyroid dysfunction", and "hypothyroidism". A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran's Q testing and heterogeneity indices (I2) were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Results: Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: -0.24 mIU/L; 95% CI -0.41, -0.07; I2 = 100%, p = 0.005), FT4 (MD: -1.18 pmol/L; 95% CI -1.43, -0.94; I2 = 99%, p < 0.000001), and FT3 (MD: -0.22 pmol/L; 95% CI -0.32, -0.12; I2 = 99%, p < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Conclusion: Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.

Spexin may induce mitochondrial biogenesis in white and brown adipocytes via the hypothalamus-pituitary-thyroid (HPT) axis

AimThe present study aimed to investigate the effect of the intracerebroventricular (icv) administration of spexin on the hypothalamus-pituitary-thyroid (HPT) axis (TRH, TSH, T4 and T3 hormones) and energy expenditure (PGC-1α and UCP1 genes) in white adipose (WAT) and brown adipose tissues (BAT) in rats. Furthermore, the study aimed to determine the effects of spexin on food-water consumption and body weight of rats. Material and methodThe study was conducted with 40 male rats that were divided into 4 groups: Control, Sham, Spexin 30 and Spexin 100 (n = 10). Spexin (1 μl/hour) was administered to rats other than those in the control group for 7 days with osmotic minipumps intracerebroventricularly, artificial cerebrospinal fluid (vehicle) was administered to the Sham group, and 30 nMol and 100 nMol spexin was infused to the Spexin 30 and Spexin 100 groups, respectively. Food-water consumption and body weight of the rats were monitored during the experiments. After the seven-day infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined with ELISA on rat blood samples. Also, TRH gene expression levels from the hypothalamus tissues and PGC-1α and UCP1 expression levels from WAT and BAT were determined by real-time PCR. FindingsIt was determined that icv spexin infusion reduced daily food consumption and body weight without leading to a significant change in water consumption (p < 0.05). Icv spexin infusion significantly decreased serum TSH, and increased fT4 and fT3 levels when compared to control and sham groups (p < 0.05). Moreover, icv spexin infusion increased the TRH expressions in the hypothalamus tissues and PGC-1α UCP1 in the WAT and BAT (p < 0.05). ConclusionIcv Spexin infusion may have effects on food consumption and body weight as well as, thyroid hormones and energy metabolism.

The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis

Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.

Analysis of thyroid function and related factors in narcolepsy patients

The loss of hypocretin is thought to be the main pathophysiological mechanism of narcolepsy. There is strong evidence that hypocretin is related to the regulation of endocrine functions and depression. To explore thyroid hormone levels in narcolepsy patients was our aim. In addition, further is to analyze the relationship between thyroid hormone levels and sleep quality, anxiety, and depression in narcolepsy patients. There are 40 patients with narcolepsy and 40 healthy controls (HCs) were conducted. Blood samples were explored for thyroid function. Correlation analysis between thyroid hormones and clinical characteristics of narcolepsy was performed using Pearson or Spearman. Narcolepsy patients had significantly lower free thyroxine (FT4) levels in comparison to controls (p < 0.001). No subject was diagnosed with primary hypothyroidism. There were 4 (10%) subjects with subclinical hypothyroidism. The serum FT4 levels were positively correlated with HAMA14 score (r = − 0.343, p = 0.030) by Pearson correlation analysis. The serum TSH levels and HAMD24 score (r = − 0.807 p ˂0.001), and ESS score (r = − 0.317, p = 0.046) both showed a negative correction. Hypocretin deficiency may be associated with the regulation of thyroid hormones in narcolepsy patients. The serum thyroid hormones may affect the severity and neuropsychological functions of narcolepsy patients.

Relationship between serum vitamin D and thyroid hormone profiles in male patients with alcohol dependence

BackgroundAlcohol dependence (AD) results in several medical problems including vitamin D deficiency and thyroid dysfunction. However, the relationship between these two complications remains unclear. The aim of the present study was to explore the relationship between serum vitamin D and thyroid hormone profiles in male patients with AD.MethodsA total of 117 male patients with AD were enrolled. Vitamin D deficiency was defined as serum concentrations of the main circulating vitamin D, 25-hydroxy vitamin D [25(OH)D], below 50 nmol/L. The AD patients were divided into two groups accordingly: 46 patients with normal vitamin D levels (normal group) and 71 patients with vitamin D deficiency (deficiency group). The levels of thyroid hormone profiles including total triiodothyronine 3 (TT3), total thyroxine 4 (TT4), thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) between the two groups were compared. Correlation between the serum levels of 25(OH)D and thyroid hormone profiles was evaluated using simple correlation (Pearson’s correlation) and multivariable analysis using linear regression models.ResultsThe prevalence of vitamin D deficiency in male patients with AD is 60.7% (71/117; 95% confidence interval: 51.6–69.1%). Moreover, the serum levels of TT3 (t = -2.682, p = 0.009), TT4 (t = -2.033, p = 0.044), fT3 (t = -2.986, p = 0.003), and fT4 (t = -2.558, p = 0.012) in deficiency group were significantly higher than those in normal group. Post hoc power analyses showed that the power for fT3 was sufficient (power > 0.80). Furthermore, univariate analysis showed that the serum vitamin D levels were negatively correlated with the TT3 (r = -0.189, p = 0.044), fT3 (r = -0.350, p < 0.001), and fT4 (r = -0.198, p = 0.033) levels, while multivariate analysis indicated that only fT3 was independently related to the serum levels of vitamin D in male patients with AD.ConclusionsThese results suggested that the serum vitamin D levels may be associated with fT3 in male patients with AD.

Curcumin exerts protective effects on the thyroid gland in propylthiouracil-treated rats.

Among the plant ingredients, some compounds interfere with the functions of the thyroid gland. However, there is limited research on the effect of curcumin (CMN) on the functions of this gland. The aim of this study was to analyze the effect of CMN on morphology, histochemical reactivity of cytochrome c oxidase (CCO) and secretion functions of the thyroid gland under conditions of hypothyroidism induced by propylthiouracil (PTU). The rats were treated for 30 days by gavage with CMN (100 mg/kg b.w.) and/or PTU (1 mg/kg b.w.). Control rats received vehicle only. Histomorphometric tests were performed on the thyroid glands, cytochrome c oxidase activity was visualized using the histochemical method, and the levels of thyroid hormones were measured using the radioimmunoassay method. Rats receiving PTU showed compensatory changes in their thyroid glands, including a significant increase in thyroid epithelium height, a decrease in colloid volumen density, a decrease in the percentage of small follicles, an increase in medium-sized follicles compared to the control group, as well as a significant increase in CCO histochemical reactivity in the columnar epithelium and a decrease in FT4 serum level compared to the control group. The administration of CMN reversed these adverse changes caused by PTU. The PTU + CMN group exhibited a significant decrease in the height of the thyroid follicle epithelium compared to the PTU group. The percentage of small and medium-size follicles in the CMN + PTU group did not differ from the control group. Furthermore, CCO reactivity in the cubic epithelium and serum FT4 levels increased compared to the PTU group. Administration of CMN alone resulted in a significant increase in FT4 levels compared to the control group. The administration of CMN to rats with induced hypothyroidism resulted in a reduction of hyperplasia, hypertrophy, and increase in secretory activity of the thyroid gland. These findings suggest the protective effect of CMN against induced hypothyroidism.

FRI472 Thyroid Hormone Resistance β (RTH- β) Syndrome In Patient With Multiple-system Atrophy Parkinsonian Type (MSA-P)

Abstract Disclosure: S. Lio: None. M. Albin: None. I. Campi: None. L. Persani: None. Background: Resistance to thyroid hormone β (RTHβ) is a rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormones (TH) due to variants in the THRB gene encoding the TH receptor β (TRβ). RTHβ patients display a distinctive biochemical feature of central hyperthyroidism with elevated serum levels of FT3 and FT4 and unsuppressed TSH. Unfortunately, this syndrome is sometimes misdiagnosed as primary hyperthyroidism, with a delayed diagnosis or inappropriate treatments. Clinical Case: A 72-year-old lady was diagnosed elsewhere in 2010 with atrial fibrillation (AF) and parkinsonian multisystem atrophy (MSA-P), an orphan disease causing progressive autonomic and motor impairment. The patient reported an unspecified dysthyroidism discovered during the diagnostic work-up of AF, but no further investigations were performed. Bisoprolol, Edoxaban and Levodopa/Benserazide were started. In 2020 she had multiple hospitalization due to fall-related injuries, and multiple rib fractures. A neurological and cardiological reassessment did not highlight new problems, nor MSA-P progression, while discrepant thyroid function tests (TFTs) were found (TSH 2.4 mU/L, fT4 3.5 ng/dl, fT3 7.9 pg/ml; normal ranges: 0.4-4.5; 0.8-1.7 and 2.-5, respectively). Anterior pituitary function and a gadolinium-enhanced pituitary MRI were normal. Thyroid ultrasound revealed a modest goiter, with a normal vascularization and multiple hypo-anechoic and spongiform nodules ≤1 cm. Propylthiouracil has been started At referral in our Center, discrepant TFTs were confirmed (TSH 6.6 mU/L, fT4 2.5 ng/dL, fT3 5.1 pg/ml). TPOAb, TgAb and TRAb were absent. We also excluded assay interferences due to heterophiles antibodies. Being T3 administration contraindicated due to AF, a TRH-test, after suspension of PTU, was performed showing an intense and prolonged response of the TSH (36.7 and 19.2 mU/L at 30 and 120 minutes, respectively), consistent with RTHβ. Consistently, molecular analysis by a targeted NGS panel revealed a heterozygous known pathogenic variant in the exon 9 of the TRHB gene (c.1033G&amp;gt;A, p.Gly345Ser). Conclusion: In the differential diagnosis of central hyperthyroidism RTHβ should be considered even in older patients, as late diagnosis may occur. The association of RTHβ with MSA-P has never been reported before, although a causal relationship is improbable. Nevertheless, central hyperthyroidism could worsen underlying neurological diseases, given the critical role of TH in CNS and muscle. A greater awareness of both neurologists and endocrinologists on rare thyroid diseases is warranted, to improve the care of patients with neurological orphan diseases. Presentation: Friday, June 16, 2023

THU091 Hypopituitarism And The Finding Of Hyperprolactinemia Following Mild Traumatic Brain Injury In Female Athletes

Abstract Disclosure: L.Ó. Eggertsdóttir Claessen: None. H. Kristjánsdóttir: None. M.K. Jónsdóttir: None. S.H. Lund: Employee; Self; Amgen Inc. I.S. Kristensen: None. H.Á. Sigurjónsdóttir: None. Background Hypopituitarism (HP) following mild traumatic brain injury (mTBI) in sports can have serious consequences making prompt diagnosis and treatment essential. Studies have focused on male populations despite female athletes being more susceptible to mTBI. To the best of our knowledge, this study is the first all-female study reporting the prevalence of HP following mTBI. Subjects The study included 508 female athletes aged 18 to 45 years currently active in or retired from soccer, team handball, basketball, ice hockey, and martial arts who answered an online questionnaire regarding mTBI history. Women who reported one or more concussions (n = 308) were invited to participate in a medical interview and a physical examination with 151 accepting. Consequently, 133 women attended pituitary hormone screening blood tests (SBT). Methods SBT were taken at 8 a.m. and included S-IGF1, S-cortisol, S-prolactin, S-TSH, S-fT4, S-FSH, S-oestrogen, and S-progesterone measurements. When SBT were repeatedly outside reference value (O-RV), participants were referred to an endocrinologist for a medical interview and physical examination. Detailed endocrinological tests for possible HP were performed as indicated. When serum levels of TSH or fT4 were O-RV, anti-TPO antibodies were measured and when negative, an MRI was performed. If S-prolactin was repeatedly above reference value (RV) an MRI was performed. When S-cortisol was below 350 mmol/L, morning plasma ACTH was added and morning Synacthen test performed. When S-IGF1 was below median RV and clinical symptoms of GHD were present, a GHRH-arginine test was performed. An ITT was performed in one woman due to practical reasons and strong clinical symptoms indicating GHD. Results etailed endocrinological evaluation for possible HP was indicated in 86 women. Pituitary dysfunction (PD) was diagnosed in 16 women (12.0%). Six (4.5%) women had HP. One woman had GH measurements below RV in a GHRH-arginine test (peak GH levels ≤11.0 µg/L for BMI &amp;lt;25 kg/m2) and one had GH below &amp;lt;3µg/L in an ITT. Four women had low or normal TSH levels (reference range 0.270 - 4.20 mIU/L), low fT4 (reference range 12 - 22 pmol/L) and a negative anti-TPO measurement. Ten women (7.5%) had hyperprolactinemia (HPRL) (reference range 4.79 - 23.3 μg/L). Four of the 10 women with HPRL were diagnosed with a prolactinoma following an MRI. Medical treatment was initiated for 13 (9.8%) women as one woman had a prolactinoma but no clinical symptoms of HPRL. Conclusions PD is an important consideration in post-concussion care as 12.0% had PD following mTBI with 9.8% requiring medical treatment. Six women (4.5%) had HP following mTBI (GHD = 2 and central hypothyroidism n = 4). This is lower than previously reported and may be due to HP recovering with time. As six women had HPRL without a prolactinoma, HRPL may represent pituitary or hypothalamic injury following mTBI. Presentation: Thursday, June 15, 2023

THU231 Thyroid Function And Childhood Bone Mineral Density: Abnormal Thyrotropin Concentration May Be Another Predictor Of Pediatric Low Bone Mass

Abstract Disclosure: M. Ahn: None. Backgrounds: Thyroid hormone (TH) whose synthesis and secretion are mainly regulated by thyrotropin (TSH) play a critical role in the metabolism, growth, and development of human body. While TH is responsible for normal growth and differentiation of various organs, bone is known to be one of the major endocrine organs affected by the regulation of TH. Low bone mass or osteoporosis of child and adolescents can occur in numerous chronic conditions, however the influence of abnormal TH and TSH on low bone mineral density (BMD) of children and adolescents remains controversial. Investigating the effect of excessive or deficient TH and TSH on childhood BMD may unveil a better understanding of uncertain role of thyroid function in bone density of pediatric population. Objective: To elucidate the connection between thyroid function and childhood low bone mass. Methods: Serum T3, FT4 and TSH of 619 children aged between 10 to 18 years and previously diagnosed with hemato-oncologic, rheumatoid, gastrointestinal, endocrine conditions whose treatment was completed were assessed simultaneously with mineral density of lumbar spine and femur measured by dual energy x-ray absorptiometry. Serum T3, FT4, and TSH were subcategorized as either high/normal/low or normal/abnormal group with respect to age-matched reference range, then LSBMD data were compared. Comparison, correlation and regression analyses were performed to examine the association between the abnormality of thyroid function and low BMD. Results: Mean LSBMD z-scores of 619 children and adolescents were 0.49±1.28 and those who were less than -1.0 accounted for 37.7 % while serum T3, FT4, and TSH levels were 1.25±0.29 ng/mL, 1.28±0.19 ng/dL, and 2.76±1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were not significantly different in between subjects with either abnormal or normal serum T3 and FT4, however were lower in children with abnormal serum TSH. LSBMD (g/cm2) was negatively correlated with serum T3 whereas its z-scores showed no correlation with any of serum T3, FT4 and TSH. In linear regression, BMI z-scores were positively associated whereas serum T3, FT4, TSH were not directly associated with LSMBD z-scores. When the abnormality of T3, FT4, and TSH was considered as determinants for decreasing LSBMD z-scores, TSH abnormality was a significant risk factor having highest odds ratio as LSBMD z-scores decreased. Conclusion: Although serum T3, FT4, and TSH did not show a direct correlation with childhood LSBMD z-scores, abnormal TSH concentration could predict low LSBMD z-scores, therefore indicate low bone mass of children with various underlying conditions. Presentation: Thursday, June 15, 2023

Development and Validation of CT-Based Dose-Volume-Radiomics Nomogram for Radiation Induced Hypothyroidism in Nasopharyngeal Carcinoma

Several studies reported hypothyroidism occurred in 40-50% of patients who were treated with neck irradiation. Post-radiation hypothyroidism impairs quality of life, increases the risk of cardiac complications, and requires lifelong thyroxine replacement in affected patients. At present, radiation dose-volume constraints of thyroid gland are used to predict thyroid function outcomes in patients with nasopharyngeal carcinoma (NPC). However, it is limited by (a) inferior predictive power, (b) a lack of analyzing individualized thyroid characteristics as a categoriad to predict radiation induced hypothyroidism (RIHT). In this study, we firstly developed and validated CT-based dose-volume-radiomics nomogram to predict RIHT in patients with NPC. A total of 451 NPC patients who underwent definitive radiotherapy were randomly assigned into the training (n = 338) and validation set (n = 113) in a 3:1 ratio. Dose-volume parameters, including the thyroid volume, mean dose (Dmean), percentage of the volume that received xGy of radiation (Vx), and the absolute volume that was spared from xGy of radiation (Vsx), were collected from radiotherapy planning databases. We defined primary hypothyroidism as an elevated TSH serum level (> 4.94 mIU/L) in combination with a normal or low serum FT4 level, regardless of symptoms. 1316 CT radiomic features were extracted and selected to construct the radiomics signature (RS). A CT-based nomogram was established by integrating clinical factors, dose-volume parameters and radiomics signature in training set and was tested in validation set. With a median follow-up period of 68 months, 301 (66.7%) patients developed RIHT. Compared with other dose-volume parameters including thyroid volume, V30, V50, Dmean, Vs45, Vs50, the thyroid volume spared from 60Gy (Vs60) had best power to predict RIHT. The radiomics signature constructed by 8 selected radiomic features showed better prognostic performance than Vs60 for predicting RIHT in training set (RIHT vs. Vs60, C-index: 0.69 vs. 0.58) and internal validation set (C-index: 0.65 vs. 0.55). Patients were stratified into high- and low-risk groups by median radiomic signature. Patients in high-risk group had higher rate of RIHT than patients in low-risk group (training set:61% vs.39%, P<0.05; validation set: 73% vs.32%, P<0.05). The nomogram established by integrating radiomics signature with Vs60 showed optimal prognostic performance with C-index of 0.71 in training, 0.66 in validation set. Calibration curves showed good agreement. CT-based dose-volume-radiomics nomogram provided an excellent prognostic tool for predict incidence rate of RITH in patients with NPC received definitive radiotherapy.

The Effects of Maternal Smoking on Thyroid Function: Findings from Routine First-Trimester Sonographic Anomaly Screening.

This study aimed to assess the effect of tobacco exposure on maternal thyroid function and investigate its relationship to subclinical hypothyroidism in pregnant women during the first trimester. A comparison of maternal thyroid function was made on 45 smokers, who composed the study group, and 72 non-smokers, pregnant women, who constituted the control group. After determining smokers by questionnaire, carbon monoxide (CO) levels in the expiratory air of the participants in both groups were measured and recorded, and the smokers' exposure was objectively confirmed. Smoking and non-smoking pregnant women were similar regarding body mass index (BMI). While the TSH and fT4 levels were respectively 1.48 mlU/L and 11.43 pmol/L in pregnant women who smoked, that ratio changed to 1.72 mlU/L and 11.17 pmol/L in the non-smokers' group. But the differences between the groups were not statistically significant (p=0.239, p=0.179). Even though the rate of subclinical hypothyroidism was 8.9% in the smoking group, it was approximately 19.4% in the non-smoker group; the difference was not statistically significant (p=0.187). This study proved that there is no statistically significant difference between maternal serum TSH and fT4 levels and the rate of subclinical hypothyroidism in smokers during pregnancy in the first trimester.

A-059 Evaluation of Free Thyroxin Levels in Patients with Low Thyroxin Binding Globulin Concentrations: Is There Interference in the FT4 Indirect Method?

Abstract Background Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in serum. Variations in the serum concentration of TBG determine proportional variations in the total serum concentrations of T4 and T3, without implying changes in function, as long as the free fraction remains normal. Several common clinical conditions lead to significant alterations in TBG levels, the most important factor behind low levels being genetic defects. As TBG is encoded by a gene located on the X chromosome, the defects are more easily manifested in males. Differences in FT4 concentrations were observed in sera from subjects with TBG abnormalities, when FT4 are measured by different immunoassays, specially at extremes of TBG concentrations. The objective of this study was to evaluate FT4 levels by indirect method in patients with low TBG concentrations. Methods We analyzed blood samples requesting serum TBG, TSH and FT4 levels from patients admitted to a private reference clinical laboratory in Brazil, from January 01, 2017 to December 31, 2022. Anonymized data on laboratory tests was available from a database of the local Laboratory Information System. All the patients included had TSH within the reference range, 0.4–4.3 mUI/mL (ECLIA, Modular, Roche). FT4 was measured by ECLIA (0.7–1.8 ng/dL) and TBG by ICMA, Immulite, Siemens, 13–39 mcg/mL. Results 357 patients with low TBG levels were evaluated, 220 (62%) men, 137 (38%) women; mean age 35 yrs (19 d to 88 yrs). They were divided in six groups according TBG levels (mcg/mL): &amp;lt;3.5–17 (M 15, F2); 3.5 to 6.0 - 26 (M 20, F 6); 6.1 to 8.0 - 30 (M 25, F 5); 8.1 to 9.9 - 59 ( M 32, F 27); 10.0 to 11.9 - 139 (M 78, F 61); 12.0 to 12.9 - 86 (M 50, F 36). Three patients had FT4 levels above 1.8 (1.85; 1.87 and 1.96) ng/mL, all them male, with TBG levels &amp;lt;3.5; 5.79 and 9.53 ng/mL, respectively. Conclusion FT4 Indirect methods are developed taking into account the presence, in the serum, of a thyroxine binding capacity within the normal range, a fact that does not occur in individuals with extreme TBG deficiency. In this study, we found only one slightly elevated FT4 value among 17 patients with TBG values below 3.5 mcg/mL, suggesting little interference of very low TBG levels in this indirect free T4 method.

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

The Association Between Hypoxic-Ischemic Encephalopathy and Thyroid Hormones.

We aimed to compare serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels in neonates with different hypoxic-ischemic encephalopathy (HIE) stages undergoing therapeutic hypothermia (TH), and to evaluate the TSH and fT4 levels in neonates with HIE/TH in comparison with a control group. This was a retrospective study conducted between January 2020 and December 2022. The neonates with HIE/TH constituted the study group and the neonates with transient tachypnea of the newborn (TTN) constituted the control group. The study group consisted of neonates with stage 2 and stage 3 HIE. Serum TSH and fT4 levels measured at postnatal fifth day were compared between the groups. Of the 202 (47.1%) neonates included in the study group, 144 (71.3%) had stage 2 HIE and 58 (28.7%) had stage 3 HIE. In the control group, there were 227 (52.9%) newborns. Serum TSH and fT4 levels were found to be lower in the newborns with stage 3 HIE compared with those with stage 2 HIE (p = 0.015, 0.002, respectively). Although the serum TSH level was higher in the newborns with HIE compared with the newborns with TTN, serum fT4 levels did not change between the groups (p = < 0.001, 0.14, respectively). When we made the analysis according to the reference intervals, HIE/TH was associated with higher rates of TSH elevation compared with TTN, and the difference was more pronounced in stage 2 HIE/TH (p < 0.001). Although stage 3 HIE/TH was significantly associated with higher rates of low fT4 compared with TTN (p = 0.006), this relationship was not significant between stage 2 HIE/TH and TTN. It would be reasonable to interpret thyroid function tests performed on the fifth day with caution in newborns with HIE/TH, because higher TSH and lower fT4 levels on the fifth day in this patient group may result in unnecessary repetition of tests.

In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable.

How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth? During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline. Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy. First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019. Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference. Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved. The numbers of participants both in the prevalence study and in pregnancy did not reach the a priori estimated numbers. For ethical reasons, the patients with preconception TSH >4.5 mIU/l were treated with thyroxine. The findings apply to infertile women only. We propose to use >4.5 mIU/l as the serum TSH threshold for supplementing women with thyroxine before pregnancy. During pregnancy, fT4 may be the better marker to monitor thyroid function. The consistent decrease of anti-TPO antibody levels during ongoing pregnancies must be considered a protective element. The prevalence part of this study was supported by Merck-Serono, Geneva (TH006/EMR200007-603). The hormone measurements of the serum samples collected during the follow-up pregnancies were made possible by financial support of Roche Diagnostica (November 1721, 2017, Rotkreuz, Switzerland). I.D.G. was supported by a grant of the Repronatal Foundation, Basel, Switzerland. All authors declare no conflict of interest. Research Database of UniBasel, project no. 576691 (2007).

Thyroid profile prognostic value on disease severity and mortality in COVID-19

Background: Precise accurate triage of Coronavirus disease 2019 (COVID-19) patients during hospitalization for early identification of individuals at risk of developing severe disease is essential as Intensive Care Units (ICUs) are overwhelmed by the pandemic burden. The aim of this study was to evaluate thyroid function in patients with COVID-19. Methods: 60 healthy controls and 180 patients were admitted to a cardiothoracic hospital, Minia University, Egypt, between March 2020 and September 2021 without a history of thyroid disease. Patients divided as 60 non-COVID pneumonia patients with a similar degree of severity were included as another control group to find any unique effects of COVID-19 on thyroid function, 120 positive COVID-19 divided according to clinical classifications into moderate (n = 58), severe (n = 21), and critical (n = 41), Critical group were admitted to ICU and classified to survivors (n = 33) and non-survivors (n = 8). COVID patients also were divided into tertiles according to their FT3 levels. Lowes tertile (n = 45), middle tertile (n = 37) and highest tertile (n = 38). All participants underwent routine physical checkups, acute physiology, and chronic health evaluation (APACHE-II) scores. The outcome measure was death during hospitalization; intensive care admission, mechanical ventilation, and length of hospitalization. We analyzed the ability of each parameter to predict mortality in participants. Further, we also evaluated whether the combination of free triiodothyronine (FT3) level with APACHE-II score could improve the mortality prediction. Results: Thyroid Stimulating Hormone (TSH) was lower than normal range in 56.7% (68/120) of patients with COVID-19. TSH and serum-free triiodothyronine (FT3) were significantly lower in COVID-19 patients than healthy control and non-COVID-19 pneumonia patients. TSH and FT3 were lower in severe COVID-19 with statistical significance (p &lt; 0.001) and both positively correlated with the severity. The free thyroxine (FT4) in COVID-19 patients was not significantly different from the control group. Patients in the lowest FT3 tertile had significantly higher rates of mortality (18/40), mechanical ventilation (24/53.3), and intensive care unit admission (20/44.4). In univariate analyses, FT3 remained the most significant independent predictor of death. Conclusion: The changes in serum TSH and FT3 levels may be important manifestations of COVID-19 courses.FT3 levels can serve as a prognostic tool for disease severity in early presentation of COVID-19.

High Thyroid-Stimulating Hormone and Low Free Triiodothyronine Levels Are Associated with Chronic Kidney Disease in Three Population-Based Studies from Germany.

High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. We used cross-sectional data from 7933 individuals aged 20 to 93 years of the Berlin Aging Study II and the Study of Health in Pomerania to associate serum TSH, fT3, and fT4 levels with eGFR and albuminuria. In multivariable analyses adjusted for confounding, we found inverse non-linear associations of serum TSH levels with eGFR, while serum fT3 levels showed a positive association with eGFR. High as well as low serum fT4 levels were associated with a lower eGFR. Age but not sex modified the association between thyroid hormone levels and eGFR. The inverse associations between serum TSH levels and eGFR were strongest in the youngest age groups, while the positive associations between serum fT3 levels and eGFR were strongest in older individuals. No significant associations between thyroid hormone levels and albuminuria were found. Our results indicate that hypothyroidism might be associated with a reduced kidney function. Thyroid function might be more tightly related to the eGFR than to albuminuria in the general population.