Normal Thyroid-stimulating Hormone Research Articles

The importance and prognostic effect of thyroid hormones in patients with transposition of the great arteries

Objectives: Transposition of the great arteries (TGA) is a rare congenital heart disease that occurs in 3 in 10,000 newborns and is rapidly fatal (90%) within one year if left untreated. The prognosis of this pathology changed after introducing an early arterial switch operation (ASO), while the left ventricle could still adapt to systemic high-pressure conditions. Appropriate regulation of thyroid hormones positively impacts metabolism, cardiac function, and postoperative recovery. Therefore, regular thyroid hormone monitoring and thyroid function monitoring of TGA patients may help to improve the health status and prognosis of this group of postoperative patients. Methods: In our study, 127 patients who underwent ASO at our pediatric cardiac surgery clinic between 01.01.2014 and 18.09.2021 were retrospectively analyzed and included. Among the patients, 43% (n=54) were females, and 57% (n=73) were males. Results: The coronary arteries were normal in 89.7% (n=114) and abnormal in 10.3% (n=13) of the patients. Twenty-one of the patients exited, and mortality was calculated to be 16.5%. There were no significant differences in mortality or thyroid stimulating hormone (TSH), free thyroxine (T4), or free triiodothyronine (T3) values (P=0.674, P=0.345, P=0.478). In our study, in which we investigated the effect of thyroid hormone levels on prognosis in neonatal patients with TGA with normal free T3, T4, and TSH values, we found that TSH levels were greater in the group with advanced aortic regurgitation and exitus, although the effect of thyroid hormones on postoperative results was not statistically significant. Conclusions: Congenital hypothyroidism is a common disease with cardiac effects. During the neonatal period, this disease may conceal itself. Careful, expert clinical follow-up and clinical trials are crucial to improve outcomes in the surgical treatment of transposition of the great arteries, a complex congenital heart disease.

Association Between Particulate Matter Exposure and Preterm Birth in Women With Abnormal Preconception Thyrotropin Levels: Large Cohort Study.

Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-μg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.

Epidemiologic changes in thyroid disease.

To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities. Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves' disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease. Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism

Introduction Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. Material and Methods The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. Results There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). Conclusion Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

O-304 Is there any association between thyroid-stimulating hormone (TSH) levels and semen parameters? A retrospective study in a European fertility clinic

Abstract Study question Is there any association between TSH levels and semen parameters considering age, body mass index (BMI), and life style? Summary answer In line with the results of logistic regression, normal TSH values increase the probability of having a higher sperm count. What is known already To date, association between TSH levels, semen parameters and other hormones have not been thoroughly investigated in European andrology labs. However, while andrology guidelines do not support a systematic evaluation of thyroid function, some studies reported that men in infertility clinics have higher risks of presenting thyroid disorders than in the general population. Study design, size, duration Both partners investigated for sterility are routinely checked for TSH in the work up of our clinic. We examined for 2021 – 2023 all 347 male patients (infertile/fertile) with complete records of demographic data, semen analysis and hormone analysis. Patients suffering from azoospermia, genital tract infections, hormonal supplementation or heavy medical treatments (radiotherapy, chemotherapy), as well as those receiving iodine supplements or drugs that could potentially affect testicular or thyroid physiology, were excluded. Participants/materials, setting, methods Age, BMI, smoking and detailed alcohol intake were recorded. A blood sample was taken from each patient in connection with the sperm collection to measure TSH, FSH, LH, prolactin and testosterone levels. Spearman’s correlation coefficients were used to determine correlations among hormones. Statistical analyses were performed using semen parameters as dichotomized using WHO reference values. Men above the reference values for count, concentration and motility were used as comparison subjects in multivariate logistic regression. Main results and the role of chance The analysis explored relationships between age, BMI, smoking, alcohol consumption and semen parameters with TSH hormone levels. The mean age of the participants was 35.8 ±7.43 years and BMI was 27.2 ±4.54 kgm-2. Of all participants, 37% reported being smokers, alcohol consumption was 3% regularly, 35% occasionally, 44% rarely, 18% none. Considering a TSH level (0.4-4 mIU/l) as normal, the prevalence of thyroid dysfunction in the cohort was 0.9% (TSH &amp;lt;0.4) and 1.1% (TSH &amp;gt;4) implying that most patients had normal TSH levels. In this cohort, TSH levels were not found to be significantly affected by age, BMI, smoking or alcohol consumption despite being known as putative confounding factors influencing TSH levels. Among the various hormones evaluated, only one significant positive correlation was found between TSH and Prolactin (r = 0.199, p = 0.0001), while a trend towards a negative correlation between TSH and LH (r=-0.101, p = 0.073) was suggested. Multivariate logistic regression analysis showed, not surprisingly, that age was a factor influencing sperm count, sperm concentration as well as total and progressive sperm motility. Logistic regression also showed that when TSH values were within the normal range, sperm counts were significantly higher (OR:1.302, P = 0.043; CI95%:1.009-1.681). Limitations, reasons for caution Sperm morphology and viability were not recorded. Evaluation of thyroxine (T4) and triiodothyronine (T3) levels could be useful. The crucial role of iodine and the complex relationship between iodine and selenium status (which depends on geographical location) in affecting thyroid function should be taken into account in future studies. Wider implications of the findings Male patients with abnormal TSH levels are not very common in this region. Normal TSH level is associated with a higher sperm count. TSH assessment in infertile couples should be routine in both partners, given the recorded worldwide increase in thyroid dysfunction and iodine deficiency. Trial registration number not applicable

The association of higher thyroid stimulating hormone levels in the normal range with unexplained infertility: A cross-sectional study.

Since thyroid hormones have an essential role in energy production, early development of the human placenta, embryo development, and implantation, abnormalities in thyroid function can significantly affect pregnancy outcomes. The present study aimed to investigate the effect of higher thyroid-stimulating hormone (TSH) levels in the normal range in euthyroid women with unexplained infertility. In this cross-sectional study, we evaluated the data for 300 euthyroid women aged between 18 and 39 yr with normal TSH levels ( 5 mIU/L) referred to Yazd Reproductive Sciences Institute, Yazd, Iran from December 2018-March 2021 in 2 groups: the case group (with unexplained infertility) and the control group (with male factor infertility). Finally, age, body mass index, and serum levels of TSH were extracted from participants' medical records and compared between groups. The mean age and TSH level of participants were 31.52 3.52 yr and 1.24 2.59 mIU/L, respectively. 142 women (47.3%) had TSH 2.5, and 158 women (52.7%) had TSH 2.5 mIU/L. The women with unexplained infertility had significantly higher TSH levels than controls in the same normal range (0.62 vs. 0.64 mIU/L, p 0.001). Although a more significant proportion of women in the case group had TSH levels 2.5 mIU/L, we did not find a significant association between TSH levels and age or body mass index. Women with unexplained infertility have a higher level of serum TSH in the normal range ( 2.5 mIU/L) than the control group. So, the effect of TSH treatment on these women should be considered.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism. Method:A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Real-world derived weight-based levothyroxine doses to achieve optimal thyrotropin target in different degrees of autoimmune hypothyroidism

Abstract Purpose All patients with overt and severe subclinical hypothyroidism (SCH), and some with mild SCH require levothyroxine (L-T4) therapy. The present study aims to report real-world derived weight-based L-T4 doses to achieve optimal–low normal–thyrotropin target in different degrees of autoimmune hypothyroidism. Methods This was a retrospective study of patients with autoimmune hypothyroidism. Inclusion criteria were consistent achievement of optimal TSH target (0.3 to 2.5 µIU/L) using a stable L-T4 dose for at least 6 months. Patients were classified into 4 groups: group 1; mild SCH, group 2; severe SCH, group 3; overt hypothyroidism, and group 4; hypothyroidism with unknown initial TSH and free T4. Weight-based L-T4 doses were calculated for each group. Results Eighty-seven, 95, 75, and 91 patients met the inclusion criteria for groups 1–4, respectively. Weight-based L-T4 dose was the lowest in group 1 (1 ± 0.25 µg/kg/day), was the highest in group 3 (1.4 ± 0.29 µg/kg/day), while in groups 2 (1.2 ± 0.26 µg/kg/day), and 4 (1.2 ± 0.31 µg/kg/day) were not statistically different from each other. There was a significant decrease in weight-based L-T4 dose with increasing body weight categories in groups 1 and 2, and a significant difference between those less than 60 or ≥ 60 years of age in group 3. Conclusion Real-world derived weight-based L-T4 doses to achieve optimal TSH target are 1, 1.2, and 1.4 µg/kg/day for patients with mild, severe SCH, and overt autoimmune hypothyroidism, respectively. Age and body weight subcategories can better fine-tune required doses.

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.

Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Thyroid hormone homeostasis in levothyroxine-treated patients: Findings from ELSA-Brasil.

The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. To assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. The ELSA-Brasil study follows 15,105 adult Brazilians (aged 35 to 74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. Initiation of therapy with LT4 resulted in a 11-19% decrease in TSH, a ∼19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and anti-diabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and, a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least one serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least one serum FT3 below the reference range (<0.23 ng/dL). The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10mU/L, > 10µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5-2.5mU/L, 0.5-2.5µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. Pregnancy outcome showed an average gestational age at delivery of 38.2weeks for hypothyroid women, compared to 40weeks for controls, and average birth weight of 2855.6g versus 3285g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Association of pro-atherogenic risk factors with thyroid-stimulating hormone level in women 25–44 years old

Thyroid hormones play an important role in regulating metabolism. A large body of literature suggests an increased risk of developing metabolic syndrome (MS) in individuals with hypothyroidism, but little data exists on the effects of high-normal levels of thyroid-stimulating hormone (TSH) on metabolism.Material and methods. The study was conducted on a representative sample of people aged 25–44 years (n = 1513, of which 840 were women). The analysis included the results of 343 women. A questionnaire, anthropometric and biochemical study were carried out. Biochemical parameters were analyzed in quartiles of TSH content. Determination of MS was carried out using the criteria of NCEP ATP III (2001), IDF (2005), VNOK (2009).Results. TSH content in the examined sample was 1.5 [1.0; 2.2] mU/l (median [lower quartile; upper quartile]). Among women 25–44 years old, women with highly normal TSH level (3.1 [2.7, 3.8] mU/l) have less favorable metabolic parameters. MS was detected in 31 % cases, with a predominant increase in the frequency of abdominal obesity – in 51 %, with increased triglyceride levels in 18 %. Women with hypertriglyceridemia had higher TSH content than those with normal triglyceride levels (2.4 ± 1.6 vs. 1.8 ± 1.3 mU/L, respectively, p = 0.007).Conclusions. In women 25–44 years of age, high-normal TSH content is more often associated with metabolic unhealth.

Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study

Background Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.Methods This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.ResultsThis study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.ConclusionsBoth low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study

PurposeThis study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). MethodsAmong patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. ResultsOf 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07–2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42–0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10–3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50–0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60–1.03) or landmark analyses (3-month HR=0.74, 0.51–1.07; 6-month HR=0.91, 0.66–1.24). ConclusionThyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Hypothyroidism among children and adolescents with nephrotic syndrome in Mulago National Referral Hospital, Kampala, Uganda; a cross-sectional study

BackgroundNephrotic syndrome (NS) is the commonest glomerular disease among children. It is characterized by heavy proteinuria and is a risk factor for hypothyroidism in the affected children. Hypothyroidism is of concern because it affects the physical and intellectual development of children and adolescents. This study sought to establish the prevalence and factors associated with hypothyroidism among children and adolescents with NS.MethodsA cross-sectional design was used to study 70 children and adolescents aged 1–19 years diagnosed with nephrotic syndrome and being followed up in the kidney clinic in Mulago National Referral Hospital. Questionnaires were used to collect patients’ socio-demographics and clinical information. A blood sample was taken for analysis for thyroid stimulating hormone (TSH) and free thyroxine (FT4), renal function tests and serum albumin. Hypothyroidism included both overt and subclinical forms. Overt hypothyroidism was defined as TSH level > 10 mU/L and FT4 < 10pmol/L, or FT4 < 10pmol/l with normal TSH, or TSH < 0.5mU/l. Sub-clinical hypothyroidism was defined as TSH ranging between 5 and10 mU/L with normal age appropriate FT4 levels. Urine samples were collected and taken for a dipstick examination. The data was analyzed using STATA version 14. The Bayesian Logistic regression analysis approach was used to estimate odds ratios (OR) and their associated 95% credible intervals. All predictor variables with p value < 0.05 at frequentist statistical analysis were considered significant.ResultsThe mean age (standard deviation) of participants was 9 years (3.8). There were more males; 36 of 70 (51.4%). The prevalence of hypothyroidism was 23% (16/70 participants). Of the 16 children with hypothyroidism, 3 (18.7%) had overt hypothyroidism while 13 had subclinical hypothyroidism. Only low serum albumin was found to be strongly associated with hypothyroidism; Bayesian OR 132.57 (CI 9.13–567.10) with a frequentist OR of 37 and a p value of 0.001.ConclusionThe prevalence of hypothyroidism among children and adolescent with nephrotic syndrome attending Mulago Hospital paediatric kidney clinic was 23%. Hypoalbuminemia was found to be associated with hypothyroidism. Therefore, children and adolescents that have severely low levels of serum albumin should be screened for hypothyroidism and linked to endocrinologists for care.

A286 MYO5B MUTATIONS AS A CAUSE OF CHOLESTASIS IN A CHILD WITHOUT MICROVILLOUS INCLUSION DISEASE

Abstract Background Biallelic Myosin Vb (MYO5B) mutations are identified in the majority of patients with microvillus inclusion disease (MVID) that requires life-long parenteral nutrition and eventually cholestatic liver disease. Biallelic MYO5B mutations have also been reported in a few children with predominant early-onset cholestatic liver disease. Aims To report on a patient with MYO5B mutations and progressive familial intrahepatic cholestasis PFIC-like phenotype and normal serum GGT without intestinal disease. Methods We describe a 2-year and 8-month-old girl, who is the first child of healthy non- consanguineous parents from the Phillipines with no family history of liver disease. She presented at the age of 10 months for evaluation of mild jaundice, which was noticed at the age of 6 months. Other symptoms included pruritus, slowly weight gain, intermittent pale stools and dark urine. Laboratory investigations revealed AST 99, ALT 87, GGT 27, conjugated bilirubin 13 and INR 0.8. Fasting abdominal ultrasound was normal apart from a possibly hypoplastic gallbladder and mild splenomegaly. Additional investigations revealed normal thyroid-stimulating hormone, cortisol, galactosemia screening and sweat chloride, but bile acids were elevated 391.6 umol/L. A liver biopsy was performed and a cholestasis genetic panel sent. The patient was started on ursodiol, hydroxyzine, rifampicin and vitamin D. Results Liver biopsy revealed moderate hepato-canalicular cholestasis, bile duct injury without prominent ductopenia, small caliber bile ducts with no features of obstructive cholangiopathy, mild periportal and pericentral fibrosis stage 1-2/ 4. Electron microscopy demonstrated cytoplasmic and canalicular bile accumulation. The bile canaliculi were variably distended by coarse granular bile. Immunohistochemical staining for BSEP and MDR3, showed canalicular staining in zones 1 and absence of staining in zones 2 and 3. Genetic analysis revealed one pathogenic variant and one variant of uncertain significance in MYO5B. No mutations in ABCB11 or ATP8B1 genes were identified. On follow-up, the jaundice improved, pruritus was managed with the medications described above. Her growth has improved and she is growing on the 25th centiles. She has not developed any gastrointestinal symptoms. Conclusions We present a patient with MYO5B mutations who presented with normal GGT cholestasis and a liver biopsy consistent with PFIC, without any evidence of intestinal disease. Because MYO5B mutations disrupt the intracellular trafficking of brush border proteins in the intestine, it has been assumed that it similarly disrupts the trafficking of the canalicular bile acid transporting and bilirubin transporting proteins in the liver. This case highlights the broad phenotype associated with MYO5B variants. Funding Agencies None

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers.

Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH. In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively. Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG (<median, OR: 2.1, 95% CI: 1.40-3.16), obesity (BMI > 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation. Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

Hypothyroxinemia and weight velocity in preterm infants.

Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA. Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children's Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity. In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA. We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Retracting the thyroid matters: Who develops asymptomatic transient thyrotoxicosis after parathyroidectomy

BackgroundHyperthyroidism after parathyroidectomy is not a well-understood complication. We sought to determine the incidence and risk factors of hyperthyroidism after parathyroidectomy. Materials and methodsThis is a prospective study of 91 patients undergoing parathyroidectomy. Pre- and post-operative thyroid-stimulating hormone(TSH) and free thyroxine(T4) levels at two-week follow-ups were collected. Bivariate analyses were conducted to compare demographics, laboratory results, and intraoperative findings between patients with normal and suppressed post-parathyroidectomy TSH. ResultsTwenty-two(24.2 ​%) patients had suppressed TSH after parathyroidectomy and 2(2.2 ​%) reported symptoms of hyperthyroidism. All hyperthyroidism resolved within 6 weeks. No patients required medical treatment. Compared to the normal TSH group, the suppressed TSH group had significantly more bilateral explorations(91.0 ​% vs. 58.0 ​%, p ​= ​0.006), and superior parathyroid resections(95.5 ​% vs. 65.2 ​%, p ​= ​0.006). ConclusionTransient hyperthyroidism is common following parathyroidectomy, which is likely associated with intraoperative thyroid manipulation. Gentle retraction of thyroid glands in parathyroidectomy is warranted, especially during superior parathyroid gland resection.