Thyroid Disease Research Articles

A comprehensive investigation of biochemical status in patients with telogen effluvium: Analysis of Hb, ferritin, vitamin B12, vitamin D, thyroid function tests, zinc, copper, biotin, and selenium levels.

The etiology of telogen effluvium (TE) includes situations that may cause physiological stress, surgical trauma, inflammatory, infectious, iatrogenic causes, medications and nutritional deficiencies. TE has been associated with iron deficiency, vitamin B12 deficiency and thyroid diseases. In recent years, the use of over-the-counter food supplements containing vitamins and minerals such as biotin, vitamin D, zinc (Zn), copper (Cu) and selenium (Se) has been increasing in TE patients. The aim of this study is to investigate whether there are differences in nutritional status, vitamin and mineral levels by comparing individuals with TE and a control group. This case-control study included 90 female patients diagnosed with chronic telogen effluvium (CTE), and 90 female controls volunteered to participate in the study who consulted for reasons other than TE. Both groups aged 18 and over and applied to dermatology polyclinic between 01.09.2022 and 01.09.2023. A detailed anamnesis was taken from all patients, a hair pull test was performed, and TE was diagnosed after a dermoscopic examination was performed on all areas of the scalp. Then, serum vitamin D, Zn, Cu, Se levels and biotin levels in serum and urine were measured. Hemoglobin (Hb), ferritin, vitamin B12 and thyroid function tests were retrospectively scanned from the hospital database. It was determined that Zn levels were significantly lower in CTE patients than in controls. Se levels were found to be significantly higher in patients than in controls. There was no difference in Hb, ferritin, vitamin B12, thyroid function tests, vitamin D, Cu levels, serum and urine biotin levels between the two groups. Zn, Cu/Zn and Se levels were found to have statistically significant diagnostic performance in predicting the diagnosis of CTE. Cu/Zn ratio and Se value were found to be significant predictors of CTE. This study shows us that nutritional deficiencies are not as common as thought in patients diagnosed with TE. Other causes that may cause TE should be investigated by a detailed anamnesis and a good physical examination. After all, tests for suspected conditions should be performed and individualized treatment options should be created for each patient.

Increased thyroid hormone action alleviates hippocampal damage by down-regulating neuronal type-Ⅰ interferon signaling/necroptosis in diabetes-associated cognitive dysfunction.

Thyroid dysfunction plays an important role in the pathology of diabetes-associated cognitive dysfunction (DACD). However, thyroid hormone (TH) signaling and action changes in DACD brains remain unknown. This study evaluated the alternations in TH signaling and action in the brains of DACD mice, and explored the beneficial effects of levothyroxine (L-T4) treatment. KK-Ay mice, serving as a spontaneous type-2 diabetes mellitus model, underwent intragastric administration of 10 ng/g and 20 ng/g of L-T4 solution or normal saline for 8 weeks. Age-matched C57BL/6J mice were used as normal controls. Cognitive and memory functions were examined through the open field and Morris water maze tests. Hippocampal TH signaling and pathogenic status were evaluated. The potential signaling pathways involved in the neuroprotective action of L-T4 were investigated through RNA sequencing and further verified through quantitative real-time PCR (qPCR), Western blotting (WB), immunofluorescence (IF), and fluorescent multiplex immunohistochemistry (mIHC) in vivo and vitro. The expressions of hippocampal TH transporters (Mct8 and Oatp1c1), Dio2, and TH receptor were up-regulated, while Dio3 as well as the TH positive-regulated genes MBP, Enpp2 and Klf9 were down-regulated in DACD mice. Exogenous L-T4 partially alleviated cognitive and memory dysfunction and restored hippocampal neuronal activity by optimizing TH signaling. RNA sequencing provided insights into the role of type-I interferon (IFN-I) signaling and necroptosis on the amelioration of hippocampal damage following L-T4 treatment. WB and qPCR further confirmed that the levels of key proteins for IFN-I signaling and necroptosis (p-STAT1, p-STAT2, IRF9, ZBP1, p-RIP3, and p-MLKL) were increased, but largely returned following L-T4 administration in vivo and T3 treatment in vitro. IF and mIHC revealed that IRF9 and p-MLKL co-localized in neurons, but not in astrocytes or microglia, of the hippocampus in DACD mice. The diabetes mellitus group had an increased number of IRF9+p-MLKL+NeuN+ cells, which decreased after L-T4 treatment. The elevated IFN-I signaling-mediated necroptosis in HT22 cells was also decreased by T3. We demonstrated abnormal hippocampal TH signaling and action in DACD. Promoting TH action with exogenous L-T4 ameliorated hippocampal impairment through inhibiting IFN-I signaling-induced necroptosis.

Effects and Action Mode of Oleic Acid and Azone on Release and Penetration Process of Levothyroxine Sodium Patches.

In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.

Effects of Insecticide and Herbicides on Thyroid Disturbances in Zebrafish

Thyroid cancer usually begins with thyroid dysfunction and nodules and has become the most common cancer globally, especially in women. Although the causes of thyroid dysfunction are complex, the presence of environmental pollutants, especially certain pesticides as established mutagens, has been widely accepted. Zebrafish (Danio rerio) have similar toxic reactions and signal transduction pathways to humans and are very similar to humans in physiology, development, and metabolic function. Here, the direct toxicity effects and mechanisms of different insecticides and herbicides on zebrafish thyroid functions and indirect toxicity effects originating from thyroid dysfunction were summarized and compared. The overall toxicity of insecticides on the zebrafish thyroid was greater than that of herbicides based on effective concentrations. Penpropathrin and atrazine were more typical thyroid disruptors than other pesticides. Meanwhile, chiral pesticides showed more sophisticated single/combined toxicity effects on both parental and offspring zebrafish. Besides thyroid hormone levels and HPT axis-related gene expression alteration, developmental toxicity, immunotoxicity, and oxidative damage effects were all observed. These data are necessary for understanding the thyroid interference effect of pesticides on humans and for screening for thyroid disruptors in surface water with zebrafish models for the pre-assessment of human health risks and ecological risk control in the future.

ANALISIS PEMERIKSAAN LABORATORIUM PADA PENYAKIT TIROID

Thyroid disease is a health problem that is commonly encountered in society. Disorders of the thyroid gland can cause various serious health conditions. Laboratory tests play an important role in the diagnosis and management of thyroid disease. This study aims to describe various types of laboratory tests used to diagnose thyroid disease. This research uses a literature review method by analyzing data from various sources, such as scientific journals, textbooks and clinical guidelines. The data collection technique in this research is literature study. After the data is collected, the analysis is carried out through three stages such as filtering data, presenting data, and making conclusions. The research findings show that several types of laboratory tests that are usually carried out for thyroid disease are Thyroid Stimulating Hormone (TSH), Thyroid Hormone (T3 and T4), Thyroglobulin (Tg), and Thyroid antibodies. Thyroid laboratory examination is an important tool for diagnosing and monitoring thyroid disease. Interpretation of thyroid laboratory examination results must be carried out taking into account the patient's clinical factors.

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.

Autoimmune Thyroid Disease: An Unusual Cause or Confounder of Vertigo.

Over the last decade, the published literature investigating the association between thyroid function and recurrent or persistent vertigo has become more robust. We present an interesting case of persistent vertigo in a healthy 31-year-old active duty Navy pilot who was restricted from operating single-pilot rotary aircraft because of the severity of her symptoms. During her work-up, she was newly diagnosed with autoimmune thyroid disease and started on thyroid hormone supplementation. Adequately treating her underlying thyroid disease was associated with resolution of dizzy symptoms and she was granted a waiver to return to flying. This case highlights the importance of autoimmune thyroid disease as a less common but important diagnosis to consider in the broad differential for vertigo. This is especially relevant to the military population since dizziness contributes to spatial disorientation for aviators and can be highly debilitating for warfighters. Astutely diagnosing and treating underlying causes of dizziness may allow service members to return to physically demanding and mentally arduous duties, improving overall military readiness.

Use of bidirectional Mendelian randomization to unveil the association of Helicobacter pylori infection and autoimmune thyroid diseases.

Previous observational studies found associations between Helicobacter pylori infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against H. pylori on AITDs using a bidirectional Mendelian randomization (MR). We found that anti-H. pylori outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti-H. pylori OMP. Our analyses indicate the mutual effects of H. pylori infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti-H. pylori OMP with hyperthyroidism and GD, resulting in a vicious circle.

Malignant thyroid lump multi classification by TIRADS using DBA with transfer learning

Thyroid diseases have developed into significant illnesses in recent decades. These diseases affect the thyroid glands and are caused by elevated thyroid hormone levels or infections in the thyroid organs. It is challenging to resolve thyroid diagnosis using conventional parametric and nonparametric statistical techniques since it can be viewed as a classification problem. However, there are certain barriers in the manner of obtaining both efficacy and accuracy in thyroid nodule diagnosis. Deep learning (DL) and machine learning (ML) models have emerged as useful instruments for the diagnosis of sickness in the modern era. For the purpose of diagnosing and classifying thyroid diseases, this research introduces a novel deep belief network (DBF) with transfer learning, known as DBNTL. In this study, the pre-processed image was first pre-processed using a conventional multiresolution bilateral technique, and then it was subjected to a novel segmentation technique called fusion pooling integrated U-net segmentation. The DBN with transfer learning model is used to classify and grade malignant thyroid nodules in compliance with thyroid imaging-reporting-and-data-system (TIRADS) guidelines. In this model, the model's weights are obtained by transfer learning. A major metric for evaluating the efficacy of biological image processing applications, good sensitivity and specificity (97.28 and 97.22, respectively) were obtained for the recommended modes.

High-Performance Metabolic Profiling of High-Risk Thyroid Nodules by ZrMOF Hybrids.

Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.

Association of latent class analysis-derived multimorbidity clusters with adverse health outcomes in patients with multiple long-term conditions: comparative results across three UK cohorts

It remains unclear how to meaningfully classify people living with multimorbidity (multiple long-term conditions (MLTCs)), beyond counting the number of conditions. This paper aims to identify clusters of MLTCs in different age groups and associated risks of adverse health outcomes and service use. Latent class analysis was used to identify MLTCs clusters in different age groups in three cohorts: Secure Anonymised Information Linkage Databank (SAIL) (n=1,825,289), UK Biobank (n=502,363), and the UK Household Longitudinal Study (UKHLS) (n=49,186). Incidence rate ratios (IRR) for MLTC clusters were computed for: all-cause mortality, hospitalisations, and general practice (GP) use over 10 years, using <2 MLTCs as reference. Information on health outcomes and service use were extracted for a ten year follow up period (between 01st Jan 2010 and 31st Dec 2019 for UK Biobank and UKHLS, and between 01st Jan 2011 and 31st Dec 2020 for SAIL). Clustering MLTCs produced largely similar results across different age groups and cohorts. MLTC clusters had distinct associations with health outcomes and service use after accounting for LTC counts, in fully adjusted models. The largest associations with mortality, hospitalisations and GP use in SAIL were observed for the "Pain+" cluster in the age-group 18-36 years (mortality IRR=4.47, hospitalisation IRR=1.84; GP use IRR=2.87) and the "Hypertension, Diabetes & Heart disease" cluster in the age-group 37-54 years (mortality IRR=4.52, hospitalisation IRR=1.53, GP use IRR=2.36). In UK Biobank, the "Cancer, Thyroid disease & Rheumatoid arthritis" cluster in the age group 37-54 years had the largest association with mortality (IRR=2.47). Cardiometabolic clusters across all age groups, pain/mental health clusters in younger groups, and cancer and pulmonary related clusters in older age groups had higher risk for all outcomes. In UKHLS, MLTC clusters were not significantly associated with higher risk of adverse outcomes, except for the hospitalisation in the age-group 18-36 years. Personalising care around MLTC clusters that have higher risk of adverse outcomes may have important implications for practice (in relation to secondary prevention), policy (with allocation of health care resources), and research (intervention development and targeting), for people living with MLTCs. This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.

Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery.

What is causing this patient's urticaria?

This article describes a teenage patient who was referred to a pediatric endocrinologist after her workup for recurring urticaria revealed a suppressed thyroid-stimulating hormone level and positive microsomal thyroid peroxidase antibodies. The patient's laboratory results revealed an autoimmune cause for the urticaria as a result of new-onset autoimmune thyroid disease.

TSHR Gene (rs179247) Polymorphism and Susceptibility to Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Both Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classified as autoimmune thyroid diseases (AITDs). It has been hypothesized that changes in the thyroid-stimulating hormone receptor (TSHR) gene may contribute to the development of these conditions. This study aimed to analyze the correlation between the TSHR rs179247 gene polymorphism and susceptibility to AITD. We conducted a thorough search of the Google Scholar, Scopus, Medline, and Cochrane Library databases up until March 2, 2024, utilizing a combination of relevant keywords. This review examines data on the association between TSHR rs179247 and susceptibility to AITD. Random-effect models were employed to assess the odds ratio (OR), and the findings are presented along with their respective 95% confidence intervals (CIs). The meta-analysis included 12 studies. All genetic models of the TSHR rs179247 gene polymorphism were associated with an increased risk of developing GD. Specifically, the associations were observed in the dominant model (OR, 1.65; P<0.00001), recessive model (OR, 1.65; P<0.00001), as well as for the AA genotype (OR, 2.09; P<0.00001), AG genotype (OR, 1.39; P<0.00001), and A allele (OR, 1.44; P<0.00001). Further regression analysis revealed that these associations were consistent regardless of the country of origin, sample size, age, and sex distribution. However, no association was found between TSHR rs179247 and the risk of HT across all genetic models. This study suggests that the TSHR rs179247 gene polymorphism is associated with an increased risk of GD, but not with HT, and may therefore serve as a potential biomarker.

Thyroid Disease Classification Using Machine Learning Algorithms

Abstract: The thyroid is very important because it helps our body function properly. It does this by secreting special hormones into our bloodstream that control how our body uses energy. Sometimes there may be problems with the thyroid gland secreting too much or too little hormone. This is because not having enough iodine, swelling of the tumor, or the body's immune system attacking the tumor. Doctors can diagnose these problems with blood tests, but sometimes the results may be confusing. Using special technology, doctors can make information easier to understand and detect how a person may have thyroid problems. This analysis includes analysis of the distribution pattern of thyroid disease and data based on the UCI Machine Learning Repository. Detection of thyroid diseases involves machine learning, which plays an vital role in detecting thyroid disease. Using this technique,doctors can better understand and treat thyroid problems.

Study of the association between thyroid dysfunction and serum lipid abnormalities

Study of the association between thyroid dysfunction and serum lipid abnormalities

Evaluation of the Most Important Ultrasound Parameters in Detection of Thyromegaly and its Relationship with Anthropometric Factors

Background: Approximately, 200 million people suffer from thyroid disorders worldwide. Thyromegaly is a disorder in which the thyroid gland becomes abnormally enlarged. High-resolution ultrasound of the thyroid is a useful diagnostic method for assessing thyroid disorders, including thyromegaly. To investigate the thyromegaly, the thyroid lobe dimensions are measured separately using an ultrasound device and, the thyroid volume is estimated using a formula which is time-consuming process. Besides, thyroid volume depends on a variety of factors such as age, sex, anthropometric parameters, and genetic factors. Objectives: The aim of the present study is to find the most important ultrasound parameters measured to increase the rate of thyromegaly detection and also to find the relationship between thyroid volume and some anthropometric characteristics in the study population. Methods: A total of 131 people were referred to the Ultrasound Department of Imam Reza Hospital in Kermanshah, Iran during July 2017 and 2019, and after recording the anthropometric characteristics, thyroid ultrasound was taken. Thyroid dimensions including longitudinal (L) and anterior-posterior or depth (AP), and width (W) diameter of the thyroid lobes and isthmus were measured and thyroid volume was calculated using the ellipsoid formula. According to the opinion of a fellow radiologist and considering cut-off point of volume (11.1 for women and 11.6 for men), individuals were divided into two groups: Case or thyromegaly (n = 69) and control or normal group (n = 62), and statistical analysis was then carried out. Results: Statistical analysis showed that the mean weight, Body Mass Index (BMI), thyroid dimensions, and total thyroid volume were significantly higher in the case group than the control group (P &lt; 0.05). In the case group, only the mean width of the right lobe is significantly larger than the left lobe, while the mean length and depth of the right lobe is significantly larger in the control group than the left lobe. In addition, cut-off point values for the width of right lobe, depth of the right lobe, length of the right lobe, volume of the right lobe, width of the left lobe, depth of the left lobe, length of the left lobe, volume of the left lobe, total volume and isthmus volume were 16.5,15.5, 47.5, 6.45, 15.5, 14.5, 44.5, 5.55, 11.15, and 2.45, respectively based on the best sensitivity and specificity of the receiver operating characteristic (ROC) curve. According to logistic regression, the three factors of width of the right lobe, depth of the right lobe, and length of the right lobe, respectively, were selected as the most important ultrasound parameters in detection of thyromegaly. Thyroid volume was not significantly related with sex, age, and height, but it was directly and significantly related with weight and BMI. Conclusions: Considering the increasing use of ultrasound in detection of thyroid disease and its acceptable accuracy in determining the thyroid volume, the radiologists need to first know the normal thyroid volume and the effect of physiological variables (such as age, sex, body weight, and BMI) on the thyroid volume in their community so that they can distinguish pathological cases from normal ones. Also, the three factors of width of the right lobe, depth of the right lobe, and length of the right lobe, respectively, were determined as the most important factors in detection of thyromegaly. Thyroid volume was not significantly related with sex, age, and height, but it was directly and significantly related with weight and BMI.

The Role of Nutrition on Thyroid Function

Thyroid function is closely linked to nutrition through the diet–gut–thyroid axis. This narrative review highlights the influence of nutritional components and micronutrients on thyroid development and function, as well as on the gut microbiota. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 influence thyroid hormone synthesis and regulation throughout life. Dietary changes can alter the gut microbiota, leading not just to dysbiosis and micronutrient deficiency but also to changes in thyroid function through immunological regulation, nutrient absorption, and epigenetic changes. Nutritional imbalance can lead to thyroid dysfunction and/or disorders, such as hypothyroidism and hyperthyroidism, and possibly contribute to autoimmune thyroid diseases and thyroid cancer, yet controversial issues. Understanding these relationships is important to rationalize a balanced diet rich in essential micronutrients for maintaining thyroid health and preventing thyroid-related diseases. The synthetic comprehensive overview of current knowledge shows the importance of micronutrients and gut microbiota for thyroid function and uncovers potential gaps that require further investigation.

Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis.

Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals. We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals. The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability. We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Thyroid scintigraphy: establishing a clinically useful normal range for 99mTc pertechnetate uptake.

This study aims to establish a normal range for the thyroid uptake derived from 99mTc pertechnetate scans. In particular, variations of uptake with TSH stimulation and other factors such as urinary iodine concentration are taken into account and compared with the calculation of a raw uptake value. Clinical multicentric (center A, B and C) prospective study on 125 consecutive healthy patients undergoing thyroid scans for thyroid nodules. Normal functional thyroid status was assured by normal TSH, normal thyroid size, no thyroid antibodies and no symptoms of thyroid functional disorders. Calculations of raw Tc-uptake (uptake) and modified uptake values regarding current TSH value (uptakeTSH1), urinary iodine concentration (uptakeTSH1&uic), gland volume, age, smoking status, weight and tissue thickness ventral to the thyroid were performed. There is a positive correlation of thyroid uptake with TSH allowing for the calculation of a normalized uptake value (uptakeTSH1). The normal range for uptakeTSH1 compares favourable to that for raw uptake in that it yields a clear distinction from thyroid functional disorders. The additional normalization for urinary iodine concentration (uptakeTSH1&uic) may even improve the distinctive power whereas further normalizations such as for gland volume, age and others are not warranted by this study. The 95% CI of uptakeTSH1 for sites A, A&B, and A&B&C were 0.21%-2.06%, 0.22%-2.38% and 0.24%-2.40%. A normal range for the thyroid uptake can be established with respect to the current TSH stimulation. This normalization (uptakeTSH1) overcomes the drawback of raw uptake by yielding a clinically useful parameter with obviously high distinctive power against functional thyroid disorders.