[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

GENDER DIFFERENCES IN THYROIDECTOMY-INDUCED WEIGHT LOSS AND IMPAIRED GLUCOSE LEVELS: ROLE OF L-THYROXINE.

Thyroxine, a key regulator of metabolic pathways, plays a pivotal role in glucose metabolism and the maintenance of glucose homeostasis. In clinical practice, L-thyroxine replacement therapy is commonly prescribed for patients with hypothyroidism. However, the specific effects of L-thyroxine and thyroidectomy (TX) on glucose levels remain an area of interest and investigation. In this study, 20 rats were divided into two groups (n=10 per group). The TX group (male and female rats) underwent thyroidectomy for 4 weeks. After 4 weeks, male and female thyroidectomized rats received L-thyroxine (10 µg/100 g/day, intraperitoneally) for 4 weeks. The rats' weights were monitored weekly post-surgery. Compared to the initial level, thyroidectomy resulted in weight loss, whereas L-thyroxine replacement therapy normalized the weight loss induced by thyroidectomy. Additionally, thyroidectomy led to impaired glucose levels, which were restored to normal levels with L-thyroxine treatment. These findings underscore the impact of thyroid function on glucose metabolism and highlight the potential therapeutic role of L-thyroxine.

The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Overall, sex-and race/ethnicity-specific prevalence of thyroid dysfunction in US adolescents aged 12-18 years.

Background: Thyroid dysfunction significantly affects the health and development of adolescents. However, comprehensive studies on its prevalence and characteristics in US adolescents are lacking. Methods: We investigated the prevalence of thyroid dysfunction in US adolescents aged 12-18 years using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and 2007-2012 cycles. Thyroid dysfunction was assessed using serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) measurements. We analyzed the prevalence across demographic subgroups and identified associated risk factors. Results: The study included 2,182 participants, representing an estimated 12.97 million adolescents. The group had a weighted mean age of 15.1 ± 0.06 years, with males constituting 51.4%. Subclinical hyperthyroidism emerged as the most prevalent thyroid dysfunction, affecting 4.4% of the population. From 2001-2002 to 2011-2012, subclinical hyperthyroidism remained consistent at 4.99% vs. 5.13% in the overall cohort. Subclinical and overt hypothyroidism was found in 0.41 and 1.03% of adolescents respectively, and overt hyperthyroidism was rare (0.04%). The prevalence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in the overall population were 5.8 and 9.8%, respectively. Positivity for TgAb was risk factors for hypothyroidism, while older age, female and Black Americans were risk factors for hyperthyroidism. Female adolescents and adolescents with an older age were more likely to be positive for TPOAb and TgAb, while Black and Mexican Americans had a lower risk of TPOAb and TgAb positivity. Conclusion: Subclinical hyperthyroidism was the most common form of thyroid dysfunction, and its prevalence remained stable from 2001-2002 to 2011-2012. Notable disparities in the prevalence of hyperthyroidism and antibody positivity were observed among different age, sex and racial/ethnic groups.

Evaluation of the value of combined thyroid function-related indexes in the prognosis prediction of patients with differentiated thyroid cancer.

This study aims to evaluate the prognostic significance of thyroid function-related indices in patients with differentiated thyroid cancer (DTC). This retrospective analysis included 90 patients diagnosed with DTC and treated at our hospital from January 2010 to January 2019. Patients were classified into 2 groups based on whole-body imaging results: 67 with a favorable prognosis and 23 with a poor prognosis. The study compared clinical data and thyroid function indices between these groups to assess their efficacy in prognostic prediction. Patients in the poor prognosis group had a higher occurrence of T3-4 stage cancer (P = .006) and ≥2 lymph node metastases (P = .019). Notably, levels of total thyroxine (TT4), thyroid-stimulating hormone (TSH), and thyroglobulin antibody (Tg-Ab) were significantly elevated in this group (P < .001 for each). Receiver operating characteristic analysis revealed substantial predictive accuracy for TT4, TSH, and Tg-Ab (area under curve of 0.747, 0.820, and 0.720, respectively). The columnar graphical model used for prediction demonstrated a high concordance index (C-index = 0.919), superior to single-indicator evaluations. Thyroid function indices, specifically TT4, TSH, and Tg-Ab, play a crucial role in the prognostic assessment of patients with DTC. The column-line diagram model effectively enhances prophetic prediction, aiding in clinical decision-making.

Pericardial Effusion as a Complication of Severe Primary Hypothyroidism.

Large pericardial effusions with associated cardiac tamponade are a rare manifestation of hypothyroidism. We present the case of a 63-year-old female with chronic heart failure and newly diagnosed hypothyroidism, who presented to her primary care physician complaining of progressively worsening dyspnea. Chest radiography showed cardiomegaly and transthoracic echocardiography (TTE) revealed a large pericardial effusion with tamponade physiology. An emergent pericardial window was performed, resulting in an improvement in left ventricular systolic function. Pericardial tissue biopsy was normal. Thyroid function tests were consistent with severe primary hypothyroidism. After inpatient treatment with intravenous levothyroxine and interval resolution of symptoms without recurrence of effusion, the patient was discharged home on oral levothyroxine therapy. Close follow up with surveillance echocardiography was planned. While metabolic disorders are seldom thought of as an etiology, it is imperative for clinicians to recognize hypothyroidism as a cause of the pericardial effusion. It is one of the few reversible causes and delay in treatment can result in fatal sequelae.

Moderation of thyroid hormones for the relationship between amyloid and tau pathology.

BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

Association between thyroid hormone resistance and obesity: a cross-sectional study and mouse stimulation test.

OBJECTIVE: Thyroid hormone influences key metabolic pathways, and reduced sensitivity to thyroid hormone is considered a new risk factor for adverse metabolic outcomes. However, the association between thyroid hormone resistance and obesity in euthyroid individuals is still unknown. METHODS: We enrolled 8021 euthyroid individuals, calculated thyroid hormone resistance indices, and analyzed the association between thyroid hormone resistance and obesity by regression analysis. Furthermore, we conducted the thyrotropin-releasing hormone stimulation test in both control and obese mice (n = 5) to demonstrate the association. RESULTS: The euthyroid adults with overweight and obesity had increased thyroid hormone resistance indices (all p < 0.05). BMI and prevalence of overweight and obesity increased (odds ratio of thyroid feedback quantile-based index [ORTFQI] = 1.164, p = 0.036; OR of free triiodothyronine/free thyroxine [ORFT3/FT4] = 1.508, p < 0.001) following the elevation of thyroid hormone resistance indices. Mediation analysis indicated a complete mediation effect (beta coefficient of indirect effect [ßInd]= 6.838, p < 0.001) of metabolic disorders in the relationship. Furthermore, in the mice with obesity, the thyrotropin response to thyrotropin-releasing hormone stimulation (68.33-90.89 pg/mL) was comparatively blunted (p = 0.029). CONCLUSIONS: Euthyroid individuals with obesity exhibit both central and peripheral thyroid hormone resistance, a phenomenon that is more pronounced in individuals with metabolic abnormalities. Thyroid hormone resistance is associated with an increased prevalence of overweight and obesity mediated by metabolic disorders.

Effects of thyroxin and luteinizing hormone releasing hormone on reproductive physiology of Rohu (Labeo rohita): Insights into spawning performance, oocyte maturation, steroidogenesis, and follicular development genes.

As the global aquaculture industry grows, attention is increasingly turning towards assisted reproductive technologies. In this study, we examined the impact of D-Ala6, Pro9-Net-mGnRH (LHRHa: 0.4 mL/kg) and two doses (1 and 10 µg/kg fish) of thyroxin (T4) administered through a single injection on oocyte maturation, spawning performance, sex steroid hormone levels, as well as the expression of genes related to steroidogenesis and follicle development (ZP2, Cyp19a1a and SF-1) in Rohu (Labeo rohita). The study found that untreated female Rohu did not spawn, while those treated with LHRHa and thyroxin ovulated and spawned across a hormonal gradient. The highest spawning success was observed with a thyroxin dosage of 10 µg/kg (no significant change with a dose of 1 µg/kg), and female latency period decreased with increasing dosage. Additionally, females treated with thyroxin exhibited significantly higher fecundity than other experimental groups. Treatment with LHRHa and two doses of thyroxin significantly increased the gonadal somatic index compared to the control and sham groups. Hormonal treatment also led to increased fertilization success, hatching rate, and larval survival. At 12 h post-injection, females treated with thyroxin exhibited a significant decline in estradiol levels and expression of Zp2, Cyp19a1a, and SF-1 compared to other experimental groups. Levels of DHP significantly increased across the hormonal gradient. Histological analyses supported a steroidogenic shift, where oocyte maturation was accelerated by hormone administration, particularly with both doses of thyroxin. In conclusion, the findings suggest that thyroxin is a recommended treatment for assisted reproduction of Rohu due to its ability to induce spawning, increase fecundity and improve larval survival.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study.

BACKGROUND: Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. METHODS: Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. RESULTS: In 9 524 participants (mean age 51.2 ±â€…8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (ß = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (ß = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (ß = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (ß = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline. CONCLUSIONS: An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

Liquid L-T4 therapy in hypothyroid patients with gastric diseases, an observational study.

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 µIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22+/-0.27 µg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 µIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up.

Binding and sensing diverse small molecules using shape-complementary pseudocycles.

We describe an approach for designing high-affinity small molecule-binding proteins poised for downstream sensing. We use deep learning-generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying shapes that depend on the geometry and number of the repeat units. We dock small molecules of interest into the most shape complementary of these pseudocycles, design the interaction surfaces for high binding affinity, and experimentally screen to identify designs with the highest affinity. We obtain binders to four diverse molecules, including the polar and flexible methotrexate and thyroxine. Taking advantage of the modular repeat structure and central binding pockets, we construct chemically induced dimerization systems and low-noise nanopore sensors by splitting designs into domains that reassemble upon ligand addition.

Severe myxedema coma and pericardial effusion in a child with Down syndrome: the importance of adherence to levothyroxine therapy.

BACKGROUND: Myxedema coma is a rare, but life-threatening endocrinological emergency. Myxedema is characterized by altered mental status, and is accompanied by hypotension, bradycardia, hypothermia, bradypnea, hyporeflexia, hyponatremia, and hypoglycemia, all stemming from reduced metabolism due to severe hypothyroidism. Additionally, patients may exhibit signs of low cardiac output, edema in the extremities, peripheral circulatory disturbances, shock, and the development of pericardial and pleural effusions, ultimately leading to confusion and coma. We present a successfully treated case of severe myxedema coma with recurrent pericardial effusion and hypotensive shock. This case is characterized by an unusual clinical presentation and required a distinct treatment strategy highlighting its exceptional rarity. CASE: A 2-year-old boy with Down syndrome presented with recurrent pericardial effusion attributed to medication non-adherence. The critically-ill patient, experiencing a severe cardiogenic shock required mechanical ventilation and inotropic infusions in the pediatric intensive care unit. Elevated thyroid stimulating hormone (TSH), and low free T4 (fT4) and free T3 (fT3) levels prompted consideration of myxedema coma. Upon reviewing the patient's medical history, it was ascertained that he had an ongoing diagnosis of primary hypothyroidism, and exhibited non-adherence to the prescribed treatment regimen and failed to attend scheduled outpatient clinic appointments for follow-up assessments. The treatment plan, devised by the pediatric endocrinology team, included the peroral administration of L-thyroxine (L-T4) at a dose of 50 micrograms per day. After beginning regular oral L-T4 treatment, a gradual improvement in the patient's condition was observed. Notably, by the 15th day of oral therapy, the patient had made a full recovery. Contrary to the recommended intravenous treatment for myxedema coma, this patient was successfully treated with oral levothyroxine, due to the unavailability of the parenteral form in Türkiye. CONCLUSIONS: This case report presents an instance of non-adherence to L-T4 therapy, which subsequently progressed to severe myxedema coma. Changes in neurologic status and hemodynamic instability in a patient with a history of hypothyroidism should raise the concern of nonadherence and, though rare, myxedema coma should be in the differential diagnosis.

Effect of recombinant human thyroid stimulating hormone on radioactive iodine uptake by thyroid carcinoma in dogs.

BACKGROUND: The high doses of radioiodine-131 (131I) and, subsequently, the high radioactive burden for dog and environment warrants optimization of 131I therapy in dogs with thyroid carcinoma (TC). HYPOTHESIS/OBJECTIVES: To evaluate the effect of a revised protocol with recombinant human thyroid stimulating hormone (rhTSH) on tumor radioactive iodine uptake (RAIU) in dogs with TC. ANIMALS: Nine client-owned dogs diagnosed with TC. METHODS: A prospective cross-over study in which tumor RAIU was calculated and compared at 8 hours (8h-RAIU) and 24 hours (24h-RAIU) after injection of radioactive iodine-123 (123I), once with and once without rhTSH (ie, 250 µg, IM, 24 and 12 hours before 123I) in each dog. Simultaneously, serum total thyroxine (TT4) and TSH were measured at baseline (T0), and 6 (T6), 12 (T12), 24 (T24), and 48 hours (T48) after the first rhTSH administration. RESULTS: Tumor RAIU was significantly higher at 24 hours with rhTSH compared to no rhTSH (mean difference = 8.85%, 95% CI of [1.56; 16.14]; P = .03), while this was non-significant at 8 hours (mean difference = 4.54%, 95% CI of [0.35; 8.73]; P = .05). A significant change of serum TT4 (median difference T24 - T0 = 35.86 nmol/L, interquartile range [IQR] = 15.74 nmol/L) and TSH (median difference T24 - T0 = 1.20 ng/mL, IQR = 1.55 ng/mL) concentrations occurred after administration of rhTSH (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Recombinant human TSH could optimize 131I treatment in dogs with TC by increasing tumor RAIU and thus 131I treatment efficacy.

Identification of a novel nonsense SLC16A2 gene mutation in an infant with severe neurologic phenotype: A case report.

RATIONALE: Allan-Herndon-Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism. PATIENT CONCERNS: A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis. DIAGNOSES: AHDS was confirmed. INTERVENTIONS: Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively. OUTCOMES: While improvements were noted in thyroid hormone levels, neurological developmental delays persisted. LESSONS: AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.