Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype-phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype-phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants.

BACKGROUND: Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed.
UNASSIGNED: We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate).
UNASSIGNED: Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.

Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p\'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%-50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4-5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%-30%, 6K-12K cells per well, and 0.03-1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200 µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7 µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p\'1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.

OBJECTIVE: Adjuvant chemotherapy is often indicated in patients diagnosed with early breast cancer (EBC). Among others, weight gain is one of the observed side effects of both chemotherapy and other cancer treatments; however, the mechanism is not well-described. In this study, we aimed to assess thyroid function before and shortly after the course of chemotherapy for EBC.
METHODS: This is a prospective cohort study of women diagnosed with EBC. The main outcome was the thyroid function and body weight before and after completing chemotherapy. Secondary outcomes were the presence of thyroid autoantibodies and treatment radiation dosage. We included 72 patients treated with adjuvant chemotherapy, whereas 59 patients also received supraclavicular locoregional radiotherapy. Triple-negative breast cancer (BC) patients receiving chemoimmunotherapy were excluded.
RESULTS: After the chemotherapy, we observed an increase in thyroid-stimulating hormone (p = 0.03) and a decrease in free-thyroxine (p = 0.0006), with no significant weight change. The prevalence of autoimmune thyroiditis was low. On average 3 months post-chemo, we found no statistically significant difference in the thyroid function of women treated versus not treated with supraclavicular locoregional radiotherapy.
CONCLUSIONS: Although statistically significant changes in thyroid hormones were observed, this study suggests no obvious clinically significant changes in thyroid function in women with early BC after the course of chemotherapy. The decrease in thyroid function was not related to autoimmunity, non-thyroidal illness, radiotherapy, or high-dose corticosteroids. Further studies with a longer follow-up of thyroid function after adjuvant chemotherapy and supraclavicular locoregional radiotherapy are needed.

UNASSIGNED: SARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase.
UNASSIGNED: This was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups.
UNASSIGNED: A history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism.
UNASSIGNED: COVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

UNASSIGNED: Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier\'s disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy.

Background and Objectives: The thyroid is a key endocrine gland for the regulation of metabolic processes. A body composition analysis (BCA) is a valuable complement to the assessment of body mass index, which is derived only from body weight and height. This cross-sectional retrospective study aimed to investigate the relationships between thyroid volume (TV) and thyroid function parameters, anthropometric measurements, BCA parameters, and the presence of metabolic syndrome (MetS) in adults without clinically overt thyroid disease. Material and Methods: This study involved 45 people (females: 57.8%; MetS: 28.9%) hospitalized for planned diagnostics without signs of acute illness or a deterioration of their health and without thyroid disease, who underwent thyroid ultrasound scans, biochemical tests to assess their thyroid function, MetS assessments, anthropometric measurements, and BCAs using the bioelectrical impedance method. Results: The TV was significantly larger in people with MetS compared to people without MetS. The TV was significantly higher and the serum thyrotropin (TSH) concentration was significantly lower in overweight and obese people than in normal and underweight people. The free triiodothyronine (FT3) serum concentration and TV were correlated with waist circumference and some parameters of the BCA, and the FT3 concentration was also correlated with the body mass index, waist-hip ratio, and waist-height ratio. No significant correlations were found between the FT4 and TSH and the results of the anthropometric and BCA measurements. Conclusions: Even in a population of euthyroid patients without clinically overt thyroid disease, there were some significant relationships between the volume and function of the thyroid gland and the results of their anthropometric parameters, BCAs, and the presence of MetS features.

BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them.
METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis.
RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females.
CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

A description of an acute hospital presentation with severe tachyarrhythmia requiring multiple direct current cardioversions in a 45-year-old male bodybuilder with underlying cardiomyopathy possibly caused by long-term anabolic steroid abuse and more recent thyroxine misuse is described. A review of the literature regarding the above associations was also done. This case report further adds to the literature regarding the harmful effect of androgenic anabolic steroid misuse (with the added effect of thyroxine misuse in this case) on the heart.

Hypothermic patients are rarely encountered in the emergency department (ED), indicating a potentially critical condition requiring immediate attention and diagnosis. Myxedema coma, a severe complication of hypothyroidism, presents as profound hypothermia and demands early recognition and proper treatment. We report the case of a 77-year-old female with no prior medical history of hypothyroidism. She presented to the ED with a one-and-a-half-month history of weakness, hypothermia, decreased mental status, and edema. Laboratory analysis confirmed hypothyroidism, leading to a diagnosis of myxedema coma. Treatment with thyroxine and glucocorticoid supplements resulted in a favorable outcome without complications. In conclusion, myxedema coma should be considered in hypothermic patients with altered mental status, even without a history of hypothyroidism. Prolonged hypothyroidism or acute events like sepsis, cerebrovascular accidents, gastrointestinal bleeding, cold exposure, trauma, or certain medications can precipitate this condition, emphasizing the need for prompt treatment initiation.