Thyroid Hormone Secretion Research Articles

Genetic Analyses in a Cohort of Pediatric Patients with Congenital Hypothyroidism Based on Congenital Hypothyroidism Consensus Guideline

Introduction: Pathogenic variants in the genes involved in the formation of thyroid tissue and thyroid hormone secretion have been reported to cause congenital hypothyroidism (CH) in some cases. This study aimed to evaluate the clinical and genetic findings of CH cases thought to be due to genetic variants. Methods: The study included cases whose genetic analysis was performed in accordance with the Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update Guidelines recommendations criteria and analyzed them using the next-generation sequencing panel. Results: Sixty one Turkish patients from 45 families were included in the study. The overall frequency of variant detection was 37.7% (out of 45 families, 17 had a positive mutation). Segregation was carried out for all families with positive variants. Variants in the TPO gene are the most frequently encountered, and this situation was identified in 10 families. Variants followed this in the TSHR gene in 7 families, variants in the DUOX2 gene in 5 families, and two variants in the TG and NKX2-1 genes in 2 families each, which are six novel variants. Furthermore, among the NKX2-1 cases, one had thyroid involvement only, while the other had chorea only. We did not find differences between cases with detected mutations and mutation-negative cases regarding gender, neonatal/perinatal parameters, initial thyroid function values, and thyroid morphology. Conclusion: In the current investigation, rare new variations in genes known to be related to CH were discovered, adding to the molecular genetic spectrum. When we compare the overall variant detection frequency, the selection criterion for genetic analysis based on the current guidelines is quite rational, considering the benefits and costs, on the other hand, present in new genes awaiting discovery. Also, TSHR mutations are likely to be common and may account for more than 5% of thyroid dysgenesis cases if we include nonfamilial thyroid dysgenesis.

6770 Graves’ disease induced by COVID-19 infection in a 49 year old male

Abstract Disclosure: N. Al-hosainat: None. A. Al Najada: None. T. Salar: None. S. Iqbal: None. K. Abdel Gadir: None. Introduction: Graves’ disease is an autoimmune disease causing hyperthyroidism, characterized by elevated thyrotropin-receptor antibodies. COVID-19 infection has been increasingly reported as a trigger of thyroid illness including Graves’ disease. We present a unique case of 49-year-old patient who was diagnosed with Graves’ disease after COVID-19 infection. Case description: A 49-year-old male patient with history of prediabetes presented with complaints of tremor, fatigue, generalized itching, and unintentional weight loss (30 Ibs in 6 months). He had COVID-19 infection 3 months prior. The remainder of review of systems was negative. No family history of thyroid disease. On exam, the patient had sinus tachycardia with otherwise normal vital signs. Diffuse thyromegaly was noted along with an intermittent fine tremor of the extremities. Blood work was notable for low TSH <0.01 uIU/mL, elevated free T4 (3.4 ng/dL), free T3 (17.6ng/dL), and TSH receptor antibody (12 IU/L). Thyroid ultrasound showed mild goiter with 2 nodules, one of which was TIRADS 4 and 1.5cm. This nodule was biopsied and found to be benign. Radioactive iodine uptake scan revealed homogeneous diffuse increased thyroid uptake. The diagnosis of Graves’ disease was made, and the patient was started on propranolol and methimazole with significant improvement of his symptoms and his laboratory tests normalizing. Discussion: Graves' disease is an autoimmune disease, characterized by hyperthyroidism, goiter, occasional orbitopathy and dermopathy. Caused by antibodies against thyroid-stimulating hormone receptors which stimulate thyroid hormone secretion and thyroid growth. Treatment is aimed to decrease thyroid hormone synthesis by either a Thionamide, radioiodine ablation, or surgery. Remission rates with antithyroid drugs average under 40 percent after one to two years of treatment and could exceed 80 percent after 5 to 10 years of treatment. COVID-19 is a multi-system disease, caused by SARS-CoV-2 virus, transmitted by large droplets and small particle aerosols, was declared a pandemic in 2020 and affected millions of people worldwide. There is emerging data showing the association of COVID-19 with various thyroid diseases including thyroiditis and relapse of known Graves' disease after the infection. We present a case of newly diagnosed Graves’ disease after COVID-19 infection in a patient with no personal or family history of such disease which raises the concern of autoimmune pathway activation induced by the infection. The onset of Graves’ disease after COVID-19 infection does not depend on the presence of pre-existing thyroid pathology and in this case responded well to antithyroid medication. Conclusion: COVID-19 can lead to the development of a range of medical illnesses. In patients who develop symptoms of thyrotoxicosis, Graves’ disease should be suspected, investigated, and treated appropriately Presentation: 6/3/2024

Histological study to the thyrotoxicity between men and women of AL- Ramadi city

Thyrotoxicosis is the clinical manifestation of excess thyroid hormone action at the tissue level due to inappropriate high circulating thyroid hormone concentrations. Hyperthyroidism, a subset of thyrotoxicosis, refers specifically to excess thyroid hormone synthesis and secretion by the thyroid gland. This study aims to show the difference between men and women affected with thyrotoxicity in different ages and the histological changes with hormonal evaluation. This study was done using 50 patients with hyperthyroidism (25 women and 25 men). Patients have been taken from Arrazzi private hospital and Al- Ramadi hospital. Hormonal testes (TSH, T3, T4) was collected and recorded. Information of patents like name, age and gender was recorded. The pathological samples of thyroidectomy were collected after operation and saved in 10% formalin for Histopathological studies. A significant (p< 0.05) increases in thyroid hormone (T3 and T 4) in women was observed as compared to men. Slides showed a diffuse area of hemorrhage and diffuse inter follicular lympho-neutrophilic infiltration was seen in the tissue. The results of the study reflected that the incidence of thyrotoxicity was more effective in women than men.

The Impact of Exposure to Iodine and Fluorine in Drinking Water on Thyroid Health and Intelligence in School-Age Children: A Cross-Sectional Investigation.

Iodine and fluorine, as halogen elements, are often coexisting in water environments, with nearly 200 million people suffering from fluorosis globally, and, in 11 countries and territories, adolescents have iodine intakes higher than that required for the prevention of iodine deficiency disorders. It has been suggested that excess iodine and/or fluorine can affect thyroid health and intellectual development, especially in children, but their combined effect has been less studied in this population. This study investigated 399 school-age children in Tianjin, China, collected drinking water samples from areas where the school-age children lived, and grouped the respondents according to iodine and fluorine levels. Thyroid health was measured using thyroid hormone levels, thyroid volume, and the presence of thyroid nodules; intelligence quotient (IQ) was assessed using the Raven's Progressive Matrices (CRT) test; and monoamine neurotransmitter levels were used to explore the potential relationship between thyroid health and intelligence. Multiple linear regression and restricted cubic spline (RCS) analyses showed that iodine and fluorine were positively correlated with thyroid volume and the incidence of thyroid nodules in school-age children, and negatively correlated with IQ; similar results were obtained in the secondary subgroups based on urinary iodine and urinary fluoride levels. Interaction analyses revealed a synergistic effect of iodine and fluorine. A pathway analysis showed that iodine and fluorine were negatively associated with the secretion of free triiodothyronine (FT3) and free tetraiodothyronine (FT4), which in turn were negatively associated with the secretion of thyroid-stimulating hormone (TSH). Iodine and fluorine may affect IQ in school-aged children through the above pathways that affect thyroid hormone secretion; of these, FT3 and TSH were negatively correlated with IQ, whereas FT4 was positively correlated with IQ. The relationship between thyroid hormones and monoamine neurotransmitters may involve the hypothalamic-pituitary-thyroid axis, with FT4 hormone concentrations positively correlating with dopamine (DA), norepinephrine (NE), and 5-hydroxytryptophan (5-HT) concentrations, and FT3 hormone concentrations positively correlating with DA concentrations. Monoamine neurotransmitters may play a mediating role in the effects of iodine and fluoride on intelligence in schoolchildren. However, this study has some limitations, as the data were derived from a cross-sectional study in Tianjin, China, and no attention was paid to the reciprocal effects of iodine and fluorine at different doses on thyroid health and intelligence in schoolchildren in other regions.

The association between serum soluble α-Klotho and thyroid profile among adults from NHANES 2007–2012

BackgroundThyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize.ObjectiveTo determine the relationship between α-Klotho and thyroid profile in adult individuals.MethodsPopulation data of 4614 adult individuals were obtained from the NHANES database during the period of 2007–2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis.Resultsα-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4.ConclusionsSerum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion.

The Multifunctional Role of KCNE2: From Cardiac Arrhythmia to Multisystem Disorders.

The KCNE2 protein is encoded by the kcne2 gene and is a member of the KCNE protein family, also known as the MinK-related protein 1 (MiRP1). It is mostly present in the epicardium of the heart and gastric mucosa, and it is also found in the thyroid, pancreatic islets, liver and lung, among other locations, to a lesser extent. It is involved in numerous physiological processes because of its ubiquitous expression and partnering promiscuity, including the modulation of voltage-dependent potassium and calcium channels involved in cardiac action potential repolarization, and regulation of secretory processes in multiple epithelia, such as gastric acid secretion, thyroid hormone synthesis, generation and secretion of cerebrospinal fluid. Mutations in the KCNE2 gene or aberrant expression of the protein may play a critical role in cardiovascular, neurological, metabolic and multisystem disorders. This article provides an overview of the advancements made in understanding the physiological functions in organismal homeostasis and the pathophysiological consequences of KCNE2 in multisystem diseases.

Artemisinin ameliorates thyroid function and complications in adult male hypothyroid rats via upregulation of the L1 cell adhesion molecule

BackgroundHypothyroidism, a common worldwide syndrome caused by insufficient thyroid hormone secretion, affects number of people at different ages. Artemisinin (ART), a well-known effective agent in the treatment of malaria, also has anti-oxidative stress functions in various diseases. The L1 cell adhesion molecule exerts multiple protective roles in diseased systems. The aim of the present study was to evaluate the role of ART in adult male hypothyroid rats and the underlying mechanisms.MethodsThe propylthiouracil (PTU) rat model was treated with or without 5 mg/kg ART and with or without L1 short-interfering RNA (siRNA), followed by the experiments to determine the effect of ART on thyroid function, depression and anxiety, cognition impairments, liver, kidney and heart functions, and oxidative stress.ResultsIn the current study, it was shown that ART can ameliorate thyroid function, mitigate depression and anxiety symptoms, attenuate cognition impairments, improve liver, kidney and heart functions, and inhibit oxidative stress; however, the effects exerted by ART could not be observed when L1 was silenced by L1 siRNA.ConclusionThese results indicated that ART can upregulate the L1 cell adhesion molecule to ameliorate thyroid function and the complications in adult male hypothyroid rats, laying the foundation for ART to be a novel strategy for the treatment of hypothyroidism.

Patients with Thyroid Dyshormonogenesis and DUOX2 Variants: Molecular and Clinical Description and Genotype-Phenotype Correlation.

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.

Investigating the mechanisms of action of thyroid disruptors: A multimodal approach that integrates in vitro and metabolomic analysis

The thyroid gland, a vital component of the endocrine system, plays a pivotal role in regulating metabolic processes, growth, and development. To better characterize thyroid system disrupting chemicals (TSDC), we followed the next-generation risk assessment approach, which further considers the mechanistic profile of xenobiotics. We combined targeted in vitro testing with untargeted metabolomics. Four known TSDC, propyl-thiouracil (PTU), sodium perchlorate, triclosan, and 5-pregnen-3β-ol-20-one-16α‑carbonitrile (PCN) were investigated using rat in vitro models, including primary hepatocytes, PCCL3 cells, thyroid microsomes, and three-dimensional thyroid follicles. We confirmed each compound's mode of action, PTU inhibited thyroperoxidase activity and thyroid hormones secretion in thyroid cells model, sodium perchlorate induced a NIS-mediated iodide uptake decrease as triclosan to a lesser extent, and PCN activated expression and activity of hepatic enzymes (CYPs and UGTs) involved in thyroid hormones metabolism. In parallel, we characterized intracellular metabolites of interest. We identified disrupted basal metabolic pathways, but also metabolites directly linked to the compound's mode of action as tyrosine derivates for sodium perchlorate and triclosan, bile acids involved in beta-oxidation, and precursors of cytochrome P450 synthesis for PCN. This pilot study has provided metabolomic fingerprinting of dedicated TSDC exposures, which could be used to screen and differentiate specific modes of action.

Immune-regulating effect of oxytocin and its association with the hypothalamic-pituitary axes

Oxytocin can regulate immunological activity directly or indirectly; however, immunological functions and mechanisms of oxytocin actions under chronic stress like cesarean delivery (CD) are poorly understood. Our study found that abnormal oxytocin production and secretion in CD rats caused atrophy of thymic tissues. Neurotoxin kainic acid microinjected into the dorsolateral supraoptic nucleus in male rats selectively reduced hypothalamic oxytocin levels, increased corticotrophin-releasing hormone and plasma interleukin-1β while reducing plasma oxytocin, thyroxine and testosterone levels and causing atrophy of immune tissues. Thus, plasma oxytocin is essential for immunological homeostasis, which involves oxytocin facilitation of thyroid hormone and sex steroid secretion.

A Review On : To Develop and Validate Analytical Method for Determination of Methimazole in Bulk and Pharmaceutical Dosage Form

Hyperthyroidism is a condition characterized by increased in synthesis and secretion of thyroid hormones from thyroid gland. Methimazole is an anti-hyperthyroidism drug. It is of great importance and significance for life science. Up to now, various different methods have been applied for the determination of methimazole, such as spectrophotometry1-3, LC4, HPLC6, RP-HPLC7, HPLC-UV8, electrochemical analysis9, kinetic method10. In this paper, a new UV-Spectrophotometric method for the determination of methimazole has been established. The chemical name of Methimazole is (1-methylimidazole-2-thiol). The chemical formula of Methimazole is C4H6N2S and the molecular weight is 114.17 g/mol. The structure of Methimazole features a 5 membered imidazole ring with a methyl group at position 1st and thione group at position 2nd. Methimazole is white colour powder and has melting point 1440 C.

Thyroid and parathyroid function disorders induced by short-term exposure of microplastics and nanoplastics: Exploration of toxic mechanisms and early warning biomarkers

Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.

Tirotoxicosis e hipertiroidismo

Thyrotoxicosis is a clinical condition secondary to excess thyroid hormones (TH). It can be caused by increased synthesis and release of TH by the thyroid gland (hyperthyroidism, the most common cause) as well as by thyroid inflammation and destruction, ectopic production, or exogenous administration of TH. The diagnosis is biochemical and based on the determination of thyroid stimulating hormone (TSH) and thyroid hormones (thyroxine and triiodothyronine). To plan effective treatment, it is crucial to identify the underlying cause. Graves-Basedow disease is the most common cause, followed by toxic multinodular goiter and toxic thyroid adenoma. Less frequent, although relevant, are thyroiditis, extrathyroidal TH production, and factitious thyrotoxicosis. Some imaging tests, such as a Doppler ultrasound and thyroid scintigraphy, are helpful in the etiological diagnosis. The goal of treatment is to achieve symptoms control and reduce TH synthesis and secretion through the use of drugs or radical treatments (radioiodine or surgery).

CHANGES OF TSH, FT3 AND FT4 LEVELS IN PATIENTS WITH HYPERTHYROIDISM

ntroduction: The thyroid hormone secretion disorders may be hyperthyroidism (reduced TSH levels and increased levels of FT3 and FT4) and subclinical hyperthyroidism (decreased concentration of TSH with normal FT3 and FT4).Aim: To investigate levels of thyroid hormones (TSH, FT3, and FT4) in patients with hyperthyroidism or subclinical hyperthyroidism treated at Tuzla Blue Clinic.Materials and methods:The study included 120 patients divided into three groups: a control group, groups with respondents who have hyperthyroidism, and a group of patients with subclinical hyperthyroidism. The concentrations of the hormones TSH, FT3, and FT4 were analyzed. The determination was carried out on the device IMMULITE 1 Siemens using the immunochemistry method. Results:TSH between our group investigated the existence of significant statistical differences between the control group and the group with hyperthyroidism (p<0.0001) and between the control group and the group withsubclinical hyperthyroidism (p=0.0001), and the parameter FT3 showed that a statistically significant difference exists between the control group and the group with hyperthyroidism (p<0.0001), and between patients with hyperthyroidism andsubclinical hyperthyroidism (p<0.0001). For FT4, we found a statistically significant difference between the control group and the group with hyperthyroidism (p<0.0001) and between groups with hyperthyroidism and subclinical hyperthyroidism (p <0.0001).Conclusions: The concentration of TSH is reduced in both hyperthyroidism and subclinical hyperthyroidism. The serum concentrations of FT3 and FT4 are elevated in hyperthyroidism, while in subclinical hyperthyroidism, the serum concentrations of FT3 and FT4 stand in the reference area.Keywords:Thyrotropin, thyroxine, TSH, FT3, FT4, hyperthyroidism

Pregnancy influences expression of interferon-stimulated genes, progesterone receptor and progesterone-induced blocking factor in ovine thyroid.

Embryonic interferon-tau (IFNT) and progesterone affect expression of interferonstimulated genes (ISGs), progesterone receptor (PGR) and progesterone-induced blocking factor (PIBF) in the ovine thyroid. Thyroids of ewes were sampled at day 16 of nonpregnancy, days 13, 16, and 25 of pregnancy, and real-time quantitative polymerase chain reaction assay, western blot and immunohistochemistry were used to detect expression of ISGs, PGR, and PIBF. Free ISG15 protein was undetected, but ISG15 conjugated proteins upregulated at day 16 of pregnancy, and expression levels of ISG15 conjugated proteins, PGR isoform (70 kDa), PIBF, interferon-gamma-inducible protein 10 and myxovirusresistance protein 1 peaked, but expression level of signal transducer and activator of transcription 1 was the lowest at day 16 of pregnancy. In addition, the expression levels of PGR isoform (70 kDa) and signal transducer and activator of transcription 1 (STAT1) decreased, but levels of PGR isoform (43 kDa), 2',5'-oligoadenylate synthetase, IP-10 and MX1 increased at day 25 of pregnancy comparing with day 16 of the estrous cycle. Early pregnancy affects expression of ISGs, PGR, and PIBF in maternal thyroid through IFNT and progesterone, which may regulate thyroid autoimmunity and thyroid hormone secretion in ewes.

IJCM_145A: A Clinico-Epidemiological Profile of Patients with Thyroid Disorders Admitted to Tertiary Care Hospitals in Mangalore

Background: Thyroid ailments are frequently encountered endocrine disorders next to diabetes. They arise either due to functional aberrations of the thyroid gland resulting in over or under secretion of thyroid hormone or due to structural anomalies. People have varied constitutional, non-specific manifestations that cause abnormal metabolic functioning of the thyroid gland. Objectives: 1. To describe the socio-demographic characteristics of patients with thyroid disorders. 2. To analyze the clinical features, laboratory findings, and clinical outcomes of these patients. Methodology: This hospital-based descriptive study was conducted at the Government Wenlock Hospital in Mangalore. The study included patients admitted with thyroid disorders in the last 2 years. Data extraction sheet was developed from patient medical records. The sheet comprised three sections: socio-demographic information, clinical features at admission, and investigations and outcomes. Results: Most of the patients (52.8%) belonged to the 20-40 age group, followed by 30.5% in the 40-60 age group. Females comprised 81.5% of the study population, males -18.5%. 74.8% had swelling, 3.2% had facial puffiness. 1.8% had weight gain, only 1.2% had weight loss .16.3% had other comorbid conditions. 31.5% had low TSH levels 49.3% had normal TSH levels, 64.5 % - normal T3 levels, 63.2% - normal T4 levels. Anaemia was reported in 15.2% o, while 7.2% developed oedema. 34.2% had multinodular goitre, 20.2% - hypothyroidism 9.5 % - hyperthyroidism and 11.1% - malignancy. Out of the total 97% recovered 1% died 1% had discharge against medical advice and 1 % got discharged on request. Conclusion: Majority were females in the 20-40 age group. Majority of them had swelling followed by facial puffiness. Most of them had normal TSH, T3 and T4 levels, anaemia and oedema was also reported in few. Majority had multinodular goitre followed by hypothyroidism, malignancy, and hyperthyroidism. Majority had recovered.

К вопросу о тиреоидной функции щитовидной железы беременных, проживающих в йододефицитном районе (Республика Дагестан, Ахтынский район, 1675 м над уровнем моря)

The work shows that currently diseases associated with iodine deficiency in the diet are one of the most common non-communicable human diseases. Iodine deficiency contributes to a decrease in the synthesis and secretion of thyroid hormones, during pregnancy leads to the formation of the neuropsychiatric status of the fetus. Thyroid pathology is more common in women than in men. During pregnancy, thyroid pathology increases dramatically – pregnancy itself is a provoking factor. One of the important reasons is the deterioration of the environmental and radiation situation, the changing nature of the population's diet. The impact of the ecosystem on the health of the population can be determined based on data on the incidence of thyroid diseases in women of reproductive age in rural areas with iodine deficiency. The article presents data on the examination and treatment of 120 pregnant women (First Trimester of pregnancy) aged 20–40 years who are registered in the women's clinic of the Akhtyn regional hospital.

Association of stress and primary hypothyroidism.

Hypothyroidism is the result of impaired production and secretion of thyroid hormones. The cardiovascular system is affected by fluctuations in thyroid hormone levels. Stressful events or stressors can affect the hypothalamic-pituitary-thyroid (HPT) axis and psychological and physiological responses. Stress increases thyroid hormone levels while decreasing TSH levels, which exacerbates autoimmune thyroid disease. To evaluate the relationship between stress and primary hypothyroidism. A total of 77 newly diagnosed hypothyroid patients (TSH >5.0 mIU/L) and 77 healthy adults (TSH 0.5-5.0 mIU/L) were enrolled. During a brief general physical examination, the following values were measured: height, weight, blood pressure, pulse, and pulse rate. A brief systemic examination of the cardiovascular system and lungs was also performed to rule out systemic diseases. Heart rate variability (HRV) processing and analysis were performed using Pro LabChart (PowerLab 8Pro) data analysis software from AD Instrument. Mean Avg. RR was significantly higher, RM SSD and pRR50 were significantly lower in cases than in controls. Mean HF was significantly lower and LF/HF (frequency range) was significantly higher in cases than in controls. Mean PSS was significantly higher in cases (25.82 ± 2.83) than in controls (22.47 ± 2.10). The majority of cases (54.5%) had a high stress level. The TSH level showed a highly significant correlation with the LF/HF ratio and with the PSS score. The mean Avg. RR and HF were significantly higher, RM SSD and pRR50 and LF/HF (frequency range) were significantly lower in hypothyroid patients.

Resistance to thyroid hormone and nonfunctioning pituitary microadenoma in a 13-year-old boy with THRB mutation.

Resistance to thyroid hormone (RTH) is a rare syndrome characterized by elevated serum free iodothyronines levels and non-suppressed thyroid stimulating hormones (TSH). The most common cause of RTH is heterozygous pathogenic mutations in thyroid hormone receptor β gene (THRB). Because of the similarities in biochemical profiles, differential diagnosis between RTHβ and TSH-secreting pituitary adenoma (TSHoma) is important, and accurate RTHβ diagnosis is essential to prevent inappropriate treatment. A 13-year-old boy was referred to our hospital for a microadenoma and uncontrolled hyperthyroidism despite use of methimazole for more than one year. He suffered from thyrotoxic clinical features and elevated serum T3 and fT4, and normal ranges for TSH and other pituitary hormones were noted. TSH receptor antibody was undetectable, and pituitary MRI revealed a 3mm-sized microadenoma. A TRH stimulation test showed normal TSH response, and the TSH-α-subunit level was not elevated, which is consistent with RTH. The patient was diagnosed with RTHβ and coexistent non-functioning pituitary microadenoma based on identification of a heterozygous mutation, c.1021C>G (p.Leu341Val), in THRB. Methimazole treatment was stopped, and a β-adrenergic blocking agent was started, subsequently thyrotoxic symptoms were relieved. Currently, only one pediatric case diagnosed with RTH and TSHoma has been reported so far, and this case is the first to report a pediatric case of coexistence of RTH and non-functioning pituitary microadenoma. Also, this case shows that inappropriate secretion of thyroid hormones requires careful clinical diagnosis to avoid unnecessary and potentially harmful management.

Bioinformatics analysis of a disease-specific lncRNA-miRNA-mRNA regulatory network in recurrent spontaneous abortion (RSA).

This study investigated the molecular mechanisms of long non-coding RNAs (lncRNAs) in RSA using the lncRNA-miRNA-mRNA regulatory network. The present study obtained expression datasets of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) from blood samples of individuals with unexplained recurrent spontaneous abortion (RSA) and healthy controls. Differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEmiRs) were identified. A regulatory network comprising lncRNA, miRNA, and mRNA was constructed, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEM. Also, a protein-protein interaction (PPI) network was made and key genes were identified. A total of 57 DELs, 212 DEmiRs, and 301 DEMs regarding RSA were identified. Later analysis revealed a lncRNA-miRNA-mRNA network comprising nine lncRNAs, 14 miRNAs, and 65 mRNAs. Then, the ceRNA network genes were subjected to functional enrichment and pathway analysis, which showed their association with various processes, such as cortisol and thyroid hormone synthesis and secretion, human cytomegalovirus infection, and parathyroid hormone synthesis. In addition, ten hub genes (ITGB3, GNAI2, GNAS, SRC, PLEC, CDC42, RHOA, RAC1, CTNND1, and FN1) were identified based on the PPI network results. In summary, the outcomes of our study provided some data regarding the alteration genes involved in RSA pathogenic mechanism via the lncRNA-miRNA-mRNA network and reveal the possibility of identifying new lncRNAs and miRNAs as promising molecular biomarkers.