Thyroid Hormone Deficiency Research Articles

Low-molecular-weight Ligand of the Thyroid-stimulating Hormone Receptor with the Activity of a Partial Agonist and a Negative Allosteric Modulator.

Graves' disease is caused by overactivation of the thyroid-stimulating hormone receptor (TSHR). One approach for its treatment may be the use of negative allosteric modulators (NAM) of TSHR, which normalize TSHR activity and do not cause thyroid hormone (TH) deficiency. The aim of the work was to study the effect of a new compound 5-amino-4-(4-bromophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxylic acid N-tert-butylamide (TPY4) on the basal and TSH-stimulated TH production in cultured FRTL-5 thyrocytes and on basal and thyrotropin-releasing hormone (TRH)-stimulated TH levels in the blood of rats. TPY4 stimulated TH production by thyrocytes and increased TH levels when administered intraperitoneally and orally in rats. It also decreased the TSH-stimulated TH production in thyrocytes and the TRH-stimulated TH levels in rats. Thus, TPY4 is the first known allosteric regulator of TSHR, combining the properties of NAM and a partial agonist, and can be considered as a prototype of drugs for the treatment of Graves' disease.

Cardiovascular Findings and Effects of Caffeine on Experimental Hypothyroidism.

Thyroid hormone deficiencies can disrupt organ functions, significantly impacting the cardiovascular system. Recently, the effects of thyroid hormones on the heart have garnered increased attention. However, most studies are conducted on humans using clinical data, while cellular-level and experimental studies remain limited. This study aimed to investigate the cardiovascular implications of hypothyroidism and evaluate the impact of caffeine on cardiac health in rats induced with hypothyroidism using propylthiouracil (PTU). The study involved 60 rats divided into six groups. Group 1 served as the untreated control. Group 2 received PTU for two months to induce hypothyroidism. Group 3 received PTU for one month, followed by caffeine for one month. Group 4 received caffeine for two months. Group 5 received both PTU and caffeine simultaneously for two months. Group 6 received PTU for one month, followed by one month under normal conditions. During necropsy, normal thyroid glands were observed in Groups 1, 4, and 6, enlarged thyroids in Group 2, and smaller thyroids in Groups 3 and 5. Microscopic examination revealed varying thyroid histologies: Group 2 showed significant epithelial cell proliferation and absent colloid, while Groups 3, 5, and 6 had altered yet colloid-containing acini. Macroscopic inspection of hearts appeared normal across all groups. However, histopathological examination revealed significant hyperemia and microhemorrhages in Group 2, contrasting with normal findings in other groups. Immunohistochemical analysis indicated reduced cardiac troponin expression in Group 2, while other groups maintained prominent expression. Additionally, Group 2 displayed increased serum TSH levels and decreased T3 and T4 levels. The findings suggest that administering caffeine alongside or after PTU treatment in rats with experimentally induced hypothyroidism may ameliorate thyroid and cardiac irregularities. This study indicates caffeine's potential in mitigating the adverse effects of hypothyroidism on thyroid and heart health.

Newborn screening and the screening laboratory: past, present and future.

Thyroid hormone (TH) is essential for brain development in utero and during the first two to three years of life. The negative effects of TH deficiency on brain development are irreversible. Early detection of TH deficiency in neonates (congenital hypothyroidism (CH) through newborn screening (NBS)) allows for early treatment, thereby preventing brain damage. Screening for CH began in 1973 with the measurement of total thyroxine (T4) in dried blood spots. The enhanced sensitivity of Thyroid Stimulating Hormone (TSH) measurement has prompted a shift in the approach to NBS for CH. Currently, worldwide, the majority of NBS programs for CH employ TSH as the primary screening marker. However, a select few programs still utilize T4 as the primary marker, enabling the detection of both primary and central CH. This review provides an overview of the laboratory aspects of the screening on CH from the start of screening to the present.

Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis.

Thyroid hormone (TH) and it most active form triiodothyronine (T3) are crucial in promoting mitochondrial biogenesis and maintaining cellular homeostasis during the stress response, but their role in paraquat (PQ)-induced pulmonary fibrosis isunclear. The aim of this study was to examine whether there was a deficiency of TH in mouse lung tissue after PQ administration, and to explore the effect of T3, and potential mechanisms of action, in alleviation of PQ-induced pulmonary fibrosis. We found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in the lungs of patients with pulmonary fibrosis than in controls. The expression of DIO2 in lung tissue of PQ injured mice was significantly increased compared to controls (P < 0.001), while the serum T3 level was significantly reduced, compared to the control group (P < 0.001). T3 nebulization significantly improved PQ-induced pulmonary fibrosis in mice, possibly by activating thyroid hormone receptor beta (THRβ). T3 and sobetirome, a specific THRβ agonist significantly upregulated peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC1α) expression, and NH-3 (an antagonist of the thyroid hormone receptor), a THRβ-specific antagonist, significantly inhibited (P < 0.0001) the beneficial effects of T3 on the PQ-induced mitochondrial apoptotic pathway in an epithelial cell line, in vitro. T3 via the THRβ / PGC1α pathway protected against PQ induced pulmonary fibrosis, furnishing a scientific basis for further research on T3 and this pathway could offer a potential novel therapeutic strategy for treating PQ poisoning in humans.

Mild Gestational Hypothyroidism in Mice Has Transient Developmental Effects and Long-Term Consequences on Neuroendocrine Systems.

Background: Thyroid hormones (TH) play a key role in fetal brain development. While severe thyroid dysfunction, has been shown to cause neurodevelopmental and reproductive disorders, the rising levels of TH-disruptors in the environment in the past few decades have increased the need to assess effects of subclinical (mild) TH insufficiency during gestation. Since embryos do not produce their own TH before mid-gestation, early development processes rely on maternal production. Notably, the reproductive network governed by gonadotropin-releasing hormone (GnRH) neurons develops during this critical period. Methods: The risk of mild maternal hypothyroidism on the development of GnRH neurons and long-term effect on neuroendocrine function in the offspring was investigated using a mouse model of gestational hypothyroidism induced by methimazole (MMI) treatment. Results: MMI treatment during gestation led to reduced litter size, consistent with increased miscarriages due to hypothyroidism. E12/13 embryos, collected from MMI-treated dams, had a decreased number of GnRH neurons, but the migration of the remaining GnRH neurons was normal. Cell proliferation was reduced in the vomeronasal organ (VNO), correlating with the reduced number of GnRH neurons detected in this region. Using a GnRH cell line confirmed attenuated proliferation in the absence of T3. Pups born from hypothyroid mothers had normal postweaning growth and estrus cycles, yet adult offspring had significantly more cells expressing estrogen receptor alpha in the arcuate nucleus. Notably, by adulthood, GnRH cell number and distribution was comparable with nontreated controls indicating that compensatory mechanisms occurred after E13. Conclusion: Overall, our work shows that mild TH disruption during gestation transiently affects proliferation of the pool of GnRH neurons within the VNO and has a long-term impact on neuroendocrine systems.

Exploring the potential regulation of DUOX in thyroid hormone‑autophagy signaling via IGF‑1 in the skeletal muscle (Review).

Dual oxidases (DUOX) are enzymes that have the main function in producing reactive oxygen species (ROS) in various tissues. DUOX also play an important role in the synthesis of H2O2, which is essential for the production of thyroid hormone. Thyroid hormones can influence the process of muscle development through direct stimulation of ROS, 5' AMP-activated protein kinase (AMPK) and mTOR and indirect effect autophagy and the insulin-like growth factor 1 (IGF-1) pathway. IGF-1 signaling controls autophagy in two ways: Inhibiting autophagy through activation of the PI3K/AKT/mTOR/MAPK pathway and promoting mitophagy through the nuclear factor erythroid 2-related factor 2-binding receptor Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3. Thyroid hormone deficiency caused by the absence of DUOX should be considered because it might have a significant effect on the growth of skeletal muscle. The effect of DUOX regulation on thyroid hormone autophagy via IGF-1 in skeletal muscle has not been well investigated. The present review discussed the regulatory interactions between DUOX, thyroid hormone, IGF-1 and autophagy, which can influence skeletal muscle development.

Growth Outcomes and Final Height in Children with Acquired Hypothyroidism: A Systematic Review.

Hypothyroidism can profoundly affect growth, particularly if it insidiously arises during early childhood. Congenital hypothyroidism is now detected through newborn screening, significantly improving the overall growth outcomes of these children. Conversely, acquired hypothyroidism often results in delayed somatic growth and shorter stature, with many affected children initially remaining non-symptomatic. The main objective of this review is to summarize the current knowledge about the impacts of acquired hypothyroidism on children's growth outcomes. We performed a literature review to analyze growth and final height in children with acquired hypothyroidism, matching the following keywords: "hypothyroidism & growth", "hypothyroidism & height", "hypothyroidism & stature", "hypothyroidism & development", "hypothyroidism & auxological parameters". We reviewed each article that met the eligibility criteria, and after a thorough selection, we included 16 studies. Growth arrest is frequently noted as a symptom in hypothyroidic children, with substantial portions of affected children presenting below the third percentile for height. The timing of diagnosis significantly influences growth outcomes: those diagnosed during puberty tend to experience less catch-up growth due to accelerated skeletal maturation. Even if thyroxine replacement can induce rapid catch-up growth, it may be incomplete if treatment begins during puberty or if there is a markedly prolonged deficiency of thyroid hormones. While levothyroxine therapy typically results in some degree of catch-up growth, many children do not reach their expected genetic height. This review highlights the necessity of both early diagnosis and treatment of acquired hypothyroidism. Even if many children show improvements in height velocity post-treatment, the complete normalization of growth may remain elusive.

Cardiovascular problems in rabbits in reference to hypothyroidism - a four-year retrospective study.

The effects of T4 are mainly manifested by positive ino- and chronotropism. The syndrome accompanying hypothyroidism in rabbits (impaired myocardial contractility and reduced ejection capacity) is caused by a deficiency of thyroid hormones - especially T4. The study group consisted of a total of 41 animals: 15 males and 26 females, ranging in age from 2 months to 8 years, with echocardiogram showing reduced fractional shortening (<30%), with normal results of heamatological and biochemical tests. Blood was collected in order to measure T4 level. Echocardiographic examinations were performed with two-dimensional (2D) imaging, M-mode measurements and the pulsed/colour-labelled Doppler technique. Statistical analysis was performed using Statistica 13.0. Correlations were determined: between serum thyroxine concentration and the value of the fraction of shortening in the groups: young animals (up to 5 years of age) and older animals, females and males, and sterilised and non-sterilised animals. Statistical analysis showed a positive correlation between T4 levels in the blood of the test animals and myocardial fractional shortening and heart rate and left-atrial to aortic ratio (LA/Ao) in the pre-treatment period. A positive correlation was also shown after dividing the patients into 2 groups based on their age (below 5 years vs. 5 years and over), sex (male and female rabbits) and fact of sterilization (yes/no). Our study unequivocally confirmed a positive correlation between the decreased serum T4 concentration and reduced fractional shortening, indicating decreased cardiac systolic function in hypothyroid rabbits.

Perinatal bisphenol A exposure has an age- and dose-dependent association with thyroid allostasis adaptive response, as well as anxiogenic-depressive-like and asocial behaviors in juvenile and adult male rats

Thyroid hormones are essential for brain development, and a shortage throughout the fetal and postnatal periods can result in mood disorders. Perinatal exposure to bisphenol A (BPA) affects thyroid activity and dependent processes indirectly during pregnancy or early postnatal life. This is particularly important because it may cause changes in tissue ontogeny, increasing the risk of developing disorders later in life. The study aimed to investigate the consequences of thyroid hormone deficiency on anxiety, social, and depressive behaviors, as well as disruption in thyroid peroxidase (TPO) gene expression, which influences the NF-κB/Nrf-2/HO-1/iNOS signaling pathway, leading to oxidative stress, inflammation, and DNA fragmentation in perinatal BPA exposure (PND18), and whether these effects can be observed in juvenile (PND60) and adult (PND95) male offspring rats. BPA increased anxiety-like behavior while decreasing sucrose preference and sociability on a choice task between novel conspecific male rats and enhanced immobility on the forced swim test. Perinatal exposure to BPA causes thyroid insult by overproducing ROS, increasing iNOS, and NF-κB levels—these effects, in turn, down-regulate Nrf-2/HO-1 signaling, resulting in DNA fragmentation within thyroid tissues. Furthermore, perinatal BPA exposure for 60 and 95 days resulted in a significant fold decrease in TPO mRNA levels in the thyroid tissues, with an insignificant fold rise in TPO expression levels in BPA 50–60. In conclusion, the present study found that perinatal BPA exposure induced thyroid allostasis-adaptive response by inhibiting the NF-κB/Nrf-2/HO-1/iNOS signaling pathway and altering the transcriptional expression of TPO, where TSH reinforced a possible association with TPO activity, disrupting thyroid hormone synthesis in juvenile rats and gradual deterioration reaching the adult stage.

A clinical review of early assessment for congenital hypothyroidism in newborns

Congenital hypothyroidism is a critical factor associated with stunting, as thyroid hormone deficiencies can impair growth starting in utero. Children with thyroid disorders, including conditions like hypoparathyroidism, often experience growth retardation due to congenital abnormalities and growth hormone deficiencies. For neonates, a lack of thyroid hormones can lead to long-term impacts, such as physical and mental disabilities, neurological disorders, and stunted growth. Early detection of congenital hypothyroidism is, therefore, essential and is typically part of newborn screening aimed at identifying congenital abnormalities. Implementing early screening protocols can diagnose and treat congenital hypothyroidism promptly, mitigating risks such as stunting and enabling better health outcomes for children. This literature review examines methods of early detection for congenital hypothyroidism across various global contexts. Three databases—PubMed, ScienceDirect, and Google Scholar—were searched using a systematic literature review approach, yielding five eligible studies with a combined study population of 920.441 newborns. These studies involved screenings for T4, TSH, 17-OHP, and G-6-PD, identifying hypothyroidism in 2.530 (27%) cases. Screening involved blood samples taken from the umbilical cord or heel within 48 to 72 hours after birth. Understanding early detection procedures for congenital hypothyroidism is essential for nurses, as it enables them to engage in early intervention and provide effective nursing care for affected infants. Early involvement can help prevent the adverse, long-term effects associated with congenital hypothyroidism, improving quality of life and supporting healthy growth trajectories for children at risk. Keywords: Congenital hypothyroidism; literature review; nursing assessment; paediatric nursing; prevention

ПАЦИЕНТ С ГИДРОПЕРИКАРДОМ, ГИДРОТОРАКСОМ, АСЦИТОМ – КЛИНИЧЕСКИЙ КВЕСТ ДЛЯ ТЕРАПЕВТА

Hypothyroidism is caused by a deficiency of thyroid hormones and presents various clinical manifestations. The possibility of tissue edema should be mentioned in addition to the classic symptoms, such as cold intolerance, fatigue, constipation, bradycardia, depression, drowsiness, hoarseness, weight gain. Tissues edema and the formation of isolated effusions in the cavities (abdominal, pleural and pericardial) are not unusual in hypothyroidism. These manifestations are caused by increased vascular permeability and transudation of fluid and albumin into the interstitial and other spaces (pericardium, pleura), inadequate secretion of antidiuretic hormone, accumulation of hydrophilic glycosaminoglycans in the intercellular spaces of the dermis and various tissues. Multiple effusions in the body cavities and tissue edema are rare to happen simultaneously. The nonspecific nature of these symptoms requires a differential diagnosis, in which hypothyroidism is not always taken into consideration. This situation leads to delay in making a diagnosis and treatment administration, especially in comorbid patients. It is advisable to pay attention to the necessity of thorough analysis of the obtained data and the use of simple differential diagnosis algorithms for the hypothyroidism.

Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.

Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure, which increases the risk of adverse events. This study examined the effects of thyroid hormones (THs) on cardiac transverse-tubule (TT) integrity, Ca2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC) coupling, including L-type calcium channel (CaV1.2), ryanodine receptor type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 wk; followed by randomization to continued PTU without or with oral triiodo-l-thyronine (T3; 10 µg/kg/day) for an additional 2 wk (PTU + T3). Confocal microscopy of isolated cardiomyocytes (CMs) showed significant misalignment of TTs and increased Ca2+ sparks in thyroid-deficient CMs. Density-based spatial clustering of applications with noise (DBSCAN) analysis of stochastic optical reconstruction microscopy (STORM) images showed decreased (P < 0.0001) RyR2 cluster number per cell area in PTU CMs compared with euthyroid (EU) control myocytes, and this was normalized by T3 treatment. CaV1.2 channels and Jph2 localized within a 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither CaV1.2 nor Jph2, suggesting fewer functional clusters in EC coupling. Nearest neighbor distances between RyR2 clusters were greater (P < 0.001) in PTU cells compared with EU- and T3-treated CMs that correspond to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and colocalization of CaV1.2 and Jph2 in optimizing EC coupling.NEW & NOTEWORTHY Thyroid hormone (TH) dysfunction exacerbates preexisting heart conditions leading to an increased risk of premature morbidity/mortality. Triiodo-l-thyronine (T3) optimizes cardiac excitation-contraction (EC) coupling by maintaining myocardial T-tubule (TT) structures and organization of calcium ion channels. Single-molecule localization microscopy shows T3 effects on the clustering of ryanodine receptors (RyR2) with colocalization of L-type calcium channels (CaV1.2) and junctophilin-2 (Jph2) at TT-SR structures. Heart disease with subclinical hypothyroidism/low T3 syndrome may benefit from TH treatment.

ВЗАИМОСВЯЗЬ СВОЙСТВ РОТОВОЙ ЖИДКОСТИ И КАЧЕСТВА ВЫПОЛНЕННЫХ РЕСТАВРАЦИЙ У ПАЦИЕНТОВ С ПЕРВИЧНЫМ ГИПОТИРЕОЗОМ

Introduction. Introduction. Primary hypothyroidism refers to a common pathological condition associated with thyroid hormone deficiency. Among all thyroid diseases, its share reaches 20%, while the detection rate tends to grow steadily every year in all age groups. An urgent task remains to study the dental status against the background of thyroid diseases developing as a result of iodine deficiency, as well as due to a relative shortage of thyroid hormones. The purpose of the work is to identify the relationship between the quality of the performed restorations and the properties of oral fluid in patients with primary hypothyroidism. Materials and methods. The main study cohort included 60 women with a primary diagnosis of primary hypothyroidism aged 44–59 years. The comparison group consisted of 30 patients without thyroid pathology, identical in sex and age. All patients were evaluated for salivary gland secretory activity, oral fluid properties, and quality of direct oral restorations performed. Results. In the main group of the study, a decrease in the salivation rate, an increase in the viscosity of the oral fluid and a shift in saliva pH to the acidic side relative to the results obtained in the comparison group were detected. Assessment of the quality of direct restorations performed showed an increase in the number of their insolvency in patients of the main group, relative to the comparison group. Discussion. Deficiency of thyroid hormones in primary hypothyroidism is accompanied by a change in the properties of the oral fluid and the quality of direct restorations performed in the oral cavity in the distant period. Conclusion. The identification of the relationship between dental and somatic health parameters will allow the development of a new treatment approach in patients with primary hypothyroidism.

The Relationship Between TSH and Indirect Bilirubin Levels in Neonates Suspected of Having Jaundice

Background: Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency that occurs at birth. The TSH (thyroid-stimulating hormone) test is crucial for diagnosing hypothyroidism. CH is known to cause prolonged unconjugated hyperbilirubinemia. Therefore, this study aimed to analyze the relationship between TSH and indirect bilirubin levels in neonates suspected of having jaundice. Methods: This is a non-experimental, retrospective study conducted at Lombok Dua Dua Lontar Mother and Child Hospital in Surabaya. The study involved data collection on neonates aged 2–7 days suspected of jaundice, whose TSH and indirect bilirubin levels were measured between November 2022 to April 2024. Results: Among 100 neonates, 62% were aged 2-4 days, while 38% were aged 5-7 days. The majority were male (56%), with female comprising 44%. Of the 100 neonates, only 1 (1%) had borderline TSH levels, while 99% had normal TSH levels. Hyperbilirubinemia was observed in 94% of the neonates, while 6% had normal indirect bilirubin levels. Statistical analysis using the Spearman correlation showed no significant link between TSH and indirect bilirubin levels (p = 0.802). Conclusions: While this study did not find a clear connection between TSH and indirect bilirubin levels in neonates suspected of having jaundice, one case of borderline TSH was identified. This neonate required referral to pediatric endocrinology, as untreated congenital hypothyroidism can lead to mental retardation. Despite limited research linking TSH and bilirubin levels in jaundiced neonates, routine screening for congenital hypothyroidism using TSH testing should be reconsidered. Future studies could benefit from focusing on specific causes of neonatal jaundice to help narrow down research questions in this area.

Deciphering the mystery of CHNG3.

Congenital hypothyroidism (CH), characterized by insufficient thyroid hormone production due to abnormalities in the hypothalamic-pituitary-thyroid axis, is the most common congenital endocrine disorder. We previously conducted comprehensive genetic screening of 102 patients with permanent CH born in Kanagawa Prefecture, Japan and identified mutations in several genes in 19 CH patients, including defects in genes encoding dual oxidase 2, thyroglobulin, thyrotropin receptor, thyroid peroxidase, and paired-box 8. Despite these findings, approximately 80% of cases remain unexplained. CH pedigrees unexplained by known genetic forms of CH have been reported in the literature and registered as congenital hypothyroidism, nongoitrous, 3 (CHNG3; %609893) in Online Mendelian Inheritance in Man. We also identified a Japanese pedigree of CH that was compatible with CHNG3. However, the exact genetic cause of CHNG3 was not revealed by standard analysis methods such as exome sequencing and array comparative genomic hybridization. We therefore took a combined approach and analyzed a total of 11 undiagnosed CH pedigrees by whole genome sequencing to analyze a 3-Mb linkage region, and found a disease-causing variant affecting a TTTG microsatellite in a noncoding region on chromosome 15. Further analysis revealed that 13.9% of 989 Japanese CH patients had abnormalities involving the TTTG microsatellite, with a substantial proportion (41.5%) of familial CH cases carrying these mutations. Identification of the genetic cause of CHNG3 provides new insights into the pathogenesis of CH, and highlights the need for continued exploration of noncoding genomic regions in Mendelian disorders of unknown etiology.

A longitudinal observational study on activated partial thromboplastin time in hypothyroidism and effect of thyroxine supplementation

Background: Hypothyroidism is a common condition characterized by thyroid hormone deficiency, which, if untreated, can lead to severe health consequences and even death. Due to the wide range of clinical presentations and non-specific symptoms, hypothyroidism is primarily diagnosed biochemically. It can result from congenital thyroid abnormalities or iodine deficiency. Aims and objectives: Aim: To evaluate the correlation between hypothyroidism and Activated Partial Thromboplastin Time (aPTT) and assess the effect of thyroxine supplementation. Objective: To study the impact of levothyroxine supplementation on aPTT in hypothyroid patients. Materials and methods: This observational study was conducted at the General Medicine outpatient clinic and inpatient wards at Al-Ameen Medical College and Hospital, Vijayapura, from September 2022 to March 2024. A total of 80 hypothyroid patients of both sexes were included. TSH, Free T4, and aPTT levels were measured with appropriate aseptic precautions. Results: The majority of subjects were females (90%), with the highest proportion (31.3%) aged 26-35 years. The mean ± SD of pre-thyroxine TSH was 25.453 ± 19.9073, which significantly decreased to 4.299 ± 0.6738 post-thyroxine. aPTT values also decreased significantly post-treatment. A positive correlation was found between TSH and aPTT, while aPTT had a negative correlation with T3 and T4 levels. Conclusion: aPTT is significantly elevated in hypothyroid patients and shows a positive correlation with TSH levels. Regular monitoring of aPTT should be included in the follow-up of hypothyroid patients.

Autoimmune thyroiditis: an update on treatment possibilities.

Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may release free thyroid hormones into the bloodstream, causing hyperthyroid symptoms. With further destruction of thyroid cells, patients develop euthyroidism and eventually chronic hypothyroidism. The diagnosis of AIT is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound, and histological features. The main goal of treatment is correcting hormonal disorders and achieving euthyroidism. Treatment of AIT involves replacing thyroid hormone deficiency with the use of synthetic hormones. Prophylactic levothyroxine (L-T4) treatment of euthyroid patients with AIT may reduce both serological and cellular markers of autoimmunisation. Attention should be paid to the starting dose of L-T4, potential drug interactions, and drug formulation. A follow-up should be planned to determine the optimal dose. The authors highlighted that a healthy lifestyle and supplementing selected vitamins and microelements appropriately are essential. In selected clinical conditions, thyroidectomy should be considered. There are also alternative therapeutic strategies, such as herbal medicine and acupuncture, but their effectiveness has yet to be conclusively confirmed in research studies. Monitoring the thyroid gland enlargement and the possibility of developing nodular goitre is integral to patient care over AIT patients. In conclusion, treating AIT is complex, involving thyroid hormone replacement therapy, taking care of a healthy diet and lifestyle, and proper supplementation. It requires an individual approach. Regular follow-up is necessary to control the disease and minimise its effects.

Thyroidectomy Induced Toxicity of Testis and Possible Amelioration by Chia (Salvia hispanica) Seeds Extract

Background: Thyroidectomy or thyroid surgery induces hypothyroidism and causes thyroid and testicular hormone deficiency. The current Study Aimed to examine the therapeutic effect of chia seeds extract against thyroidectomy-induced testicular toxicity, oxidative stress, DNA damage, proliferation in rats. Methods: 40 male rats were equally divided into 4 groups [Gp1, control ; Gp2, CSE ; Gp3, thyroidectomies rats; Gp4, treated thyroidectomies rats with chia seeds extract (Thy+CSE )]. Result: Following a thyroidectomy, significant reductions (P less than 0.05) were observed in The Levels of triiodothyronine (T3), thyroxine (T4), sexual hormones (Testosterone (tt), Follicle-Stimulating Hormone and Luteinizing Hormone And prolactin), count of sperm, index of morphology, vitality, progressive motility, total motility (PR+NP), Glutathione, Superoxide Dismutase, Glutathione S-Transferase and PCNA expressions compared to the control and CSE after three weeks. Additionally, thyroidectomy leads to significant (P less than 0.05) increases in the serum of thyrotropin (TSH), alanine transaminase, alkaline phosphatase, non-progressive sperms, immotile sperms, malondialdehyde, DNA damage and injury of testis and significant (P less than 0.05) decreases in blood. Thy+CSE treatment helped to modulate most of these changes and recover testicular injury when compared To The Control and CSE. Rats treated with CSE after thyroidectomy Showed gradual improvements in testicular functions, histology and spermatogenesis due to its beneficial affection in free radicals’ scavenger.

5155 Benign Paroxysmal Positional Vertigo as a Potential Manifestation of Hypothyroidism, a Case Report

Abstract Disclosure: M. Ahmad: None. M. Herrera: None. D. Deyar: None. P. Gill: None. Introduction: Benign Paroxysmal Positional Vertigo (BPPV) is a vestibular disorder characterized by recurrent episodes of vertigo triggered by specific head movements. The pathophysiology of BPPV involves the displacement of otoconia within the semicircular canals of the inner ear. However, emerging evidence suggests that BPPV may manifest as a consequence of hypothyroidism. In this case report, we present a clinical case of a patient who exhibited symptoms of BPPV and was subsequently diagnosed with hypothyroidism. We aim to elucidate the relationship between these two seemingly distinct conditions and highlight the importance of considering hypothyroidism as a potential cause of BPPV. Case presentation: A 56-year-old female with a past medical history of migraines presented to the hospital for three days of dizziness. She had multiple bouts of vomiting and right-sided headaches similar to her prior migraine headaches. The patient also noted dry skin, constipation, and hair loss for the past few months. The patient’s vital signs were as follows: temperature: 35.6 C, heart rate: 65 beats per minute, blood pressure: 153/66 mmHg, and respiratory rate: 18 breaths per minute. On physical examination, the Dix-Hallpike maneuver was positive on the right side and the patient was noted to have diffusely dry skin. The patient’s labs were significant for the following: sodium: 137 mmol/L, potassium: 3.7 mmol/L, creatinine: 0.88 mg/dL, thyroid stimulating hormone: 31.2 uIU/ml, free T4 ng/dL, hemoglobin: 10.8 g/dL (MCV of 87), and TPO antibody: 2350 IU/ml. The patient underwent CT and MRI imaging of the brain without contrast, which was negative for any acute intracranial abnormalities. The patient was diagnosed with BPPV and hypothyroidism secondary to Hashimoto’s thyroiditis and subsequently underwent vestibular physical therapy with improvement in her vertigo and was started on 112 mcg of levothyroxine daily. She is set to follow up with her primary care provider as an outpatient. Discussion: BPPV generates significant repercussions to an individual’s quality of life, autonomy, and functionality. Hypothyroidism is a common condition characterized by thyroid hormone deficiency that has been linked with a wide array of clinical manifestations, including vestibular disturbances. Autoimmune dysfunction, anomalies of the endolymphatic flow and low perfusion to the inner ear are potential etiological factors that can explain the relationship between thyroid disorders with BPPV. Some studies mention that thyroid autoantibodies could induce autoimmune-complex deposition in the inner ear, which might change the endolymphatic flow and induce BPPV. Raising awareness regarding this potential manifestation of hypothyroidism can guide clinical and diagnostic decisions that improve patient care, especially in individuals under evaluation for BPPV with other symptoms of hypothyroidism. Presentation: 6/3/2024

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024