Elevated Thyroid Hormone Levels Research Articles

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

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

Proportion of hydatidiform molar gestations among patients undergoing uterine evacuation for missed abortions, associated demographics and risk factors -Experience at a single center over 18 months

Objectives: Gestational trophoblastic diseases represent a significant obstetric morbidity among women of reproductive age, with a potential to impact women’s health substantially. Molar pregnancies present as clinical aberrations in embryogenesis and placentation during the first trimester of pregnancy. Cases with missed abortions and spontaneous incomplete abortions requiring uterine evacuation, could be an opportunity to look for molar pregnancies through histopathology which otherwise could be missed. We aim to study the proportion of hydatidiform molar gestations among patients undergoing uterine evacuation in cases of missed abortion and to evaluate the demographic and risk factors associated with hydatidiform molar gestations. Material and Methods: A prospective observational, descriptive study was conducted at the Department of Obstetrics and Gynecology of a tertiary care teaching hospital over a period of 18 months. Data was collected using a pre-tested study questionnaire which included the objectives, besides the inclusion and exclusion criteria. The abortus and uterine evacuated tissue was sent for histopathologic examination by a single histopathologist. Analysis of various epidemiological characteristics and risk factors was done using the Statistical Package for the Social Sciences software version 21. Results: Out of 67 patients presenting with missed abortions or incomplete abortions during the study period, five had hydatidiform molar gestations; an incidence of 7.5%. Upon histological examination 3 (4.5%) patients had a complete mole, 2 (3%) had a partial mole while 62 (92.5%) had non-molar histopathology. Eleven (16.4%) of the study participants had a history of previous spontaneous pregnancy loss/recurrent pregnancy losses. Three among five cases detected to have molar gestations had a history of prior spontaneous abortions (60%), and the difference observed was statistically significant (P = 0.019; Odds Ratio [95% Confidence interval] 10.25 [1.459–70.257]). Hyperthyroidism and high levels of serum beta-human chorionic gonadotrophin (β-HCG) were associated with molar gestations and this was statistically significant. Conclusion: The risk of developing molar gestation is higher in patients who had previous first-trimester losses. Importantly, this should be a differential diagnosis in instances with elevated β-HCG and high thyroid hormone levels. Histopathological examination of products of conception should be considered as an essential assessment in all presentations of spontaneous abortions requiring uterine evacuation.

P 022: Myopericarditis associated with herpes zoster infection presented with STEMI

We describe a case of an 18-year-old male with no known medical illness who presented with a history of fever and skin rash for the previous 2 days. The patient presented with symptoms of acute nausea, vomiting, and chest discomfort. The initial electrocardiogram (ECG) revealed an inferior ST-segment elevation myocardial infarction (STEMI), which prompted the administration of thrombolysis using streptokinase at the district hospital. However, consecutive ECGs showed no change, prompting the patient to be referred to our centre for a rescue percutaneous coronary intervention (PCI). The coronary angiography showed normal coronaries, whereas an echocardiogram showed good LV functions without any regional wall motion abnormalities and with normal valves. Upon further examination, the patient exhibited herpes zoster lesions along the T5–T6 dermatome. Blood investigations revealed elevated levels of thyroid hormones, as well as increased creatinine kinase and troponin I. The cardiac MRI showed the presence of mid-wall enhancement in the septal and lateral myocardium of the left ventricle, sub-epicardium of the right ventricle, and apical region of the left ventricle, which is indicative of myocarditis. The patient was diagnosed with myopericarditis and was treated with IV acyclovir, colchicine, high-dose aspirin, and carbimazole. He subsequently showed significant improvement and was successfully discharged. Although type 1 STEMI remains the prevailing diagnosis, this case emphasises the distinctive differential diagnosis of myopericarditis in patients presenting with chest discomfort and herpes zoster. Clinicians must obtain a thorough medical history and conduct a comprehensive evaluation to identify potential secondary aetiologies.

Insights into spirotetramat-induced thyroid disruption during zebrafish (Danio rerio) larval development: An integrated approach with in vivo, in vitro, and in silico analyses

Spirotetramat (SPT), a tetronic acid-derived insecticide, is implicated in reproductive and lipid metabolism disorders, as well as developmental toxicity in fish. While these effects are documented, the precise mechanisms underlying its developmental toxicity are not fully elucidated. In this study, zebrafish embryos (2 h post-fertilization, hpf) were exposed to four concentrations of SPT (0, 60, 120, and 240 μg/L) until 21 dpf (days post-fertilization). We delved into the mechanisms by examining its potential disruption of the thyroid endocrine system, employing in vivo, in vitro, and in silico assays. The findings showed notable developmental disturbances, including reduced hatching rates, shortened body lengths, and decelerated heart rates. Additionally, there was an increase in malformations and a decline in locomotor activity. Detailed analyses revealed that SPT exposure led to elevated thyroid hormone levels, perturbed the hypothalamic-pituitary-thyroid (HPT) axis transcript levels, amplified deiodinase type I (Dio1) and deiodinase type II (Dio2) activities, and both transcriptionally and proteomically upregulated thyroid receptor beta (TRβ) in larvae. Techniques like molecular docking and surface plasmon resonance (SPR) confirmed SPT's affinity for TRβ, consistent with in vitro findings suggesting its antagonistic effect on the T3-TR complex. These insights emphasize the need for caution in using tetronic acid-derived insecticides.

FRI567 Insulin Autoimmune Syndrome And Grave’s Disease

Abstract Disclosure: A.M. Skariah: None. T. Porter: None. Background: Insulin autoimmune syndrome (IAS), also known as Hirata’s disease, is a rare condition characterized by immune mediated post prandial hypoglycemia, due to presence of high titers of insulin autoantibodies (IAA). Most cases reported in Asian population with strong association with HLA-DR4 and specifically with the DRB1*0406. Clinical case: Patient is 36-year-old Asian female with no significant past medical history got evaluated by primary care physician because of fatigue, weight loss and neck swelling. Her symptoms are consistent with hyperthyroidism, got evaluated and found to have elevated thyroid hormone levels and suppressed TSH. At the time of diagnosis, free T3 2922 pg/dl(230-420pg/dl), free T4 > 7.7 ng/dl (0.9-1.7 ng/dl), TSH < 0.01uIU/ml (3-4uIU/ml), total T3 599 ng/dl (80-195 ng/dl), total T4 19.6Ug/dl (5-11 Ug/dl). Patient was started on methimazole, and beta blocker. Other labs including autoimmune panel were positive for TSI (2.8 with normal <1.3) and thyroid receptor antibody >40 (<15.5 IU/l) confirming Graves' disease. 4 weeks after starting treatment with methimazole, patient was experiencing episodes of hypoglycemia, related to food intake. She checked her blood sugar and the lowest blood sugar she noticed was 53 mg/dl. She had no history of diabetes and never used insulin or any other oral diabetic medications. Insulin levels >1000 uIU/ml (2.6-24.9uIU/ml), insulin antibody levels >625 uU/ml (<5 uU/ml), C-peptide as high as 9.5ng/ml (1.1-4.4 ng/ml), Insulin/C-peptide ratio 105, proinsulin elevated 40.3pmol/l (0.0-10 pg/l), and oral hypoglycemic agent screening negative. With the lab results, diagnosis of Hirata’s syndrome was made, Management discussed with the patient. Since patient still having labs consistent with hyperthyroidism, continued methimazole and started on diet interventions including low-carb diet and including complex carbohydrates in the diet. Patient gradually responded to dietary interventions with decrease episodes of hypoglycemia. Never required acarbose or steroids. Follow-up labs shows that patient is responding decrease in the levels of insulin antibodies 116 uU/ml and insulin levels 19.5 uIU/ml. Patients’ hyperthyroidism responded to methimazole, and dose reduced eventually to 5 mg daily with latest labs of free T4 1.21 ng/dl, Free T3 2.7 pg/ml and TSH 2.010 uIU/ml. Conclusion: Association between methimazole and IAS has been already reported before. When a patient is presenting outside Asian countries with similar symptoms, differential of IAS can be missed due to its rarity. But because of globalization; people from all races are seen in every part of the world. It will be beneficial to screen patients for IAS which can decrease cost of work up and treatment, when considering imaging modalities which were included as the part of the work up. Presentation: Friday, June 16, 2023

THU667 Severe Hypothyroidism With Paradoxically Elevated Direct Free T4 Due To Anti-thyroxine Antibodies

Abstract Disclosure: O. Magvanjav: None. M.J. McPhaul: None. I. Choucair: None. E. Holt: None. Introduction Laboratory interference may cause abnormal thyroid function test (TFT) results, leading to misdiagnosis and inappropriate patient care. There are several major types of interference. Here, we describe a hypothyroid patient with an elevated thyroid stimulating hormone (TSH) level with a paradoxically elevated direct free thyroxine (FT4) level caused by interference from anti-thyroxine autoantibodies (THAAB). Clinical Case Our patient is a 38-year-old man who was found to have markedly elevated TSH and FT4 levels during an outpatient workup for Lyme disease. The patient was overall well-appearing but reported some symptoms suggestive of hypothyroidism including excessive fatigue, non-pitting edema, and dry skin. Physical exam was notable elevated blood pressure (systolic blood pressure of 150 mmHg and diastolic blood pressure of 95 mmHg), normal temperature, normal heart rate (72 bpm), regular heart rhythm, and normal body mass index. He had non-tender thyromegaly without nodules, non-pitting edema of bilateral hands and legs, decreased leg hair over bilateral shins, and coarse, dry skin of his hands. Initial TSH level was >150 mIU/ml, with a paradoxically elevated direct FT4 of 10 ng/dl (normal range 0.80-1.70 ng/dL). The FT4 level by equilibrium dialysis was <0.2 ng/dl. Outside laboratory testing to eliminate the effect of heterophile antibodies using two different assays again returned with elevated FT4 levels. Screening for macro TSH confirmed the markedly elevated TSH level. Further investigations at a second outside laboratory revealed that he had THAAB. A repeat FT4 level by dialysis confirmed the markedly low FT4 levels. He was empirically started on low dose levothyroxine and after increasing the levothyroxine dose, he showed improvement in clinical symptoms and the expected decline in TSH. Conclusions Here we present a rare case of THAAB that caused laboratory interference during thyroid function testing, leading to falsely elevated thyroid hormone levels on immunoassays. This case shows the importance of suspecting interference when there is a discrepancy between clinical symptoms and laboratory results or between results obtained from different testing methods. Our patient likely had a genetic predilection for autoimmunity, and Lyme disease is a known trigger for various autoimmune conditions. Our case also emphasizes the importance of taking a systematic approach to investigate the cause of the laboratory interference. This will help prevent misdiagnosis of thyroid disorders that may lead to additional unnecessary testing and treatment. Presentation: Thursday, June 15, 2023

Elevated Free Thyroxine Levels Might Alter the Effect of the Lipid Profile on Insulin Resistance in Type 2 Diabetes Mellitus.

Previous studies have shown that hyperthyroidism is associated with heightened insulin resistance and dyslipidemia. Therefore, in this study, we aim to explore the relationship between elevated thyroid hormone levels and the lipid profile in insulin resistance in patients with type 2 diabetes mellitus (T2DM) with hyperthyroidism. A total of 177 participants were included and grouped according to diagnosis. The serum test results demonstrated that free thyroxine (FT4) increased the insulin resistance index (HOMA-IR) by positively correlating with triglyceride (TG) levels (p = 0.005, r2 = 0.35). In patients with T2DM with hyperthyroidism, the decreasing high-density lipoprotein levels showed an association with HOMA-IR (p = 0.005). Among all the patients, with different levels of FT4, the areas under the ROC curve (AUCs) of the TG level, TG/high-density lipoprotein ratio, and HOMA-IR were 0.620 (95% CI: 0.536 to 0.698), 0.614 (95% CI: 0.530 to 0.692), and 0.722 (95% CI: 0.645 to 0.791), respectively. Our results suggest that elevated FT4 levels due to hyperthyroidism could alter the association with the lipid profile and insulin resistance in patients with T2DM. We also suggest that among all the included patients with T2DM, irrespective of the presence of hyperthyroidism, FT4 levels are positively correlated with insulin resistance.

Cardio-Thyrotoxicosis Syndrome: A Review of Thyrotoxic Cardiovascular Disease.

Thyrotoxicosis, an endocrine disorder characterized by elevated serum thyroid hormone levels of tri-iodothyronine (T3) and/or thyroxine (T4), can impact cardiovascular health in several ways. The cardiovascular system is often severely targeted by the thyrotoxic state, and the term "Cardio-thyrotoxic syndrome" has been proposed to encompass the various cardiovascular disease states resulting from thyrotoxicosis. In this review, we discuss various cardiovascular disorders resulting from the effects of thyrotoxicosis. It is important to keep a high index of suspicion for thyroid disorder in the setting of new atrial fibrillation, heart failure, and tachycardia-induced cardiomyopathy. Management of cardio-thyrotoxicosis involves control of heart rate and blood pressure and treatment of acute cardiovascular complications. Thyroid-specific therapy to achievea euthyroid state will not only improve but even potentially reverse cardiovascular abnormalities.

Falsely elevated thyroid hormone levels associated with fibrin interference in patients receiving oral anticoagulant therapy.

Unique clinical courses were observed in two asymptomatic patients receiving warfarin who referred to our hospital because of suspected central hyperthyroidism. We eventually diagnosed these patients with falsely elevated thyroid hormone levels caused by macroscopically invisible fibrin. Although false results caused by fibrin interference in vitro have been identified in various immunoassays, especially in blood samples from patients receiving anticoagulant therapy, no studies on thyroid function testing have been reported. The experience in evaluating these cases prompted us to investigate the independent influence of oral anticoagulants via putative fibrin interference on thyroid function testing. We retrospectively reviewed known contributing factors that affect thyroid function testing including age, gender, medication history, body mass index, estimated glomerular filtration rate, smoking status, alcohol consumption, and the seasons of hospital visits from participants who presented the Department of Health Checkup between April 2010 and December 2020. A propensity-matched analysis revealed that the median serum free thyroxine levels under oral anticoagulant were significantly higher (17.9 pmol/L, n = 60) than those without anticoagulants (16.0 pmol/L, n = 60; p < 0.001). It was noted that this difference was the largest among contributing factors we analyzed. No significant differences were noted in serum thyroid-stimulating hormone levels. We report two patients receiving warfarin with falsely elevated thyroid hormone levels caused by fibrin interference resembling central hyperthyroidism for the first time. Our retrospective study suggests that the medication status of oral anticoagulants should be considered when evaluating thyroid function tests.

Does altered thyroid hormone status affect resting systolic blood pressure significantly in premenopausal women? - A cross-sectional comparative study

Background: Hypothyroid or hyperthyroid state affects all the physiological systems including cardiovascular system, central nervous system, digestive system, and blood. Among all adverse changes, systolic blood pressure (SBP) can also be affected in patients with thyroid disorders. Aims and Objectives: The present study was carried out to compare SBP in newly diagnosed patients of hypothyroidism, hyperthyroidism and age and gender matched euthyroid subjects and to assess correlation between Tri-iodothyronine (T3) level and resting SBP. Materials and Methods: The present study was carried out in 90 female subjects in the age group of 30 to 45 years. Diagnosis of hypothyroidism and hyperthyroidism was based on both clinical and biochemical criteria. Subjects were divided in euthyroid, hypothyroid and hyperthyroid groups with each group containing 30 subjects. Resting SBP was measured in all the groups. Results: Hyperthyroid group had significantly higher SBP as compared to euthyroid group and hypothyroid group. The difference in SBP between euthyroid and hypothyroid group was statistically non-significant. There was a significant correlation between Total T3 level and resting SBP. Conclusion: Elevated levels of thyroid hormone increases the cardiac output by increasing heart rate and increasing force of contraction. This elevated cardiac output in hyperthyroid subject is reflected as increase in resting SBP. Hence, thyroid hormone concentration should be kept within normal limits by appropriate therapeutic measures so as to prevent ill effects of resultant elevated SBP.

ASSOCIATION OF THYROID HORMONE LEVELS WITH LUTEAL PHASE DEFICIENCY IN INFERTILE WOMEN

Objectives: To find out the association of thyroid hormone levels with Luteal Phase Deficiency (LPD) Methodology: This prospective study was conducted at Peshawar Medical College, from April to August 2013. The sample size was 125 infertile women of the reproductive age group (18-42 years) selected through consecutive sampling technique. On the 22nd and 23rd of the menstrual cycle, endometrial biopsies were performed. Chemilu­minescence Immunoassay was used to estimate the serum levels of the thyroid hormones. SPSS version 19 was used to conduct the statistical analysis. The Chi-square test was used to see whether there was any statistically significant difference between the endometrial findings of patients with normal thyroid profiles and those who had elevated thyroid hormone levels. It was deemed statistically significant when the probability value was p&lt;0.05. Results: The majority of infertile patients (n=99) had normal thyroid profiles, followed by hyperthyroid cases (n=23). Only three turned out to be hypothyroid. There was no significant difference in endometrium between the patients with normal and increased thyroid hormone levels. Conclusion: Although no statistically significant association between the thyroid hormones levels and the endo­metrium in cases of Luteal Phase Deficiency could be found in this study, their role cannot be ignored and needs further evaluation

Abstract LB023: Thyroid hormone receptor signaling promotes antiandrogen resistance and bone metastasis in prostate cancer

Abstract Background: Systemic factors from the tumor microenvironment (TME) promote prostate cancer (PCa) progression, metastasis, and drug resistance. Therefore, the identification of the systemic factors that can modulate the tumor cells and promote metastases will be critical to improve the efficacy of clinical treatment. Both mechanistic and functional studies revealed that acquisition of an open chromatin state on master regulators or cis-regulatory elements allow them to respond readily to microenvironment signals, thereby increasing cancer cell plasticity, tumorigenicity and malignant potential. Accordingly, analysis of open chromatin regions can help prioritize and identify risk of functionally noncoding variants. Given the power of open chromatin profiling on environmental risk prediction, we hypothesized that analysis of open chromatin regions may enable us to recognize functional trans-regulatory elements with their relevant systemic factors. Methods and Results: In human prostate cancer cells, AR blockage by enzalutamide can induces cell reprogramming, as well as transcriptional dysregulation of the heterochromatin compaction pathway. Hence, we proposed that the cells were undergoing chromatin decondensation followed by epigenetic reprogramming. To detect the genome-wide open chromatin changes in this process, we performed time course ATAC-seq and H3K27ac ChIP-seq experiments on LNCaP cells treated with enzalutamide over a 2 weeks period. Bioinformatic analysis was performed to identify the “open” enhancers and the transcriptional factors potentially bound to these enhancers. Integrated transcription factor binding motif analysis of metastatic castration-resistant prostate cancer (mCRPC) associated enhancer regions (GSE130408) and multiplexed siRNA screening revealed Thyroid Hormone Receptor Beta (THRB) as the top candidate. THRB is regulated by the thyroid hormone (T3), a systemic nuclear hormone that, in enzalutamide pretreated LNCaP, VCaP and 3PDXs, is able to induce subsequent reprogramming to a fully enzalutamide-resistant and metastatic state. Interestingly, we observed that THRB regulated genes are upregulated in T3-induced resistant prostate cancer cells. Consistently, the THRB protein, TRβ, is abundant in several aggressive PCa cell lines. Notably, knockdown of THRB reverted the growth and the bone metastatic potential of highly aggressive PCa models, such as Ptenpc-/-Smad4pc-/- and PC3M cells. Furthermore, both transcriptomic and functional analyses identified RUNX2 as a transcriptional target of THRB. In summary, we identify a novel mechanism of THRB-mediated tumor progression and drug resistance in PCa cells. Conclusion: Epidemiologic evidence indicates a higher incidence of PCa in men with elevated thyroid hormone levels. Accordingly, our results suggest a new mechanism for thyroid hormone signaling regulating metastasis potential and drug resistance. This study will provide a new perspective to identify the signals from the TME that may increase the risk of PCa progression. Citation Format: Yan Wang, Gurrapu Harsha, Dhiraj Kumar, Josue Curto, Xiaobo Wang, Filippo Giancotti. Thyroid hormone receptor signaling promotes antiandrogen resistance and bone metastasis in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB023.

Maternal Exercise Before and During Pregnancy Facilitates Embryonic Myogenesis by Enhancing Thyroid Hormone Signaling.

Background: Maternal exercise (ME) improves fetal and offspring muscle development, but mechanisms remain to be established. Since the thyroid hormone (TH) is critical for cell differentiation during embryonic development, we hypothesized that ME elevates TH receptor (THR) signaling in embryos, which promotes embryonic myogenesis. Methods: Female mice were exercised daily on a treadmill or received a daily TH, triiodothyronine (T3) injection. Embryos (embryonic day 12.5 [E12.5]) and P19 cells were used for studying effects of TH on embryonic myogenesis. TH levels in serum and embryos after ME or T3I were analyzed. Expression of TH signaling related genes and myogenic genes was assessed. THRα binding to the promoters of myogenic genes was investigated by chromatin immunoprecipitation-qantitative polymerase chain reaction (ChIP-qPCR). A CRISPR/CAS9 plasmid was utilized to knock out THRα in P19 cells. Results: ME elevated TH levels in both maternal circulation and embryos, which were correlated with enhanced TH signaling and myogenesis. At E12.5, both myogenic determinants (Pax3, Pax7) and myogenic regulatory factors (Myf5, Myod) were upregulated in ME embryos. ME increased THRα content and elevated messenger RNA (mRNA) expression of TH transporter Slc16a2 and deiodinase Dio2. In addition, the THRα binding to the promoters of Pax3/7 was increased. In P19 embryoid bodies, T3 promoted myogenic differentiation, which was abolished by ablating THRα. Furthermore, maternal daily injection of T3 at a level matching exercised mothers promoted embryonic myogenesis. Conclusions: ME promotes TH delivery to the embryos and enhances embryonic myogenesis, which is partially mediated by enhanced TH signaling in ME embryos.

Thyrotoxic Hypokalemic Periodic Paralysis: Case Report

Introduction: &#x0D; Thyrotoxic Hypokalemic Periodic Paralysis (THPP) is a rare hereditary disorder which is characterized by thyroid hormone elevation, low blood potassium level and recurrent acute muscle weakness. Basic pathology is thought to be the increase in activity in the sodium-potassium pump (Na+/K+ATPase). &#x0D; &#x0D; Case report: &#x0D; Here we report the case of a 31-year-old male that presented with weakness in his legs, and inability to walk. The patient had elevated thyroid hormone levels (FT3 and FT4) and lower TSH levels, lower serum potassium levels, and recurrent acute muscle weakness. The diagnosis was made to be Thyrotoxic Hypokalemic Periodic Paralysis precipitated after intense physical activity. &#x0D; &#x0D; Conclusion: &#x0D; THPP is a reversible medical emergency. Early diagnosis, and rapid treatment is lifesaving. Although rare, THPP must be considered as a differential diagnosis in patients presenting with hypokalemia and paralysis.

Мінеральна щільність та метаболізм кісткової тканини у разі тиреотоксикозу

Introduction. Hyperthyroidism is a pathological condition of the body due to increased of thyroid hormones in blood. The prevalence of this pathology increases with age. In the age period from 40 to 60 years it is 0.45%, and after 60 years the risk of the disease increases and is 1.4%. Aim is to analyze the condition of bone tissue in the conditions of thyrotoxicosis on the basis of literature data. Materials and methods are content analysis of the literature on studies of mineral density and bone metabolism in patients with thyrotoxicosis syndrome. Results. Thyroid hormones at physiological concentrations have an important role in skeletal development, reaching peak bone mass and maintaining bone mass during adulthood. It is proved that the effect of thyroid hormone on bone cells is carried out by hormone-receptor interactions. Receptors for thyroid hormones and TSH are found on osteoblasts and osteoclasts, which testifies to their direct action on the cell. The presence of calcium in the skeleton is mainly determined the bone mineral density. Hyperthyroidism is associated with negative calcium balance. When thyrotoxicosis decrease the bone density is observed in 10–20% of patients. This is due to a violation of bone remodeling by increasing metabolism with a disproportionate increase in bone resorption and increased bone formation, but the activation of bone formation cannot fully compensate for the loss of bone mass in the background enhanced resorption. With increasing severity of hyperthyroidism concentration in serum alkaline phosphatase, osteocalcin, and osteoprotegerin growth factor FGF-23 of fibroblasts, indicating increased bone metabolism accompanied by activation of bone resorption. When reducing subclinical hyperthyroidism TSH with normal T3 and T4, or elevated levels of thyroid hormones in the suppression of TSH. It is associated with decreased bone mineral density, increased fragility of bones with a high risk of fractures. Conclusions. Skeletal development and maintenance is regulated by a normal balance of thyroid hormones. Hyperthyroidism is associated with a prolonged cycle of bone remodeling, increased resorption and bone formation. However, the activation of bone formation observed in thyrotoxicosis is not able to fully compensate for the loss of bone mass against the background of increased resorption, which leads to osteoporosis and increased risk of fractures.

Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

Resistance to thyroid hormone beta (RTHβ) is an inherited syndrome caused by mutations in the thyroid hormone receptor β (THRB) gene. Patients with RTHβ typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHβ patients and further to explore their association with THRB gene mutations. We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHβ patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHβ patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHβ. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. The frequency of AITD in male RTHβ patients was significantly higher compared to unaffected relatives. More than 20% of RTHβ patients temporarily showed laboratory findings atypical of RTHβ during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Selective Pituitary Resistance to Thyroid Hormone: Clinical Hyperthyroidism with High TSH on Levothyroxine Administration in I-131 Ablated “Graves Disease”

Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.

Clinical outcomes of 34 patients with resistance to thyroid hormone beta: a twenty-year experience in Japan.

Resistance to thyroid hormone beta (RTHβ) caused by germline mutations in genes encoding thyroid hormone receptor beta (TRβ) is a rare disorder. Little information is available regarding the clinical experience of this syndrome in Japan. We retrospectively reviewed the records of 34 patients with RTHβ (21 adult females and 13 adult males) with positive TRβ mutations identified at our division between 2000 and 2020. Of the 24 patients with available clinical history, 10 (41.7%) received inappropriate treatments such as antithyroid drugs, thyroidectomy, or radioactive iodine. Diagnostic delay and inappropriate management of RTHβ are still present in Japan. Every patient except one demonstrated thyroid hormone profiles indicative of syndrome of inappropriate secretion of thyrotropin (SITSH), characterized by a hormonal profile of hyperthyroxinemia with a non-suppressed TSH concentration. Since the most common forms of hyperthyroidism including Graves' disease feature elevated thyroid hormone levels with suppressed TSH concentrations, early diagnosis of SITSH is critical for preventing inappropriate management. One patient positive for anti-thyroglobulin antibody (Tg-Ab) and anti-thyroperoxidase antibody (TPO-Ab) showed remarkably elevated TSH (>200 μIU/mL) despite thyroid hormone concentrations within the reference ranges. At least one thyroid autoantibody (Tg-Ab, TPO-Ab, or thyrotropin receptor antibodies) was identified in 37.9% (11/29) of the patients tested. One patient developed overt Graves' disease nine years after RTHβ diagnosis. These findings suggest that RTHβ is frequently comorbid with additional autoimmune thyroid disorders. Further research is required to identify the most appropriate treatments for RTHβ patients who develop a second thyroid disorder.

A systematic review of euthyroid Graves' disease (Review).

Euthyroid Graves' Disease (EGD) is a challenging pathology, due to its atypical clinical manifestations and the absence of abnormal thyroid function. Typically, thyroid ophthalmopathy is associated with elevated thyroid hormone levels and with the presence of thyrotropin receptor antibodies (TRAb) but a low percentage of patients remain euthyroid without developing hyperthyroidism during long-term follow-up periods. Although it is considered a different pathology, it shares a lot of similarities with Graves' disease, rendering the diagnosis more difficult. It is also important to note that ophthalmopathy may be the first clinical manifestation of Graves' disease and that thyroid function examinations do not present abnormalities over a long period. Treatment choices for euthyroid disease do not differ from those described in Graves' ophthalmopathy. However, it is considered that since euthyroid patients develop milder ophthalmic symptoms and their clinical activity score is lower, they tend to have better responses to treatment. Moreover, atypical sight-threatening cases such as exposure keratopathy and dysthyroid optic neuropathy with variable responses to therapy also exist. Disease management consists of a favorable collaboration between ophthalmologists and endocrinologists because patients with EGD can develop thyroid abnormalities over time. In conclusion, the diagnosis of EGD is difficult, clinical manifestations and evolution are variables depending on several factors, including the heterogeneity of TRAb. This review aimed to identify the characteristics of this disease by reviewing the clinical studies and case reports published in previous years.

Thyreotroop adenoom van de hypofyse: een zeldzame oorzaak van hyperthyreoïdie

TSH-secreting pituitary adenoma: a rare cause of hyperthyroidism Central hyperthyroidism is noted in a 35-year-old man with recurrent panic attacks. Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-secreting adenoma) is found to be the underlying etiology. A pituitary adenomectomy is carried out, with regression of the symptoms and hyperthyroidism. TSH-secreting adenomas are rare and cause hyperthyroidism due to autonomous TSH secretion. In addition to hyperthyroidism, dysfunction of other pituitary axes and neurological problems due to local compression may also be present. Biochemically, TSH adenoma is characterized by elevated levels of thyroid hormones without suppression of the TSH concentration. After analytical interference has been ruled out, additional biochemical and radiological investigations are necessary in the differential diagnosis and to establish diagnostic certainty. Neurosurgical resection is the cornerstone of the treatment, although radiotherapy and somatostatin analogs may also be considered.