To Thyroid-stimulating Hormone Research Articles

Stimulating thyroglobulin to TSH ratio predict long-term efficacy of 131I therapy in patients with differentiated thyroid cancer after total thyroidectomy: a retrospective study.

This study utilized the stimulated thyroglobulin (sTg) to thyroid stimulating hormone (TSH) ratio to predict the long-term efficacy of 131I therapy in patients with moderate-to-high-risk differentiated thyroid cancer (DTC). This study retrospectively analyzed 960 DTC patients with a median follow-up time of 30 months (6-92 months). The median age was 44 years. All patients underwent total thyroidectomy, lymph node dissection, and at least one 131I therapy. Patients were subjected to a final efficacy evaluation according to American Thyroid Association's 2015 guidelines. Patients were grouped according to their TSH levels before the initial 131I therapy and the final efficacy evaluation, and factors influencing TSH levels and final efficacy were analyzed. Construction of nomograms using independent risk factors affecting long-term outcomes. The cut-offs of sTg and sTg/TSH ratios were calculated for different long-term outcomes. Progression-free survival (PFS) of patients was analyzed by making Kaplan-Meier survival according to the cut-offs of sTg and sTg/TSH ratio. TSH (mU/L) levels were more concentrated at 60-90 in females (71.5%) and 30-60 in males (39.0%), while patients with younger age, more lymph node metastases, shorter time interval between surgery and the first 131I therapy, and lower dose of levothyroxine sodium taken prior to the first 131I therapy would have higher TSH levels (All P < 0.05).Patients who are male, have primary tumor involvement of the strap muscles, lymph node metastasis, distant metastasis, and higher sTg and sTg/TSH are more likely to have poor long-term outcomes (All P < 0.05).The cut-offs of sTg and sTg/TSH for long-term efficacy were 7.515 and 0.095. STg, sTg/TSH, tumor size, lymph node metastasis, and distant metastasis were shown to be independent risk factors for long-term efficacy. The mean PFSs were longer for patients who had sTg/TSH ≤ 0.095 and/or sTg≤7.515 ug/L. For patients with moderate-to-high-risk DTC, when sTg>7.515 ug/L and/or sTg/TSH > 0.095 before the first 131I therapy, patients are more likely to have a poor long-term efficacy after full 131I therapy. This means that this group of patients may require further surgical treatment or targeted drug therapy after 131I therapy.

A-060 Thyroid Laboratory Database Assessment Shows that Total Triiodothyronine Significantly Decreases with Age

Abstract Introduction The effects of aging on human thyroid function are well studied in relationship to thyroid stimulating hormone (TSH) and free tiroxine (FT4); TSH increases, while FT4 decreases with age. Although animal studies show that total triiodotironine (TT3) is lower in aged male rats, these changes are still not clear enough in humans. The National Academy of Clinical Biochemistry (NACB) suggests that TT3 levels would be lower in subjects over 60 years (y.), but the number of elderly assessed was too small for a robust statistical analysis. In search on PubMed, crosschecking the terms elderly/age/aging, with triiodothyronine/T3/total T3, there are a few studies available using current assays with a significant number of patients. Therefore, the demonstration of how the TT3 performs with age is still an opened question. Objective The aim of this study was to observe if TT3 changes significantly with age. Methods We, retrospectively, analyzed blood samples requesting serum TT3 of unique patients, who had TSH measured on the same day; and thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), anti TSH receptor antibodies (TRAb) or TSH receptor-stimulating immunoglobulin (TSI) at any time since patient admission. Subjects were adults ≥20 y., admitted to a private reference clinical laboratory in Brazil, from January 01, 2014 to December 31, 2022, using anonymized data. Serum TT3 was measured in Cobas Roche, by electrochemiluminescence assay, reference interval 70–210 ng/dL. Exclusion criteria were (and/or): tests performed in hospitals, use of drugs that could interfere on TT3 or TSH, TSH ≤ 0.1 mIU/L or ≥10.0 mIU/L, and any positive antibody at any time. The level of statistical significance was P &amp;lt; 0.05. Results Initially, 959 297 records from the database were surveyed. After applying the exclusion criteria, 141 819 subjects were eligible: mean age = 45 y.; median = 42 y., 62% female (F). Statistically significant differences - P &amp;lt; 0.05 for all comparisons between groups - were found by age and gender in TT3 mean values (in ng/dL). Regarding age: from 20 to 59 y. = 120 ± 26.6; 60 to 79 y. = 109 ± 20.7; and 80 y. and over = 97.2 ± 20.0. By gender: F = 120 ± 28.9; male = 114 ± 20.4. It was also observed that, in elderly, while TT3 decreases, TSH increases (results not shown). Comparing TT3 means by age groups, it is 9% lower in subjects aged 60–79 y. and 19% lower in those aged 80 y. and older, compared to younger (20–59 y.) subjects. Conclusion TT3 results is influenced by several factors, including age, gender and laboratory assay. As far as we know, searching in PubMed, this is the largest collection of data on the relationship between TT3 and age. The data obtained showed a statistically significant decrease in TT3 in elderly, and mainly in very elderly, and higher levels in women than in men. This finding draws call attention to the fact that these parameters should taken into account when evaluating TT3 levels.

B-032 Total lab Automation Validation/Verification Protocol: First Step of Process Excellence Journey in Smart Core Lab in Kokilaben Dhirubhai Ambani Hospital &amp; Medical Research Institute, Mumbai, India

Abstract Background The total laboratory automation (TLA) involves the integration, automation, consolidation and digitalization of pre-examination, examination, and post-examination processes. It is far simpler to introduce TLA in a lean, highly standardized smart core lab setting than it is to replicate complex procedures based on manual workflows, therefore harmonization/standardization is a requirement. In this era of modern clinical laboratory, a very important step with respect to the quality of the entire process is method validation/ verification. Hence, it is fundamental to verify/validate TLA process flow, new techniques, new methods and new test parameters.During laboratory accreditation process, the most frequently cited deficiency involves inappropriate PQ (Performance Qualification) and verification protocol. The main principles to the PQ laboratory test validation or verification protocol are Accuracy, Precision, Reference Interval, Detection Limit (LOD), Analytical Measurement Range (AMR) and Clinically Reportable Range (CRR), etc. Hence a clinically appropriate turnaround time is guaranteed via validation, which also provides accurate and precise readings. Methods Around 250 parameters, of biochemical and immunoassay for samples like serum/plasma/cerebrospinal fluid/urine have been validated/verified on this automated system. Clinical Laboratory Standards Institute (CLSI) and best practise checklist as per international and national accreditation bodies served as the foundation for verification. Following are the steps for verification. Analytical Accuracy: Run samples by both methods to evaluate bias. Verify Precision: Run 5 replicates per run for 5 days, at all levels of control sera. Check Reference Intervals: Representative 20 healthy individuals are selected. Verify LOB and LOD Values: Run 20 blank (zero calibrator) or low patient samples. Pneumatic System Verification Protocol: 20 samples carried manually by health care assistants and 20 samples transported via the pneumatic system. We have done sigma metrics of 250 parameters in the lab. Results With particular reference to Thyroid Stimulating Hormone (TSH), we have obtained the following results: For the Reference interval study, out of 353 volunteers recruited, 8 volunteer data were excluded (7 outliers, 1 abnormal TPO values). We obtained the reference interval of 0.53–4.489 μIU/mL, which is within the range specified by the manufacturer's reference range. A good level of analytical accuracy is demonstrated between the two instruments with r2 = 0.9938 having a coefficient of variation of 4.32%. The coefficient of variation values of precision for inter laboratory method comparison for lower and high-level values is 1.39% and 1.76% respectively, which is comparable with the manufacturers claims values. The coefficient of repeatability is 1.3442 is higher than 0.7 and hence considered as the two instruments having a good retest reliability. We observed more than six sigma performance of TSH. Based on Operational Specification (OPSpecs) Chart and Method Decision Chart sigma values of all the parameters are evaluated and quality control strategies have been defined. Conclusion Thus, validation of all biochemistry &amp; immunoassay parameters in TLA set up of the smart core laboratory promotes an environment, emphasizing patient safety and quality patient care.

Assessment of thyroid function in patients with rheumatoid arthritis in Kunming, China: A case-control study.

The present study aimed to analyze the prevalence of hypothyroidism in patients with rheumatoid arthritis (RA). In addition, the study aimed to elucidate the correlation of hypothyroidism with RA activity and to investigate the relationship between RA and thyroid dysfunction. A total of 314 patients were categorized into two groups according to thyroid stimulating hormone (TSH) level: RA without hypothyroidism and RA with hypothyroidism. All patients underwent routine laboratory investigation, including thyroid function testing, and complete clinical assessment. These included the determination of the erythrocyte sedimentation rate as well as the level of TSH, free triiodothyronine, free thyroxine, total triiodothyronine level, total thyroxine level, C-reactive protein, rheumatoid factor immunoglobulin (RF-Ig), RF-IgA, RF-IgG, RF-IgM, cyclic citrullinated peptide immunoglobulin G (CCP IgG), complement component 3, and complement component 4. Based on these data, thyroid function, and rheumatoid factor levels were analyzed. Curve estimation using linear regression revealed that CCP Ig level was significantly correlated with the TSH level (r=0.122, P=0.031). TSH level may be used as an auxiliary test to assess disease severity in patients with RA and to evaluate thyroid function. This evaluation parameter may be considered for determining clinical prognosis in patients with RA.

Analysis of Hematological Parameters According to TSH Levels in Thyroid Patients

Objective: In this study, it was aimed to investigate hematological parameters according to thyroid stimulating hormone (TSH) levels in thyroid patients.&#x0D; Materials and Methods: Thyroid function tests and hemogram data of 5130 thyroid patients admitted to our hospital between January 2019 and August 2021 were analyzed retrospectively. &#x0D; Results: There was no significant difference between hemoglobin, MCH, leukocyte, basophil and thrombocyte levels according to TSH levels. When compared in terms of MCV, a significant difference was found between group 1 (TSH

Novel Antimurine Thyroid-Stimulating Hormone Receptor Monoclonal Antibodies.

Autoantibodies against thyroid proteins are present in several thyroid diseases. Thyroid-stimulating hormone receptor (TSHR) is a G-protein-coupled receptor (GPCR) that binds to thyroid-stimulating hormone (TSH) and stimulates production of thyroxine (T4) and triiodothyronine (T3). When agonized by anti-TSHR autoantibodies, aberrant production of thyroid hormone can lead to Graves' Disease (GD). In Hashimoto's thyroiditis (HT), anti-TSHR autoantibodies target the thyroid for immune attack. To better understand the role of anti-TSHR antibodies in thyroid disease, we generated a set of rat antimouse (m)TSHR monoclonal antibodies with a range of affinities, blocking of TSH, and agonist activity. These antibodies could be used to investigate the etiology and therapy of thyroid disease in mouse models and as building blocks in protein therapeutics that target the thyroid for treatment in either HT or GD.

The electromagnetic field and thyroid reactivity to thyroid stimulating hormone (TSH)

Wydawnictwo SIGMA-NOT wydaje czasopisma fachowe informujące swoich czytelników o najnowszych osiągnięciach naukowych i nowoczesnych rozwiązaniach technicznych w Polsce i na świecie, popularyzuje problemy techniczne oraz poszerza wiedzę i kulturę techniczną.

Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism

BackgroundTo evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT).MethodsA retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25–75th percentile) age was 52 (49–54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6–18 month cycles, serum endocrine hormone and metabolic indices were reassessed.ResultsCompared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment.ConclusionMHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.

Effect of Vitamin – D Supplementation On Serum TSH Levels in Pregnant Women and Its Co Relation to Age and Body Mass Index.

The main aim of the study is to investigate the association between vitamin D after insufficiency and thyroid hormone levels in pregnancy. The objective of the present study is to see how serum vitamin D levels are related to Thyroid stimulating hormone (TSH) during the first trimester of after pregnancy in relation to the age and BMI of the pregnant women. In this crosssectional study 100 pregnant women (50as control group, 50 as vitamin D supplementation group) are included and categorized as per their age and BMI. Vitamin D supplementation is done under the supervision of the gynecologist at the start of 1st trimester and at the end of the first-trimester, serum TSH levels are estimated in them. The mean was analysed by two-way ANOVA (Twoway analysis of variance with Bonferroni‘t’ test method). For all the statistics and graph plotting, SigmaPlot 13.0 (Systat software, USA) was used. P &lt;0.05 is considered significant. The difference in the mean values among the different levels of the group is not significant enough to exclude the after possibility that the difference is just due to random sampling variability after allowing for the effects of differences in BMI Category. There is not a statistically significant difference (P = 0.506). According to the findings of this study, there is no correlation between vitamin D levels and TSH levels in relation to the age and BMI of pregnant women; therefore, more research should be done on groups of pregnant women divided by weeks of pregnancy and age, and vitamin D supplementation should be recommended.&#x0D;

Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity

To normalize the thyroid status in hypothyroidism caused by resistance to thyroid-stimulating hormone (TSH), low-molecular-weight allosteric agonists of TSH receptor can be used. A new compound ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]-pyrimidine-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), which stimulated the production of thyroxine when administered to rats (25 mg/kg, i.p.) and also increased the expression of thyroidogenic genes in the cultured FRTL-5 thyrocytes (30 μM) and the rat thyroid gland. The in vitro and in vivo treatment with TPY3m did not lead to a decrease in the expression of the TSH receptor gene in thyrocytes, restoring it under the conditions of receptor hyperactivation by the hormone. This determines the retaining and, in some cases, potentiation of the thyroidogenic effects of TSH (FRTL-5) or thyroliberin (rats) when they are coadministered with TPY3m. TPY3m is a prototype drug for correcting thyroid system functions in subclinical hypothyroidism.

Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism.

Objective: There is little literature about whether antihypertensive drugs would affect thyroid function in patients with euthyroid type 2 diabetes, which was significant in maintaining a proper balance of thyroid function. A retrospective cohort study was conducted to evaluate the influence of antihypertensive drugs on thyroid function in patients with type 2 diabetes with euthyroidism. Design and Methods: The study involved dividing 698 patients with antihypertensive monotherapy into five groups according to the antihypertensive drugs they were treated with. Antihypertensive drugs included in this study were β-blockers, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB). The clinical data and thyroid function level between or within groups were compared. Multiple logistic regression analysis was conducted to evaluate the association of antihypertensive drugs with thyroid function level. Results: Selective β1- adrenergic receptor blockers treatment was related to thyroid-stimulating hormone (TSH), increasing in patients with diabetes and euthyroidism as shown by multiple logistic regression analysis. The association existed after adjustment for confounding factors. No significant influence on thyroid function was found among other antihypertensive drugs. Conclusion: These data show the TSH-lifting effect of selective β1-adrenergic receptor blockers in patients with type 2 diabetes with euthyroidism.

Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period

Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood are rare and contradictory. Approaches for the correction of metabolic and hormonal disorders caused by premature cessation of breastfeeding have not been developed yet. The aim of the work was to study the metabolic and hormonal parameters and changes in the hormonal status of the gonadal and thyroid systems in 10-month-old male rats with interruption of breastfeeding on days P19-P21, as well as to evaluate the restorative effect on them of four weeks of treatment with intranasal insulin (II) administered in the postnatal period (P28-P55) or in adulthood (P183-P210). Lactation interruption has been induced by treatment of lactating females with bromocriptine (10 mg/day/rat, P19-P21). Male rats with temporary cessation of breastfeeding developed characteristic signs of the metabolic syndrome (obesity, dyslipidemia, impaired glucose tolerance, hyperleptinemia), decreased levels of testosterone and thyroid hormones (fT4, tT3) and weakened the synthesis of testosterone and thyroxine, stimulated respectively by GnRH and thyroliberin. This was due to a decrease in the sensitivity of the testes to luteinizing hormone (LH) and the thyroid gland to thyroid-stimulating hormone (TSH). Treatment with II in early ontogenesis reduced body weight and fat, improved lipid profile, sensitivity to insulin, leptin, LH and TSH, restored the levels of testosterone and thyroid hormones and their stimulation by releasing factors. Treatment with II in adulthood normalized the levels of testosterone, thyroid hormones, their stimulation by releasing factors, but had a little effect on metabolic and hormonal parameters. The obtained data point to a wide range of metabolic and hormonal disorders in adult male rats with the "neonatal" model of metabolic syndrome and to the effectiveness of various strategies for their correction using long-term II treatment.

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder.

The present study was aimed to investigate the relationships between serum thyroid hormones (THs), frontal gray matter volume, and executive function in selected patients with major depressive disorder (MDD). One hundred and four MDD patients and seventy-five healthy controls (HCs) were subjected to thyroid-stimulating hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), and executive function tests and underwent structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis was performed to compare group differences in the gray matter for the frontal lobe. Furthermore, mediation analysis was used to investigate whether gray matter volumes of the frontal gyrus mediated the relationship between serum THs and executive function in MDD patients. MDD patients exhibited significant gray matter volume reduction in several brain regions, including the left rectus, right middle frontal cortex, and left middle frontal cortex. Serum TSH levels are positively associated with altered regional gray matter volume patterns within MFG and executive function. Importantly, gray matter in the right MFG was a significant mediator between serum TSH levels and executive function. These findings expand our understanding of how thyroid function affects brain structure changes and executive function in MDD patients.

Pseudohypoparathyroidism-Ib due to novel heterozygous stop gain mutation in exon 8 of STX16 gene: A case report

We report a case of pseudohypoparathyroidism type 1b (PHP1b) manifesting in childhood with hypocalcemic seizures. Symptomatic hypocalcemia is a common emergency in the pediatric age group with vitamin D deficiency being a frequent underlying etiology and PHP is rare. Patients with PHP1b do not depict the Albright’s hereditary osteodystrophy (AHO) phenotype typical of patients with PHP1a and pseudopseudohypoparathyroidism (PPHP). The resistance to parathyroid hormone (PTH) is documented mostly at renal tubular site of action in patients with PHP1b. Hypothyroidism is reported occasionally, signifying resistance to thyroid-stimulating hormone (TSH). Individuals with autosomal dominant and maternally inherited form of PHP harbor methylation defects at GNAS exon A/B, while sporadic and non-familial cases harbor methylation defects at other locus sites, including differentially methylated regions (GNAS-DMR). A novel heterozygous stop gain mutation c.C910T/p.Arg304X in exon 8 of the STX16 gene (Syntaxin 16) was observed in our case. Resistance seems limited to the renal action of PTH alone as currently, TSH level is normal. Maternal STX16 gene analysis results confirmed the modality of inheritance.

P–424 Evaluating the relationship between endoplasmic reticulum stress and recurrent pregnancy loss in a young population cohort

Abstract Study question Does endoplasmic reticulum (ER) stress evaluated by X-box binding protein 1 (XBP–1) among patients aged 18–30 years play a role in recurrent pregnancy loss (RPL)? Summary answer High levels of XBP–1 observed in patients with known RPL indicate that ER stress plays an important role in RPL. What is known already Female reproductive tract undergoes dynamic changes during oogenesis which require protein synthesis, folding, maturation, which take place in the ER. ER is also responsible for destruction of unfolded/misfolded proteins. Excess accumulation of these faulty proteins leads to ER stress, which actives unfolded protein response (UPR). XBP–1 is a transcription factor involved in UPR and regulates ER stress-mediated apoptosis. Regulation of ER homeostasis is important in folliculogenesis, oocyte maturation and embryogenesis. It is also known that ER stress has a positive correlation with age and it is associated with age-related diseases. Study design, size, duration This prospective case-controlled study was conducted at University of Health Sciences Turkey, Istanbul Kanuni Sultan Suleyman Training and Research Hospital Department of Obstetrics and Gynecology between March 2020 – September 2020. A total of 70 subjects were included in the study. All patients gave their written informed consent before their enrollment in the study. Participants/materials, setting, methods 38 patients aged 18–30 years with a history of RPL were included in the study. Patients who had miscarriages due to fetal abnormalities, patients with infections, endocrine or genetic disorders, smokers, alcohol and/or drug abusers, with acute/chronic inflammatory diseases, patients using steroids, anti-inflammatory and antioxidant medications were excluded from the study. Age-matched 32 healthy subjects without RPL were included in the control group. XBP–1 levels were determined using Human XBP–1 ELISA Kit (Elabscience Co., USA). Main results and the role of chance The mean age in the control group and in the study group were 25.21±3.3 and 25.26±2.6, respectively and they were statistically similar (p = 0.324). When groups were compared according to thyroid stimulating hormone (TSH) levels and body mass index (BMI), which are additional risk factors of RPL both groups were statistically similar (p = 0.642 and 0.942, respectively). As expected gravidity and abortus numbers were significantly higher in the study group (p &amp;lt; 0.001). A mean XBP–1 level of 1233.41± 3902.97 was determined in the control group. The mean value of the study group was calculated to be 2251.49± 9621.12. Mean XBP–1 level in the study group was significantly high (p &amp;lt; 0.001). A receiver operating curve (ROC) analysis was conducted in the study group. The area under the curve was found to be 87% (95% CI: 79% - 95%). The specificity was 75%, sensitivity was 89%, positive LR was 3.5, negative LR was 0.15, positive predictive value was 80% and negative predictive value was 87% for the cut-off XBP–1 level at 1364.68 pg/mL. Limitations, reasons for caution Small sample size is an important limitation of this study. In addition, evaluating XBP–1 only in serum samples does not let us drive any conclusions on the local changes of ER stress. Studies with larger samples sizes and studying XBP–1 levels in tissue samples of endometrial material is needed. Wider implications of the findings: The significantly high levels of XBP–1 in RPL patients younger than 30 years, indicate higher ER stress in this group even when age dependent increase in ER stress is calculated out of the equation. XBP–1 can be a promising marker in evaluating patients with a fertility wish for RPL risk. Trial registration number NCT04455256

Subclinical hypothyroidism contributes to poor glycemic control in patients with type 2 diabetes mellitus, and ellagic acid attenuates methimazole-induced abnormal glucose metabolism in mice model.

Subclinical hypothyroidism (SCH) as mild thyroid disorder or comorbidity in patients with endocrine disorders is closely related with insulin resistance (IR) and poor glycemic control. The present study attempted to investigate the effect of SCH on IR and glycemic control in patients with type 2 diabetes mellitus (T2DM). In addition, the effects of ellagic acid (EA) on SCH C57BL/6J and db/db mice were also investigated to explore potential therapeutic drug against SCH-induced abnormal glucose metabolism. T2DM patients were recruited in our study and categorized into two groups accordingto thyroid stimulating hormone (TSH) value: T2DM without SCH group (TSH ≤4μIU/ml; n=30) and T2DM with SCH group (TSH >4μIU/ml; n=60). Methimazole (MMI; 0.08mgkg-1 day-1 ) was intragastrically administrated for 12weeks to establish SCH in C57BL/6J and db/db mice. Compared with T2DM patients without SCH, poor glycemic and cholesterol control were emerged in T2DM patients with SCH and that were prominent in patients with TSH more than 10μIU/ml. In addition, a significant positive correlation between serum TSH and fasting plasma-glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or glycated hemoglobin (HbA1c) was observed in T2DM patients with SCH. Moreover, abnormal glucose metabolism in C57BL/6J and db/db mice with SCH has been attenuated by EA administration. Our findings provided data regarding the positive correlation between high TSH level with poor glycemic control in T2DM patients with SCH. EA might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism. PRACTICAL APPLICATIONS: Subclinical hypothyroidism (SCH) is a potential risk factor associated with abnormal glucose metabolism in patients with type 2 diabetes mellitus (T2DM). A clinical theory of a positive correlation between high TSH level and poor glycemic control was validated in type 2 diabetes mellitus patients and mouse models. Ellagic acid (EA) might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism that provided a treatment option in T2DM patients with subclinical hypothyroidism in clinical practice.

Delayed Postnatal Growth and Anterior Pituitary Development in Growth-Retarded (grt) Female Mice.

Growth-retarded (grt) mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined somatic growth, anterior pituitary development, and hormonal profiles in female grt mice and normal ones. Although growth in grt females was suppressed 2 weeks after birth, the measured growth parameters and organ weights gradually increased and finally reached close to the normal levels. Grt mice exhibited delayed eye and vaginal openings and remained in a state of persistent diestrus thereafter, plasma estrogen levels being lower than those in normal mice. Grt mice that received normal-donor thyroids showed accelerated growth and their body weights increased up to the sham-normal levels, indicating the importance of early thyroid hormone supplementation. In the anterior pituitary, there were fewer growth hormone (GH) and prolactin (PRL) cells in grt mice than in normal mice as examined at 12 weeks after birth, but the numbers of these cells did not differ from those in normal mice after 24 weeks. Grt mice had more TSH cells than normal mice until 48 weeks. Plasma GH levels in grt mice were lower than those in normal mice at 2 weeks, but did not differ substantially after 5 weeks. Compared with normal mice, grt mice had significantly lower plasma PRL and thyroxine levels, but notably higher TSH levels until 48 weeks. These findings indicate that thyroid hormone deficiency in grt mice causes delayed development and growth, and inappropriate development of GH, PRL and TSH cells, followed by the abnormal secretion of hormones by these pituitary cells.

The diagnostic and predictive accuracy of thyroglobulin to TSH ratio and TSH to thyroglobulin ratio in detecting differentiated thyroid carcinoma in normothyroid patients with thyroid nodules: A retrospective cohort study and systematic review of the literature

The purpose of the present study is to examine the diagnostic and predictive accuracy of the thyroglobulin (Tg) to thyroid stimulating hormone (TSH) and TSH/Tg ratios in normothyroid patients with differentiated thyroid cancer (DTC). We conducted a retrospective cohort study evaluating the diagnostic accuracy of the serum Tg/TSH and TSH/Tg ratios in normothyroid patients with thyroid nodules. We also systematically searched the international literature using the Medline, Cochrane’s CENTRAL, Scopus, Clinicaltrials.gov, EMBASE, and Google Scholar databases for evidence concerning the diagnostic and predictive accuracy of these ratios. Overall, 374 patients were identified in our cohort study of whom 240 were treated for benign disease and 134 were treated for DTC. Significant differences were noted in the Tg/TSH and TSH/Tg values among cases with malignant and benign disease (P=0.020). However, the diagnostic ROC curve did not confirm these results (Tg/TSH=0.572 and TSH/Tg=0.428). After searching the international literature, we identified 8 studies. The majority of the included data reported significant differences among patients with benign/malignant disease and those with successful iodine therapy compared to those with disease relapse. However, the clinical relevance was clearer among studies that investigated the usefulness of these ratios in predicting recurrent disease. The findings of our study support that the Tg/TSH ratio increases in patients with DTC and can, thus, become useful in the future as a predictive marker of ablative 131I therapy success. However, given the significant variability of Tg its diagnostic accuracy remains to date minimal; thus, the actual cut-off value that can be used to discriminate cancer cases from benign disease has not been determined yet.

Long-Term Follow-Up and Outcomes of Autoimmune Thyroiditis in Childhood.

Background: Autoimmune thyroiditis (AIT) is the most common cause of acquired hypothyroidism in children. The natural outcome of AIT in childhood has been reported previously however follow-up duration is generally short and results variable.Objectives: To characterize clinical and biochemical findings at presentation of AIT, evaluate long-term outcomes and assess which factors at presentation predict evolution over time.Study cohort: 201 children under 18 years of age at presentation (82% female) were enrolled. Subjects were divided into five subgroups according to thyroid stimulating hormone (TSH) level at referral.Results: Mean follow-up was 8.1 years (range 0–29 years). At presentation, 34% of patients had overt hypothyroidism, 32% subclinical hypothyroidism (SCH), 16% compensated hypothyroidism, 14% were euthyroid, and 3.7% had Hashitoxicosis. Children with overt hypothyroidism were younger (10.6 vs. 13.2 years) and had higher thyroid peroxidase antibody titers. At the time of the study, levothyroxine (LT4) therapy was required in 26% of children who were euthyroid at presentation, 56% of SCH patients, 83–84% of those with TSH above 10 mIU/L, and 57% of those with Hashitoxicosis. Over the years, 16% of children presenting with overt hypothyroidism stopped therapy. Free T4 at presentation was the only predictor of outcome over time.Conclusions: Our findings suggest that only 26% children who were euthyroid at presentation developed hypothyroidism, whereas over 50% of those with SCH went on to require treatment. Of those presenting with overt hypothyroidism, 16% recovered with time. The only predictive parameter for LT4 therapy at the end of the study was free T4 levels at presentation. Long-term follow-up is required to determine ongoing therapy needs and screen for additional autoimmune diseases.

SUN-524 Patient with Pseudohypoparathyroidism Type 1B, Graves Disease, and False Positive HIV Screen- a Rare Presentation

Background: Pseudohypoparathyroidism 1B (PHP1B) is a disorder that can lead to thyroid stimulating hormone (TSH) resistance and hypothyroidism, although it is rarely associated with thyrotoxicosis.Clinical Case: A 25-year-old female with a history of PHP1B, seizures due to hypocalcemia, and family history of PHP1B in her three sisters and brother presented to our emergency room with a fever of 1030F and generalized malaise. Two months prior, she was seen at an outside hospital with palpitations and bulging of the left eye. There, she was diagnosed with hyperthyroidism, started on methimazole, and asked to continue levetiracetam and calcitriol upon discharge.On our exam, she had tachycardia of 120 beats per minute, left eye proptosis, positive Chvostek sign, and a large goiter with bruit. Reflexes were 3+.Laboratory evaluation revealed corrected serum calcium of 6.1 (8.5-10.5 mg/dL), TSH < 0.01 (0.34-5.60 mU/L), free T4 2.81 (0.60-1.60 ng/dL), free T3 13.0 (2.4-4.2 ng/dL), and iPTH 131 (12-88 pg/mL). ELISA testing for screening of HIV was positive. She was treated with IV calcium gluconate, methimazole, propranolol, and hydrocortisone. Her home doses of calcitriol and calcium were resumed. She was referred for total thyroidectomy as an outpatient once she became euthyroid. The confirmatory Western blot test for HIV was negative. It was determined that presence of thyroid stimulating immunoglobulin resulted in the false positive ELISA test.Discussion: Hyperthyroidism with Graves disease seen in PHP has only very rarely been reported. (1) It has been postulated that abnormal electrolytes and elevated parathyroid hormone from PHP may lead to stimulation of the thyroid gland and perpetuate Graves disease symptoms. (2) Furthermore, the presentation of thyrotoxicosis despite TSH resistance in PHP indicates that there may be other mechanisms for TSH receptor antibodies to take effect in these patients which have not yet been determined. (3) Lastly, autoimmune diseases, including Graves disease, can cause a false-positive HIV ELISA as seen in our patient.Conclusion: Although rare, thyrotoxicosis may present in patients with PHP1B. Additionally, it should be kept in mind that autoimmune diseases such as Graves disease can cause a false positive HIV ELISA, and follow-up Western blot testing should therefore be performed.