High T3 Research Articles

Utility of Thyroid Stimulating Hormone (TSH) in Atrial Fibrillation

Atrial fibrillation (AF) has become increasingly common in the inpatient setting. Current practices in new onset AF include obtaining laboratory values such as thyroid stimulating hormone (TSH) with reflex thyroxine (T4). We aim to prove that such practices rarely change management and should be limited to patients with additional indicators of hyperthyroidism. From January 2015 to August 2021, a total of 59,470 patients that were 18 years and older were identified with an admission diagnosis of atrial fibrillation using the ICD-10 code I48.92. Patients were excluded if their sex or age were not identified and if they had a previous admission for atrial fibrillation. Out of the 54,968 patients admitted with AF, TSH was ordered in 7,444 (13.54%), free T4 was ordered in 2,669 (4.85%), and both in 2,285 (4.16%). Only 29 (0.013%) of the 2,285 patients who had orders for both TSH and T4 were found to have both low TSH and high T4, indicating an overt hyperthyroid state. Overall, of the 7,444 patients with TSH labs drawn, only 404 (5.43%) were discharged on methimazole or Propylthiouracil (PTU). While we recognize the importance of identifying modifiable risk factors, we propose that TSH levels should not be reflexively ordered during hospitalization for patients with new onset AF without further clinical suspicion of thyroid disease.

Unraveling the Role of Thyroid Hormones in Seasonal Neuroplasticity in European Starlings (Sturnus vulgaris).

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing toward an active role of thyroid hormones during this window of possible neuroplasticity. In contrast, DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Both under natural conditions as with methimazole treatment, circulating thyroid hormone levels decreased during the photosensitive period, which coincided with the onset of neuroplasticity. This inverse relationship between thyroid hormones and neuroplasticity was further demonstrated by the negative correlation between plasma T3 and the microstructural changes in several song control nuclei and cerebellum. Furthermore, maintaining hypothyroidism during the photostimulated period inhibited the increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic–pituitary–gonadal (HPG) axis. The lack of high testosterone levels influenced the song behavior of hypothyroid starlings, while the lack of high plasma T4 during photostimulation affected the myelination of several tracts. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake on neuroplasticity imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Whereas, an increase in circulating T4 during the photostimulated period potentially influences the myelination of several white matter tracts, which stabilizes the neuroplastic changes. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.

Evaluating maternal exposure to an environmental per and polyfluoroalkyl substances (PFAS) mixture during pregnancy: Adverse maternal and fetoplacental effects in a New Zealand White (NZW) rabbit model

Mixtures of per- and polyfluoroalkyl substances (PFAS) are often found in drinking water, and serum PFAS are detected in up to 99% of the population. However, very little is known about how exposure to mixtures of PFAS affects maternal and fetal health. The aim of this study was to investigate maternal, fetal, and placental outcomes after preconceptional and gestational exposure to an environmentally relevant PFAS mixture in a New Zealand White (NZW) rabbit model. Dams were exposed via drinking water to control (no detectable PFAS) or a PFAS mixture for 32 days. This mixture was formulated with PFAS to resemble levels measured in tap water from Pittsboro, NC (10 PFAS compounds; total PFAS load = 758.6 ng/L). Maternal, fetal, and placental outcomes were evaluated at necropsy. Thyroid hormones were measured in maternal serum and kit blood. Placental gene expression was evaluated by RNAseq and qPCR. PFAS exposure resulted in higher body weight (p = 0.01), liver (p = 0.01) and kidney (p = 0.01) weights, blood pressure (p = 0.05), and BUN:CRE ratio (p = 0.04) in dams, along with microscopic changes in renal cortices. Fetal weight, measures, and histopathology were unchanged, but a significant interaction between dose and sex was detected in the fetal: placental weight ratio (p = 0.036). Placental macroscopic changes were present in PFAS-exposed dams. Dam serum showed lower T4 and a higher T3:T4 ratio, although not statistically significant. RNAseq revealed that 11 of the 14 differentially expressed genes (adj. p < 0.1) are involved in placentation or pregnancy complications. In summary, exposure elicited maternal weight gain and signs of hypertension, renal injury, sex-specific changes in placental response, and differential expression of genes involved in placentation and preeclampsia. Importantly, these are the first results to show adverse maternal and placental effects of an environmentally-relevant PFAS mixture in vivo.

Anxiety in patients with hyperthyroidism

IntroductionMental symptoms are the first manifestations of hyperthyroidism. They include anxiety, dysphoria, irritability, emotional lability, sleep disorders, intellectual dysfunction, mania or depression. Anxiety is the main symptom and requires more detailed study.ObjectivesThe objective was to determine symptomatology of anxiety in patients with hyperthyroidism and compare with euthyroid patients.MethodsThe study included 56 patients with hyperthyroidism (high free T3 and free T4, suppressed TSH) and 32 euthyroid patients (normal free T3, free T4 and TSH) of the control group. For psychiatric assessment State-Trait Anxiety Inventory [STAI], Hamilton Depression Rating Scale [HAM-D], and Hamilton Anxiety Rating Scale [HAM-A] were used.ResultsTotal scores obtained from STAI, HAM-D and HAM-A were significantly greater in the hyperthyroidism group than that of the euthyroid group (p&lt;0.05). The level of state anxiety in patients with hyperthyroidism was 51.39 ± 0.95 (high level) compared with 41.59 ± 2.41 (moderate level) in the control group. The level of trait anxiety in patients with hyperthyroidism was 46.86 ± 0.69 (high level), and 44.16 ± 2.17 (moderate level) in the control group. Psychomotor agitation (HAM-D # 9), psychic anxiety (HAM-D # 10), insomnia (HAM-A # 4) and weight loss (HAM-D # 16) were typical for patients with hyperthyroidism, while in the control group predominate the feelings of fatigue, weakness and loss of interest in working (HAM-D # 7).ConclusionsThe prevalence of anxiety in patients with hyperthyroidism is significantly more frequent compared to euthyroid patients. Anxiety and other psychiatric symptoms should be considered by both endocrinologists and psychiatrists.DisclosureNo significant relationships.

NEOPRISM-CRC: Neoadjuvant pembrolizumab stratified to tumor mutation burden for high-risk stage 2 or stage 3 deficient-MMR/MSI-high colorectal cancer.

TPS3645 Background: The prognostic advantage of early stage deficient-MMR/MSI-High CRC is lost after relapse, so there is a pressing clinical need to maximize the chance of cure in the early stages where prevalence of dMMR is higher comprising approximately 12% of Stage 3 and 20% of Stage 2 CRC. The efficacy of adjuvant checkpoint inhibition in this patient group has yet to be demonstrated in the context of micrometastatic disease without a supporting immune-competent microenvironment. Longitudinal studies especially in the neoadjuvant setting would optimally interrogate post-immunotherapy changes both in time and space. The NEOPRISM-CRC (NEOadjuvant PembRolizumab In Stratified Medicine – ColoReCtal) study is a Phase II Trial to determine whether neoadjuvant Pembrolizumab stratified to tumour mutation burden (TMB) is efficacious and safe. It will also be a platform to explore the relationships between possible predictive novel biomarkers and response to Pembrolizumab in blood, tumour tissue and microbiome. Methods: The study population consists of subjects with newly diagnosed operable dMMR/MSI-H CRC. Patients must be fit and eligible for planned curative surgery based on a) radiological node positive T1-4 CRC or b) high risk T3 defined as EITHER ≥ 5mm of extramural depth of invasion or unequivocal EMVI on imaging (regardless of depth), or T4 disease. They will receive one of two pre-operative regimens depending upon their TMB based on the FoundationOne®CDx test (FM1CDx). All patients will have one 21 day cycle of Pembrolizumab 200 mg IV. Prior to cycle 2 and with the result of the FM1CDx test, patients will continue their treatment as follows: A) TMB-high (defined as ≥20 mutations per Mb) or TMB-medium (defined as 6-19 mutations per Mb), or MSI-H on PCR if FM1CDx test is not evaluable: A further 2 cycles of Pembrolizumab 200 mg IV every 21 days. B) TMB-low (defined as ≤5 mutations per Mb), or if FM1CDx and PCR tests are not evaluable: No further Pembrolizumab given. Surgery to remove the CRC will be performed 4-6 weeks after the last dose of Pembrolizumab in both arms. Following resection patients may receive adjuvant chemotherapy in accordance with local institutional guidelines. The primary end point is pathological complete response rate (pCR). Secondary endpoints include 3 year RFS, OS, safety and health-related quality of life. Up to 32 patients will be registered over a 18-24 month period assuming that the pCR with 3 cycles of Pembrolizumab will be ≥ 33% for patients with high or medium TMB based on the FM1CDx profile, and intend to rule out a percentage ≤10%. To reach 80% power with 5% statistical significance, 19 patients are required in the high/medium TMB arm. The trial will be considered a success if at least 5/19 patients have a pCR after 3 cycles of Pembrolizumab. Enrolment will commence in March 2022. Clinical trial information: NCT05197322.

Association of Thyroid Peroxidase Antibodies and Thyroglobulin Antibodies with Thyroid Function in Pregnancy: An Individual Participant Data Meta-Analysis.

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.

An institutional report of heparin induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients.

Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse. We report our institution's incidence and outcomes of HIT-II in aSAH patients. We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA). 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores. Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.

The Pretreatment Systemic Inflammation Response Index as a Useful Prognostic Factor is Better Than Lymphocyte to Monocyte Ratio in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

It has been reported that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR), as well as systemic inflammation response index (SIRI), are closely related with overall survival (OS) in breast cancer patients. However, which one is the optimal indicator is vague. This study incorporates 280 breast cancer patients who received NACT. A cut-off value of LMR, PLR, SIRI and NLR is determined by Youden index. The Pearson's X2 test or Fisher's exact test is applied to compare the correlation of different clinicopathologic characteristics divided by SIRI. The K-M survival curves and log-rank test were applied to determine OS. Univariate and multivariable analysis are explored by the Cox regression model. We apply the Z test to contrast the prognostic capacity of SIRI, LMR, PLR, and NLR. At the meanwhile, we construct the nomogram based on the results of multivariable analysis. All enrolled cases are divided into two parts by pretreatment SIRI (cut-off value = 0.52). Compared to high pre-treatment SIRI, high pre-treatment NLR and clinical T3 + T4 stage, the low pre-treatment SIRI, low pretreatment NLR and clinical T1 + T2 stage had longer OS time. The Z test showed that the SIRI group had bigger AUC than LMR and PLR, and the difference is statistically significant. The ability of nomogram, based on pretreatment SIRI, pre-treatment NLR and clinical T stage, to predict the 3-year, 5-year, and 8-year overall survival rates of breast malignant tumor patients is better than clinical TNM stage. Pre-treatment SIRI was a more crucial and integral prognostic index for breast malignant tumor patients receiving NACT. It could be helpful for doctors to predict the prognosis of breast malignant tumor patients and to evaluate the treatment status of patients.

GROWTH, DEVELOPMENT AND BIOCHEMICAL RESPONSE OF APPLE AS INFLUENCED BY LIQUID FERTILIZERS (BIOFERT) APPLICATION

Apple is the major fruit crop due to its high nutritional significance and taste. High yield and better quality in apple is highly dependent of optimum fertilizer doses. The present study was aimed in 2012 to check the effect of liquid fertilizers (Biofert (N=3%, P=1%, K=2%) and micronutrients (Ca, Zn, S, Mg, Cl, B, Mo, Cu, Fe, Mn, Co and Ni less than 1%) on growth and yield off apple, alone and in combination with conventional fertilizers (N: P: K 800: 400: 400 g/plant). The experiment was done according to randomized complete block design (RCBD) comprised of six treatments and four replications, in consecutive four years. Parameters regarding the physiological, growth aspects of the apple trees as well as pre and post-harvest analysis of fruit were carried out to evaluate the effect of different nutrient doses on plant growth and produce. Among the growth parameters maximum fruit weight was found in T3 (155 g) and comparatively higher results of fruit yield per plant were obtained in T5 (42 kg). Post-harvest fruit analysis given the best results regarding Juice (56.7%) and Pulp (39.1%) with T3. Vitamin C (2.8 mg/100 ml) was higher T3 and T4 and highest TSS 11.6% was observed in T3. It was concluded that liquid fertilizers along with the conventional fertilizers played an important role to enhance the fruit quality and yield in the climatic conditions of Sunny Bank (7000 ft altitude), Murree.

Wide Spectrum of Thyroid Function Tests in COVID-19: From Nonthyroidal Illness to Isolated Hyperthyroxinemia

BackgroundChanges in thyroid function test (TFT) in COVID-19 patients have been reported in several studies. However, some features such as thyrotoxicosis are inconsistent in these studies. In addition, some drugs such as heparin interfere with the free T4 assay.ObjectivesThis study was designed to examine TFT abnormalities in COVID-19, utilizing direct and indirect methods of free T4 assay.MethodsThis prospective cross-sectional study was conducted on 131 hospitalized COVID-19 patients. Serum levels of total T3, TSH, T3RU, and total T4 were measured. The free T4 assay was performed using direct (free T4) and indirect (free thyroxin index or FT4I) methods. The patients were categorized into different TFT groups. The clinical characteristics, laboratory findings, and outcomes were compared between the groups.ResultsThe frequencies of nonthyroidal illness (NTI), subclinical/overt hypothyroidism and subclinical/overt thyrotoxicosis were 51.7, 6.9, and 6.9%, respectively. Besides, 6 and 8.1% of the patients had isolated high free T4 and isolated high FT4I without any other TFT abnormality, respectively. The lymphocyte percent was lower in the subclinical/overt group than in other TFT groups (P = 0.002). Atrial Fibrillation (AF) was found in 37.5% of subclinical/overt thyrotoxicosis patients versus 1.7% in the NTI and nil in the other three groups (P < 0.001).ConclusionsIn addition to the reported TFT abnormalities in COVID-19 in previous studies, some new features like isolated hyperthyroxinemia were found in our study. We found a strong association between subclinical/overt thyrotoxicosis and AF. Regarding the high prevalence of AF in hospitalized COVID-19 patients, request for thyroid function test is rational in COVID-19 patients with this arrhythmia.

Screening for Hypothyroidism in children with severe acute malnutrition at Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan.

Objective: To determine the percentage of Hypothyroidism in children with severe acute malnutrition. Study Design: Cross Sectional study. Setting: Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan. Period: January 2019 to December 2019. Material &amp; Methods: A total of 255 malnourished patients (as per inclusion criteria) were included in current study. A written Performa was designed to collect history, anthropometric measurements and systemic examination. Taking aseptic measures venous blood was sent for baseline tests as well as for T3, T4 and TSH, total serum protein albumin and total ferritin levels to hospital laboratory. Correlation between serum thyroid concentrations and total protein, albumin, hemoglobin and serum ferritin were estimated by using t-test and p-vlaue less than 0.05 was considered as significant. Total collected data was entered and analyzed in SPSS version 21.0. Results: A total of 255 malnourished children were included in this study. Majority of studied subjects were male (52.5%) with 83.92%, 3-5 years of age. Amongst the 255 children mean values of T3 in MAM and SAM patients were 105.4 ng/dl and 89.7 ng/dl respectively. There was a statistically significant (p &lt;0.001) association between decreased T3 and type of malnutrition. Similarly, mean values of T4 in MAM and SAM patients were 6.3 ug/dl and 5.7 ug/dl respectively that was statistically significant (p &lt;0.05). Lower values of T4 were higher among SAM children in 1 to 3 years age group compared to respective MAM children with p value .0.05 and high T4 value in 3-5 years age group of MAM children were both statistically insignificant. Higher mean Values of TSH was found in SAM compared to MAM children both age groups. Conclusion: Severe acute malnutrition (SAM) is associated with reduction in T3 and T4 levels and higher levels of TSH in SAM children as compared to MAM. The altered thyroid hormone status in children with PEM is perhaps a protective phenomenon to limit protein catabolism and lower energy requirements.

Alterations in the Hemato-biochemical, Endocrine, Somatic Cell Count and Milk Composition in Lactating Tarai Buffaloes during Different Lactation Stages

Background: Tarai buffalo is indigenous buffalo breed of Uttarakhand state, dual purpose, well adapt to hot-humid climatic condition of Tarai area. This study aimed to evaluate the alterations in the hemato-biochemical, endocrine, milk somatic cell count and milk composition in lactating Tarai buffaloes. Methods: Thirty-six healthy Tarai buffaloes were selected from four different Gujjar farms and divided into four groups consisting nine buffaloes in each group as early (60±30 days), mid (120±30 days) and late (180±30 days) lactation stages and dry buffaloes. Both blood and milk samples were collected once from each lactation stage of selected animals. Hematological parameters and milk composition were evaluated by standard procedures and methods. Biochemical and endocrine parameters were evaluated using commercially available kits as per manufacturer’s protocol. Milk somatic cell count (SCC) was done by direct microscopic counts using Newman Lampert stain. Result: It observed significantly (p less than 0.05) higher TLC value but lower plasma glucose, cholesterol, calcium, phosphorus and urea levels during early lactation stage. Significantly (p less than 0.05) declined in plasma total protein during late lactation stage and triglyceride in dry cows. Plasma hormone significantly (p less than 0.05) higher in cortisol during early lactation while higher T4 and insulin in late lactation stages. Milk fat, urea and total solids were significantly (p less than 0.05) decreased during early lactation and again increased during late lactation while milk SCC significantly (p less than 0.05) higher during early and late lactation stages.

AACE2021-A-1003: Metastatic Choriocarcinoma in a Young Woman Presenting as Thyroid Storm

Thyroid Storm is an endocrine emergency and a life threatening condition which was first discovered in 1926.[1] Its diagnosis is based on a clinical scoring system that includes Burch-Wartofsky point scale and Japanese thyroid association scoring system.[2] The management is based on early diagnosis, immediate initiation of anti-thyroid medications, intensive care monitoring and prevention of multi-organ failure.[3] Here we report a case of thyroid storm in a patient with metastatic choriocarcinoma. A young woman presented with headache vomiting and weakness was in thyroid storm. Later diagnosed as Metastatic choriocarcinoma. A 30 year old female, presented with headache, vomiting and generalized weakness for 3 weeks. She had an episode of seizure like activity at home which cause them to rush to the emergency department. She was febrile on presentation. Thyroid examination revealed a soft, non-tender gland with no enlargement or bruit, and no exophthalmos was identified. Her TSH was extremely low with high free T3 and T4. She also had a high levels of beta-human chorionic gonadotropin hormone. Our patient scored 65 in Burch-Wartofsky point scale. As per Japanese thyroid association scoring system, our patient lies in “definite thyroid storm”.Table: 1Burch-Wartofsky Point Scale (BWPS)Patient parametersPoint scoresTemperature (0C)380C10 pointsCentral Nervous System manifestationSeizures30 pointsGastrointestinal manifestationNausea/Vomiting10 pointsHeart rate105 beats per minute5 pointsCongestive heart failureAbsent0 pointsAtrial FibrillationAbsent0 pointsPrecipitating eventsPresent10 pointsTotal score = 65 points Open table in a new tab She was initiated on propranolol to achieve adequate control of her heart rate and dexamethasone. She was also started on carbimazole. She was then started on cholestyramine to help bind and excrete excess thyroid hormone and Lugol’s iodine solution. Her thyroid function repeated after 2 weeks of treatment shows significant improvement.Table: 2Thyroid profile of the patientInitialAfter treatment (2weeks)Reference RangeTSH<0.010 uIU/ml<0.010 uIU/ml0.4 – 4.2Free T44.74 ng/dl1.61 ng/dl0.89 – 1.76Free T317.90 pg/ml3.40 pg/ml2.1 – 4.4 Open table in a new tab Choriocarcinoma is not only associated with hyperthyroidism but can induce thyroid storm. Beta-hCG has a direct association in promoting thyroid dysfunction. Patient with gestational trophoblastic disease should be closely monitored to prevent thyroid storm.

Prevalence of transient congenital hypothyroidism among neonates

ObjectivePersistence of low levels of thyroid hormone from the time of birth is one of the significant causes of the mental retardation. The aim of this study was to determine the prevalence of transient congenital hypothyroidism among neonates in (XXX). MethodsThis cross-sectional study, neonates aged 3–5 days who were referred to our center for checkup were screened for thyroid stimulating hormone. Those with TSH < 5mIU/l were, infants were subjected to retesting after one week for TSH and T4 levels. A questionnaire consisting of test results, demographic characteristics, place of sampling, gender, need for re-sampling after the second week for TSH level, birth weight, type of hypothyroidism and prematurity was filled for all the neonates. ResultsOf 3600 neonates screened, 126 were presented with had TSH above 5 mIU/l, of which 7 had high TSH and low T4 and were diagnosed with transient hypothyroidism (5.3%). The mean weight of the neonates with hypothyroidism of significantly lower, p = 0.001. However, the type of delivery was not associated with the prevalence of hypothyroidism, p = 0.999. The relationship between maternal hypothyroidism, preterm birth and intake of antithyroid drugs and transient hypothyroidism was statistically significant, p < 0.001, respectively. ConclusionsThe incidence of congenital hypothyroidism was 1 in 514 births and was significantly associated with preterm birth, mean weight, maternal hypothyroidism and intake of antithyroid drugs. Routine screening in high prevalence regions are therefore importance, considering the associated factors.

Thyroid Disorders.

Thyroid Disorders.

Platelet Function in Overt Hypothyroidism

BACKGROUND: Hypothyroidism is associated with a shift of the hemostatic system to a hypocoagulable state and inhibited platelet function. However, previous studies did not consider the different degrees of response to thyroxine treatment and its effect on platelet function. This raises the need for further studies to clarify the effect of different degrees of responses to treatment on platelet function in hypothyroid disease. OBJECTIVES: To characterize the abnormalities in the primary hemostasis (platelet adhesion and aggregation) in patients with overt hypothyroidism on L-thyroxine therapy and to study the effect of variation of the responses to treatment on platelet function. MATERIALS AND METHODS: This cross-sectional study includes 64 patients with overt hypothyroidism on L-Thyroxine treatment. The patients were divided into three groups according to their response to treatment. Group-I: euthyroid patients (ET) (n = 25): (normal thyroid-stimulating hormone [TSH] and free T4), Group II: subclinical hypothyroid (SH) (n = 22): (high TSH and normal free T4), and Group III: inadequately treated hypothyroid (IH) (n = 17) (high TSH and low T4). Platelet function was assessed by light transmissiom aggregation response to adenosine diphosphate (ADP), arachidonic acid (AA), epinephrine (EPN), collagen, and ristocetin and by the platelet function analyzer (PFA-100) closure times (CTs). RESULTS: Platelet aggregation responses showed a significant reduction to ADP in ET patients (42.9 ± 20.7), SH patients (41.8 ± 24.2), and IH patients (46.9 ± 20.1) and to risocetin in ET patients (62.9 ± 22.8), SH patients (62.6 ± 21.2), and IH patients (61.3 ± 14.6) as compared to the controls (59.1 ± 9.5) and (75.3 ± 6.9), respectively. There is a significant prolongation of C/EPN: (175.6 ± 82.5) in the IH patients as compared to the controls (141.6 ± 26.8). Significant prolongation of C/ADP CT (132.2 ± 72.5) in IH patients as compared to the controls (100.7 ± 24.1) was found with normalization of both CT in ET patients. CONCLUSIONS: In overt hypothyroidism using two different tests of platelet function, we confirmed that the existence of a hypocoagulable state is due in part to a defect in primary hemostasis. Moreover, the defect varies according to the degree of response to L-Thyroxine treatment; it is more pronounced in inadequately treated hypothyroid patients and less in the subclinical hypothyroid.

Thyroid function in COVID-19 and the association with cytokine levels and mortality.

The hypothalamic–pituitary–thyroid hormone axis might be affected in COVID-19, but existing studies have shown varying results. It has been hypothesized that hyperinflammation, as reflected by the secretion of cytokines, might induce thyroid dysfunction among patients with COVID-19. We explored thyroid hormone involvement in the acute phase of symptomatic COVID-19 and its possible associations with cytokine levels and mortality risk. This was a single-center study of 116 consecutive patients hospitalized for moderate-to-severe COVID-19 disease. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), and 45 cytokines/chemokines were measured in all patients within 3 days of admission. Data were extracted retrospectively through a manual review of health records. At admission, 95 (81.9%) were euthyroid; while 21 (18.1%) had biochemically thyroid dysfunction including subclinical thyrotoxicosis (n = 11), overt thyrotoxicosis (n = 2), hypothyroidism (n = 1), non-thyroidal illness (n = 2), and normal TSH but high free T4 (n = 5). TSH levels were inversely correlated with IL-8 (rs = –0.248), IL-10 (rs = –0.253), IL-15 (rs = –0.213), IP-10 (rs = –0.334), and GM-CSF (rs = –0.254). Moreover, IL-8 levels, IP-10, and GM-CSF were significantly higher in patients with serum TSH < 0.4 mIU/L. Lastly, a two-fold increment of IL-8 and IL-10 was associated with significantly higher odds of having TSH < 0.4 mIU/L (odds ratio 1.86 (1.11–3.10) and 1.78 (1.03–3.06)). Serum TSH was not associated with 30- or 90-day mortality. In conclusion, this study suggests that fluctuations of TSH levels in patients with COVID-19 may be influenced by circulating IL-8, IL-10, IL-15, IP-10, and GM-CSF as previously described in autoimmune thyroid diseases.

Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study

BackgroundThis study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).MethodsA case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.ResultsExcessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.ConclusionExcessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

Management in Mitral Valve Replacement with Pulmonary Hypertension and Thyroid Storm: A Case Report

Introduction: We reported a case of patient after mitral valve replacement (MVR) with pulmonary hypertension (PH) and thyroid storm that is rare, but life-threatening condition. Case Illustration: A 57-year-old-male with a subclinical hyperthyroidism underwent MVR due to severe mitral regurgitation (MR) and high possibility for PH. He showed atrial fibrillation with normal left ventricular ejection fraction (LVEF). In the intensive care unit (ICU), four hours postoperatively, he developed thyroid storm with heart rate of 226 times/min, temperature 39oC, and thyroid function showed low TSH (&lt;0.05 uIU/mL), high fT4 (25.4 pmol/L), and high T3 (3.3 nmol/L). He was administered with propranolol, propylthiouracil, hydrocortisone, and lugol. Discussion: Trauma of cardiac surgery might trigger thyroid storm in this patient. The post-operative period represented a high-risk time for PH patients, moreover with thyroid storm. Therapy for thyroid storm was multimodal, including anti-thyroid, beta blockers, iodine, and glucocorticoid. Hemodynamic goals were avoidance of elevation in pulmonary vascular resistance (PVR), avoidance of myocardial depressants and maintenance of systemic vascular resistance (SVR), myocardial contractility and preload. Conclusion: Thyroid storm and PH complicating MVR was rare, but life-threatening. Comprehensive management could decrease morbidity and mortality of thyroid storm. Keywords: mitral valve replacement surgery; pulmonary hypertension; thyroid storm

Spectrum of Endocrine Dysfunction and Association With Disease Severity in Patients With COVID-19: Insights From a Cross-Sectional, Observational Study.

IntroductionEvidence on new-onset endocrine dysfunction and identifying whether the degree of this dysfunction is associated with the severity of disease in patients with COVID-19 is scarce.Patients and MethodsConsecutive patients enrolled at PGIMER Chandigarh were stratified on the basis of disease severity as group I (moderate-to-severe disease including oxygen saturation <94% on room air or those with comorbidities) (n= 35) and group II (mild disease, with oxygen saturation >94% and without comorbidities) (n=49). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes, and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed.ResultsPatients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% of patients without significant difference between both groups.ConclusionCOVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease.