TSH enhances neurite outgrowth.

Extra-thyroidal effects of TSH have been reported in various tissues expressing the TSH receptor (TSHR) including several areas of the brain. However, the influence of TSH on neuronal phenotypes has not been examined. Using a well-characterized human neuroblastoma cell line (SH-SY5Y), we have examined TSH signaling effects on the phenotype of these cells after their neuronal differentiation. Following an 18-day differentiation protocol, we successfully redifferentiated the SH-SY5Y cells into ~100% neuronal cells as indicated by the development of extensive neurofilaments with SMI-31 expression. Furthermore, using absolute digital PCR, we quantified TSHR mRNA, and also TSHR protein expression, in the redifferentiated cells and found that the neuronal cells expressed high quantities of both TSHR message and protein at baseline. Exposure to TSH induced primary, secondary, and tertiary neurite outgrowths, which are essential for cell-cell communication. Quantitative analysis of neurites using ImageJ showed a dose-dependent increase in neurites. The addition of TSH up to 1 mU/ml resulted in a ~2.5-fold increase in primary, and ~1.5-fold in secondary and tertiary neurites. The lengths of the neurites remained unaffected with the dosage of TSH treatment. Furthermore, TSHR signaling in the differentiated cells resulted in enhanced generation of cAMP, pPI3K, pAKT, and pNFkB pathways and suppression of pMAPK suggesting an influence of these signals in driving neurite outgrowth. These data showed that the TSH/TSHR axis in neurons may contribute to enhanced neurite outgrowth. The potential pathophysiological effects of TSH on the induction of neurite outgrowth and its relationship to neurodegenerative diseases remain to be explored.

Investigation of the Relationship between Plasma Nesfatin-1 Levels and Neutering in Dogs.

Neutering of dogs, whether male or female, provides various benefits such as contraception, population control, and the prevention of reproductive disorders and undesirable sexual behaviors. However, it is also associated with an increased risk of obesity, which may be directly linked to post-neutering hormonal changes. Our study aims to determine the effects of neutering on plasma levels of nesfatin-1, serotonin, dopamine, TSH, and T4-hormones implicated in obesity and metabolic regulation. Fourteen dogs (seven males and seven females), aged between 1 and 3 years, were included in this study. Male dogs underwent orchiectomy and females underwent ovariohysterectomy. Blood samples were collected before surgery and on days 7 and 14 post-operatively to measure the plasma levels of these hormones using ELISA. The results showed a significant decrease in nesfatin-1, serotonin, and T4 levels, along with a significant increase in TSH levels in both male and female dogs post-neutering. While these hormonal changes are likely part of the body's adaptive response to neutering, they may represent a potential mechanism that contributes to the long-term tendency toward obesity in neutered dogs.

Estimation of urea, uric acid and creatinine levels in patients of primary hypothyroidism - A cross-sectional study.

Background: The thyroid gland is one of the largest endocrine glands in the body, secreting thyroxine (T4) and triiodothyronine (T3). Mild hypothyroidism can have negative consequences for a variety of tissues, even though clinically the patients are euthyroid. Many research studies were conducted to evaluate the serum creatinine levels of people with hypothyroidism; however, relatively little research was conducted to evaluate serum urea and serum creatinine levels in subclinical hypothyroidism. As a result, the current study was carried out to investigate urea, uric acid, and creatinine levels in hypothyroidism. Objectives: Our study aimed to determine and correlate the levels of urea, uric acid and creatinine in newly diagnosed primary hypothyroidism cases. Materials and Methods: In this cross-sectional study, 96 newly diagnosed cases of primary hypothyroidism were included. The findings were correlated with 20-60-year-old and sex-matched cases. Serum urea was determined by the kinetic method (Glutamate Dehydrogenase Method), serum uric acid by the uricase method and serum creatinine by Jaffe's method in Erba's Mannheim fully automated analyser. Result: This study showed a positive correlation between uric acid and thyroid stimulating hormone (TSH) and a negative correlation between urea and creatinine. There was no statistical significance in the mean values of urea, uric acid and creatinine but an increased level of urea, uric acid and creatinine was seen in the age group 20-30 years when compared with the other age groups. Conclusion: The study concludes that serum urea showed a positive correlation with TSH, whereas uric acid and creatinine showed a negative correlation with TSH, and there was no statistical significance in the mean values of urea, uric acid and creatinine in hypothyroid patients.

Clinical analysis of bleeding and thrombotic events in haematological-oncology patients with severe thrombocytopenia and a high risk of thrombosis.

BACKGROUND: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. METHODS: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 109/L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction. RESULTS: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613-0.858, P = 0.003) and a cut-off value of 42.5 × 109/L. CONCLUSIONS: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 109/L.

Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism.

PURPOSE: Hypothalamic-pituitary thyrotropic activity (HPta) is crucial since TSH is the mainstay for evaluating primary hypothyroidism (hT) and replacement therapy in clinical practice. Despite TSH values, some patients experience symptoms and metabolic alterations, raising several issues about hT. The aim of the study was to investigate factors influencing the TSH values achieved after a period of hT induced in a standardized and controlled manner (TSH_time1). METHODS: Our institutional database was searched to extract records of differentiated thyroid cancer (DTC) patients undergoing a LT4 withdrawal protocol prior to radioiodine (RAI) administration. We collected clinical and biochemical parameters before LT4 discontinuation and after one month of induced hT. We performed Mann-Whitney U-test and linear regression analyses. RESULTS: We included 102 patients, with a median age of 44 years. In univariate analyses, TSH_time1 was correlated with age (p 0.005) and the dose pro Kg/die of LT4 assumed until the discontinuation of LT4 (LT4_dose) (p 0.023). The higher the age, the lower the TSH_time1 level. The higher the LT4_dose, the higher the TSH_time1 level. After multivariate analysis, the fittest model included age, BMI, LT4_dose, and systemic inflammation response index with an adjusted R2 of 0.4. CONCLUSION: The study highlights new mechanisms that influence HPta. HPta progressively reduces with age, and this must be considered when evaluating TSH values in the elderly. Furthermore, we report for the first time a rebound effect of HPta, determined by the dose pro Kg/die of LT4 taken prior to its discontinuation. Inflammation and metabolic status also affect these phenomena.

Effects of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetes patients: a post-hoc analysis of the MARCH study.

PURPOSE: While metformin is known to regulate thyroid stimulating hormone (TSH) levels, the effects of acarbose on thyroid function remain unreported. Our study was designed to evaluate the impact of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetic patients. METHODS: In the MARCH study, 788 patients with type 2 diabetes were randomly assigned to treat with acarbose (300 mg) or metformin (1,500 mg) for 48 weeks. Thyroid function was assessed at baseline, 24 weeks, and 48 weeks, and the thyroid feedback quantile index (TFQI) and parameterized thyroid feedback quantile index (PTFQI) were calculated. Generalized estimating equations adjusted for confounders were used to analyze changes over time. RESULTS: Eighty-four patients with subclinical hypothyroidism (SCH) exhibited a decrease in TSH levels (p = 0.001) with no significant differences between the two treatment groups (p = 0.460). Both TFQI (p = 0.029) and PTFQI (p < 0.001) also decreased over time. Mediation analysis revealed that these change over time were not mediated by BMI (all p < 0.05). Among the 489 euthyroid subjects, no significant changes in TSH levels were observed (p > 0.05). Stratification by baseline TSH levels revealed significant increases in TSH, TFQI, and PTFQI (all p < 0.05) in the normal-low TSH group and significant decreases in PTFQI (all p < 0.05) in the normal-high TSH group after treatment with acarbose and metformin. CONCLUSIONS: Acarbose and metformin have similar buffering effects on TSH levels, the TFQI and the PTFQI. In patients with lower TSH levels, acarbose and metformin do not further decrease TSH levels. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR-TRC-08000231.

Multidisciplinary approach to redefining thyroid hormone reference intervals with big data analysis.

OBJECTIVES: This study aimed to employ big data analysis to harmonize reference intervals (RI) for thyroid function tests, with refinement to the TSH upper reference limit, and to optimize the TSH reflex algorithm to improve clinical management and test utilization. DESIGN & METHODS: TSH, free T4, and free T3 results tested in Alberta, Canada, on Roche Cobas and Siemens Atellica were extracted from the laboratory information system (N = 1,144,155 for TSH, N = 183,354 for free T4 and N = 92,632 for free T3). Results from specialists, inpatients, or repeat testing, as well as from positive thyroid disease, autoimmune disease, and pregnancy biomarkers were excluded. RIs were derived using statistical models (Bhattacharya, refineR, and simple non-parametric) followed by endocrinology and laboratory review. RESULTS: The TSH RIs for 0 to 7 days, 8 days to 1 year, and ≥1 year were 1.23 to 25.0 mIU/L, 1.00 to 6.80 mIU/L and 0.20 to 6.50 mIU/L, respectively. The free T4 RIs for 0 to 14 days, 15 to 29 days, and ≥30 days were 13.5 to 50.0 pmol/L, 8.7 to 32.5 pmol/L, and 10.0 to 25.0 pmol/L, respectively. An updated TSH reflex algorithm was developed based on the optimized TSH and free T4 RIs, with free T4 reflexed only at a TSH of <0.1 mIU/L. CONCLUSIONS: The collaboration of a multidisciplinary team and the utilization of big data analysis led to the enhancement of thyroid function RIs, specifically resulting in the widening of the upper TSH reference limit to 6.50. Application of these optimized RIs with the TSH reflex algorithm will serve as a guide for improvement in interpretation of thyroid function tests.

Autoimmune thyroiditis: an update on treatment possibilities.

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

TSH-secreting pituitary adenomas and bone.

TSH-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary tumor, with an increasing incidence over the last decades. Diagnosis is often delayed, exposing patients to a high risk of developing chronic complications of long-standing hyperthyroidism. Although thyroid hormone excess is a recognized cause of secondary osteoporosis, very few studies have investigated skeletal damage in patients with TSHoma, with data limited to bone turnover markers (BTM) and a study on the prevalence of radiological vertebral fractures (VFs) incidentally detected on chest X-ray, whereas data on bone mineral density (BMD) are anecdotal. Bone resorption is increased in TSHoma compared to controls, whereas few case reports described osteoporosis and spine fractures as early complications of TSHoma. A high prevalence of morphometric VFs was described in TSHoma compared to nonfunctioning pituitary adenoma (NFPA). Patients with fracture were older and had higher free thyroxine (fT4) levels than patients without fracture. In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.

Thyroid cancer and autoimmune connective tissue disorders.

There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 separate diseases because of their relatively high incidence rates in the population. They can arise from each other due to the increased risk of thyroid cancer in patients with idiopathic inflammatory myositis, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and systemic lupus erythematosus. Moreover, in some scarce cases, CTDs may act as the paraneoplastic syndromes of thyroid cancer. The presence of CTDs may impact the diagnostic process, especially distorting the results of imaging tests or falsely indicating the increase of thyroglobulin or calcitonin. Finally, TSH suppression is a crucial element of the treatment of differentiated thyroid cancer, which may decrease bone mineral density and increase the risk of osteoporosis by accelerating bone turnover and shortening the bone remodeling cycle. The aim of this review is to emphasise the vital aspects of this interrelationship. The authors discuss this phenomenon aiming at the explanation of possible linking mechanisms. The impact of selected CTDs on thyroid cancer management is presented, as well as the possible effects of cancer therapy on skeletal health.

The change in thyroid function categories with time in patients with subclinical hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Subclinical hypothyroidism (SCH) is characterized by elevated levels of thyroid hormone (TSH) and normal levels of free thyroxine (FT4). The outcomes of SCH patients are crucial for determining treatment plans; therefore, our aim is to summarize the existing prospective studies to understand the changes in thyroid function over time in SCH patients and the factors influencing these changes, providing references for clinical diagnosis and treatment. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for prospective follow-up studies on natural outcomes of SCH published until September 2024. Results are presented as the overall risk ratio (RR) and 95% confidence intervals (CI). RESULTS: We reviewed 8 prospective follow-up studies involving 1,859 individuals and extracted data from them for a meta-analysis. We found that when TSH levels are ≥ 10 mU/L, patients with SCH are more likely to progress to overt hypothyroidism (OH) (RR11.38, 95%CI 4.98-26.03, P<0.001) and were less likely to return to normal TSH levels (RR 0.20, 95%CI 0.09-0.42, P<0.001) compared to patients with TSH between 4.5 and 9.9 mU/L. In addition, patients who test positive for thyroid peroxidase antibodies (TPOAb) are more likely to progress to OH (RR 2.53, 95% CI 1.86-3.44, P < 0.001) and less likely to return to euthyroidism (RR 0.68, 95% CI 0.60-0.76, P < 0.001) compared to TPOAb-negative patients. CONCLUSION: The results indicated that a large proportion of patients diagnosed with SCH will return to normal TSH levels or maintain SCH. Additionally, patients with TSH levels ≥ 10 mU/L or positive for TPOAb are more likely to experience progression and should be closely monitored. However, we did not find any gender differences in the natural outcome of SCH.

Pain as a presenting symptom of hypothyroidism.

Chronic back or limb pain is often debilitating and disabling resulting in loss of efficiency, depression, and low self-esteem. Diagnosis usually suggests arthritis or nerve root pathology and patients receive long-term oral analgesics and invasive procedures with little or no relief. Hypothyroidism may present as peripheral neuropathy which may be clinically indistinguishable from entrapment neuropathy as occurs with neural canal stenosis. Muscle cramps, aches, proximal symmetrical muscle weakness, stiffness, polymyositis, and exercise intolerance may be the only presenting symptom indicating hypothyroidism. We present five cases of acute on chronic pain that improved significantly on treatment with thyroxine. Neuromuscular pain may be the only presenting symptom of hypothyroidism. Thyroid profile (TSH, FT3, FT4) and anti-thyroid peroxidase (anti-TPO) antibodies should be screened before subjecting the patient to multiple analgesics and procedures.

A Study of Non-alcoholic Fatty Liver Disease in Patients With Hypothyroidism: A Cross-Sectional Study in a Tertiary Care Hospital.

Background Hypothyroidism occurs when the thyroid gland is underactive and fails to produce sufficient thyroid hormones. It can affect multiple organs including the heart, brain, liver, kidneys, and reproductive system, leading to symptoms such as fatigue, cognitive impairment, elevated cholesterol, fluid retention, fatty liver, and menstrual irregularities. Given the higher prevalence of fatty liver disease in patients with hypothyroidism, it is important to evaluate the need for routine screening for fatty liver in these patients. Materials and methods This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from October 2022 to June 2024. The study included 60 patients aged over 12 years who were known or recently diagnosed with hypothyroidism. Patients with type 2 diabetes mellitus, pregnant women, or those with chronic liver disease were excluded. Data collected included physical examination findings and laboratory test results. Fatty liver was diagnosed using magnetic resonance elastography. Statistical analysis was performed using IBM SPSS statistics for Windows, version 20 (IBM Corp., Armonk, New York). The statistical significance of parametric data was evaluated using the Chi-square test. A p-value less than 0.05 and a confidence interval of 95% were considered statistically significant. Result The study population had an average age of about 45 years, with most participants aged between 40 and 49 years. The majority of the participants were female, making up over 83% of the group, while males constituted about 17%. The most commonly reported symptom was weight gain, followed by constipation and fatigue. For individuals with fatty liver, the average thyroid-stimulating hormone (TSH) level was notably higher compared to those without fatty liver. Additionally, low-density lipoprotein (LDL) levels were higher in individuals with non-alcoholic fatty liver disease (NAFLD) compared to those without. Both TSH and LDL levels showed a statistically significant association with the occurrence of NAFLD. Conclusion Hypothyroidism was more prevalent in females and in the age group 40-49 years. There was a statistical significance between TSH and the occurrence of NAFLD. In this study, statistical significance was also found between LDL and the occurrence of NAFLD.

Abnormal TSH Level as a Predictor of Severe Outcomes Among Patients Hospitalized With COVID-19.

Objective: To assess the association between thyroid dysfunction and mortality among patients hospitalized with COVID-19. Design: This is a retrospective multi-center study, which examined all patients admitted with Covid-19 diagnoses, and thyroid function results in absence of known thyroid disease. Results: 10,933 hospitalized COVID-19 positive patients were included in the study. These patients were without prior diagnosis or treatment of thyroid disease. Outcomes assessed were mortality, ICU admission, Ventilator use, length of stay, readmission and complications during hospital stay. Patients with low TSH and Low free T4 had odds of mortality of 10.07(95% CI [7.44-13.6]) compared to patients with Normal TSH and any free T4 levels. Patients with Low TSH and High free T4 also had odds of mortality of 1.38 (95% CI [1.19-1.59]) compared to patients with Normal TSH and Any free T4 level. Patients with Low TSH and Normal free T4 levels also had an Odds of mortality of 1.46 (95% CI [1.31-1.62]) compared to patients with Normal TSH and any free T4 level. Patients with Low TSH also had higher odds of ICU admission and Ventilator use when compared to patients with normal TSH. Conclusions: This study shows that patients with low TSH, regardless of free T4 level, indicates poor prognosis for hospitalized patients with SARS-CoV-2 infection and offers further insights into possible prognostic value of TSH levels for severe COVID-19 outcomes.

Hypothyroidism Induced by a TSH Receptor Peptide-Implications for Thyroid Autoimmunity.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro. During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered in vivo. Methods: In order to examine the effect of in vivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

OBJECTIVES: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. METHODS: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. RESULTS: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. CONCLUSIONS: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

IODINE STATUS IN ROMANIA AFTER 20 YEARS OF MANDATORY SALT IODIZATION: DISCORDANT RESULTS IN SCHOOLCHILDREN AND NEONATES.

Objective: To monitor the iodine status in Romanian schoolchildren and neonates after 20 years of mandatory salt iodization. Subjects and methods: In a national representative sample of 1352 children (7-12 years) we measured median urinary iodine concentration (mUIC) and creatinine (UCC) in spot urine samples and investigated household use of iodized salt. From 18349 neonates registered in the MEDILOG program for TSH screening we calculated the percentage of neonatal TSH >5 mIU/L (<3% indicating adequate iodine intake). Results: mUIC in schoolchildren was 141 µg/L (bootstrapped 95% CI 134, 146), showing adequate iodine intake in all but 1 county; mUIC was similar in historical endemic and non-endemic counties (140 µg/L and 143 ug/L, respectively) and in urban and rural areas (140 µg/L and 142 µg/L, respectively); mUIC/UCC = 118 ug/g. Iodized salt was used in 62% of households. In children using iodized salt (61.7%), mUIC was higher than in those using coarse (non-iodized) salt (24.6%): 150 vs. 121 µg/L (p<0.001). The percentage of nTSH >5 mIU/L was 14.7% (3.2%-27.3%), higher in non-endemic counties and urban areas. Conclusion: The current salt iodization program for households and bakery industry ensures an adequate iodine intake in schoolchildren. Discordantly, nTSH levels indicate a mild-moderate ID in neonates, suggesting ID in pregnant women. The percentage of households using iodized salt is below the recommended >90% needed for an efficient ID prevention program. More efforts should be directed to increase the public awareness on the health risks of ID and the benefits of ID prevention, notably for the neurointellectual development in children.

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

OBJECTIVE: A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. DESIGN: Retrospective cohort study. PARTICIPANTS: Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. MEASUREMENTS: Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aß). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. RESULTS: Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aß 0.62, 95% CI: 0.51-0.76) and higher fT4 (aß 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aß 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aß 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). CONCLUSIONS: In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Efficacy of Anti-Thyroid Medications in Patients with Graves' Disease.

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use. METHOD: We conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study. RESULTS: The study sample consisted of 189 patients, 72% of whom were female. The patients' median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001. CONCLUSION: The remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

Resolution of Breast Cancer in a Patient With Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor With the Combination of Chemotherapy and Lanreotide.

Thyroid stimulating hormone-secreting pituitary neuroendocrine tumor (TSH-PitNET) is a rare disease in which pituitary adenomas secrete excessive amounts of TSH, and TSH is not suppressed despite high blood levels of thyroid hormone. Somatostatin analogs (SSAs) like lanreotide are used to control TSH secretion and manage symptoms in cases where surgery is not fully effective or feasible. The treatment of choice for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer is generally chemotherapy and anti-HER2 therapy. A 52-year-old woman was diagnosed with Graves' disease 26 years ago and stopped going to the hospital after several years of treatment with thiamazole. She had a right breast mass two years prior and visited the Department of Breast and Endocrine Surgery in our hospital one year prior, where she was diagnosed with T3N3M1, stage 4 breast cancer with a mass 52 mm in diameter in the right breast and metastasis in the 12th thoracic vertebra. Breast cancer receptor status was negative for the estrogen receptor, negative for the progesterone receptor, and positive for HER2. She was also found to have an enlarged thyroid gland, palpitations, inappropriate TSH secretion, and a 6 mm nodule on the pituitary gland, which was diagnosed as a TSH-PitNET. She was treated for breast cancer with trastuzumab deruxtecan therapy and for TSH-PitNET with lanreotide. One month after starting lanreotide, pituitary, and thyroid function improved to normal, and four months later, the breast mass was significantly reduced to 16 mm in diameter and a mastectomy was performed. The size of the pituitary adenoma remained unchanged during observation. Remarkably, the mastectomy specimen was free of cancer cells and showed a pathologically complete response. Needle biopsy specimens at the time of breast cancer diagnosis were positive for somatostatin receptor 2 (SSTR2) and insulin-like growth factor 1 receptor (IGF-1R) immunostaining. However, both were negative in the mastectomy specimen. Recently, SSTR2 and IGF-1R were reported to be expressed in breast cancer, and several clinical trials of SSAs for breast cancer have been conducted. SSAs are effective in improving pituitary and thyroid functions against TSH-PiTNET, and in combination with chemotherapy, they may have synergistic antitumor effects in patients with SSTR2-positive breast cancer.