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.

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.

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.

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.

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.

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.

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.

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.

Interpretation of TSH results can be improved by reference values fluctuating in time.

OBJECTIVES: The secretion of thyroid stimulating hormone (thyrotropin, TSH), is characterized by a marked circadian rhythm. Plasma or serum TSH values are significantly lower in the afternoon and in the evening as compared to the early morning. As in clinical practice, blood sampling time shows an important variation, a reliable assessment of thyroid status is often not an easy task for the clinician. The biological variation of TSH plays a major role in the intra-individual variability of TSH results in serum or plasma. The observed intra-day variation largely exceeds the reported inter-vendor variation and the coefficient of variation of clinical TSH assays. Therefore, a mathematical solution was sought for correcting interpretation of TSH results for sampling time. METHODS: We have developed a cosinor model which allows to compensate TSH decision values for the fluctuating serum or plasma TSH concentrations throughout the day. RESULTS: The following mathematical function could be derived: corrected TSH cutoff_value (mIU/L)=0.40 + 0.24*cos(((π/12) *T) + 6) in which T represents the time (hours). This mathematical function can be easily implemented into a laboratory's informatics system and furthermore allows a better tailored diagnosis of (subclinical) hyperthyroidism, regardless the blood sampling time. CONCLUSIONS: Implementing the corrected cut-off values result in a marked reduction of apparent (false positive) hyperthyroidism diagnosis, in particular in the afternoon.

Evaluation of MELD Scores and Thyroid Hormones as Prognostic Factors of Liver Cirrhosis.

Background and Objectives: Hepatic cirrhosis is a disease with an increasing frequency globally, but its mechanisms of disease development are not yet completely known. The aim of this study was to evaluate the relationship between thyroid hormone levels (T3, fT4, and TSH) and survival in patients with chronic liver disease. Materials and Methods: A total of 419 patients diagnosed with liver cirrhosis were included in the study. The MELD score was computed, and TSH, T3, and fT4 were collected from each patient using the ELISA procedure. Signs and symptoms of liver failure and portal hypertension confirmed the clinical diagnosis of liver cirrhosis, and biological tests and imaging methods confirmed the diagnosis. Results: The MELD score was positively associated with TSH on admission and TSH on discharge and negatively associated with T3 at discharge. TSH levels were higher in non-survivors than in survivors. The values of T3 and fT4 present no significant changes to be considered as prognostic factors. Conclusions: Although the differences between the median TSH values of the patients who died and those who survived are not very large, the statistical significance of the data obtained demonstrates that there are changes in metabolism of the thyroid hormones during the progression of liver cirrhosis. It is possible that TSH is the one which maintains the normal balance of thyroid activity for patients with liver cirrhosis, so it can be considered as an important marker of evolution of these patients.

A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs.  Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients.  Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management. Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Correlation between ultrasonographic and cytologic features of thyroid nodules: a single-center cross-sectional study.

A thyroid nodule is managed according to the clinical context, ultrasound (US) findings, and fine needle aspiration (FNA) results. Most thyroid nodules are benign; however, nodule classification is crucial to avoid unnecessary thyroid surgery. We conducted this study to compare the findings of fine-needle aspiration cytology (FNAC) expressed using the Bethesda system with the features of thyroid US classified using the EU-TIRADS classification to assess the risk of malignancy. A descriptive and analytical study involving 99 patients with thyroid nodules followed up in the Department of Endocrinology-Diabetology and Nutrition. Data were collected from medical records and analyzed using SPSS software V21. FNA was performed on 121 nodules using the BETHESDA system. These nodules were classified as malignant, suspicious for follicular neoplasm, and suspicious for malignancy in 5.8%, 5%, and 1.7% of cases, respectively. As for the EU-TIRADS 2017 classification, 59.5% of benign nodules were classified as EU-TIRADS III, whereas 66.7% of malignant nodules were classified as EU-TIRADS V and significantly related to malignant prediction (P = 0.000). The size of nodules was significantly correlated to the risk of malignancy (P = 0.013). Seventy-five percent of nodules with central vascularity were malignant (P = 0.012). Irregularity of nodule contours was significantly associated with the risk of malignancy, as 30% of nodules with irregular contours were Bethesda VI (P = 0.003). Hypoechogenicity was found in 77.8% of malignant nodules (P = 0.004). Additionally, only 9.2% of the nodules were taller than wide, of which 37.5% were malignant (P = 0.012). For a safe management strategy, US-guided FNAC should be performed on each suspicious thyroid nodule, given the correlation between EU-TIRADS classification features and the risk of malignancy.

Familial Nonautoimmune Hyperthyroidism Due to a TSH Receptor Gene Pathogenic Variant.

Familial nonautoimmune hyperthyroidism (NAH) is a rare type of autosomal dominant hyperthyroidism caused by constitutively active pathogenic variants of the thyrotropin receptor (TSHR) gene. Although affected family members present with varied levels of hyperthyroid features, even when the same pathogenic variant is present, total thyroidectomy followed by radioiodine therapy is recommended for long-term management. Herein, we present the case of an 18-year-old proband and her family members with NAH (TSHR-I640V), who presented with diverse thyroid dysfunctions: fluctuations between euthyroid and subclinical hyperthyroidism, mild hyperthyroidism, and overt hyperthyroidism. Almost all affected adult family members, except the proband, showed no progression of hyperthyroidism or thyroid enlargement. A family history of thyrotropin receptor antibodies (TRAb)-negative hyperthyroidism is important for the identification of NAH in adults before TSHR genetic testing can be performed. Ablative therapy is not necessary when familial NAH presents with late-onset mild hyperthyroidism without coexisting diseases.

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.

Development and primary characterization of a human thyroid organoid in vitro model for thyroid metabolism investigation.

A 3D thyroid model was developed to address the limitations of 2D cultures and study the effects of compounds like 3-MNT on dehalogenase 1 (IYD) and metabolic activity. Morphology was assessed by TEM, and the expression of tissue-specific genes (TPO, TSHR, PAX8, TTF-1, NIS, IYD, TG) and metabolic features were analyzed using qRT-PCR, immunofluorescence, western blotting, ELISA, and LC-MS/MS, with and without TSH stimulus and 3-MNT treatment. Confocal and TEM analyses confirmed a follicle-like 3D structure. Expression of TPO, NIS, TG, TSH, and PAX markers was significantly higher (p < 0.05) in 3D versus 2D cultures, and ELISA showed increased TG protein production. 3-MNT treatment inhibited IYD activity, indicated by increased MIT and DIT in the media, and significantly altered (p < 0.05) NIS, TG, IYD, TSHR, and TPO expression. These findings suggest 3D thyroid cultures closely replicate tissue traits and functionality, providing a valuable tool for thyroid research.

Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR).

Genetic defects in the TSH receptor (TSHR) can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype-phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4-100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP-response-element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in TSHR is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient's genotype for a correct diagnostic confirmation.