Elevated Thyroid Research Articles

Unmet patient needs in monocarboxylate transporter 8 (MCT8) deficiency: a review.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the SLC16A2 gene and resulting from dysfunctional thyroid hormone transport. This disorder is characterized by profound neurodevelopmental delay and motor disability due to a lack of thyroid hormone in the brain, and coexisting endocrinological symptoms, due to chronic thyrotoxicosis, resulting from elevated thyroid hormone outside the central nervous system (CNS). In February 2024, we reviewed the published literature to identify relevant articles reporting on the current unmet needs of patients with MCT8 deficiency. There are several main challenges in the diagnosis and treatment of MCT8 deficiency, with decreased awareness and recognition of MCT8 deficiency among healthcare professionals (HCPs) associated with misdiagnosis and delays in diagnosis. Diagnostic delay may also be attributed to other factors, including the complex symptomology of MCT8 deficiency only becoming apparent several months after birth and pathognomonic serum triiodothyronine (T3) testing not being routinely performed. For patients with MCT8 deficiency, multidisciplinary team care is vital to optimize the support provided to patients and their caregivers. Although there are currently no approved treatments specifically for MCT8 deficiency, earlier identification and diagnosis of this disorder enables earlier access to supportive care and developing treatments focused on improving outcomes and quality of life for both patients and caregivers.

Frequency of Mutations in the TPO Gene in Patients with Congenital Hypothyroidism Due to Dyshormonogenesis in Chile.

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon-intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.

Graves' Disease in Hypopituitarism Due to Pituitary Apoplexy.

Central hypothyroidism and autoimmune hyperthyroidism are contrasting pathologies requiring careful hormone monitoring for restoring euthyroidism. Their coexistence is rare and challenging for clinicians [1, 2]. We have, herein, presented the case of a 41-year-old female patient with an unremarkable clinical history except for chronic autoimmune thyroiditis in euthyroidism. At the 21st week of gestation, she experienced a spontaneous abortion. The patient underwent an assessment of the uterine cavity, which was complicated by bleeding and hypotensive shock. In the postoperative course, the patient presented worsening headache, and after an MRI, the diagnosis of pituitary apoplexy due to an ischemic-hemorrhagic base was made. Laboratory tests showed anterior panhypopituitarism. Multiaxial replacement therapy was initiated with hydrocortisone, levothyroxine (LT4), and subsequently estrogen-progestin and GH. After two years of good recovery with stable LT4 dosage, the patient experienced palpitations and fine tremors; blood tests showed hyperthyroidism with suppressed Thyroid-stimulating Hormone (TSH) levels and elevated free thyroid fractions and anti-TSH receptor antibodies. Diagnosis of Graves' disease was made, and therapy with methimazole was initiated. During antithyroid therapy, TSH remained persistently suppressed, consistent with the underlying central hypothyroidism. This condition required close follow-up, with monitoring based solely on free thyroid hormone levels. After six months of antithyroid therapy, disease remission was achieved, with negative antibodies and mild hypothyroxinemia. Therefore, methimazole was discontinued and replacement therapy gradually resumed until optimal hormone levels were reached. This case is unique demonstrating autoimmune hyperthyroidism to coexist with central hypothyroidism, rendering TSH a misleading disease progression indicator. Consequently, managing Graves' disease has become more complex and challenging.

Elevated Thyroid Autoantibodies and Intracranial Stenosis in Early-Onset Stroke

Elevated Thyroid Autoantibodies and Intracranial Stenosis in Early-Onset Stroke

Endoscopic Endonasal Resection of a Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma With Invasion of the Medial Wall of the Cavernous Sinus.

Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy postoperatively if subtotal resection, especially with cavernous sinus invasion.2 We present the case of a 29-year-old man with TSH-oma with cavernous sinus medial wall invasion. This is the first documented case with selective resection of the cavernous sinus medial wall to achieve a complete resection and biochemical remission in TSH-oma through endoscopic endonasal approach. The patient had elevated TSH and thyroid hormones with symptoms of weight loss, palpitations, excess sweating, and decreased endurance. MRI revealed a 1.3 × 2.1 × 1.2 cm contrast-enhancing sellar mass with rightward pituitary gland displacement without evidence of cavernous sinus invasion (Knosp 2). The patient consented to procedure/publication. No institutional review board approval needed per institution. We performed standard resection of the firm sellar tumor portion and noted that there was tumor invasion into the left cavernous sinus medial wall dura. The bony opening was expanded to expose the anterior wall of the cavernous sinus, which was opened to identify the cavernous internal carotid artery and the medial wall attachments. The thickened medial wall was completely resected. We achieved a complete tumor resection, and the patient's TSH and thyroid hormone dropped to a desired threshold.3 Tumor stained for GATA3 and PIT1, characterizing the TSH-oma.4,5 Understanding cavernous sinus vascular and ligamentous anatomy allows for safe separation of invaded medial wall dura from the cavernous internal carotid artery,6 allowing for a more complete tumor resection, improving surgical cure rates, and sparing the patient from future radiation and pharmacotherapy.

Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter.

Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations and (2) unexpectedly develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn levels and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly generated Slc30a10 knockout rats despite an increase in thyroid Mn levels, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn levels. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely used animal models.

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

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

Successful Pregnancy and Delivery after Premature Ovarian Insufficiency Combined with Undifferentiated Connective Tissue Disease: A Case Report

Background:: Premature ovarian insufficiency (POI) is extremely rare in the early stage of undifferentiated connective tissue disease. Patients with POI find it difficult to achieve successful pregnancy and delivery. Case Presentation:: A 27-year-old female visited an outpatient department for premature ovarian insufficiency (POI) and infertility. She had regular menstrual periods since she was 14 years old and had no history of systemic disease. Laboratory tests showed low estrogen (15 ng/L, range 19.6-144.2 ng/L), elevated follicle-stimulating hormone (34 U/L), low anti-Mullerian hormone (0.1 μg/L), normal prolactin (11.48 ng/mL), and thyroid stimulating hormone (TSH) levels (0.97 mU/L). She demonstrated smaller bilateral ovarian volume and positivity to antinuclear and antiphospholipid antibodies. After the failure of conventional drug therapy and in vitro fertilization, the patient became pregnant naturally after treatment with glucocorticoids. Conclusion:: Immunosuppression could help improve ovarian function and pregnancy outcomes in POI patients, but the therapeutic mechanisms are not clear and should be elucidated with more clinical studies.

Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by 18F-BMS-986192 PET: pooled analysis of data from four solid tumor types

IntroductionImmune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using 18F-BMS-986192 positron...

Elevated thyroid stimulating hormone and metabolic syndrome risk in patients with first-episode and drug-naïve major depressive disorder: a large-scale cross-sectional study

BackgroundMetabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients.MethodsWe recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust.ResultsThe prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40–1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001).ConclusionsThis study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.

Falsely elevated thyroid function tests due to laboratory interference

Falsely elevated thyroid function tests due to laboratory interference

Abstract PO3-06-07: Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial

Abstract Background: Antiangiogenic drugs have demonstrated synergistic effect with anti-PD-1 antibody in advanced triple negative breast cancer (TNBC). Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Preclinical studies showed that metronomic chemotherapy inhibited angiogenesis and enhanced the efficacy of immunotherapy in TNBC via modulation of the tumor immune microenvironment. We hereby conducted a single-arm, multicenter, phase II trial to investigate the efficacy and safety of sintilimab (anti-PD-1 antibody) plus anlotinib and metronomic chemotherapy as a potential novel therapeutic strategy in advanced TNBC and explore potential biomarkers. Methods: Forty-four cases were planning to be included in this trial. The eligible patients who had received no more than two lines of chemotherapy for metastatic disease were enrolled and received sintilimab (200 mg iv q3w) and anlotinib (12 mg po d1-14 q3w) plus capecitabine (500 mg po, tid) or vinorelbine (40 mg po, tiw) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR) and secondary endpoints are disease control rate (DCR), progression free survival (PFS), and overall survival (OS). The safety profile has also been assessed. Results: As of April 2023, a total of 44 patients were enrolled, and 42 patients were evaluable for efficacy. 3 patients (7.1%) achieved complete response (CR). 6 patients (14.3%) achieved partial response (PR). 25 patients (59.5%) achieved stable disease (SD).The ORR is 21.4% (95%CI 0.103-0.368) and DCR is 81.0% (95%CI 0.810-0.659). The median PFS was 5.06 months (95%CI 2.051-8.069). The most common grade 1 or 2 adverse events (AEs) include elevated thyroid stimulating hormone (52.38%, 22/42), elevated bilirubin (23.81%, 10/42), hand-foot syndrome (22.22%, 8/42), leukopenia (16.67%,7/42), nausea (14.29%, 6/42). Grade 3 AEs include elevated bilirubin (2.38%, 1/42), hypertension (2.38%, 1/42) and herpes zoster (2.38%, 1/42). No grade 4 or 5 AEs occurred. Conclusions: Our date showed that sintilimab in combination with anlotinib plus metronomic chemotherapy have shown favorable efficacy and acceptable safety profile in patients with advanced TNBC. Clinical trial information: ChiCTR2100044725 Citation Format: huihui Li, Dongdong Zhou, Zeshun Yv, Yuqian Liao, Jie Huang, Shujuan Sun, fangchao zheng, Baojiang Li, Shu Fang, Ling Qiang, Guohua Ren, Bing Bu, Pengfei Qiu, Xinzhao Wang, Chao Li, Fangli Cao, Qian Shao, Dali Han, Lihua Song, Baoxuan Zhang, Bingjie Fan, Liang Xu, Xuemei Xie, Xianguang Zhao, Lanping Liu, Wanlong Li, Zhenbo Wang, Changmin Liu, Hui Fu, Xiao Sun, Zhiqiang Shi, Fengxiang Li. Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-07.

The role of autoimmune thyroid disorders in patients with alopecia areata

Objective: The aim of this study was to investigate the association of thyroid autoimmunity with alopecia areata (AA) by examining thyroid stimulating hormone (TSH) and thyroid autoantibody levels. In addition, to compare the epidemiologic data obtained with the data of our country. Methods: Our study was organized as a cross-sectional, retrospective study. The study was performed on patients between the ages of 2-65 years who were admitted to our outpatient clinic between 01.01.2008 and 31.12.2011, who were clinically or histopathological diagnosed with AA, examined for etiology and thyroid autoantibodies were requested. Patients under two years of age and over 65 years of age, patients with no thyroid autoantibodies and pregnant patients were excluded. Results were expressed as mean±standard deviation and median values. Mann-Whitney U test was used to compare TSH, anti-TG antibody (Anti-TG) and anti-TPO (Anti-TPO) antibody values in the variables of nail involvement, psychiatry, comorbidity and family history. Spearman correlation analysis was used to examine the relationships between age and disease duration and TSH, Anti-TPO and Anti-TG variables. Results: In our study, 65 (42.8%) of 152 patients were female and 87 (57.2%) were male. The ages of the patients ranged between 2-65 years and the mean age was 26.5±14.6 years. The mean age of females was 27.5±14.4 and 25.7±14.9 in males. Elevated thyroid autoantibodies were found in a total of 29 patients, 21 of whom were female and 8 of whom were male. Of these 29 patients, 10 had hypothyroidism, 2 had chronic thyroiditis and 3 had toxic multinodular goiter. 14 patients did not return after the examination at the internal medicine outpatient clinic, so the diagnosis of thyroid disease could not be reached. The mean TSH, Anti-TG and Anti-TPO values were 2.27±1.57, 29.2±99 and 71.5±2.2, respectively. When these values were analyzed separately as men and women, they were found to be 2.6±2.02, 41.8±1.23 and 134±2.8 in women and 1.99±1.03, 19.8±75.6 and 24.5±1.32 in men. There was a significant difference between men and women in terms of Anti-TG and Anti-TPO values (p=0.011 and p=0.001, respectively). A significant correlation was found between disease duration and Anti-TPO positivity (p=0.045); however, a similar relationship was not found between disease duration and Anti-TG positivity (p=0.34). Conclusions: As a result of this study, although there was a significant correlation between anti-TPO and duration of AA, the association between thyroid autoimmunity and AA was not found to be statistically significant. This may be due to the fact that humoral autoimmunity plays a role in thyroid autoimmunity and primarily cellular autoimmunity plays a role in AA. In addition, the epidemiologic data of our study were similar to the data of studies conducted in our country.

Challenging diagnosis of resistance to thyroid hormone in a patient with COVID-19, pituitary microadenoma and unusual response to octreotide long-acting release test.

The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed. RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms. Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual. Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient's phenotype. Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis. Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies. Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.

Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient's concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer.

Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

PurposeOvert hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications.MethodsGroup 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5–2.5 mU/L, 0.5–2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale.ResultsPregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores.ConclusionFetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Hashimoto’s Thyroiditis Negatively Influences Intracytoplasmic Sperm Injection Outcome in Euthyroid Women on T4 Substitution Therapy: A Retrospective Study

Objective: The objective of this study was to analyze the impact of thyroid autoimmunity (TAI) on reproductive outcome parameters of intracytoplasmic sperm injection (ICSI) cycles as compared to TAI-negative ICSI cycles. Design: In this single in vitro fertilization (IVF) center retrospective study, 86 infertile women with elevated thyroid peroxidase or TGAb levels, but euthyroid after thyroxine replacement (study group), were compared to 69 female patients with no thyroid abnormalities (controls). Following ICSI treatment fertilization rate (FR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR) were analyzed. Materials, Setting, Methods: All subjects with various infertility factors were treated with ICSI in university-based IVF center. Patients in the study group received thyroxine replacement and were euthyroid at IVF treatment. Before the IVF cycles, endocrinological parameters were uniformly assessed: thyroid function and antibodies, reproductive hormones (anti-Müllerian hormone [AMH], follicular stimulating hormone [FSH], luteinizing hormone, E2, PRL, testosterone, DHEAS, 17-OHP, AD) and OGTT (0–60–120 min glucose and insulin). Following descriptive comparison of laboratory parameters, age-adjusted analyses of FR, CPR, MR, and LBR were performed. Results: TAI-positive women were older (mean age 35.31 ± 4.95 vs. 32.15 ± 4.87 years; p = 0.002), had higher FSH (8.4 ± 3.4 vs. 7.4 ± 2.32 U/L; p = 0.024), higher E2 (53.94 ± 47.61 vs. 42.93 ± 18.92 pg/mL; p = 0.025) levels, while AMH (2.88 ± 2.62 vs. 3.61 ± 1.69 ng/mL; p = 0.0002) was lower. There were no differences in TSH levels (1.64 ± 0.96 vs. 1.66 ± 0.65 µIU/mL; p = 0.652) between the two groups. FT3 (2.63 ± 0.58 vs. 2.98 ± 0.55 pg/mL; p = 0.002) was lower and FT4 (1.3 ± 0.29 vs. 1.13 ± 0.21 ng/dL; p = 0.0002) was higher in the TAI-positive group, reflecting clinically irrelevant differences. Egg cell counts (6 ± 3.8 vs. 7.5 ± 3.95; p = 0.015) were lower in TAI and remained so following age adjustment. Although the overall ICSI FR did not differ (62.9% vs. 69.1%, p = 0.12), it was lower for patients under 35 with TAI showing decreasing differences in line with age. The CPR (36.04% vs. 69.56%; p < 0.001) and LBR (23.25% vs. 60.86%; p < 0.001) were lower, the MR (35.48% vs. 12.5%; p = 0.024) was higher in the TAI group, and these differences remained after age adjustment. Limitations: Since the higher age of the study group may interfere with the effect of TAI, age adjustment calculations were necessary to perform to eliminate this confounding factor. Conclusion: Despite optimal thyroid supplementation in clinical or subclinical hypothyroidism, the presence of TAI negatively influences CPR and is connected to a higher MR, thus resulting in a lower LBR after ICSI. Decreased FR with ICSI in TAI patients may also contribute to poorer outcomes, especially in younger women.

The association between per-/polyfluoroalkyl substances in serum and thyroid function parameters: A cross-sectional study on teenagers living near a Chinese fluorochemical industrial plant

Thyroid hormones (THs) play an important role in a wide range of crucial biological functions related to growth and development, and thyroid antibodies (TAs) can influence the biosynthesis of THs. Epidemiological studies have indicated that per- and polyfluoroalkyl substances (PFAS) could induce thyroid disruption, but studies on teenagers living in areas with high PFAS exposure are limited. This cross-sectional study focused on 836 teenagers (11– 15 years) living near a Chinese fluorochemical industrial plant. Decreased levels of free thyroxine (FT4, ﹤9.6 pmol/L, abnormal rate = 19.0 %) and elevated levels of free triiodothyronine (FT3, ﹥6.15 pmol/L, abnormal rate = 29.8 %) were observed. Correlations of serum PFAS concentrations and TAs/THs were analyzed. Increased PFOA was identified as a risk factor of decreased FT4 by using unadjusted (OR: 11.346; 95 % CI: 6.029, 21.352, p < 0.001) and adjusted (OR: 12.566; 95 % CI: 6.549, 24.115, p < 0.001) logistic regression models. In addition, significantly negative correlations were found between log10 transformed PFOA and FT4 levels using linear (unadjusted: β = −1.543, 95 % CI: −1.937, −1.148, p < 0.001; adjusted: β = −1.534, 95 % CI: −1.930, −1.137, p < 0.001) and BKMR models. For abnormal FT3, a significantly positive association between PFHxS and FT3 levels was observed in a regression model (unadjusted: β = −0.903, 95 % CI: −1.212, −0.595, p < 0.001; adjusted: β = −0.894, 95 % CI: −1.204, −0.583, p < 0.001), and PFHxS was identified as a risk factor (unadjusted: OR: 4.387; 95 % CI: 2.619, 7.346, p < 0.001; adjusted: OR: 4.527; 95 % CI: 2.665, 7.688, p < 0.001). Sensitivity analyses confirmed the robustness of the above results. This study reported the elevated PFAS exposure and thyroid function of teenagers living near a fluorochemical industrial plant from China.

Lack of Association Between Depression and Subclinical Hypothyroidism in Adolescents Presenting for Routine Physical Examinations.

There are conflicting results in the existing studies regarding the association between depression and subclinical hypothyroidism in adolescents. Subclinical hypothyroidism is defined as elevated thyroid stimulating hormone (TSH) levels above the reference range without signs or symptoms of hypothyroidism. The focus of this study is to determine whether there is any association between depression and subclinical hypothyroidism, (as defined by the serum TSH levels) in a population of healthy adolescents. Quantitative-based cross-sectional study of a representative subset of the adolescent population. We carried out a cross-sectional study to determine the association between major depressive disorder (MDD) and subclinical hypothyroidism, in adolescents presenting for annual physical examinations during the peak period of the COVID-19 pandemic in the USA, a period deemed high for adolescent depression. All the adolescents were screened for depression by the PHQ-9 screening tool and had their TSH measured. Of the 304 subjects analyzed, 179 (58.88%) were minimally or not depressed according to the Patient Health Questionnaire (PHQ-9) screening tool (mean PHQ 1.80 ± 1.49). 70 (23.03%) had mild depression (mean PHQ 6.59 ± 1.46), 50 (16.45%) had moderate depression (mean PHQ 13.70 ± 2.75), and 5 (1.64%) had severe depression (mean PHQ 21.40 ± 1.67). Mean TSH values were 1.93 ± 0.99, 1.77 ± 1.05, 2.10 ± 0.98, and 1.57 ± 0.32 mIU/L, respectively in the four groups. All values were within the recommended range of 0.50 to 4.30 mIU/L, without statistically significant inter-group differences. We conclude that there is no statistically significant association between depression and subclinical hypothyroidism, in a population of adolescents presenting for physical examinations, and if the screening for depression by the PHQ-9 tool indicates depression, a screening TSH test for subclinical hypothyroidism is not justified.

Роль субклинического гипотиреоза в патогенезе и течении хронической сердечной недостаточности

Aim. To summarize the currently available information about the mechanism of development of chronic heart failure against the background of subclinical hypothyroidism. Key points. The review article is devoted to the influence of subclinical hypothyroidism on the course of cardiovascular pathologies, in particular chronic heart failure. The mechanisms of molecular cellular disorders in this disease are presented. A special role is assigned to the protein of the myocardium phospholamban. The importance of subclinical hypothyroidism as a risk factor and as an independent nosology within the framework of comorbid conditions associated with pathology of the vascular bed is described. The pathogenesis of left ventricular dysfunction in a patient and, as a consequence, chronic heart failure in patients with subclinical hypothyroidism is shown. Data from studies of patients with cardiovascular diseases against the background of elevated thyroid stimulating hormones levels are presented. The topic of the relationship between heart rhythm disturbances and thyroid hormone deficiency is also touched upon. Conclusion. The role of subclinical hypothyroidism in the pathogenesis of chronic heart failure has been established, not only as a risk factor for its development, but also as an independent nosological form, the presence of which naturally leads to adverse cardiovascular events. Keywords: subclinical hypothyroidism, chronic heart failure, left ventricular dysfunction, heart rhythm disturbances, brain natriuretic peptide.