Low Thyroid Research Articles

SMIM1 absence is associated with reduced energy expenditure and excess weight

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Evolution in the management of thyroid surgery over a period of 15 years in a Belgian center

BackgroundGuidelines for thyroid surgery have evolved to reflect advances in medical knowledge and decrease the overdiagnosis of low-risk thyroid cancer. Our goal was to analyze the change made in operative thyroid management and the impact on thyroid cancer diagnosis.BackgroundGuidelines for thyroid surgery have evolved to reflect advances in medical knowledge and decrease overdiagnosis of low risk thyroid cancer. Our goal was to study the evolution, over a long period, of pre- and postoperative management and the influence on histological cancer diagnosis and, more particularly, microcancer.MethodsIn this retrospective cohort study, we included 891 consecutive patients who underwent thyroid surgery between 2007 and 2020.ResultsRespectively 305, 290 and 266 patients underwent surgery over the 3 periods of 2007–2010, 2011–2015 and 2016–2020. In all three periods, women represented approximately 70% of the population, and the mean age was 54 years old (range: 67). Most surgeries (90%) involved total thyroidectomies. Over the study period, the proportion of preoperative fine needle aspiration (FNA) increased from 13 to 55%, p < 0,01. Cancer was found in a total of 116 patients: 35 (11%) patients between 2007 and 2010, 50 (17%) between 2011 and 2015 and 32 (12%) between 2016 and 2020 (p = 0.08). For all 3 periods, papillary thyroid cancer (PTC) was the most prevalent, at approximately 80%. The proportion of thyroid cancer > T1a increased significantly from 37% (2011–2015 period) to 81% (2016–2020 period), p = 0.001. Patients treated with radioiodine remained relatively stable (approximately 60%) but were more frequently treated with a low dose of radioiodine (p < 0.01) and recombinant human TSH (p < 0.01). Operative thyroid weight decreased over time in all but the low-risk T1a PTC cases.ConclusionsOver a period of 15 years and according to the evolution of recommendations, the care of patients who underwent thyroid surgery changed with the increased use of preoperative FNA. This change came with a decrease in low-risk T1a PTC.

Thyroid Function and Sleep Patterns: A Systematic Review.

Hypothyroidism, defined as a low metabolic function of the thyroid gland that results in low thyroid hormone levels, and insomnia, a condition with the inability to sleep, are two distinct conditions with little overlap that have been extensively established. Both conditions have been studied independently in terms of epidemiology, pathophysiology, diagnosis, and management. The exact causal relationship between the two conditions has yet to be elucidated, and a direct underlying pathophysiology has not been pinpointed. To gain further insight into the relationship between hypothyroidism and insomnia, we performed a systematic review to explore this relationship using predetermined guidelines. Out of 59 studies assessed, four studies evaluated the mechanisms of these two potentially comorbid conditions. Our findings suggest that hypothyroidism and insomnia may have a bidirectional relationship, with symptomatic overlap that is tied to increased metabolic comorbidities and hormonal dysregulation. These findings warrant further research to verify these early findings and gain further insight into the relationship between these conditions. A better understanding of the pathophysiology of overlap between these two conditions will help improve diagnosis and target treatment more effectively.

Description of a patient with Graves’ disease post COVID-19 with negative serology

We are presenting a 62-year-old African-American female who was admitted to our Emergency Department (ED) with septic shock due to pneumonia and diverticulitis. After improvement of the admitting conditions, we found out that the patient developed 1-month post-COVID-19 pneumonia Graves’ disease. The diagnosis was challenging because the patient was negative for thyroid-stimulating immunoglobulin (TSI) and thyroid receptor antibodies (TRAb). The clinical picture was highly suggestive of GD. The patient complained of increased sweating, palpitation, lower extremities weakness, and lack of sleep before the septic shock and after the COVID-19 infection. We palpated a trill and we heard a bruit on her thyroid gland which was a specific finding for the hypervascular gland as in GD. Our physical findings were confirmed by the laboratory findings of thyrotoxicosis with increased free thyroxin levels (Ft4) and very low thyroid stimulating hormone (TSH). The Doppler flow ultrasound of the thyroid confirmed bilateral hypervascular thyroid gland suggestive of hyperthyroidism without nodules. The patient did not have any thyroid disease or complaints before her COVID-19 infection. This is as far as we know the first described patient post-COVID-19 induced GD without TSI and TRAb.

#2856 Sleep disturbances in non-dialysis dependent chronic kidney disease—The CKD-REIN cohort study

Abstract Background and Aims Sleep disturbances are common in patients on dialysis, but little is known about their prevalence and determinants in earlier chronic kidney disease (CKD) stages. We assessed the prevalence of insomnia, excessive daytime sleepiness (EDS), and sleep apnea, and studied their relation with kidney function, before and after accounting for various other potential determinants in patients with moderate or severe CKD. Method This study included 2657 nephrology outpatients with non-dialysis dependent CKD (mean age, 67 ± 12 years; 66% men; mean eGFR, 33 ± 12 mL/min/1.73 m2) from the French CKD-REIN (CKD-Renal Epidemiology and Information Network) cohort study who completed the Basic Nordic Sleep Questionnaire at baseline. Insomnia was defined as having badly or rather badly been sleeping, or having had difficulties falling asleep or awakened too early without being able to fall asleep again at least 3 times per week, over the past 3 months. And EDS, as feeling excessively sleepy during daytime at least 3 times per week over the past 3 months. Sleep apnea with or without continuous positive airway pressure use were identified from medical records. For each sleep disturbance, we assessed the crude prevalence by sex and by estimated glomerular filtration rate (eGFR) categories. We estimated adjusted odds ratios (OR) with 95% confidence interval (95% CI) associated with eGFR decrease (per 10 mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (ACR) categories (A1-A3), as well as with age, sex, education (years), smoking, alcohol consumption, physical activity (estimated by the Global Physical Activity Questionnaire), performance score in Instrumental Activities of Daily Living [IADL], obesity, diabetes, cardiovascular disease, depression, patient-reported cramps, itching and stress or worry about CKD, and relevant drug use. Results Overall prevalence of insomnia, EDS, and sleep apnea were 23%, 15%, and 14%, respectively, with differences between women and men for insomnia, 30% vs 19%, EDS, 17% vs 13%, and sleep apnea, 10% vs 17%, respectively (all P-values &amp;lt;.001). Crude prevalence of EDS significantly increased with decreasing eGFR category (without interaction with sex), but not those for insomnia and sleep apnea (Figure). ACR categories were not associated with either sleep disturbances. In multivariable analyses, factors significantly associated with higher prevalence of insomnia included female sex, smoking, low physical activity, depression, and thyroid hormone use. There were also strong dose-response relations between insomnia prevalence and to what extend patients reported being bothered by cramps or itching, or stressed/worried about CKD. The crude relation of eGFR with EDS tended to weaken (ORs [95% CI], 1.10 [0.99-1.22] per 10 mL/min decrease, p-value 0.09) in multivariable analysis, which showed higher ORs associated with past smoking, depression, lower IADL score, insomnia, and betablocker use, as well as dose-response relations with itching, and stress/worry about CKD. Factors significantly associated with increased prevalence of sleep apnea included male sex, alcohol consumption, lower IADL score, obesity, depression, and cardiovascular disease. Conclusion This analysis of baseline data from the CKD-REIN cohort shows that, in patients with non-dialysis dependent CKD, EDS alone appeared to be related to kidney function level. The study, however, suggests the potential role of modifiable CKD-related symptoms, cramps and itching, and of being stressed or worried about CKD, in addition to that well-documented for behavioral and clinical risk factors, and drugs in the risk of insomnia and EDS.

EVALUATION OF THYROID FUNCTION AND THYROID DISEASES IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: To explored the thyroid function and prevalence of thyroid diseases in primary aldosteronism (PA) and PA subtypes. Design and method: Patients with PA and Essential hypertension (EH) in our hypertension center between August 2011 to June 2022 were enrolled in this observational study. All PA patients underwent adrenal venous sampling (AVS), thus receiving the most accurate subtype diagnosis available. The differences of thyroid function and the prevalence of thyroid diseases between PA and EH patients were analyzed. Results: 7161 participants were included in the study with a mean age of 48.20±8.83 years and a mean BMI of 26.52±3.45 kg/m2. Two groups: PA patients showed lower FT4, FT3, TT4, TT3, positive TPOAb and higher prevalence of thyroid nodules (22.5%) than EH patients. PA was significantly associated with thyroid nodules (OR: 1.245, 95%CI: 1.052-1.473, P= 0.011). Three groups: statistical differences in FT4, FT3, TT4, TT3, and positive TPOAb levels were found in APA, IHA and EH. Thyroid nodules are most prevalent in APA (26.00%), followed by IHA (20.80%) and EH (17.80%). APA showed a significant association with thyroid nodules (OR: 1.345, 95%CI: 1.015-1.781, P=0.039). Additionally, it was found that FT4, FT3, TT4, and TT3 were negatively correlated with the PAC levels in patients. The stratification analysis showed that the prevalence of thyroid nodules was higher in subjects with PAC levels great than or equal to 12ng/dL. Conclusions: Compared to EH groups, PA patients had lower thyroid function and higher prevalence of thyroid nodules.

TO EXPLORED THE THYROID FUNCTION AND PREVALENCE OF THYROID DISEASES IN PRIMARY ALDOSTERONISM (PA) AND PA SUBTYPES

Objective: To explored the thyroid function and prevalence of thyroid diseases in primary aldosteronism (PA) and PA subtypes. Design and method: Patients with PA and Essential hypertension (EH) in our hypertension center between August 2011 to June 2022 were enrolled in this observational study. All PA patients underwent adrenal venous sampling (AVS), thus receiving the most accurate subtype diagnosis available. The differences of thyroid function and the prevalence of thyroid diseases between PA and EH patients were analyzed. Results: 7161 participants were included in the study with a mean age of 48.20±8.83 years and a mean BMI of 26.52±3.45 kg/m2. Two groups: PA patients showed lower FT4, FT3, TT4, TT3, positive TPOAb and higher prevalence of thyroid nodules (22.5%) than EH patients. PA was significantly associated with thyroid nodules (OR: 1.245, 95%CI: 1.052-1.473, P= 0.011). Three groups: statistical differences in FT4, FT3, TT4, TT3, and positive TPOAb levels were found in APA, IHA and EH. Thyroid nodules are most prevalent in APA (26.00%), followed by IHA (20.80%) and EH (17.80%). APA showed a significant association with thyroid nodules (OR: 1.345, 95%CI: 1.015-1.781, P=0.039). Additionally, it was found that FT4, FT3, TT4, and TT3 were negatively correlated with the PAC levels in patients. The stratification analysis showed that the prevalence of thyroid nodules was higher in subjects with PAC leve greater than or equal to 12ng/dL. Conclusions: Compared to EH groups, PA patients had lower thyroid function and higher prevalence of thyroid nodules.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Decision Regret Following the Choice of Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: A Prospective Cohort Study.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

Impending thyroid storm caused by hydatidiform mole

Introduction: Thyroid storm is a rare but life-threatening endocrine emergency. It is an acute exaggerated clinical manifestation of thyrotoxic state. We report an impending thyroid storm caused by a hydatidiform mole in a 14-year-old girl. This paper intends to describe hyperthyroidism secondary to molar pregnancy highlighting the rare but essential evaluation of hyperthyroidism. Case: A 14-year-old girl was consulted by the obstetric division to evaluate and manage hydatidiform mole with suspected hyperthyroidism. She had frequent palpitations and tremors for 1 week ago. She also complained of nausea and vomiting 1 week before admission to the hospital. We found a Burch-Wartofsky score of 25, which was categorized as an impending thyroid storm. Laboratory results showed mild anemia, low thyroid stimulating hormone (TSH) levels, high free thyroxine (T4) levels, and markedly elevated beta-human chorionic gonadotropin (beta-hCG) levels, normal Thyroid-stimulating hormone receptor antibodies (TRAb). Other laboratory parameters are mediocre. The ECG results showed sinus tachycardia. A mole tissue biopsy of the uterus confirms the morphology of the hydatidiform mole. These findings established the diagnosis of Impending Thyroid Storm caused by a hydatidiform mole. Conclusion: A hydatidiform mole can cause thyroid storm because the hormone hCG has similar structure to TSH. Doctors should always estimate the possibility of hyperthyroidism in a molar pregnancy.

Factors affecting timing of hypothyroidism following radioactive iodine therapy (RAIT) for patients with Graves' disease: A 12-month observational study.

This retrospective study analyzed factors influencing hypothyroidism development after radioactive iodine therapy for Graves' disease. Three hundred and three patients with Graves' disease treated with radioactive iodine (RAI) from 2013 to 2022 at two Egyptian hospitals were included. Data collected included demographics, lab values, thyroid imaging, RAI doses, and outcomes. Patients were followed for ≥1 year to assess hypothyroidism onset. At the end of 1 year, around 79.5% of the individuals developed hypothyroidism while 12.5% continued to experience hyperthyroidism. The onset of hypothyroidism occurred earlier in those with thyroid volume (≤75.5 cm 3 ), lower thyroid weight (≤84.7 g), thyroid uptake (≤18.8%), and higher RAI dose/volume (≥0.1022 mCi/ml) ( P < 0.001). Additionally, there was a correlation between anti-thyroid peroxidase (anti-TPO) antibodies and faster development of hypothyroidism compared to those who were negative for antibodies (2.9 vs 8.9 months, P = 0.001). When considering factors in analysis it was found that anti-TPO antibodies were the only independent predictor, for developing hypothyroidism (hazard risk 30.47, P < 0.001). Additionally, thyroid volume and uptake independently predicted successful treatment outcomes ( P < 0.05). Positive anti-TPO antibodies strongly predict hypothyroidism risk after RAI therapy for Graves' disease. Smaller thyroid size, lower uptake, and higher RAI dose/volume correlate with earlier hypothyroidism onset but are less significant predictors than anti-TPO status. Findings can guide RAI therapy personalization to optimize outcomes.

Comparison of the five different definitions of equol producers: The relationship between blood and urine equol concentrations and blood parameters in 466 healthy men and women

Background and aimsNo studies have compared various definitions of “equol producers” until now. Therefore, we aimed to explore the accuracy of five different definitions of equol producers (EQP) and their associations with health benefits. MethodsThis is a cross-sectional study of 466 healthy Japanese men and women aged between 22 and 88 years. Equol producer proportions were calculated from their serum and urine isoflavone concentrations using five commonly used definitions. We then examined their accuracy, and associations with the blood parameters. ResultsProportions of equol ranged from 29 % in the most stringent definition to 47.6 % in the most sensitive definition. EQP identified under all definitions had significantly low serum PSA11PSA: prostate specific antigen. levels compared to nonequol producers (NEQP). The most stringent definition, which is defined as the urinary equol level of 1.0 μM and above, corresponded to the highest median serum equol level and was associated with better health outcomes. Male EQP identified by this definition seemed to have reduced risk of LDL22LDL: low density lipoprotein-hypercholesterolemia by 50 %, and female EQP identified by this definition seemed to have lower risk of high hs-CRP,33CRP: C-reactive protein compared to NEQP. Both the first and second stringent definition, which is defined as the serum equol level of 1.0 ng/mL and above, was associated with lower thyroid stimulating hormone level. ConclusionsMore stringent definitions were associated with better parameters in general. Combined with the dietary inquires, a reliable definition for equol producer is crucial to evaluate the health benefits of equol.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry

Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. This research was not funded by any public, commercial, or not-for-profit agencies.

Preventive central neck lymph node dissection as a stage in the treatment of papillary thyroid cancer

Relevance: The need of prophylactic cervical lymph node dissection for the detection of low grade thyroid cancer remains debatable since preoperative examination does not always allow determining the involvement of a group VI regional lymph collector.Objective: to evaluate the frequency of group VI nodes involvement with clinical N0–Nx based on the results of a morphological examination after performing a preventive central neck lymph node dissection.Materials and methods: the study included 295 patients who underwent surgery from 2016 to 2022 for papillary thyroid cancer with cT1–T2, N0–Nx. There were 11.5 % of men included (n = 34) and 88.5 % of women (n = 261). Of these, 40.7 % (n = 120) were less than 55 years old. All patients underwent surgical treatment which included thyroidectomy or hemithyroidectomy with cervical lymph node dissection.Results: The study included 295 patients with cT1 — 247 (83.7 %) and cT2 — 48 (16.3 %). Pathomorphological examination changed the T index in some patients: pT1 was found in 80.3 % of cases (n = 237); рТ2 — in 9.2 % (n = 27); рТ3 — in 10.5 % (n = 31). Central neck lymph nodes involvement was detected in 77 (26.1 %) out of 295 patients. There was a correlation between the frequency of metastases detection and the size of the primary tumor: 22.8 % (n = 54) of metastases with pT1, 33.3 % (n = 9) with pT2, and 45.2 % (n = 14) with pT3. Transient hypocalcemia was found in 32 % of patients with pT1, 69 % with pT2, and 84 % with pT3. Two patients had unilateral transient paresis of the larynx.Conclusions: Our analysis demonstrates that the preventive central neck lymph node dissection in patients with low grade thyroid cancer is an important component of surgical treatment, which allows to improve the treatment results with a possible subsequent reduction in the risk of distant progression. In this study 77 (26.1 %) of 295 patients had metastases in the lymph nodes of the central neck. The number of postoperative complications affecting the quality of life of patients was acceptable with 0.67 % of paresis of the larynx and 39 % of mild hypocalcemia.

Prevalence of Endocrinopathies in a Cohort of Patients with Rett Syndrome: A Two-Center Observational Study.

Systematic data on endocrinopathies in Rett syndrome (RTT) patients remain limited and inconclusive. The aim of this retrospective observational two-center study was to assess the prevalence of endocrinopathies in a pediatric population of RTT patients. A total of 51 Caucasian patients (47 girls, 4 boys) with a genetically confirmed diagnosis of RTT were enrolled (mean age 9.65 ± 5.9 years). The patients were referred from the Rett Center of two Italian Hospitals for endocrinological evaluation. All the study population underwent clinical and auxological assessments and hormonal workups. MeCP2 mutations were detected in 38 cases (74.5%), CDKL5 deletions in 11 (21.6%), and FOXG1 mutations in 2 (3.9%). Overall, 40 patients were treated with anti-seizure medications. The most frequent endocrinological finding was short stature (47%), followed by menstrual cycle abnormalities (46.2%), weight disorders (45.1%), low bone mineral density (19.6%), hyperprolactinemia (13.7%) and thyroid disorders (9.8%). In the entire study population, endocrinopathies were significantly more frequent in patients with MeCP2 mutations (p = 0.0005), and epilepsy was more frequent in CDKL5 deletions (p = 0.02). In conclusion, our data highlighted that endocrinopathies are not rare in RTT, especially in patients with MeCP2 deletions. Therefore, in the context of a multidisciplinary approach, endocrinological evaluation should be recommended for RTT patients.

Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study.

Current therapeutic measures for thyroid dysfunction are limited and often accompanied by adverse effects. The use of lipid-lowering drugs like statins has recently been associated with lower thyroid eye diseases risk. To investigate the implications of genetically proxied lipid-lowering drugs on thyroid dysfunction. In this drug-target Mendelian randomization (MR) study, we utilized genetic variants within drug target genes associated with low-density lipoprotein (LDL) or triglyceride (TG), derived from a genome-wide association study (GWAS) meta-analysis (N ≤ 188,577), to simulate lifelong drug interventions. Genetic summary statistics for thyroid dysfunction outcomes were retrieved from GWAS datasets of Thyroid Omics Consortium (N ≤ 54,288) and UK Biobank (N = 484,598). Inverse-variance-weighted MR (IVW-MR) method was performed as primary analysis, followed by validation in colocalization analysis. A subsequent two-step MR analysis was conducted to identify biomarkers mediating the identified drug-outcome association. In IVW-MR analysis, genetic mimicry of 3-hydroxy-3-methylglutarylcoenzyme reductase (HMGCR) inhibitors (e.g. statins) was significantly associated with lower risk of hyperthyroidism in two independent datasets (OR1, 0.417 per 1-mmol/L lower in LDL-C; 95% CI 0.262 to 0.664; P1=2.262 × 10-4; OR2 0.996; 95% CI 0.993-0.998; P2=0.002). Two-step MR analysis revealed eighteen biomarkers linked to genetic mimicry of HMGCR inhibition, and identified insulin-like growth factor 1 (IGF-1) levels mediating 2.108% of the negative causal relationship between HMGCR inhibition and hyperthyroidism. This study supports HMGCR inhibition as a promising therapeutic strategy for hyperthyroidism and suggests its underlying mechanisms may extend beyond lipid metabolism. Further investigations through laboratory studies and clinical trials are necessary to confirm and elucidate these findings.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

Low thyroid function is associated with metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non-alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict-normal thyroid function and low thyroid function groups (low-normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. During a median follow-up of 15.6 months, 165 (8.9%) strict-normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22-1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47-2.60). MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent.

Hypothyroxinemia and weight velocity in preterm infants.

Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA. Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children's Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity. In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA. We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Clinical Efficacy of Virechana Karma in Hypothyroidism- A Single Case Study

Hypothyroidism (underactive,low thyroid). It is one of the most prevalent disorders affecting 2-5% of global population which is more prevalent among females. Thyroid gland produces two hormones Thyroxin(T4) and Triiodothyronine(T3) playing an important role in metabolism, growth and development of the body. In Ayurveda hypothyroidism can be co- releated with Agnimandhya Avastha especially Dhatuagnimandhya which has specific symptoms according to different stages, very similar with the symptoms of Hypothyroidism. Samshodhana is the principle therapy as hypothyroidism is a Bahudosh Awastha so here Virechana Karma is opted for the management of Hypothyroidism. Here, a traditional Ayurvedic regimen was attempted to treat a 25year old female with known case of hypothyroidism for last 5 years. This study shows significant improvement in sign, symptoms of Hypothyroidism and Thyroid function Test.