Metabolic syndrome and risk of subclinical hypothyroidism: a systematic review and meta-analysis.

Background: Subclinical hypothyroidism (SCH) is a common endocrine subclinical disorder, the main adverse consequences of which are the development of clinical hypothyroidism and the promotion of ischemic heart disease. Metabolic syndrome (MetS) is a collection of metabolic problems. The goal of this meta-analysis was to evaluate the relationship between MetS and SCH. Methods: Suitable publications were identified using PubMed, Embase, and the Cochrane Library. The meta-analysis included only studies in English that reported odds ratio (OR) data for MetS and SCH. Two researchers combined data using a random-effects model. OR and 95% confidence intervals (CIs) were used to present the results. Results: MetS was associated with an elevated risk of developing SCH (OR 2.56, 95% CI 1.44-4.55). However, the individual components of MetS were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH. Sensitivity analysis confirmed that our results were robust. Conclusions: This meta-analysis indicates that patients with MetS have an increased risk of SCH, while there is no significant association between the five individual components of MetS and the risk of SCH. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023454415.

Thyroid complications after hemopoietic stem cell transplantation in children and adolescents.

PURPOSE: To evaluate the prevalence of thyroid dysfunction and its association with possible contributing factors related to diagnosis and treatment in children who received hematopoietic stem cell transplantation (HSCT) in the only national transplant unit in Greece. METHODS: This is an observational, retrospective, single center cohort study that included 194 patients (58.6% boys) who survived for at least 1 year following allogeneic HSCT. Conditioning regimens depended upon diagnosis and protocols active at the time of transplantation. Some patients received irradiation, either central nervous system prophylaxis (n = 20), or total body irradiation (TBI) (n = 8). Thyroid gland evaluation included thyroid-stimulating hormone, free thyroxine, thyroid autoantibodies, and sonogram. Univariate and multivariate logistic models were used to examine the association of the above-mentioned factors with hypothyroidism. RESULTS: The mean age at diagnosis and at bone marrow transplant (BMT) in years was 7.51 ± 0.46 and 7.58 ± 0.36, respectively. The median follow-up time was 4.83 years. Hypothyroidism was detected in 33 cases (17.7%), four of those patients having received TBI. Factors contributing to hypothyroidism as per the multivariate analysis were male sex, [OR: 3.005, 95% CI (1.145-7.890)], irradiation, [OR: 2.876, 95% CI (1.120-7.386)], and years after HSCT [OR: 1.148, 95% CI (1.042-1.266)], while malignancy was identified only in the univariate analysis. The multivariate model presents a good class separation capacity [AUC = 72%, 95% CI (61.4%-82.4%)], Two patients had papillary thyroid cancer, both among children who had received TBI. CONCLUSION: These data highlight the fact that male sex and radiotherapy are two independent factors that lead to increased risk for hypothyroidism. Furthermore, the prevalence of hypothyroidism increases with time post HSCT.

Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Nutritional and exercise interventions to improve conception in women suffering from obesity and distinct nosological entities.

Infertility among women, particularly those living with obesity, presents a multifaceted challenge with implications for reproductive health worldwide. Lifestyle interventions, mainly focusing on weight loss, have emerged as promising strategies to improve fertility outcomes in this population. This review aims to explore the effectiveness of various lifestyle interventions, encompassing dietary modifications and exercise regimens, in enhancing fertility outcomes among women with obesity and associated conditions such as polycystic ovary syndrome, congenital adrenal hyperplasia, type 2 diabetes mellitus, premenopause, hypothyroidism and eating disorders. Methodology of study search encompass a broad spectrum, ranging from interventions targeting weight management through slow or rapid weight loss to dietary approaches emphasizing whole food groups, specific nutrients, and dietary patterns like low-carbohydrate or ketogenic diets, as well as the Mediterranean diet. By synthesizing existing findings and recommendations, this review contributes to the understanding of lifestyle interventions in addressing infertility, with an emphasis on the population of women of reproductive age with excess weight and known or unknown infertility issues, while promoting their integration into clinical practice to optimize reproductive health and overall well-being.

The role of severity and duration of inflammation and hematological parameters on the outcome of subacute thyroiditis.

Background: The role of severity and duration of inflammatory findings on the development of persistent hypothyroidism and anemia has not been clarified in subacute thyroiditis (SAT). Methods: Demographic data and laboratory parameters of patients with SAT were analyzed retrospectively. Results: Permanent hypothyroidism was observed in 28.1% of patients. Baseline elevated erythrocyte sedimentation rate as defined >74.5 mm/h was found to be associated with permanent hypothyroidism, but the duration of inflammation was not different between the recovered and hypothyroid patients. Baseline hemoglobin values improved without specific therapy in 3.5 months. Conclusion: The initial severity but not the duration of inflammation increases the risk for the development of permanent thyroid dysfunction, and anemia improves with the resolution of inflammation.

[Box: see text].

Solving the Dilemma: Van Wyk-Grumbach Syndrome.

The Van Wyk-Grumbach syndrome (VWGS) (hypothyroidism, ovarian mass, and precocious puberty) has been extensively documented in the literature as long-term hypothyroidism manifesting as an ovarian mass. The authors of this study describe this entity in a young girl, aged 10, who presented with abdominal pain with a multiloculated ovarian cyst. She was evaluated, and it was discovered that she had delayed bone age, precocious puberty, and a small height. Following her diagnosis of autoimmune thyroiditis and the initiation of thyroxine replacement therapy, the ovarian cysts spontaneously regressed. To avoid needless assessment and surgical mishaps, this entity should be considered in situations of ovarian mass, particularly those with precocious puberty and thyroid disorders.

The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

The longitudinal growth trajectory of children with congenital hypothyroidism during the first 3 years of life.

Congenital hypothyroidism (CH) is detected through a newborn screening program in Iran, enabling early detection and prompt treatment. This study addresses the longitudinal growth trajectory of Iranian children with CH and explores associated factors during the first 3 years of life. Data from 1474 children with CH in Isfahan, Iran (2002-2022), were analyzed. Weight, height, and head circumference were measured, and z-scores for age were calculated. Group-based trajectory modeling was applied to distinct growth trajectories. Factors influencing growth patterns, including gender, treatment initiation age, delivery method, parental consanguinity, history of familial hypothyroidism, and thyroid-stimulating hormone (TSH) levels at 3-7 days, were investigated. Thirty-seven percent of children diagnosed with CH faced a delay in weight, while 36.6% experienced stunted height, and 25.7% showed a retardation in head circumference growth. The initiation of treatment, parental consanguinity, and family history of hypothyroidism varied among these groups. Children exhibiting an optimal growth pattern in the initial 3 years of life demonstrated lower average TSH levels. CONCLUSION: This research emphasizes the complexity of managing CH and stresses the importance of tailoring interventions based on individualized characteristics and the ongoing growth patterns of the children. Future research is required to understand the intricate relationships between growth patterns and various determinants and optimize the growth and developmental outcomes of children with CH. WHAT IS KNOWN: • Iran has a higher prevalence of congenital hypothyroidism (CH) with a nationwide screening program. • There are concerns about delayed growth in CH children, but limited research on long-term patterns and contributing factors. WHAT IS NEW: • Distinct patterns in weight, height, and head circumference among children with CH were identified. • Factors such as consanguinity, parental hypothyroidism, and TSH levels impact growth outcomes. • CH management is complicated, and there is a need for individualized interventions.

Cerebral Infarction After Switching From Roxadustat to Daprodustat in a Patient With Renal Anemia.

Renal anemia is generally caused by a decrease in the production of erythropoietin in kidney due to renal dysfunction, and this may be associated with the increase in mortality and cardiovascular events in addition to subjective symptoms such as fatigue and wobbliness. We report a case of an 87-year-old man with type 2 diabetes, hypertension, and dyslipidemia who had received roxadustat (a hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitor) for renal anemia due to diabetic nephropathy and in whom roxadustat was switched to daprodustat (another HIF-PH inhibitor) due to the onset of central hypothyroidism. About three weeks after this change, the patient developed acute asymptomatic cerebral infarction with an elevation of hemoglobin (Hb). It is unclear if the change to daprodustat was involved in the onset of cerebral infarction. However, this case suggests that particular caution should be paid to unexpected acute elevation of Hb after a change from one HIF-PH inhibitor to another, especially in a patient at high risk for cardiovascular events.

Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

Association between Benign Paroxysmal Positional Vertigo and Thyroid Diseases: Systematic Review and Meta-Analysis.

Introduction Benign paroxysmal positional vertigo (BPPV) is the peripheral vestibular dysfunction that most affects people worldwide, but its etiopathogenesis is still not fully understood. Considering the etiological diversity, some studies highlight the association between BPPV and thyroid diseases. Objective To investigate the association between thyroid diseases and BPPV. Data Synthesis Systematic review and meta-analysis of epidemiological studies searched in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases. Studies that were fully available and investigated the association between BPPV and thyroid diseases were selected. The articles that composed the meta-analysis were analyzed using the dichotomous model, the Mantel-Haenszel statistical test, odds ratio (OR), and a 95% confidence interval (CI). Of the 67 articles retrieved from the databases, 7 met the eligibility criteria of the systematic review, and 4 had data necessary to perform the meta-analysis. Qualitative analysis revealed that the studies were conducted in the European and Asian continents. The predominant methodological design was the case-control type, and thyroid dysfunctions, hypothyroidism, and Hashimoto thyroiditis occurred more frequently. The meta-analysis showed no association between hypothyroidism and BPPV; however, there was a statistically significant relationship between Hashimoto thyroiditis and BPPV. Conclusion The meta-analysis results suggest a possible association between BPPV and Hashimoto thyroiditis. Nevertheless, we emphasize the need for further studies to elucidate the evidence obtained.

Roxadustat-Induced Central Hypothyroidism in Renal Anemia Patients: Insights From Antineutrophil Cytoplasmic Antibody-Related Vasculitis Cases.

The introduction of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors in Japan in 2019 for treating renal anemia in hemodialysis patients has resulted in an adverse event: central hypothyroidism. Although this adverse event was not widely recognized by the public, it was first documented in Japan in 2021. Despite limited case reports on roxadustat, an oral HIF-PH inhibitor that induces central hypothyroidism, this condition typically improves rapidly upon discontinuation of the drug. In this report, we present rare cases of roxadustat-induced central hypothyroidism in two patients: a woman in her 80s and a man in his 60s, neither of whom had prior thyroid disease. Both patients developed central hypothyroidism shortly after starting roxadustat treatment for renal anemia associated with antineutrophil cytoplasmic antibody-related vasculitis. Notably, neither patient had pituitary tumors or other pituitary hormone disorders. Thyroid function improved with levothyroxine treatment, even when oral roxadustat was continued. Roxadustat may induce central hypothyroidism, highlighting the importance of regularly measuring and evaluating thyroid function when administering this drug to monitor possible changes in thyroid hormone levels.

Hypothyroidism after hemithyroidectomy: a systematic review and meta-analysis.

BACKGROUND: The incidence of hypothyroidism following hemithyroidectomy and risk factors associated with its occurrence are not completely understood. This systematic review investigated the incidence and risk factors for hypothyroidism, thyroxine supplementation following hemithyroidectomy as well as the course of post-operative hypothyroidism, including the time to hypothyroidism and incidence of transient hypothyroidism. METHODS: Searches were conducted in MEDLINE, EMBASE, Scopus, and Cochrane library for studies reporting the incidence of hypothyroidism or thyroxine supplementation following hemithyroidectomy. RESULTS: Sixty-six studies were eligible for inclusion: 36 reported risk factors, and 27 reported post-operative course of hypothyroidism. Median follow-up was 25.2 months. The pooled incidence of hypothyroidism was 29% (95% CI, 25-34%; P<0.001). Transient hypothyroidism occurred in 34% of patients (95% CI, 21-47%; P<0.001). The pooled incidence of thyroxine supplementation was 23% (95% CI, 19-27%; P<0.001), overt hypothyroidism 4% (95% CI, 2-6%, P<0.001). Risk factors for development of hypothyroidism included pre-operative thyroid stimulating hormone (TSH) (WMD, 0.87; 95% CI, 0.75-0.98; P<0.001), TSH ≥ 2 mIU/L (RR, 2.87; 95% CI, 2.43-3.40; P<0.001), female sex (RR, 1.19; 95% CI, 1.08-1.32; P=0.007), age (WMD, 2.29; 95% CI, 1.20-3.38; P<0.001), right sided hemithyroidectomy (RR, 1.35; 95% CI, 1.10-1.65, P=0.003), the presence of autoantibodies anti-TPO (RR, 1.92; 95% CI, 1.49-2.48; P<0.001), anti-Tg (RR, 1.53; 95% CI, 1.40-1.88; P<0.001), and Hashimoto's thyroiditis (RR, 2.05; 95% CI, 1.57-2.68; P=0.001). CONCLUSION: A significant number of patients will develop hypothyroidism or require thyroxine following hemithyroidectomy. An awareness of patient risk factors and postoperative thyroid function course will assist in counselling patients on their risk profile and guiding management.

Schmidt's Syndrome: An Uncommon Cause of Spontaneous Hypoglycemia.

Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

Serum Vitamin B12 and Holotranscobalamin Levels in Subclinical Hypothyroid Patients in Relation to Thyroid-Stimulating Hormone (TSH) Levels and the Positivity of Anti-thyroid Peroxidase Antibodies: A Case-Control Study.

Background Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels, while thyroid hormones (free thyroxine (T4) and free triiodothyronine (T3)) remain within the reference ranges. Vitamin B12 (cobalamin) deficiency is common in patients with autoimmune disorders, including autoimmune hypothyroidism. The study was aimed at evaluating serum vitamin B12 levels and holotranscobalamin (HoloTC) levels in SCH patients and ascertaining their association with a risky level of TSH and the positivity of anti-thyroid peroxidase (anti-TPO) antibodies. Methodology A case-control study was conducted at Azadi Teaching Hospital, Duhok, a city in the Kurdistan region of Iraq, involving 153 participants, including 72 newly diagnosed SCH patients and 81 healthy controls. Serum levels of vitamin B12, HoloTC, TSH, free T4, free T3, and anti-TPO antibodies were measured based on different principles. Results The mean age of patients with SCH was 32.87±8.7 years, with predominantly females comprising 75% and 77.8% being less than 40 years of age. Moreover, the mean levels of serum TSH (6.96±2.68 µIU/L), anti-TPO antibodies (53.31±81.32 IU/ml), and HoloTC (41.93±19.42 pmol/l) were significantly higher in patients with SCH compared to healthy control participants (p < 0.05), whereas there was a non-significantly higher level of vitamin B12(320.72±98.42 pg/ml) among SCH patients compared to healthy control participants (p = 0.220). The mean levels of vitamin B12 (345.33±103.22 pg/ml) and HoloTC (40.14±18.16 pmol/l) were insignificantly lower in SCH patients with TSH levels more than 7 µIU/L (p > 0.05), as well as the mean levels of vitamin B12 (308.82±96.12 pg/ml) and HoloTC (41.14±19.29 pmol/l) insignificantly lower in SCH patients with positive anti-TPO antibodies (p > 0.05).  Conclusions This study highlights the potential association between SCH and altered vitamin B12 status, particularly evident in HoloTC levels. The presence of positive anti-TPO antibodies and the degree of elevation in TSH levels may exacerbate vitamin B12 deficiency in SCH patients.

The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

Alterations in corpus callosum subregions morphology and functional connectivity in patients with adult-onset hypothyroidism.

BACKGROUND: Magnetic resonance imaging (MRI) brain abnormalities have been reported in the corpus callosum (CC) of patients with adult-onset hypothyroidism. However, no study has directly compared CC-specific morphological or functional alterations among subclinical hypothyroidism (SCH), overt hypothyroidism (OH), and healthy controls (HC). Moreover, the association of CC alterations with cognition and emotion is not well understood. METHODS: Demographic data, clinical variables, neuropsychological scores, and MRI data of 152 participants (60 SCH, 37 OH, and 55 HC) were collected. This study investigated the clinical performance, morphological and functional changes of CC subregions across three groups. Moreover, a correlation analysis was performed to explore potential relationships between these factors. RESULTS: Compared to HC, SCH and OH groups exhibited lower cognitive scores and higher depressive/anxious scores. Notably, rostrum and rostral body volume of CC was larger in the SCH group. Functional connectivity between rostral body, anterior midbody and the right precentral and dorsolateral superior frontal gyrus were increased in the SCH group. In contrast, the SCH and OH groups exhibited a decline in functional connectivity between splenium and the right angular gyrus. Within the SCH group, rostrum volume demonstrated a negative correlation with Montreal Cognitive Assessment and visuospatial/executive scores, while displaying a positive correlation with 24-item Hamilton Depression Rating Scale scores. In the OH group, rostral body volume exhibited a negative correlation with serum thyroid stimulating hormone levels, while a positive correlation with serum total thyroxine and free thyroxine levels. CONCLUSIONS: This study suggests that patients with different stages of adult-onset hypothyroidism may exhibit different patterns of CC abnormalities. These findings offer new insights into the neuropathophysiological mechanisms in hypothyroidism.

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism.

INTRODUCTION: Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. MATERIAL AND METHODS: The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. RESULTS: There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). CONCLUSION: Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

Targeting the Manifestations of Subclinical and Overt Hypothyroidism Within the Hippocampus.

BACKGROUND: The past decade has witnessed a surge of articles describing the neurocognitive sequelae and associated structural and functional brain abnormalities of patients with overt (OH) and subclinical hypothyroidism (SCH). Findings show effects primarily within the frontal lobes with usually worse outcomes for OH than SCH. Several recent studies have also indicated hypothyroid patients may have smaller hippocampi, a key structure for memory. CONTEXT: The current JCEM paper by T. Zhang and colleagues applies two novel approaches for analyzing hippocampal structure and function. One uses an automated processing tool that segments the hippocampus into distinct subregions and the other, performs connectivity analysis to assess the relationships between specific hippocampal subregions and cortical areas. Relatively large samples of OH and SCH patients and healthy controls received a test of global cognitive functioning and structural and functional MRIs. Results showed hypothyroid groups scored significantly below controls on the memory scale and also had smaller hippocampal volumes in selective subregions. Effects were stronger for SCH than OH groups, who also showed different patterns of interconnectivity between hippocampal subregions and specific frontal-lobe areas. INTERPRETATION: To make sense of these findings, I explored the rodent and human literatures on thyroid hormone's role in hippocampal functioning and on hippocampal subfields and their purported functions and interconnections. Because current results suggest SCH may represent a distinct clinical entity with unique brain manifestations, I hypothesized two explanations for these findings, one involving transporter defects in the brain barriers and the other, differential neurodegeneration of the blood-brain-barrier vascular unit.