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.

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.

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.

Hypothyroidism and metabolic cardiovascular disease.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH.

Frequency-Specific Alterations of Fractional Amplitude of Low-Frequency Fluctuations in Adult-Onset Hypothyroidism.

BACKGROUND: The neuropathophysiological mechanisms of brain damage underlying hypothyroidism remain unclear. Fractional amplitude of low-frequency fluctuations (fALFF) has been established as a reliable indicator for investigation of abnormal spontaneous brain activity that occurs at specific frequencies in different types of mental disorder. However, the changes of fALFF in specific frequency bands in hypothyroidism have not yet been investigated. METHODS: Fifty-three hypothyroid patients and 39 healthy controls (HCs) underwent thyroid-related hormone levels tests, neuropsychological assessment, and magnetic resonance imaging (MRI) scans. The fALFF in the standard band (0.01-0.1 Hz), slow-4 (0.027-0.073 Hz), and slow-5 bands (0.01-0.027 Hz) were analyzed. An analysis of Pearson correlation was conducted between fALFF, thyroid-related hormone levels, and neuropsychological scores in hypothyroid patients. RESULTS: Compared to HCs, within the routine band, hypothyroidism group showed significantly decreased fALFF in left lingual gyrus, middle temporal gyrus (MTG), precentral gyrus, calcarine cortex, and right inferior occipital gyrus; within the slow-5 band, the hypothyroidism group exhibited decreased fALFF in left lingual gyrus, MTG, superior temporal gyrus, postcentral gyrus, and paracentral lobule, and increased fALFF in supplementary motor area (SMA) and right middle frontal gyrus; additionally, fALFF in the left lingual gyrus within the routine and slow-5 bands were negatively correlated with the level of thyroid stimulating hormone. CONCLUSIONS: In this study, the slow-5 frequency band exhibits better sensitivity than the standard band in detecting fALFF values. A decrease of fALFF values in the lingual gyrus and MTG was observed in both the standard and slow-5 bands and might present potential neuroimaging biomarkers for hypothyroidism. CLINICAL TRIAL REGISTRATION: No: ChiCTR2000028966. Registered 9 January, 2020, https://www.chictr.org.cn.

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis.

Objective: The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Research methods and procedures: Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Results: Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Conclusion: Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. Systematic review registration: https://inplasy.com, identifier (INPLASY202440114).

Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis.

Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.

The interplay between subclinical hypothyroidism and poor sleep quality: A systematic review.

BACKGROUND: The relationship between subclinical hypothyroidism (SHYPO) and sleep disturbances is still poorly investigated. This systematic review aims to critically appraise the existing literature to provide more insights in understanding whether SHYPO favors sleep disturbances or it is the sleep disturbance per se that affects the hypothalamus-pituitary-thyroid axis regulation. METHODS: Original studies on sleep quality and duration in patients with SHYPO were searched in the PubMed/MEDLINE, Embase, Web of Science and Scopus databases. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of included studies. RESULTS: Eight studies, including 2916 patients with SHYPO and 18,574 healthy controls, were retrieved. An overall agreement (7 out of 8 studies), about a positive correlation between decreased sleep quality and/or duration and SHYPO was observed. Five studies investigated sleep quality through self-reported surveys; only two studies explored both subjective and objective assessment of sleep quality with actigraphy (n = 1) or polysomnography (n = 1); finally, one study assessed subjective evaluation of sleep quality through a single question regarding the number of sleeping hours. A high level of heterogeneity among studies was manifest due to differences in population source, sleep measure assessment and criteria for diagnosing SHYPO. DISCUSSION: Overall, the existing literature data suggest a link between SHYPO and sleep disturbances, but further studies on larger populations of patients with homogeneous study designs and outcomes are warranted.

The impact of thyroid function on total spine bone mineral density in postmenopausal women.

PURPOSE: Osteoporosis has been a widespread concern for older women, especially postmenopausal women. Thyroid function is crucial for bone metabolism. However, the relationship between thyroid function variation within thyroxine reference range and bone mineral density (BMD) remains ambiguous. The objective of this study was to evaluate the effect of subclinical hypothyroidism or hyperthyroidism on total spinal BMD in postmenopausal women. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010, multivariable weighted logistic regression was used to evaluate the relationships between total spine BMD and TSH among postmenopausal women aged ≥50. RESULTS: After accounting for a number of variables, this study discovered that the middle TSH tertile was associated with a decreased probability of osteoporosis. Additionally, the subgroup analysis revealed that postmenopausal women over the age of 65 or people with an overweight BMI had a clearer relationship between total spine BMD and TSH. CONCLUSION: The total spinal BMD had a positive relationship with thyroid stimulating hormone in postmenopausal women, and that appropriate TSH level (1.38-2.32 mIU/L) was accompanied by higher total spinal BMD.

Structural and Functional Alterations of Hippocampal Subfields in Patients With Adult-Onset Primary Hypothyroidism.

CONTEXT: Hypothyroidism is often associated with cognitive and emotional dysregulation; however, the underlying neuropathological mechanisms remain elusive. OBJECTIVE: The study aimed to characterize abnormal alterations in hippocampal subfield volumes and functional connectivity (FC) in patients with subclinical hypothyroidism (SCH) and overt hypothyroidism (OH). METHODS: This cross-sectional observational study comprised 47 and 40 patients with newly diagnosed adult-onset primary SCH and OH, respectively, and 53 well-matched healthy controls (HCs). The demographics, clinical variables, and neuropsychological scale scores were collected. Next, the hippocampal subfield volumes and seed-based FC were compared between the groups. Finally, correlation analyses were performed. RESULTS: SCH and OH exhibited significant alterations in cognitive and emotional scale scores. Specifically, the volumes of the right granule cell molecular layer of the dentate gyrus (GC-ML-DG) head, cornu ammonis (CA) 4, and CA3 head were reduced in the SCH and OH groups. Moreover, the volumes of the right molecular layer head, CA1 body, left GC-ML-DG head, and CA4 head were lower in SCH. In addition, the hippocampal subfield volumes decreased more significantly in SCH than OH. The seed-based FC decreased in SCH but increased in OH compared with HCs. Correlation analyses revealed thyroid hormone was negatively correlated with FC values in hypothyroidism. CONCLUSION: Patients with SCH and OH might be at risk of cognitive decline, anxiety, or depression, and exhibited alterations in volume and FC in specific hippocampal subfields. Furthermore, the reduction in volume was more pronounced in SCH. This study provides novel insights into the neuropathological mechanisms of brain impairment in hypothyroidism.

Correlation of subclinical hypothyroidism with sarcopenia and its components in the Chinese older adults.

OBJECTIVE: To identify the correlation of thyroid function and subclinical hypothyroidism (SCH) with sarcopenia and its components in the older Chinese adults. METHODS: Older adults were recruited and divided into SCH group and non-SCH group. Free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescence. Appendicular skeletal muscle mass (ASM) was measured, and skeletal muscle index (SMI) was further calculated. Grip strength was measured. Physical performance was graded by the Short Physical Performance Battery (SPPB) scores of the gait speed test, chair stand test and balance test. RESULTS: Of the 240 older adults included, 48 (20.00%) presented with SCH. The prevalence of sarcopenia in SCH group was higher than that in non-SCH group (33.33% v.s. 18.75%). Grip strength was significantly lower in patients with SCH than those without sarcopenia. In terms of physical performance, 6-meter gait speed and SPPB score were lower in subjects with SCH than those without SCH, while 5 sit-to-stand movements was longer score in subjects with SCH than those without SCH. SCH was significantly correlated with sarcopenia, while FT3, FT4, and TSH levels were not. SCH was significantly correlated with low muscle strength and low muscle mass, but not with low physical performance. FT3 level was positively correlated with grip strength and SMI. TSH level was negatively correlated with grip strength, 6-meter gait speed, and SPPB score, but positively correlated with the time of 5 sit-to-stand movements. CONCLUSION: SCH is a risk factor for sarcopenia in the older adults and correlated with low muscle strength and low muscle mass, but not with low physical performance. FT3, FT4 and TSH levels are associated with sarcopenia components, but not with sarcopenia.

Acoustic and perceptual voice parameters in subclinical and overt primary hypothyroidism.

OBJECTIVE: Hypothyroidism is a common endocrine disorder affecting various systems of the body. Only a few studies have focused on the effect of primary hypothyroidism on voice with objective parameters, and none of them compared the effect of subclinical and overt hypothyroidism on voice. The aim of the present study is to evaluate and compare the acoustic and perceptual parameters of voice in patients newly diagnosed with subclinical and overt hypothyroidism. METHODS: The study included 26 subclinical hypothyroidism, 26 overt hypothyroidism patients and 30 euthyroid control participants. Perceptual evaluation of voice with GRBAS (grade, roughness, breathiness, asthenia, strain) scale, voice handicap index (VHI)-10, and acoustic voice analysis by using Multi-Dimensional Voice Program were performed for all the participants. RESULTS: The voice parameters which showed a statistically significant difference between the groups were frequency parameters (Fo; p= 0.003, Fhi; p=0.010, Flo; p= 0.002) and VHI-10 (p= 0.047). A statistically significant decrease in frequency parameters and a statistically significant increase in VHI-10 were found in overt hypothyroidism group comparing with control group (Fo; p= 0.002, Fhi; p=0.009, Flo; p= 0.001 and VHI-10; p= 0.046). Voice parameters in subclinical hypothyroidism group did not show a statistically significant difference comparing with both control and overt hypothyroidism groups. CONCLUSION: In the present study, overt hypothyroidism is found to affect frequency parameters and patients' own subjective assessment of voice. Primary hypothyroidism does not seem to have significant effect on voice parameters until thyroxine levels are affected.

XB130 Plays an Essential Role in Folliculogenesis Through Mediating Interactions Between Microfilament and Microtubule Systems in Thyrocytes.

Background: XB130 (actin filament-associated protein 1-like 2, AFAP1L2) is a thyroid-abundant adaptor/scaffold protein. Xb130-/- mice exhibit transient growth retardation postnatally due to congenital hypothyroidism with diminished thyroglobulin iodination and release at both embryonic and early postnatal stages due to disorganized thyroid apical membrane structure and function. We hypothesized that XB130 is crucial for polarity and folliculogenesis by mediating proper cytoskeletal structure and function in thyrocytes. Methods: Primary thyrocytes isolated from thyroid glands of Xb130-/- mice and their wild-type littermates at postnatal week 2 were cultured in 10% Matrigel for different time periods. Folliculogenesis was studied with immunofluorescence staining, followed by confocal microscopy. Cells were also transfected to express human XB130 fused Green Fluorescent Protein (XB130-GFP) or Green Fluorescent Protein (GFP) only before morphological analysis. Cytoskeletal structures from embryo and postnatal thyroid glands were also studied. Results: In three-dimensional cultures of thyrocytes, XB130, aligned with actin filaments, participated in defining the site of apical membrane formation and coalescence to form a thyroid follicle lumen. Xb130-/- thyrocytes displayed delayed folliculogenesis, reduced recruitment of a microtubule (MT)-associated proteins, and disorganized acetylated tubulin under the apical membrane, resulting in delayed folliculogenesis with reduced efficiency in formation of the thyroid follicle lumen. Conclusions: XB130 critically regulates thyrocyte polarization by functioning as a link between the actin filament cortex and MT network at the apical membrane of thyrocytes. Defects of adaptor scaffold proteins may affect cellular polarity and cytoskeletal structure and function and result in disorders of epithelial function, such as congenital hypothyroidism.

Thyroid Function and Risk of Anemia: A Multivariable-Adjusted and Mendelian Randomization Analysis in the UK Biobank.

CONTEXT: Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear. OBJECTIVE: This study aimed to investigate the association between thyroid function and anemia. METHODS: This cross-sectional and Mendelian randomization study included 445 482 European participants from the UK Biobank (mean age 56.77 years (SD 8.0); and 54.2% women). Self-reported clinical diagnosis of hypothyroidism was stated by 21 860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3431 (0.8%). Anemia, defined as hemoglobin level of < 13 g/dL in men and < 12 g/dL in women, was present in 18 717 (4.2%) participants. RESULTS: In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12; 95% CI, 1.05-1.19 and OR 1.09; 95% CI, 0.91-1.30), although with wide confidence intervals for hyperthyroidism. We did not observe an association of higher or lower genetically influenced thyrotropin (TSH) with anemia (vs middle tertile: OR for lowest tertile 0.98 [95% CI, 0.95-1.02]; highest tertile 1.02 [95% CI, 0.98-1.06]), nor of genetically influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05; 95% CI, 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes. CONCLUSION: While self-reported clinical diagnosis of hypothyroidism was associated with higher anemia risk, we did not find evidence supporting a causal association with variation of thyroid function within the euthyroid range. However, intracellular regulation of thyroid hormones might play a role in developing anemia.

Mecanismos fisiopatológicos del hipotiroidismo en la infertilidad femenina / Physiopathological mechanisms of hypothyroidism on feminine infertility

INTRODUCCIÓN Y OBJETIVO: El hipotiroidismo es una condición frecuente en mujeres en Chile. Existe evidencia contundente de una fuerte asociación entre esta patología e infertilidad femenina. El objetivo de esta revisión es resumir los principales mecanismos fisiopatológicos descritos en la literatura que explicarían la infertilidad femenina en mujeres hipotiroideas. MÉTODOS: Se llevó a cabo una búsqueda bibliográfica por medio PubMed con los términos: hipotiroidismo, infertilidad y fisiopatología. De todos los artículos se seleccionaron únicamente los correspondientes a población femenina. Incluimos tanto hipotiroidismo clínico como subclínico, y mujeres eutiroideas con anti-TPO (+). RESULTADOS: Clasificamos la literatura disponible en tres grupos de mecanismo fisiopatológicos. En primer lugar, la deficiencia de hormonas tiroideas T3 y T4 producirían alteraciones en la foliculogénesis, ovulación, implantación y placentación. En segundo lugar, la hiperprolactinemia secundaria al hipotiroidismo llevaría a un hipogonadismo hipogonadotrópico e insuficiencia en la fase lútea. En tercer lugar, los anticuerpos anti-TPO, independientemente de los niveles de hormonas tiroideas, podrían tener una reacción cruzada con proteínas presentes en el útero, afectando el proceso de implantación. CONCLUSIONES: El hipotiroidismo produce infertilidad femenina por variados mecanismos fisiopatológicos. Dada la variabilidad de estos, existe un mayor espectro de aproximaciones terapéuticas para tratar mujeres hipotiroideas con problemas de fertilidad.

INTRODUCTION AND OBJECTIVE: Hypothyroidism is a frequent condition in Chile in women in Chile. There is strong evidence of an association between this pathology and feminine infertility. The objective of this review is to summarize the main physiopathological mechanisms described in the literature that explain infertility in women with hypothyroidism. METHODS: We performed a bibliographic search on PubMed with the terms: hypothyroidism, infertility, physiopathology. Among all the articles we selected only the ones regarding to feminine population. We included both clinical and subclinical hypothyroidism, and euthyroid women with Anti-TPO (+). RESULTS: We classified the available literature into three groups of physiological mechanisms. In the first place, decreased thyroid hormones T3 and T4 may lead to alterations on folliculogenesis, ovulation, implantation and placentation. Secondly, hyperprolactinemia secondary to hypothyroidism would produce hypogonadotropic hypogonadism and luteal phase insufficiency. Thirdly, anti-TPO antibodies, independently on thyroid hormones levels, may have a cross reactivity towards proteins in the womb, negatively affecting the process of implantation. CONCLUSIONS: Hypothyroidism produces infertility through varied physiopathological mechanisms. Due to their variability, there is a wider scope for therapeutical approaches to treat women with hypothyroidism and fertility problems.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Relación entre hipotiroidismo y síndrome de ovario poliquístico / The relationship between hypothyroidism and polycystic ovary syndrome

INTRODUCCIÓN: Se ha documentado la asociación del síndrome de ovario poliquístico con alteraciones metabólicas y enfermedades cardiovasculares. Su relación con trastornos autoinmunitarios no está claramente establecida, pero se ha encontrado una importante prevalencia de desórdenes tiroideos en pacientes con síndrome de ovario poliquístico. OBJETIVO: Describir las diferentes teorías existentes que puedan explicar la relación entre hipotiroidismo y síndrome de ovario poliquístico, junto con su posible impacto en la morbilidad asociada. Método: Se realizó una búsqueda en PubMed y LILACS con las palabras clave "Polycystic ovary síndrome", "Hypotyroidism", "thyroid disease" y sus respectivos términos en español, durante julio de 2020. Resultados: Se seleccionaron 51 artículos relacionados con el tema, publicados en los últimos 10 años. La fisiopatogenia entre ambos trastornos no está claramente establecida. Se ha encontrado un importante impacto metabólico en este grupo de pacientes y se considera que su riesgo cardiovascular podría estar aumentado. CONCLUSIONES: Al considerarse la prevalencia significativa y las complicaciones que tanto a corto como a largo plazo podrían tener las mujeres con ambas alteraciones, se hace necesario discutir la necesidad de la exclusión del hipotiroidismo de los criterios diagnósticos aplicados para el síndrome, la tamización temprana y el estudio de las implicaciones terapéuticas que trae su abordaje.

INTRODUCTION: The association of polycystic ovary syndrome with other metabolic disorders and cardiovascular diseases has been documented; nevertheless, its relationship with autoimmune disorders is not clearly established, however, an important prevalence of thyroid disorders has been found in this group of patients. OBJECTIVE: To describe the different existing theories that can explain the relationship between hypothyroidism and polycystic ovary syndrome along with its possible impact on associated morbidities. Method: A search was conducted in PubMed and LILACS with the keywords of "Polycystic ovary syndrome", "Hypothyroidism", "Thyroid disease" and with its respective Spanish terms, in July 2020. Results: 51 articles related to the subject were selected, published in the last 10 years. The pathogenesis between both disorders is not clearly established. An important impact has been found at the metabolic level in this group of patients and it is considered that their cardiovascular risk could be increased. CONCLUSIONS: Considering the significant prevalence and complications that both short and long term, women with both alterations could have, it is necessary to discuss the need for the exclusion of hypothyroidism from the diagnostic criteria applied for the syndrome, early screening of the syndrome, and the study of the therapeutic implications that its approach brings.

Association of serum proprotein convertase Subtilisin/Kexin Type 9 (PCSK9) level with thyroid function disorders.

OBJECTIVE: We aimed at demonstrating the effect of thyroid function status on proprotein convertase subtilisin kexin type 9 (PCSK9) and determining the effect of thyroid hormones on lipid metabolism by comparing the PCSK9 levels of patients with subclinical hypothyroidism, overt hypothyroidism, and hyperthyroidism. PATIENTS AND METHODS: 124 patients with thyroid disorders, aged between 18 and 65 years, were included in this study. The participants were divided into 3 groups. Group 1 comprised 52 patients with subclinical hypothyroidism, Group 2 comprised 40 patients with overt hypothyroidism, and Group 3 comprised 32 patients with hyperthyroidism. In all of these groups, the thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, fasting serum glucose, antithyroid peroxidase antibody, antithyroglobulin antibody, and PCSK9 levels were measured. RESULTS: No significant difference was found between the 3 groups in terms of age, gender, and body mass indices. Median PCSK9 measurements were 14.55 ng/mL in Group 1, 14.895 ng/mL in Group 2, and 9.775 ng/mL in Group 3. There was a significant difference in the PCSK9 levels between Group 1-Group 3 and Group 2-Group 3 (p <0.0001 and p <0.0001, respectively). A positive correlation between PCSK9 and the TSH levels (r = 0.211, p= 0.019), and a negative correlation (r = -0,239, p = 0.009 and r = -, 0.218, p = 0.015) between the fT3 and fT4 levels were found. CONCLUSIONS: The serum PCSK9 levels were shown to be associated with thyroid dysfunction. However, no relationship was observed between the serum PCSK9 level and thyroid autoantibody positivity, and obesity in this study.

Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.

Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and "pearls on strings" structures, supported by high levels of Pex11ß and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.