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.

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.

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.

Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism.

The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic parameters and markers involved in the regulation of synaptic plasticity and cell damage in an animal model of coexisting depression and hypothyroidism, namely, Wistar Kyoto rats treated with propylthiouracil. In this model, in relation to the depression model itself, the glycolysis process in the brain was weakened, and a reduction in pyruvate dehydrogenase in the frontal cortex was normalized only by the combined treatment with L-thyroxine and venlafaxine, whereas changes in pyruvate and lactate levels were affected by all applied therapies. None of the drugs improved the decrease in the expression of mitochondrial respiratory chain enzymes. No intensification of glucocorticoid action was shown, while an unfavorable change caused by the lack of thyroid hormones was an increase in the caspase-1 level, which was not reversed by venlafaxine alone. The results indicated that the combined administration of drugs was more effective in normalizing glycolysis and the transition to the Krebs cycle than the use of venlafaxine or L-thyroxine alone.

The Impact of Subclinical Hypothyroidism on Patients with Polycystic Ovary Syndrome: A Meta-Analysis.

The association between subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) has been shown in many studies. These findings are still controversial, however. It is unclear whether the co-incidence of subclinical hypothyroidism and polycystic ovary syndrome will affect the severity of metabolism. Therefore, we performed this meta-analysis to investigate the association. A comprehensive search strategy was developed to obtain all relevant studies published in PubMed, EMBASE, Cochrane Library, and Chinese Academic Journal Full-text Database (CNKI) up to 31 December 2020. We adopted the standardized mean difference (SMD) with 95% confidence intervals (CI) for evaluation, and sensitivity analysis was performed. Publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger's test. Twenty-seven studies with 4821 participants (1300 PCOS patients with SCH, 3521 PCOS patients without SCH) were included in the present meta-analysis,among which 71.31% chinese patients out of the total. The results showed that PCOS patients with SCH had higher levels of HOMA-IR, TG, TC, LDL, FBG, FCP, PRL and lower levels of HDL, LH and T. It also recognized the limitation of the lack of a consistent definition of hypothyroidism in the 27 studies included. The results of this study indicated that SCH may aggravate lipid and glucose metabolism in patients with PCOS.

Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.

INTRODUCTION: Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients. METHODOLOGY: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS: Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS: As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.

Physical activity, sports participation and exercise-related constraints in adult women with primary hypothyroidism treated with thyroid hormone replacement therapy.

Awareness of physical activity (PA) constraints in patients with primary hypothyroidism on thyroid hormone replacement therapy (THR) is important. Hence, this cross-sectional matched case-control study aimed to determine PA and sports participation (SP) in patients with hypothyroidism on THR in comparison to control subjects. Accordingly, survey questions were selected from the National Survey on Injuries and Physical Activity in the Netherlands (IPAN), supplemented with questions related to self-reported clinical characteristics and exercise-related constraints (ERC) of patients. In total, 1,724 female patients (mean age 53.0 years ±11.6) and 1,802 controls (mean age 52.6 ± 13.2) were included. Compared to controls, patients were less likely to comply with the moderate-intensity PA guideline (OR 0.70; 95% CI: 0.611-0.803), although patients were more actively participating in sports (OR 1.40; 95% CI: 1.156-1.706). Two-thirds of patients reported that hypothyroidism was limiting their PA performance. These limitations were more pronounced in patients with autoimmune thyroiditis (AIT) than in patients with hypothyroidism from other aetiology (OR 1.93; 95% CI: 1.518-2.457), representing disease-specific exercise intolerance. In order to establish effective intervention programmes to encourage regular PA in hypothyroid patients on THR with exercise intolerance, further research is warranted to better understand PA barriers.

The Role of Thyroid in Renovascular Function: Independent Association of Serum TSH With Renal Plasma Flow.

CONTEXT: There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state. OBJECTIVE: This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals. METHODS: This cross-sectional, multicenter study of the HyperPATH Consortium took place in 5 US and European academic institutions. A total of 789 individuals, aged 18 to 65 years, with serum thyrotropin (TSH) 0.4 to 5.5 mIU/L, participated; individuals with uncontrolled or secondary hypertension or on medication affecting the hypothalamus-pituitary-thyroid axis were excluded. Hemodynamic parameters including RPF, thyroid function testing, and the Thr92Ala deiodinase 2 (D2) polymorphism were assessed in the setting of a liberal and restricted salt diet. We searched for associations between thyroid function and renovascular parameters and accounted for confounding factors, such as older age, hypertension, and diabetes. RESULTS: Serum TSH was inversely associated with RPF assessed in the setting both of liberal and restricted salt diets. This association remained significant and independent when accounting for confounding factors, whereas free thyroxine index (fTI) and the Thr92Ala polymorphism, associated with lower D2 catalytic activity and disrupted thyroid hormone tissue availability, were not independently associated with RPF. Serum TSH remained an independent predictor of RPF on a liberal salt diet when the analysis was restricted to healthy young individuals. CONCLUSION: Serum TSH levels, but not fTI nor the Thr92Ala D2 polymorphism, were independently inversely associated with RPF in individuals of the HyperPATH Consortium. These findings suggest a direct interconnection between TSH and renovascular dynamics even with TSH within reference range, warranting further investigation.

Understanding the Pathogenesis of Gestational Hypothyroidism.

Pregnancy is a complex state with many endocrinological challenges to a woman's physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.

Changes of Certain Metabolic and Cardiovascular Markers Fructosamine, H-FABP and Lipoprotein (a) in Patients with Hypothyroidism.

BACKGROUND: Disorders of thyroid gland are common in general population, and it's the most common affecting the endocrine system after diabetes mellitus. Thyroid function regulates a wide range of metabolic parameters, as well as affects some cardiovascular disease risk factors. Fructosamine is produced by a reaction between albumin (protein) and glucose; it is used to monitor patients with diabetes for short-term glycemic changes. H-FABP is present in the cytoplasm of cardiac myocytes, and delivers fatty acids into these cells. It has been shown to increase in myocardial injury. Lipoprotein LP(a) is consist of a special apolipoprotein called apoprotein (a), and it's recognized as a cardiovascular disease independent risk factor. OBJECTIVE: To study whether certain metabolic and cardiovascular markers (fructosamine, H-FABP and lipoprotein (a) are changed in hypothyroid patients. METHODS: The current study included 280 overt hypothyroid, 272 with subclinical hypothyroidism compared with 270 healthy individuals of matched age and gender. For all subjects serum (TSH, T4, T3, FBS, HbA1c, fructosamine, triglycerides, cholesterol, lipoprotein (a), and Heart-type Fatty Acid-Binding Protein (H-FABP)) was measured. RESULTS: Serum fructosamine level significantly elevated (p value <0.05) in patient with hypothyroidism when compared with control group, and no significant change between subclinical and control groups. There is no significant change in serum H-FABP between study subjects. There is significant increase in lipoprotein (a) in patient with hypothyroidism and those with subclinical group when compared with control group. CONCLUSION: Serum fructosamine and level is significantly changed in patients with overt hypothyroidism when compared with euthyroid subjects. Also, we conclude that hypothyroidism increase risk of cardiovascular diseases by changing non-traditional marker such as lipoprotein (a), and no effect on H-FABP concentration.

Thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones in conscious dogs.

This study was conducted to clarify the relationship between thyroid function and gastrointestinal motility. We established an experimental configuration in which the feedback of thyroid function was completely removed using conscious dogs. With hypothyroidism, time of phase I of interdigestive migrating contractions (IMC) was longer, time of phase II and phase III was significantly shortened, and both the continuous time of strong tetanic contraction at antrum and 10-h frequency of phase III counted from the first IMC after meal significantly decreased. Whereas, hyperthyroidism caused the opposite events to those with hypothyroidism. Furthermore, We found giant migrating contractions (GMC) occurred from the upper gastrointestinal tract when we administrated high dose of thyroid hormone. One GMC occurred from anal sides propagated to cardiac, and this propagation was similar to the emesis-like interdigestive motor activity, the other GMC occurred from oral sides propagated to anal sides and this was similar to the diarrhea-like interdigestive motor activity. We examined the relationship between thyroid function and gastrointestinal hormones including of ghrelin, GLP-1, and cholecystokinin (CCK). However, we could not find significant differences under different thyroid hormone status. This is the first report that thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones.

The association between subclinical hypothyroidism and TPOAb positivity with infertility in a population-based study: Tehran thyroid study (TTS).

BACKGROUND: Thyroid autoimmunity(TAI) is the most prevalent autoimmune condition in women of fertile age. There are increasing data regarding the association of thyroid dysfunction and thyroid autoimmunity with adverse pregnancy outcomes but there is no consensus regarding infertility and TPOAb positivity; thus we aimed to evaluate the association between thyroid TPOAb positivity and infertility in females and males in a population-based study (TTS). METHODS: Cross-sectional study of 3197 female and male participants in Tehran Thyroid Study (TTS) at the framework of the Tehran Lipid and Glucose Study (TLGS). Data included biochemical measurements and a self-administered questionnaire. RESULTS: A total of 12,823 cases in phase 4, 3719 cases (2108 female and 1611 male) were analyzed. The mean TSH of the infertile female and male was 2.52 ± 2.68 µIU/ml and 3.24 ± 10.26 µIU/ml respectively. The TPO median(IQR) of women with and without a history of infertility were 6.05 (3.30-13.96)and 6.04 (3.17-11.15);(P = 0.613), they were 5.08 (3.20-125.68) and 5.31 (3.93-125.68);(P = 0.490) in male participants, respectively. Results of crude and adjusted logistic regression analysis of the development of infertility by thyroid function and TPOAb, except for fT4 in male subjects, depicted no association between infertility and other variables in both crude and adjusted models. CONCLUSION: Based on the result, thyroid autoimmunity was not associated with infertility in both females and males.

Hypothyroidism: Diagnosis and Treatment.

Clinical hypothyroidism affects one in 300 people in the United States, with a higher prevalence among female and older patients. Symptoms range from minimal to life-threatening (myxedema coma); more common symptoms include cold intolerance, fatigue, weight gain, dry skin, constipation, and voice changes. The signs and symptoms that suggest thyroid dysfunction are nonspecific and nondiagnostic, especially early in disease presentation; therefore, a diagnosis is based on blood levels of thyroid-stimulating hormone and free thyroxine. There is no evidence that population screening is beneficial. Symptom relief and normalized thyroid-stimulating hormone levels are achieved with levothyroxine replacement therapy, started at 1.5 to 1.8 mcg per kg per day. Adding triiodothyronine is not recommended, even in patients with persistent symptoms and normal levels of thyroid-stimulating hormone. Patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of levothyroxine (12.5 to 50 mcg per day). Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week (i.e., take one extra dose twice per week), followed by monthly evaluation and management. Patients with persistent symptoms after adequate levothyroxine dosing should be reassessed for other causes or the need for referral. Early recognition of myxedema coma and appropriate treatment is essential. Most patients with subclinical hypothyroidism do not benefit from treatment unless the thyroid-stimulating hormone level is greater than 10 mIU per L or the thyroid peroxidase antibody is elevated.

Thyroid function modifications in women undergoing controlled ovarian hyperstimulation for in vitro fertilization: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) on thyroid function. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing conventional IVF or intracytoplasmic sperm injection. INTERVENTION(S): Systematic search of PubMed, MEDLINE, Embase, Scopus, and Web of Science from inception until November 2020. Studies could be included only if they met the following criteria: subjects were classified as euthyroid or hypothyroid; serum thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) levels were evaluated before COH; and the same thyroid function test was reassessed after COH (i.e., at the time of trigger for final follicle maturation and/or at pregnancy test). MAIN OUTCOME MEASURE(S): Mean difference (MD) between the serum TSH or FT4 levels assessed after COH and before COH. RESULT(S): In euthyroid women, the serum TSH levels assessed at the time of trigger and at the time of pregnancy test were significantly higher than those at baseline (MD: 0.69 mIU/L, 95% confidence interval [CI]: 0.30-1.08, I2 = 93% and MD: 0.67, 95% CI: 0.49-0.85, I2 = 72%, respectively). The serum FT4 levels did not undergo significant changes. Subanalysis confirmed an increase in the TSH level after restricting the analysis to women treated with gonadotropin-releasing hormone agonist protocols and to those who achieved pregnancy. A pronounced increase in the TSH level was observed in women treated for hypothyroidism (MD: 1.50 mIU/L, 95% CI: 1.10-1.89, I2 = 0%). CONCLUSION(S): Pooling of the results showed a significant increase in serum TSH level in women undergoing COH for IVF. This change was particularly pronounced in women treated for hypothyroidism. New thyroid function screening strategies for women undergoing COH are warranted.