LT4/LT3 Combination Therapy vs. Monotherapy with LT4 for Persistent Symptoms of Hypothyroidism: A Systematic Review.

Regardless of the cause, hypothyroidism should be treated with levothyroxine. The objectives of management are the normalization of TSH levels and the relief of symptoms. In general, the vast majority of patients who achieve normalization of TSH levels show a resolution of symptoms; however, for a small number of individuals, symptoms persist (despite adequate control of TSH). This scenario generates a dilemma in the therapeutic approach to these patients, because even when excluding other causes or concomitant diseases that can explain the persistence of symptoms, pharmacological management strategies are scarce. Consequently, the efficacy of some less conventional approaches to therapy, such as the use of LT3 monotherapy, desiccated thyroid extracts, and LT4/LT3 combinations, in addressing persistent hypothyroid symptoms have been evaluated in multiple studies. The majority of these studies did not observe a significant benefit from these "nonconventional" therapies in comparison to results with LT4 monotherapy alone. Nevertheless, some studies report that a significant proportion of patients prefer an alternative to monotherapy with LT4. The most common approach has been to prescribe a combination of LT4 and LT3, and this review describes and analyzes the current evidence of the efficacy of LT4/LT3 combination therapy vs. LT4 monotherapy in addressing persistent hypothyroidism symptoms to provide suggested guidelines for clinicians in the management of these patients.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Real-world effectiveness and safety of insulin glargine 300 U/ml in insulin-naïve people with type 2 diabetes in the Latin America region: A subgroup analysis of the ATOS.

AIM: To evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in achieving glycaemic goals in insulin-naïve people with type 2 diabetes (T2D) in Mexico, Colombia and Peru (Latin America region) in the A Toujeo Observational Study (ATOS). MATERIALS AND METHODS: ATOS was a multicentre, prospective, 12-month observational study, which included 4422 insulin-naïve adults (age ≥ 18 years) with T2D uncontrolled (HbA1c > 7% and ≤11%) on at least one oral antidiabetic drug (OAD) who initiated Gla-300 treatment as per routine practice. The primary endpoint was the percentage of participants achieving their predefined individualized HbA1c goal at month 6. Key secondary endpoints included change from baseline in HbA1c, fasting plasma glucose (FPG), fasting self-monitored blood glucose (SMBG), body weight and incidence of hypoglycaemia. RESULTS: In this subgroup analysis, a total of 314 participants with T2D received Gla-300. At baseline, mean ± SD age was 56.0 ± 11.6 years, duration of diabetes was 9.7 ± 6.6 years and 65.9% of participants were on at least two OADs. The individualized HbA1c target was achieved by 25.8% of participants (95% confidence interval [CI]: 20.3-31.9) at month 6 and by 35.3% (95% CI: 28.5-42.5) at month 12. Gla-300 treatment improved glycaemic control with meaningful reductions in mean HbA1c, FPG and fasting SMBG. The incidence of hypoglycaemia reported was low and body weight remained stable. CONCLUSIONS: In a real-world setting in the Latin America region, the initiation of Gla-300 in people with T2D uncontrolled on OADs resulted in improved glycaemic control with a low incidence of hypoglycaemia and no change in body weight.

Thyroid Dysfunction and Heart Failure: Mechanisms and Associations.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the current knowledge of the pathophysiology, the mechanisms, and the cardiovascular impact of the different stages of thyroid dysfunction (TD) in heart failure (HF) patients. RECENT FINDING: The influence of thyroid hormones (THs) on the cardiovascular system involves the regulation of key processes related to maintenance of cardiac function; however, there are no long-term studies available showing that intervening the TD changes the incidence or the prognosis in HF individuals. Future research shall focus on the effects of cardiovascular morbidity and mortality associated with different treatment modalities for hyper and hypothyroidism. TD has been associated with different clinical results in HF individuals; treatment with THs in patients with hypothyroidism improves cardiovascular risk factors, but the effect on cardiovascular events has not been assessed in randomized, controlled trials.

Autoimmune Thyroid Disease and Differentiated Thyroid Carcinoma: A Review of the Mechanisms That Explain an Intriguing and Exciting Relationship.

Autoimmune thyroid disease is a complex and highly frequent disease, where a wide variety of genetic, epigenetic and environmental factors (among others) come together and interact, and is characterized by the presence of two clinical outcomes: hypothyroidism (in Hashimoto's thyroiditis) and hyperthyroidism (in Graves-Basedow disease). For its part, differentiated thyroid carcinoma (mainly papillary carcinoma) is the most common type of cancer affecting the thyroid (and one of the most prevalent worldwide). An important co-occurrence between autoimmune thyroid disease and differentiated thyroid carcinoma has been documented. In this article, studies that have evaluated possible associations and relationships between autoimmune thyroid disease and differentiated thyroid cancer are systematically described and summarized. To date, the underlying mechanism that explains this association is inflammation; however, the characteristics and designs of the studies evaluated do not yet allow a causal relationship between the two entities to be established. These aspects have made it difficult to establish "causality" in the continuum of the pathogenesis between both conditions.

Molecular Mechanisms in Autoimmune Thyroid Disease.

The most common cause of acquired thyroid dysfunction is autoimmune thyroid disease, which is an organ-specific autoimmune disease with two presentation phenotypes: hyperthyroidism (Graves-Basedow disease) and hypothyroidism (Hashimoto's thyroiditis). Hashimoto's thyroiditis is distinguished by the presence of autoantibodies against thyroid peroxidase and thyroglobulin. Meanwhile, autoantibodies against the TSH receptor have been found in Graves-Basedow disease. Numerous susceptibility genes, as well as epigenetic and environmental factors, contribute to the pathogenesis of both diseases. This review summarizes the most common genetic, epigenetic, and environmental mechanisms involved in autoimmune thyroid disease.

Population status of selenium in Colombia and associated factors: a cross-sectional study.

OBJECTIVES: This study aims to investigate the population status of selenium in Colombia and other associated factors. METHODS: Cross-sectional study, in population of urban or rural origin (n=412). Main outcome measures were: median serum selenium, thyrotropin, the prevalence of and positivity of anti-thyroid peroxidase, anti-thyroglobulin, and anti-TSH receptor. RESULTS: This study found that 96.6% of the subjects had normal selenium levels, and no significant associations were found between the population median of selenium and overweight/obesity, sociodemographic variables, age, goiter, and thyroid antibody positivity. CONCLUSIONS: In Colombia, the population status of selenium is normal, and the geological characteristics may contribute to the state of selenium in this population. However, additional studies are required to evaluate the content of selenium in plants and other foods.

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

Fixed-ratio Combinations (basal Insulin Plus GLP-1RA) In Type 2 Diabetes. an Analytical Review Of Pivotal Clinical Trials.

In type 2 diabetes, therapeutic failure to the oral anti diabetics is frequent, the use of schemes with basal insulin or with multiple doses of insulin (basal insulin and short-acting insulins) are a widely accepted way to intensify therapy. The use of GLP-1 receptor agonists is another intensification strategy. The fixedratio combinations with molecules such as insulin degludec + liraglutide, and insulin glargine + lixisenatide have proven useful in intensifying treatment of individuals with type 2 diabetes. The purpose of this review was to evaluate and analyze the results of pivotal studies with both fixed-ratio combinations in individuals with type 2 diabetes, finding that, they are capable of achieving better glycemic control when compared with each of its components separately (with a lower risk of hypoglycemia vs basal insulin and lower risk of gastrointestinal adverse effects vs GLP-1 receptor agonists) in various clinical scenarios, especially in individuals who do not achieve control with oral antidiabetics or who do not achieve control with basal insulin (associated with oral antidiabetics) or in those under management with GLP-1RA plus oral antidiabetics.

Prevalence of Functional Alterations and the Effects of Thyroid Autoimmunity on the Levels of TSH in an Urban Population of Colombia: A Population-Based Study.

BACKGROUND: The population prevalence of functional alterations and thyroid autoimmunity is high, and numerous genetic and environmental aspects have been described as triggering factors. OBJECTIVES: The objective of this study was to determine the prevalence of functional alterations and thyroid autoimmunity in an urban population of Colombia. MATERIALS AND METHODS: It is a cross-sectional, population-based study (n = 9,638) conducted on an urban population of Popayán-Cauca-Colombia between February 5th, 2018, to December 11th, 2021. The variables evaluated were thyrotropin (TSH), free T4 (FT4), and anti-thyroid antibodies (thyroid peroxidase antibodies: TPOAb, and thyroglobulin antibodies: TgAb). RESULTS: TSH in men was significantly higher than in women. No differences were observed in the values of FT4, TPOAb, and TgAb (according to sex). The prevalence of normal thyroid function and subclinical hypothyroidism was significantly higher in men. The positivity of TPOAb and TgAb was 22.3% and 19.2%, respectively. TSH levels increased with age (both in men and in women). In participants with normal FT4 and negative TPOAb, the TSH was significantly higher. TSH was significantly higher in TPOAb-positive individuals and among those with TPOAb and TgAb positives, as well as in women with positive TPOAb and men with positive TPOAb and TgAb. CONCLUSION: In an urban population of Colombia, TSH was found to be higher than in populations of other geographical areas, especially in older individuals and in the presence of positive anti-thyroid antibodies, a high prevalence of functional alterations and thyroid autoimmunity was also found. These findings can be explained by excess iodine consumption and some environmental factors.