Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Current Progress for the Use of miRNAs in Glioblastoma Treatment

Glioblastoma (GBM) is a highly aggressive brain cancer with the worst prognosis of any central nervous system disease despite intensive multimodal therapy. Inevitably, glioblastoma is fatal, with recurrence of treatment-resistant tumour growth at distal sites leading to an extremely low median survival rate of 12–15 months from the time of initial diagnosis. With the advent of microarray and gene profiling technology, researchers have investigated trends in genetic alterations and, in this regard, the role of dysregulated microRNAs (highly conserved endogenous small RNA molecules) in glioblastoma has been studied with a view to identifying novel mechanisms of acquired drug resistance and allow for development of microRNA (miRNA)-based therapeutics for GBM patients. Considering the development of miRNA research from initial association to GBM to commercial development of miR-based therapeutics in less than a decade, it is not beyond reasonable doubt to anticipate significant advancements in this field of study, hopefully with the ultimate conclusion of improved patient outcome. This review discusses the recent advancements in miRNA-based therapeutic development for use in glioblastoma treatment and the challenges faced with respect to in vivo and clinical application.     

Life in Sulfidic Environments: Historical Perspective and Current Research Trends

SYNOPSIS. The discovery of the deep-sea hydrothermal vents andtheir associated fauna in 1977 was a watershed for the recentinterest in the biology of sulfidic environments. From the initialquestions concerning how organisms survived at the high sulfideconcentrations around the vents, research quickly focused onthe previously unrecognized sulfuroxidizing chemoautotrophicinvertebrate/bacterial symbioses whose nature was discoveredin 1980. There followed a successful and frenzied search forother reducing habitats harboring non-vent chemoautotrophicsymbioses. The interest in the biology of species living insulfidic habitats has since expanded to include the non-symbioticspecies, species with sulfuroxidizing symbionts and specieswith methanotrophic symbionts, all of which must be adaptedto tolerate sulfide and many of which are adapted to utilizesulfide in various ways.     

Clinical Aspects of Hyperthyroidism,Hypothyroidism, and Thyroid Screening in Pregnancy

ObjectiveTo evaluate the peer-reviewed literature on hypothyroidism, hyperthyroidism, and thyroid autoimmunity in pregnancy.MethodsWe review published studies on thyroid autoimmunity and dysfunction in pregnancy, the impact of thyroid disease on pregnancy, and discuss implications for screening.ResultsOvert hyperthyroidism and hypothyroidism are responsible for adverse obstetric and neonatal events. Several studies of association suggest that either subclinical hypothyroidism or thyroid autoimmunity increase the risk of complications. One randomized controlled trial showed that pregnant women with subclinical hypothyroidism benefit from treatment in terms of obstetric and neonatal complications, whereas another study demonstrated no benefit in the intelligence quotient of babies born to women with subclinical hypothyroidism. Thyroid autoimmunity has been associated with increased rate of pregnancy loss, recurrent miscarriage, and preterm delivery.ConclusionCurrent guidelines agree that overt hyperthyroidism and hypothyroidism need to be promptly treated and that as potential benefits outweigh potential harm, subclinical hypothyroidism also requires substitutive treatment. The chance that women with thyroid autoimmunity may benefit from levothyroxine treatment to improve obstetric outcome is intriguing, but adequately powered randomized controlled trials are needed. The issue of universal thyroid screening at the beginning of pregnancy is still a matter of debate, and aggressive case-finding is supported. (Endocr Pract. 2014;20:597-607)     

Historical Land Use Explains Current Distribution of Calcareous Grassland Species

In this study we analyzed if characteristic calcareous grassland species persist in forest habitats after land use change. Furthermore, we investigated whether the current distribution of such species is related to historical land use of the mid-19th century. Current distributions of nine calcareous grassland species were recorded in a region of Upper Franconia, Germany. Historical (up to 1850) and current land-use data were analyzed using historical maps and aerial photographs. To study the effects of historical land use in current species distributions, we used Generalized Estimating Equations (GEE) and ANOVA, accounting for spatial autocorrelation. Variance partitioning was applied to separate the influence of historical versus current land use. On average 26% of the recorded grassland species occurrences are located in sub-optimal forest habitats. Grassland populations are likely to persist in forest for at least 50 years. Even though current land use explains a higher proportion of the variation in species distribution than historical land use alone, model fit could be significantly improved (P?<?0.001) considering the historical component. We conclude that consideration of historical land use is essential to understand the current grassland species distributions and may be of general importance for perennial species of temperate grasslands. In addition, historical legacy has far-reaching implications for conservation biology in terms of realistic assessments of species threat status in present landscapes.     

Brain Fog in Hypothyroidism: Understanding the Patient’s Perspective

ObjectivePatient-centered studies have shown that several patients on thyroid hormone replacement therapy for hypothyroidism exhibit persistent symptoms, including “brain fog.” Here, we aimed to determine which of these specific symptoms are associated with brain fog, identify patient-reported factors that modify these symptoms, and identify patient concerns related to brain fog not included in thyroid-specific questionnaires.MethodsA survey on brain fog symptoms adapted from thyroid-specific patient-reported outcome was distributed online. Textual data analysis was performed to identify common areas of concern from open-ended survey responses.ResultsA total of 5170 participants reporting brain fog while being treated for hypothyroidism were included in the analysis. Of these, 2409 (46.6%) participants reported symptom onset prior to the diagnosis of hypothyroidism, and 4096 (79.2%) participants experienced brain fog symptoms frequently. Of the symptoms listed, participants associated fatigue and forgetfulness most frequently with brain fog. More rest was the most common factor provided for improving symptoms. The textual data analysis identified areas of concern that are not often included in thyroid-specific quality of life questionnaires, including a focus on the diagnosis of hypothyroidism, the types and doses of medications, and the patient-doctor relationship.ConclusionBrain fog in patients treated for hypothyroidism was associated most frequently with fatigue and cognitive symptoms. Several additional areas of patient concern were found to be associated with brain fog, which are not typically addressed in thyroid-specific questionnaires.     

Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association

ObjectiveHypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients.MethodsThe development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assem bled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incor porated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommen dations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines—2010 update.ResultsTopics addressed include the etiology, epide miology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered.ConclusionsFifty-two evidence-based recommenda tions and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medi cal practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpa tient clinical situations. The standard treatment is replace ment with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.     

Evaluation of Treatment of Central Hypothyroidism Versus Primary Hypothyroidism in Relation to Levothyroxine Replacement Dose

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO).Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients.Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 μg (CeH) and 89.3 ± 32.0 μg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 μg/kg (CeH) and 1.2 ± 0.4 μg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies.Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases.Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

A Current Perspective on the Historical Geographic Distribution of the Endangered Muriquis (Brachyteles spp.): Implications for Conservation

The muriqui (Brachyteles spp.), endemic to the Atlantic Forest of Brazil, is the largest primate in South America and is endangered, mainly due to habitat loss. Its distribution limits are still uncertain and need to be resolved in order to determine their true conservation status. Species distribution modeling (SDM) has been used to estimate potential species distributions, even when information is incomplete. Here, we developed an environmental suitability model for the two endangered species of muriqui (Brachyteles hypoxanthus and B. arachnoides) using Maxent software. Due to historical absence of muriquis, areas with predicted high habitat suitability yet historically never occupied, were excluded from the predicted historical distribution. Combining that information with the model, it is evident that rivers are potential dispersal barriers for the muriquis. Moreover, although the two species are environmentally separated in a large part of its distribution, there is a potential contact zone where the species apparently do not overlap. This separation might be due to either a physical (i.e., Serra da Mantiqueira mountains) or a biotic barrier (the species exclude one another). Therefore, in addition to environmental characteristics, physical and biotic barriers potentially shaped the limits of the muriqui historical range. Based on these considerations, we proposed the adjustment of their historical distributional limits. Currently only 7.6% of the predicted historical distribution of B. hypoxanthus and 12.9% of B. arachnoides remains forested and able to sustain viable muriqui populations. In addition to measurement of habitat loss we also identified areas for conservation concern where new muriqui populations might be found.     

Antimetabolites in the Treatment of Arthritis: Current Status of the Use of Antimetabolites

Rheumatoid arthritis (RA) is an autoimmune disease characterized by a chronic inflammation of the synovial joints and infiltration of blood‐derived cells. In daily practice rheumatologists use the antimetabolites methotrexate (MTX) and leflunomide for the treatment of patients with rheumatoid arthritis. The current clinical status (efficacy/toxicity) of these 2 antimetabolites in the treatment of RA will be discussed.     

Controlled Clinical Trial of Combined Triiodothyronine and Thyroxine in the Treatment of Hypothyroidism

A -double-blind crossover trial of a combined preparation of triiodothyronine and thyroxine (1:4 ratio) compared with thyroxine alone was conducted with 99 patients previously stabilized on. thyroxine as treatment for hypothyroidism. Four patients were excluded during the trial and eight afterwards owing to gross deficiencies in taking the tablets. Of the remaining 87 patients 42 (48%) had no -preference for either medication, 29 (33%) preferred thyroxine alone, and 16 (18%) the combination. A high incidence of unpleasant symptoms was experienced during the two months'' treatment with the combined preparation. The serum protein-bound iodine levels were lowered (mean reduction 1·8 μg./100 ml.) on the combination, but the labelled T₃-resin sponge uptake values were not altered and remained in the normal range. on both treatments.     

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience

ObjectiveWe aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter.MethodsWe retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi.ResultsThe median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005).ConclusionOverall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.