The effect of levothyroxine and prednisolone treatment on pregnancy in in vitro fertilization patients with positive thyroid autoantibodies.

AIM: To investigate the effects of levothyroxine and prednisolone treatment, or in combination, on positive thyroid autoantibodies in infertile patients undergoing in vitro fertilization (IVF) therapy. METHODS: This retrospective study included a total of 190 patients with positive thyroid autoantibodies (anti-T and anti-TPO) who underwent IVF treatment between January 2008 and March 2016. Patients were divided into four groups: group 1-levothyroxine group (n = 50), group 2-prednisolone group (n = 50), group 3-levothyroxine and prednisolone combination (n = 25), group 4-control group (n = 65). Anti-T and anti-TPO levels before IVF and at the time of embryo transfer (ET), b-hcg positivity, clinical and biochemical pregnancy, miscarriage rate, and live birth rate were compared among groups. RESULTS: In levothyroxine-treated group, mean anti-TPO levels significantly decreased at the time of ET compared to before IVF treatment levels (p = 0.036). In group 3, mean anti-T and anti-TPO levels significantly decreased at the time of ET compared to levels before IVF treatment (p < 0.05). Patients who became pregnant in group 1, mean anti-T anti-TPO levels significantly decreased compared to before IVF treatment levels (p < 0.05). The biochemical pregnancy rate was significantly higher in group 2 (p = 0.03). Abortion rates were the highest in group 3, but no significant difference was found among groups. The group treated with levothyroxine had a significantly increased rate of live birth compared to the control group (p = 0.02). CONCLUSIONS: Levothyroxine addition during IVF treatment of patients with positive thyroid antibodies in subclinical hypothyroidism increases the take-home baby pregnancy rate. Whether subclinical hypothyroidism or not in IVF treatment, levothyroxine is more effective than low-dose corticosteroids.

Effects and Action Mode of Oleic Acid and Azone on Release and Penetration Process of Levothyroxine Sodium Patches.

In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.

Exploring the mechanism of interaction between TBG and halogenated thiophenols: Insights from fluorescence analysis and molecular simulation.

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.

Neuroprotective effects of levothyroxine on cognition deficits and memory in an experimental model of Huntington's disease in rats: An electrophysiological study.

Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive deficits and motor function. Levothyroxine (L-T4) is a synthetic form of Thyroxine (T4), which can improve cognitive ability. The aim of the present study was to determine the neuroprotective effect of L-T4 administration in rats with 3-nitropropionic acid (3-NP)-induced Huntington's disease. Forty-eight Wistar male rats were divided into six groups (n = 8): Group 1 control group that received physiological saline, Group 2 and 3: which received L-T4 (30 and 100 µg/kg), Group 4: HD group that received 3-NP and Groups 5 and 6: The treatment of the HD rats with L-T4 (30 and 100 µg/kg). Spatial memory, locomotor activity, and frequency of neuronal firing were assessed. After decapitation, the Brain-Derived Neurotrophic Factor (BDNF) and Total antioxidant capacity (TAC) levels in the striatum was measured. The results showed that the indices of spatial memory (mean path length and latency time) and motor dysfunction (immobility time) significantly increased, while time spent in the goal quadrant, swimming speed, spike rate, and striatum levels of BDNF significantly decreased in the HD group compared to the control group. L-T4 treatment significantly enhanced time spent in the goal quadrant, swimming speed, motor activity (number of line crossing and rearing), spike rate and striatal BDNF level. This research showed that L-T4 prevented the disruption of motor activity and cognitive deficiencies induced by 3-NP. The beneficial effects of L-T4 may be due to an increase in the concentration of BDNF and enhancement of the spike rate in the striatum.

The mechanism of 14-3-3η in thyroxine induced mitophagy in cardiomyocytes.

Hyperthyroidism is becoming increasingly important as an independent risk factor for cardiovascular disease, eventually resulting in cardiac hypertrophy and heart failure. The 14-3-3 protein family subtypes regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. Considering that the 14-3-3η protein protects cardiomyocytes by affecting mitochondrial function, exploring the biological influence and molecular mechanisms by which 14-3-3η alleviates the cardiac hypertrophy of hyperthyroidism is imperative. In vivo and in vitro, RT-PCR, Western blot, and Mitochondrial tracking assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. The in vivo and in vitro results indicated that overexpression of the 14-3-3η ameliorated thyroxine-induced cardiomyocyte hypertrophy, whereas knockdown of the 14-3-3η protein aggravated thyroxine-induced cardiomyocyte hypertrophy. Additionally, overexpression of the 14-3-3η protein reduces thyroxine-induced mitochondrial damage and mitophagy in cardiomyocytes. Overexpression of 14-3-3η protein improves excessive mitophagy in the myocardium caused by thyroxine and thus prevents cardiac hypertrophy.

Effects of thyroxin and luteinizing hormone releasing hormone on reproductive physiology of Rohu (Labeo rohita): Insights into spawning performance, oocyte maturation, steroidogenesis, and follicular development genes.

As the global aquaculture industry grows, attention is increasingly turning towards assisted reproductive technologies. In this study, we examined the impact of D-Ala6, Pro9-Net-mGnRH (LHRHa: 0.4 mL/kg) and two doses (1 and 10 µg/kg fish) of thyroxin (T4) administered through a single injection on oocyte maturation, spawning performance, sex steroid hormone levels, as well as the expression of genes related to steroidogenesis and follicle development (ZP2, Cyp19a1a and SF-1) in Rohu (Labeo rohita). The study found that untreated female Rohu did not spawn, while those treated with LHRHa and thyroxin ovulated and spawned across a hormonal gradient. The highest spawning success was observed with a thyroxin dosage of 10 µg/kg (no significant change with a dose of 1 µg/kg), and female latency period decreased with increasing dosage. Additionally, females treated with thyroxin exhibited significantly higher fecundity than other experimental groups. Treatment with LHRHa and two doses of thyroxin significantly increased the gonadal somatic index compared to the control and sham groups. Hormonal treatment also led to increased fertilization success, hatching rate, and larval survival. At 12 h post-injection, females treated with thyroxin exhibited a significant decline in estradiol levels and expression of Zp2, Cyp19a1a, and SF-1 compared to other experimental groups. Levels of DHP significantly increased across the hormonal gradient. Histological analyses supported a steroidogenic shift, where oocyte maturation was accelerated by hormone administration, particularly with both doses of thyroxin. In conclusion, the findings suggest that thyroxin is a recommended treatment for assisted reproduction of Rohu due to its ability to induce spawning, increase fecundity and improve larval survival.

Thyroxine regulates pig Sertoli cell line proliferation and maturation through the IKK/NFκB and p38 MAPK signaling pathways.

The aim of this study was to investigate the signaling pathways involved in the proliferation and differentiation of pig Sertoli cells (SCs) mediated by thyroid hormone (T3) to provide a theoretical and practical basis for enhancing pig semen production. The effects of different concentrations of T3 on the proliferation of pig SCs were evaluated using the CCK8 assay. The impact of T3 on the proliferation and differentiation of pig SCs was further examined using RNA-seq, qPCR, and Western Blotting techniques. Additionally, the involvement of the p38 MAPK and NFκB pathways in mediating the effects of T3 on SCs proliferation and differentiation was investigated. Our findings revealed a strong correlation between the dosage of T3 and the inhibition of pig SCs proliferation and promotion of maturation. T3 regulated the activation state of the NFκB signaling pathway by upregulating IKKα, downregulating IKKß, and promoting IκB phosphorylation. Furthermore, T3 facilitated SCs maturation by upregulating AR and FSHR expression while downregulating KRT-18. In conclusion, T3 inhibits pig SCs proliferation and promote pig SCs maturation through the IKK/NFκB and p38 MAPK pathways. These findings provide valuable insights into the mechanisms by which T3 influences the proliferation and maturation of pig SCs.

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.

Effect of indoxyl sulfate on the morphology and function of the thyroid gland - ex vivo studies in rabbits.

Indoxyl sulfates are uremic indolic toxins known to participate in the pathogenesis of cardiovascular diseases during chronic kidney disease in humans and some animal species. However, nothing is known about the indoxyl sulfate effect on the thyroid gland which is especially responsible for the general organism metabolism. This study determines the morpho-functional status of the thyroid gland after exposure to indoxyl sulfate (10, 25, and 50 mM) with the use of an ex vivo system and rabbit (n=10) as an experimental model thyroid gland histology, immunoexpression of thyrotropin receptor (TSHR), and concentrations of thyroxine (T4) and triiodothyronine (T3) were evaluated. Statistical analyses were performed using one-way analysis of the variance (ANOVA) followed by Tukey's post hoc comparison test. Minor alterations in thyroid tissue structure e.g. very rare exfoliated epithelial cells, condensed colloid fluid, or slight loosening of the epithelium were found. In addition, modulated dose dependent-expression of TSHR (p<0.01, p<0.001) together with a decreased level of T4 and T3 (p<0.001, p<0.01) exception of an increased level of T4 after the middle dose of indoxyl sulfate were revealed. We report here, for the first time, that indoxyl sulfate affects the thyroid gland mainly at the molecular level. The rabbit thyroid gland ex vivo system seems to be suitable for further studies on the thyroid gland in health and disease. However, the effect of TSH-TSHR signaling at ultrastructural, and epigenetic levels needs supplementary appraisal.

Low-dose Potassium bromate enhances ischemia-reperfusion-induced gastric ulcer healing in Thyroidectomised Rats.

Gastric ulcer healing is impaired in both hypothyroid and hyperthyroid conditions.  Thyroid hormones regulate growth, energy metabolism and mitochondrial oxidative metabolism. Xenobiotics have been documented to negatively impact the thyroid gland at high doses but the redox and cellular interactions at low doses during wound healing process remains unclear. Potassium bromate has been documented to be toxic at high doses but there is dearth of information on its activities at a low dose in varied thyroid states which was evaluated in this study. 60 male Wistar rats (g, n=10) were randomised into 2 conditions: Normal, ulcerated untreated, ulcerated treated with 12.5mg/kg p.o KBrO3 and thyroidectomised groups: thyroidectomised ulcerated, thyroidectomised ulcer treated with KBrO3 and thyroidectomised treated with thyroxine (100µg/kg) Total thyroidectomy was used to model hypothyroidism, and ischaemia-reperfusion-induced gastric ulcers were monitored for healing. Daily body weights, Levels of thyroxine, Gastric mucin content, redox and sodium pump activity were examined alongside other markers of hepatic and haematological toxicity by days 3 and 7 post ulceration. Data were analysed using descriptive statistics and ANOVA α 0.05. The bromate-exposed hypothyroid rats showed increased gastric ulcer healing potential with reduced gastric epithelial oedema and inflammation; hepatic steatosis, and periportal inflammation. Haematological variables and markers of hepatic functions were normal. There were reduced levels of gastric and hepatic malondialdehyde levels. Thyroxine and potassium bromate treatment resolved the redox and cellular toxicity possibly via increasing catalase and sulfhydryl levels and increased Na+ K+ pump activity. We conclude that potassium bromate enhanced gastric ulcer healing in hypothyroid state, similar to thyroxine treatment.

Síndrome nefrótico asociado a hipotiroidismo severo / Nephrotic syndrome associated to severe hypothyroidism

Las hormonas tiroideas tienen acciones renales directas en conjunto con efectos dinámicos y cardiovasculares que influyen en la función renal. Cuadros de hipotiroidismo con enfermedad renal son una combinación peculiar y poco descrita, es por ello que el propósito de este trabajo es exponer el caso de dos pacientes con síndrome nefrótico asociado a hipotiroidismo severo, los cuales presentaron disminución de la proteinuria y casi normalización de función renal luego de iniciar tratamiento de reemplazo con levotiroxina.

Thyroid hormones have direct renal actions in conjunction with dynamic and cardiovascular effects that influence renal function. Cases of primary hypothyroidism with renal disease are a peculiar and poorly described combination, is for it that the objective of this work is to expose the cases of two patients with nephrotic syndrome associated with severe hypothyroidism, whom presented decreased proteinuria and almost normalized renal function after starting replacement therapy with levothyroxine.

Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression

ABSTRACT Objective: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL). Subjects and methods: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase). Results: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group. Conclusion: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.

The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism

ABSTRACT Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (762 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs. −20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 762 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs. −19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r = −0.15, p < 0.05), E/A (r = −0.14, p < 0.05), GLS (r = −0.26, p < 0.001), and S/TDI (r = −0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

ABSTRACT Objective To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

ABSTRACT Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7.

Effects of thyroid hormone replacement on glycated hemoglobin levels in non diabetic subjects with overt hypothyroidism

Objective Glycated hemoglobin (HbA1c) may not accurately reflect the level of glycemia in conditions of altered erythrocyte turnover. Hypothyroidism is one condition associated with sluggish erythropoesis. To assess changes in HbA1c, independent of changes in plasma glucose after initiation of thyroxine replacement in patients with overt hypothyroidism. Materials and methods In this prospective longitudinal study carried out in a tertiary care centre, adult non-diabetic patients with overt hypothyroidism recruited between March 2012 to August 2013 were rendered euthyroid on thyroxine. They underwent testing for hemoglobin, HbA1c, reticulocyte count, thyroxine, thyrotropin and a standard oral glucose tolerance test, both before and at 3 months after restoration to the euthyroid state. Main outcome assessed was the change in HbA1c independent of the change in glucose parameters. Results Thirty eight patients (35 female and 3 male) aged 37.8 ± 10.2 years with overt hypothyroidism (thyroxine 12.6 ± 13.4 ng/mL and thyrotropin -98.1 ± 63.7 µIU/mL respectively) were recruited. While HbA1c fell from 5.8 ± 0.7% to 5.6 ± 0.5% (p = 0.009) at 3 months following the correction of hypothyroidism, there were no changes in the fasting and the 2 hr post oral glucose tolerance test glucose (p = 0.67 and 0.56 respectively). The number of patients with dysglycemia diagnosed by HbA1c (i.e HbA1c≥ 5.7%) fell from 25 (65.78%) to 17 (44.7%) after treatment (p = 0.008). There were 7 (18.4%) patients with HbA1c ≥ 6.5% at baseline, but this fell to just 4 (10.5%) (p < 0.001) after 3 months of euthyroidism. Conclusion HbA1c is not a reliable diagnostic test for diabetes in the presence of hypothyroidism.

A case of thyroid hormone resistance: a rare mutation / Caso de resistência aos hormônios tireóideos: mutação rara

Reduced sensitivity to thyroid hormones (RSTH) is a rare disease that affects about 3,000 individuals, belonging to about 1,000 families. It results from reduced intracellular action of thyroid hormones (TH) genetically determined and manifests as persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH). We describe a 67-years old, Caucasian woman, with past history of subtotal thyroidectomy due to diffuse goiter, who presents with a recurrence of goiter. Although she is clinically euthyroid, laboratory evaluation shows persistent hyperthyroxinemia with non-suppressed TSH. Response to thyrotropin releasing hormone (TRH) test was normal and TSH concentrations were not suppressed during oral administration of suprafisiologic doses of levothyroxine (L-T4). Peripheral blood DNA was extracted from the patient and a mutation was found localized in cluster one, at codon 346 of the ligand binding domain of the THRB gene. The patient’s son underwent thyroid function testing (TFT) and genetic study, both negative, suggesting a sporadic mutation. RSTH should be considered in all hyperthyroxinemic patients who are clinically euthyroid. Mutations interfering with three major steps required for TH action on target tissues have been, so far, identified (TR-β, TR-α, MCT8, SPB2). Each mutation is associated with a distinctive syndrome. Goal of management is to maintain a normal serum TSH level and a eumetabolic state and offer appropriate genetic counselling and prenatal diagnosis. Inappropriate treatment of eumetabolic patients results in hypothyroidism and need for TH replacement.

A sensibilidade reduzida aos hormônios tiroidianos (RSTH) é uma doença rara que afeta cerca de 3.000 indivíduos em 1.000 famílias. Ela resulta de uma ação intracelular reduzida de hormônios tiroidianos (TH), é geneticamente determinada e se manifesta como hipertiroxinemia persistente com hormônio tireoestimulante (TSH) não suprimido. Descrevemos o caso de uma mulher caucasiana de 67 anos de idade com histórico de tiroidectomia subtotal por bócio difuso e que apresentou recorrência do bócio. Embora ela fosse clinicamente eutiroide, a avaliação laboratorial mostrou hipertiroxinemia persistente com TSH não suprimido. A resposta ao hormônio liberador da tireotrofina (TRH) foi normal e as concentrações de TSH não foram suprimidas durante a administração oral de doses suprafisiológicas de levotiroxina (L-T4). Foi extraído DNA de sangue periférico da paciente e encontrada uma mutação no cluster um do códon 346 do domínio de ligação do ligante do gene THRB. O filho da paciente foi submetido a um teste de função da tiroide e a um estudo genético, ambos negativos, o que sugeriu uma mutação esporádica. O RSTH deve ser considerado em todos os pacientes hipertiroxinêmicos que sejam clinicamente eutiroides. Foram identificadas, até hoje, mutações que interferem com os três passos principais necessários para a ação do TH sobre os tecidos-alvo (TR-b, TR-α, MCT8, SPB2). Cada mutação está associada com uma síndrome distinta. O objetivo do manejo é manter o nível sérico normal de TSH e um estado eumetabólico, além de se oferecer aconselhamento genético adequado e diagnóstico pré-natal. O tratamento inadequado de pacientes eumetabólicos leva ao hipotireoidismo e requer reposição de TH.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 µg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

Adherencia y conocimiento del tratamiento en pacientes hipotiroideos desde una farmacia comunitaria en Sevilla. Estudio piloto / Adherence and knowledge of treatment in hypothyroid patients from a community pharmacy in Seville. A pilot study

No disponible

Oftalmopatía distiroidea asociada a hipotiroidismo / Dystrophy ophthalmology associated with hypothyroidism

Caso clínico: La oftalmopatía por enfermedad de Graves (exoftalmos, infiltración muscular y palpebral) se asocia casi sistemáticamente a hipertiroidismo. Paciente diagnosticada de hipotiroidismo subclínico y tratada adecuadamente con tiroxina oral. Unos meses después desarrolla un exoftalmos bilateral y simultáneamente presenta anticuerpos séricos antireceptor de TSH positivos. Se suspende entonces el tratamiento con tiroxina, y se comprueba que el hipotiroidismo ha progresado hasta hacerse primario. Se establece el diagnóstico de enfermedad de Graves hipotiroidea. Discusión: El diagnóstico se basó en la existencia de la oftalmopatía y los anticuerpos positivos, ambos específicos de la enfermedad de Graves. La coexistencia de hipotiroidismo es excepcional, pero posible

Clinical case: Graves' ophthalmopathy (exophthalmos, muscular and eyelid infiltration) is associated almost systematically to hyperthyroidism. A female patient was diagnosed with subclinical hypothyroidism and treated with oral thyroxine. Months later she developed bilateral exophthalmos and was serum-positive for thyrotropin receptor antibodies. Thyroxine treatment was suspended, and it was verified that her condition had developed into primary hypothyroidism. A diagnosis of Graves’ disease with hypothyroidism was made. Discussion: The diagnosis was based on the existence of ophthalmopathy and positive serum antibodies, both specific indicators of Graves' disease. The coexistence of hypothyroidism with Graves’ disease is exceptional, but possible