RESUMEN
Hypothyroidism is one of the most common endocrinopathies worldwide, the treatment of which is based on replacement therapy with levothyroxine. However, this seemingly simple treatment method is fraught with many difficulties and frequent dissatisfaction among patients. In fact, differences in response to levothyroxine probably depend on a complex interaction between individual, environmental, genetic, and epigenetic factors that are still not sufficiently understood. Immunological disturbances, underlying Hashimoto's disease, the most common cause of hypothyroidism, probably play a significant role in these relationships. Indeed, a growing number of studies indicate that autoimmunity through activation of low-grade inflammation can lead to impaired absorption, transport, metabolism, and action of thyroid hormones. This review provides an up-to-date overview of the causes responsible for both the difficulty in achieving target thyrotropin levels and persistence of nonspecific symptoms despite adequate hormone replacement from an immunoendocrine perspective. Understanding these mechanisms points to a new direction in the approach to hypothyroidism, indicating the need for new personalized treatment strategies.
Asunto(s)
Terapia de Reemplazo de Hormonas , Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Enfermedad de Hashimoto/tratamiento farmacológico , Enfermedad de Hashimoto/inmunología , Femenino , MasculinoRESUMEN
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.
Asunto(s)
Quimioterapia Combinada , Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Triyodotironina/uso terapéutico , Tirotropina/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: The thyroid gland is an endocrine gland that has an impact on the body's general metabolism. Thus, the secretions of the thyroid gland can modify the overall metabolism of the entire body. The prevalence of hypothyroidism is increasing quickly, with rates of 2%-5% in affluent countries and 11% in India. Individuals diagnosed with hypothyroidism need to take medication for the rest of their lives, resulting in significant stress. Therefore, conducting a study in this area is imperative. OBJECTIVE: This study aims to assess the effectiveness of the therapeutic enema (Kshar Basti) and oral Kanchanar Guggul in the treatment of hypothyroidism. METHODS: The trial group (n=45) will receive a therapeutic enema (Kshar Basti) followed by oral Ayurvedic drugs for 180 days. The control group (n=45) will be given levothyroxine tablets at a dosage of 1.6 µg/kg/day for the same duration. The objective is to examine the alterations in thyroid stimulating hormone (TSH) levels before and after the treatment. RESULTS: Any deviation of the serum TSH by more than 20% from the initial values, while keeping triiodothyronine (T3), and thyroxine (T4) levels within the normal range, will be deemed statistically significant. Consequently, we anticipate a statistically significant variation in serum TSH levels between the therapeutic enema and Kanchanar Guggul treatments. Presently, the drug preparation operations are in progress. We expect to start enrolling patients in June 2024, do data analysis in December 2025, and acquire results by early 2026, marking the end of this trial. CONCLUSIONS: This study will evaluate the efficacy of the therapeutic enema, specifically Kshar Basti, in treating hypothyroidism. Furthermore, more research can determine the efficacy of a therapeutic enema (Kshar Basti) in treating overt hypothyroidism and hypothyroidism during pregnancy. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/05/052389; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Nzk1NjY=&Enc=&userName=052389. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57287.
Asunto(s)
Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , India , Adulto , Femenino , Masculino , Medicina Ayurvédica , Enema , Gomas de Plantas/uso terapéutico , Commiphora/química , Ensayos Clínicos Controlados Aleatorios como Asunto , Extractos Vegetales/uso terapéutico , Extractos Vegetales/administración & dosificación , Persona de Mediana EdadRESUMEN
Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95-105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation.
Asunto(s)
Personal de Salud , Tiroxina , Humanos , Tiroxina/administración & dosificación , Tiroxina/farmacocinética , Equivalencia Terapéutica , Comités Consultivos , Testimonio de Experto , Comunicación , Composición de Medicamentos/métodos , Composición de Medicamentos/normas , Hipotiroidismo/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Administración Cutánea , Ácido Oléico , Absorción Cutánea , Tiroxina , Ácido Oléico/química , Tiroxina/administración & dosificación , Tiroxina/farmacología , Tiroxina/farmacocinética , Animales , Absorción Cutánea/efectos de los fármacos , Parche Transdérmico , Piel/metabolismo , Piel/efectos de los fármacos , Liberación de Fármacos , Ratones , Permeabilidad , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/metabolismo , Humanos , Química Farmacéutica/métodos , MasculinoRESUMEN
The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU-POG; and PTU-RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted longterm potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using highfrequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10-90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10-90%), and amplitude of the fEPSP in the PTUPOG or PTURSG groups compared to the PTU group. TUNELpositive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU-POG or PTU-RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU-POG or PTU-RSG groups, respectively, compared to the PTU group. This study's results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.
Asunto(s)
Apoptosis , Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Hipotiroidismo , Potenciación a Largo Plazo , PPAR gamma , Ratas Wistar , Rosiglitazona , Animales , Apoptosis/efectos de los fármacos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/inducido químicamente , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Rosiglitazona/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , PPAR gamma/agonistas , PPAR gamma/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Tiazolidinedionas/farmacología , Pioglitazona/farmacología , Ratas , Propiltiouracilo/farmacología , Modelos Animales de Enfermedad , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Óxido Nítrico/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismoAsunto(s)
Catatonia , Hipotiroidismo , Tiroxina , Humanos , Catatonia/tratamiento farmacológico , Catatonia/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Tiroxina/uso terapéutico , Diagnóstico Diferencial , Femenino , Cumplimiento de la Medicación , Persona de Mediana EdadRESUMEN
Thyroxine, a key regulator of metabolic pathways, plays a pivotal role in glucose metabolism and the maintenance of glucose homeostasis. In clinical practice, L-thyroxine replacement therapy is commonly prescribed for patients with hypothyroidism. However, the specific effects of L-thyroxine and thyroidectomy (TX) on glucose levels remain an area of interest and investigation. In this study, 20 rats were divided into two groups (n=10 per group). The TX group (male and female rats) underwent thyroidectomy for 4 weeks. After 4 weeks, male and female thyroidectomized rats received L-thyroxine (10 µg/100 g/day, intraperitoneally) for 4 weeks. The rats' weights were monitored weekly post-surgery. Compared to the initial level, thyroidectomy resulted in weight loss, whereas L-thyroxine replacement therapy normalized the weight loss induced by thyroidectomy. Additionally, thyroidectomy led to impaired glucose levels, which were restored to normal levels with L-thyroxine treatment. These findings underscore the impact of thyroid function on glucose metabolism and highlight the potential therapeutic role of L-thyroxine.
Asunto(s)
Glucemia , Tiroidectomía , Tiroxina , Pérdida de Peso , Tiroidectomía/efectos adversos , Animales , Tiroxina/sangre , Femenino , Masculino , Pérdida de Peso/efectos de los fármacos , Ratas , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Hipotiroidismo/tratamiento farmacológico , Factores SexualesRESUMEN
Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.
Asunto(s)
Medios de Contraste , Histerosalpingografía , Yodo , Índice de Embarazo , Humanos , Femenino , Yodo/orina , Yodo/deficiencia , Adulto , Histerosalpingografía/métodos , Estudios Prospectivos , Embarazo , Infertilidad Femenina/epidemiología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Fertilidad/efectos de los fármacos , Nueva Zelanda/epidemiología , Aceites , Estudios de Cohortes , Pruebas de Función de la TiroidesRESUMEN
BACKGROUND: Myxedema coma is a rare, but life-threatening endocrinological emergency. Myxedema is characterized by altered mental status, and is accompanied by hypotension, bradycardia, hypothermia, bradypnea, hyporeflexia, hyponatremia, and hypoglycemia, all stemming from reduced metabolism due to severe hypothyroidism. Additionally, patients may exhibit signs of low cardiac output, edema in the extremities, peripheral circulatory disturbances, shock, and the development of pericardial and pleural effusions, ultimately leading to confusion and coma. We present a successfully treated case of severe myxedema coma with recurrent pericardial effusion and hypotensive shock. This case is characterized by an unusual clinical presentation and required a distinct treatment strategy highlighting its exceptional rarity. CASE: A 2-year-old boy with Down syndrome presented with recurrent pericardial effusion attributed to medication non-adherence. The critically-ill patient, experiencing a severe cardiogenic shock required mechanical ventilation and inotropic infusions in the pediatric intensive care unit. Elevated thyroid stimulating hormone (TSH), and low free T4 (fT4) and free T3 (fT3) levels prompted consideration of myxedema coma. Upon reviewing the patient's medical history, it was ascertained that he had an ongoing diagnosis of primary hypothyroidism, and exhibited non-adherence to the prescribed treatment regimen and failed to attend scheduled outpatient clinic appointments for follow-up assessments. The treatment plan, devised by the pediatric endocrinology team, included the peroral administration of L-thyroxine (L-T4) at a dose of 50 micrograms per day. After beginning regular oral L-T4 treatment, a gradual improvement in the patient's condition was observed. Notably, by the 15th day of oral therapy, the patient had made a full recovery. Contrary to the recommended intravenous treatment for myxedema coma, this patient was successfully treated with oral levothyroxine, due to the unavailability of the parenteral form in Türkiye. CONCLUSIONS: This case report presents an instance of non-adherence to L-T4 therapy, which subsequently progressed to severe myxedema coma. Changes in neurologic status and hemodynamic instability in a patient with a history of hypothyroidism should raise the concern of nonadherence and, though rare, myxedema coma should be in the differential diagnosis.
Asunto(s)
Coma , Síndrome de Down , Mixedema , Derrame Pericárdico , Tiroxina , Humanos , Masculino , Mixedema/tratamiento farmacológico , Mixedema/diagnóstico , Mixedema/complicaciones , Tiroxina/uso terapéutico , Tiroxina/administración & dosificación , Coma/etiología , Coma/tratamiento farmacológico , Preescolar , Derrame Pericárdico/tratamiento farmacológico , Derrame Pericárdico/etiología , Derrame Pericárdico/diagnóstico , Síndrome de Down/complicaciones , Cumplimiento de la Medicación , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/complicacionesRESUMEN
Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 µIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22+/-0.27 µg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 µIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up.
Asunto(s)
Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Tiroxina/uso terapéutico , Tiroxina/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Gastropatías/tratamiento farmacológico , Tirotropina/sangre , Adulto , Terapia de Reemplazo de Hormonas/métodos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L.
Asunto(s)
Hipotiroidismo , Complicaciones del Embarazo , Humanos , Embarazo , Femenino , Hipotiroidismo/inmunología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/complicaciones , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/tratamiento farmacológico , Tiroxina/uso terapéutico , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/tratamiento farmacológico , Autoinmunidad/efectos de los fármacosRESUMEN
This article includes a review of information primary care physicians need to know direct their evaluation and treatment of thyroid disorders that include sick euthyroid, hyperthyroidism, hypothyroidism, and subclinical thyroid disorders.
Asunto(s)
Atención Primaria de Salud , Enfermedades de la Tiroides , Humanos , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/terapia , Atención Primaria de Salud/organización & administración , Hipertiroidismo/diagnóstico , Hipertiroidismo/terapia , Hipotiroidismo/diagnóstico , Hipotiroidismo/terapia , Hipotiroidismo/tratamiento farmacológico , Pruebas de Función de la TiroidesRESUMEN
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.
Asunto(s)
Ansiedad , Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Hipotiroidismo , Condicionamiento Físico Animal , Tiroxina , Animales , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/metabolismo , Hipotiroidismo/terapia , Hipotiroidismo/fisiopatología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Tiroxina/farmacología , Tiroxina/administración & dosificación , Ratas , Ansiedad/terapia , Ansiedad/etiología , Ansiedad/tratamiento farmacológico , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Femenino , Condicionamiento Físico Animal/fisiología , Embarazo , Ratas Wistar , Efectos Tardíos de la Exposición Prenatal/terapia , Efectos Tardíos de la Exposición Prenatal/metabolismo , Aprendizaje Espacial/efectos de los fármacos , Aprendizaje Espacial/fisiología , Terapia Combinada , Propiltiouracilo/farmacología , Propiltiouracilo/administración & dosificaciónRESUMEN
ABSTRACT: Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier's disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy.
Asunto(s)
Acitretina , Enfermedad de Darier , Hipotiroidismo , Queratolíticos , Humanos , Acitretina/efectos adversos , Acitretina/uso terapéutico , Masculino , Adulto , Hipotiroidismo/inducido químicamente , Hipotiroidismo/tratamiento farmacológico , Enfermedad de Darier/tratamiento farmacológico , Enfermedad de Darier/inducido químicamente , Queratolíticos/efectos adversos , Queratolíticos/uso terapéutico , Tiroxina/uso terapéuticoRESUMEN
INTRODUCTION: Drug therapy for Graves' disease (GD) is the first-line treatment in Europe. The use of a specific regimen for the administration of anti-thyroid drugs (ATDs) is still controversial. The objective was to compare block-and-replace therapy (BRT) with a titration (T) regimen in terms of incidence of overt hypothyroidism and development of Graves' orbitopathy (GO) over 18 months of treatment. MATERIAL AND METHODS: Two databases (PubMed, Cochrane Library) and reference lists were searched. Prospective and retrospective observational cohort studies were included. Data collection and analysis were performed independently by 2 authors. RESULTS: Two studies with 716 GD patients (40.36% treated with BRT, 59.64% with T regimen) were included. No statistically significant differences were observed between the ATDs regimens used in terms of incidence of overt hypothyroidism during 18 months of treatment [Mantel-Haenszel (M-H) odds ratio (OR): 1.54, 95% confidence interval (CI): 0.75-3.16, p-value = 0.24]. GD patients who followed BRT were less likely to achieve control of thyroid function than patients on T regimen (M-H OR: 0.55, 95% CI: 0.34-0.88, p = 0.01). One study reported fewer thyroid function tests (TFT) during BRT than during the T regimen. The other study included patients without GO at baseline and reported a lower incidence of GO during BRT than in the T regimen (9.1% versus 17.8%), with no statistical difference between the 2 regimens (M-H OR: 0.47, 95% CI: 0.19-1.14, p = 0.10). CONCLUSION: BRT may be more useful than the T regimen for patients with complicated GD or for those who required fewer TFTs.
Asunto(s)
Antitiroideos , Enfermedad de Graves , Humanos , Antitiroideos/uso terapéutico , Antitiroideos/administración & dosificación , Enfermedad de Graves/tratamiento farmacológico , Femenino , Masculino , Hipotiroidismo/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Oftalmopatía de Graves/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: One common problem in various patient groups is excessive hair loss on the head. One such group is people struggling with hypothyroidism. The market for preparations for hair growth and hair loss prevention includes betulin. PURPOSE: This pilot study investigated its effect on hair loss in hypothyroid patients. STUDY DESIGN: The study included a group of hypothyroid patients and a control group of people without hypothyroidism. Participants were randomly divided into a group taking placebo and betulin. METHODS: Results were investigated using photographic assessment of hair, trichoscopy and subjective evaluation of participants. CONCLUSION: The study did not conclusively prove that betulin would contribute to the inhibition of hair loss or regrowth.
Asunto(s)
Cabello , Hipotiroidismo , Triterpenos , Humanos , Proyectos Piloto , Triterpenos/administración & dosificación , Triterpenos/farmacología , Femenino , Adulto , Hipotiroidismo/tratamiento farmacológico , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Persona de Mediana Edad , Masculino , Alopecia/tratamiento farmacológico , Aceites de Plantas/administración & dosificación , Resultado del Tratamiento , Ácido BetulínicoRESUMEN
BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.
Asunto(s)
Hipotiroidismo , Tiroxina , Triyodotironina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Tiroxina/administración & dosificación , Triyodotironina/sangre , Quimioterapia Combinada , Calidad de Vida , Resultado del Tratamiento , Terapia de Reemplazo de Hormonas/métodos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patologíaRESUMEN
Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1ß, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.