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Lancet (London, England) Sep 2017Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The... (Review)
Review
Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The definition of hypothyroidism is based on statistical reference ranges of the relevant biochemical parameters and is increasingly a matter of debate. Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms. The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine. However, a substantial proportion of patients who reach biochemical treatment targets have persistent complaints. In this Seminar, we discuss the epidemiology, causes, and symptoms of hypothyroidism; summarise evidence on diagnosis, long-term risk, treatment, and management; and highlight future directions for research.
Topics: Disease Management; Hormone Replacement Therapy; Hypothyroidism; Thyroxine
PubMed: 28336049
DOI: 10.1016/S0140-6736(17)30703-1 -
Thyroid : Official Journal of the... Feb 2021Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these... (Review)
Review
Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 μg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.
Topics: Consensus; Drug Combinations; Evidence-Based Medicine; Humans; Hypothyroidism; Thyroxine; Treatment Outcome; Triiodothyronine
PubMed: 33276704
DOI: 10.1089/thy.2020.0720 -
PeerJ 2023To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP). (Observational Study)
Observational Study
AIM
To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP).
METHODS
Ninety-eight inpatients experiencing FEP and with less than 6 weeks of antipsychotic treatment were included in the study and were followed up for one year. Baseline psychiatric evaluation included assessment of prodromal symptoms, positive and negative symptoms, depressive symptoms, stressful life events and cycloid psychosis criteria. Thyroid function (thyroid-stimulating hormone (TSH) and free thyroxin (FT4)) was determined at admission. Partial correlation analysis was conducted to analyse the correlation between levels of TSH/FT4 and symptoms. Logistic regression was performed to explore the association between psychopathological symptoms, 12-month diagnoses and thyroid hormones while adjusting for covariates.
RESULTS
Patients with prodromal symptomatology showed lower baseline FT4 levels (OR = 0.06; = 0.018). The duration of untreated psychosis (DUP) was inversely associated with FT4 concentrations ( = - 0.243; = 0.039). FEP patients with sudden onset of psychotic symptoms (criteria B, cycloid psychosis) showed higher FT4 levels at admission (OR = 10.49; = 0.040). Patients diagnosed with affective psychotic disorders (BD or MDD) at the 12-month follow-up showed higher FT4 levels at admission than patients diagnosed with nonaffective psychosis (schizophrenia, schizoaffective) (OR = 8.57; = 0.042).
CONCLUSIONS
Our study suggests that higher free-thyroxine levels are associated with a specific clinical phenotype of FEP patients (fewer prodromal symptoms, shorter DUP duration and sudden onset of psychosis) and with affective psychosis diagnoses at the 12-month follow-up.
Topics: Humans; Thyroxine; Prodromal Symptoms; Psychotic Disorders; Thyroid Hormones; Thyrotropin; Phenotype
PubMed: 37283900
DOI: 10.7717/peerj.15347 -
BMJ Clinical Evidence Feb 2014Hypothyroidism is six times more common in women, affecting up to 40 in 10,000 each year (compared with 6/10,000 men). (Review)
Review
INTRODUCTION
Hypothyroidism is six times more common in women, affecting up to 40 in 10,000 each year (compared with 6/10,000 men).
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for clinical (overt) hypothyroidism? What are the effects of treatments for subclinical hypothyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found nine studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: levothyroxine, and levothyroxine plus liothyronine.
Topics: Drug Combinations; Humans; Hypothyroidism; Safety; Thyroxine; Treatment Outcome; Triiodothyronine
PubMed: 24807886
DOI: No ID Found -
Frontiers in Endocrinology 2020Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in... (Review)
Review
Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis, either one associated with a number of symptoms/complications. Most literature regarding the LT4 dosage deals with the treatment of primary hypothyroidism, whereas a limited number of studies handle the issue of thyroxin replacement after total thyroidectomy. A literature review was performed focusing on all papers dealing with this topic within the last 15 years. Papers that reported a scheme to calculate the proper LT4 dose were collected and compared to set up a review exploring limits and drawbacks of LT4 replacement therapy in the wide population of patients who had undergone thyroidectomy. Most of the methods for monitoring and adjusting thyroid hormone replacement after thyroidectomy for benign disease use LT4 at an empirical dose of approximately 1.6 μg/kg, with subsequent changes according to thyroid function test results and assessments of the patient's symptoms. Approximately 75% of patients require a dose adjustment, suggesting that factors other than body weight play a role in the determination of the proper LT4 dose. Hence, several schemes are reported in the literature for the proper initial dose of LT4. An inadequate level of thyroid hormone levels in these patients can be due to several factors. The most common ones that lead to the necessity of LT4 dose adjustments include lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits. Moreover, concomitant ingestion of calcium supplements, ferrous sulfate, proton-pump inhibitors, bile acid sequestrants, and sucralfate might influence LT4 absorption and/or metabolism. Furthermore, some gastrointestinal conditions and their treatments can contribute to suboptimal LT4 performance by altering gastric acidity and thereby reducing its bioavailability, particularly in the solid form. Beyond the classic tablet form, new formulations of LT4, such as a soft gel capsule and an oral solution, recently became available. The liquid formulation is supposed to overcome the food and beverages interference with absorption of LT4 tablets.
Topics: Animals; Biomarkers; Dose-Response Relationship, Drug; Humans; Hypothyroidism; Thyroid Function Tests; Thyroid Neoplasms; Thyroidectomy; Thyroxine
PubMed: 33584551
DOI: 10.3389/fendo.2020.626268 -
CMAJ : Canadian Medical Association... Feb 2015
Topics: Humans; Hypothyroidism; Thyrotropin; Thyroxine
PubMed: 25601999
DOI: 10.1503/cmaj.141596 -
Frontiers in Endocrinology 2021Levothyroxine (L-T4) absorption can be impaired by various causes: a) L-T4 ingestion during breakfast, or with food; b) conditions of reduced gastric acidity; c)... (Review)
Review
Levothyroxine (L-T4) absorption can be impaired by various causes: a) L-T4 ingestion during breakfast, or with food; b) conditions of reduced gastric acidity; c) intestinal procedures and diseases such as bariatric surgery, lactose intolerance (LI), celiac disease (CD), inflammatory bowel disease; d) drugs that alter L-T4 absorption, increasing the gastric pH, or preventing the dissolution of tablets. The development of new oral formulations, i.e. the liquid preparation and the soft gel capsule, represents the most recent advance regarding L-T4 therapy. Treating hypothyroidism with L-T4 tablets can lead to an improper control of thyroid-stimulating hormone (TSH) in ~10%-15% of patients. The improperly elevated TSH is usually managed by increasing the L-T4 daily dose, and revaluating TSH upon 2-6 months. The increase of the L-T4 dosage may cause iatrogenic hyperthyroidism, especially when the underlying disorders are cured. Liquid L-T4 can be administered in patients unable to swallow capsules or tablets, and this is one of its major benefits. Liquid L-T4 can: 1- overcome food and beverages interference; 2- bypass the malabsorption associated with an increased gastric pH; 3- circumvent the issue of malabsorption in patients who underwent bariatric surgery; 4-maintain TSH values under control better than L-T4 tablets in hypothyroid patients with typical or atypical CD, or in patients with LI. Few clinical studies evaluated soft gel L-T4 with encouraging findings in patients with gastric- or coffee-related malabsorption, or hypothyroid patients without malabsorption. Additional research is necessary to investigate liquid L-T4, or soft gel capsule, in other conditions of altered L-T4 absorption.
Topics: Administration, Oral; Hormone Replacement Therapy; Humans; Malabsorption Syndromes; Thyroxine
PubMed: 33708175
DOI: 10.3389/fendo.2021.626371 -
Journal of Clinical Pathology Sep 1992To examine the relation between plasma total thyroxine and free thyroxine in children with congenital hypothyroidism.
AIMS
To examine the relation between plasma total thyroxine and free thyroxine in children with congenital hypothyroidism.
METHODS
Regression analysis was performed on 114 cases on the paired total thyroxine and free thyroxine measurements taken from the same blood sample. Conversion equations were derived using structural relation models.
RESULTS
A linear relation was found between log total thyroxine and log free thyroxine values. The regression slopes for values taken before treatment and values taken while patients were receiving replacement treatment were significantly different.
CONCLUSIONS
The data suggest that there is a close association between total and free thyroxine in congenital hypothyroidism, but that the relation is changed by thyroid replacement treatment.
Topics: Congenital Hypothyroidism; Humans; Hypothyroidism; Regression Analysis; Thyroxine
PubMed: 1401216
DOI: 10.1136/jcp.45.9.819 -
Theriogenology Apr 2020Numerous studies have reported the importance of thyroid hormones on the development of later preantral and antral follicles, but their interactions with other hormones...
Numerous studies have reported the importance of thyroid hormones on the development of later preantral and antral follicles, but their interactions with other hormones and effects in regulating early preantral follicle growth remain unclear. Here we investigated the in vitro effects of thyroxine combined with insulin on caprine preantral follicle survival and development. Sliced ovarian tissues were cultured for 1 or 7 days using 10 ng/mL (low) or 10 μg/mL (high) insulin in the presence of thyroxine at 0, 0.5, 1 or 2 μg/mL. Post-culture, we evaluated the follicular survival and development, assessed the expression of apoptotic-related genes (Bcl2/Bax) and receptors of insulin and thyroid hormones, and quantified the estradiol and reactive oxygen species (ROS) production levels. Follicular survival in low-insulin culture conditions was enhanced by the presence of 0.5 μg/mL thyroxine (P < 0.05) as compared to the thyroxine-free medium but remained similar to non-cultured control in the presence of 2 μg/mL (P > 0.05). Significantly higher ROS production was measured from Day 1 to Day 7 in low-insulin culture media containing 0.5 or 2 μg/mL thyroxine (P < 0.05). When compared to high insulin level, the presence of thyroxine in low insulin culture conditions yielded higher stromal cell density (P < 0.05), increased estradiol production on Day 1, and higher Bcl2/Bax ratio on Day 7. Cultures with high levels of both insulin and thyroxine led to follicles and oocytes with larger diameters (P < 0.05). The RNA transcript levels of insulin and thyroid receptors were reduced in the presence of high insulin cultures when compared to controls (non-cultured). In conclusion, the combination of low concentrations of insulin and thyroxine better maintained follicle survival, while high levels ensured better follicular development.
Topics: Animals; Dose-Response Relationship, Drug; Estradiol; Female; Gene Expression Regulation; Goats; Insulin; Ovarian Follicle; Reactive Oxygen Species; Thyroxine; Tissue Culture Techniques
PubMed: 32074494
DOI: 10.1016/j.theriogenology.2020.01.013 -
Frontiers in Endocrinology 2022
Topics: Humans; Cardiovascular Diseases; Thyroxine; Triiodothyronine
PubMed: 36605935
DOI: 10.3389/fendo.2022.1065155