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Thyroid : Official Journal of the... Apr 2016The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients.
METHODS
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66-2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score.
CONCLUSIONS
SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.
Topics: Abortion, Spontaneous; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Risk Assessment; Thyroxine; Treatment Outcome
PubMed: 26837268
DOI: 10.1089/thy.2015.0418 -
JAMA Psychiatry Dec 2021Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of the association. It is also unclear whether the link is largely due to subsyndromal depression or holds true for clinical depression.
OBJECTIVE
To estimate the association of hypothyroidism and clinical depression in the general population.
DATA SOURCES
PubMed, PsycINFO, and Embase databases were searched from inception until May 2020 for studies on the association of hypothyroidism and clinical depression.
STUDY SELECTION
Two reviewers independently selected epidemiologic and population-based studies that provided laboratory or International Statistical Classification of Diseases and Related Health Problems diagnoses of hypothyroidism and diagnoses of depression according to operationalized criteria (eg, Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases and Related Health Problems) or cutoffs in established rating scales.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and evaluated studies based on the Newcastle-Ottawa Scale. Summary odds ratios (OR) were calculated in random-effects meta-analyses.
MAIN OUTCOMES AND MEASURES
Prespecified coprimary outcomes were the association of clinical depression with either hypothyroidism or autoimmunity.
RESULTS
Of 4350 articles screened, 25 studies were selected for meta-analysis, including 348 014 participants. Hypothyroidism and clinical depression were associated (OR, 1.30 [95% CI, 1.08-1.57]), while the OR for autoimmunity was inconclusive (1.24 [95% CI, 0.89-1.74]). Subgroup analyses revealed a stronger association with overt than with subclinical hypothyroidism, with ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28), respectively. Sensitivity analyses resulted in more conservative estimates. In a post hoc analysis, the association was confirmed in female individuals (OR, 1.48 [95% CI, 1.18-1.85]) but not in male individuals (OR, 0.71 [95% CI, 0.40-1.25]).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. Autoimmunity alone may not be the driving factor in this comorbidity.
Topics: Depressive Disorder; Female; Humans; Hypothyroidism; Male; Sex Factors
PubMed: 34524390
DOI: 10.1001/jamapsychiatry.2021.2506 -
Fertility and Sterility Mar 2020To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
University obstetrics and gynecology departments.
PATIENT(S)
Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment.
RESULT(S)
After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%-35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43-2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity.
CONCLUSION(S)
Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed.
Topics: Abortion, Habitual; Asymptomatic Diseases; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Diagnosis; Risk Factors; Thyroid Function Tests; Thyroiditis, Autoimmune
PubMed: 32192591
DOI: 10.1016/j.fertnstert.2019.11.003 -
JAMA Oct 2018The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of... (Meta-Analysis)
Meta-Analysis Review
Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis.
IMPORTANCE
The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses.
OBJECTIVE
To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism.
DATA SOURCES
PubMed, EMBASE, ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and Academic Search Premier from inception until July 4, 2018.
STUDY SELECTION
Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in nonpregnant adults with subclinical hypothyroidism were eligible. Two reviewers independently evaluated eligibility based on titles and abstracts of all retrieved studies. Studies not excluded in this first step were independently assessed for inclusion after full-text evaluation by 2 reviewers.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data, assessed risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence (GRADE tool). For synthesis, differences in clinical scores were transformed (eg, quality of life) into standardized mean differences (SMDs; positive values indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to small, moderate, and large effects, respectively). Random-effects models for meta-analyses were applied.
MAIN OUTCOMES AND MEASURES
General quality of life and thyroid-related symptoms after a minimum follow-up of 3 months.
RESULTS
Overall, 21 of 3088 initially identified publications met the inclusion criteria, with 2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L) but was not associated with benefit regarding general quality of life (n = 796; SMD, -0.11; 95% CI, -0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n = 858; SMD, 0.01; 95% CI, -0.12 to 0.14; I2=0.0%). Overall, risk of bias was low and the quality of evidence assessed with the GRADE tool was judged moderate to high.
CONCLUSIONS AND RELEVANCE
Among nonpregnant adults with subclinical hypothyroidism, the use of thyroid hormone therapy was not associated with improvements in general quality of life or thyroid-related symptoms. These findings do not support the routine use of thyroid hormone therapy in adults with subclinical hypothyroidism.
Topics: Adult; Blood Pressure; Humans; Hypothyroidism; Practice Guidelines as Topic; Quality of Life; Thyrotropin; Thyroxine
PubMed: 30285179
DOI: 10.1001/jama.2018.13770 -
Pharmaceuticals (Basel, Switzerland) Mar 2021Levothyroxine (l-thyroxine, l-T4) is a drug of choice for treating congenital and primary hypothyroidism. Although clinically significant interactions between l-T4 and... (Review)
Review
Levothyroxine (l-thyroxine, l-T4) is a drug of choice for treating congenital and primary hypothyroidism. Although clinically significant interactions between l-T4 and food can alter the safety and efficacy of the treatment, they still seem to be generally underestimated by patients, physicians and pharmacists. This review aimed to investigate the effects of meals, beverages, and dietary supplements consumption on l-T4 pharmacokinetics and pharmacodynamics, to identify the most evident interactions, and to perform the recommendations for safe co-administering of l-T4 and food. A total of 121 studies were identified following a systematic literature search adhering to PRISMA guidelines. After full-text evaluation, 63 studies were included. The results proved that l-T4 ingestion in the morning and at bedtime are equally effective, and also that the co-administration of l-T4 with food depends on the drug formulation. We found limited evidence for l-T4 interactions with coffee, soy products, fiber, calcium or iron supplements, and enteral nutrition but interestingly they all resulted in decreased l-T4 absorption. The altered l-T4 efficacy when ingested with milk, juices, papaya, aluminium-containing preparations, and chromium supplements, as well as observed enhancement effect of vitamin C on l-T4 absorption, shall be further investigated in larger, well-designed studies. Novel formulations are likely to solve the problem of coffee, calcium and iron induced malabsorption of l-T4. Maintaining a proper time interval between l-T4 and food intake, especially for coffee and calcium, or iron supplements, provides another effective method of eliminating such interactions.
PubMed: 33801406
DOI: 10.3390/ph14030206 -
BMJ (Clinical Research Ed.) Mar 2018To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov.
STUDY SELECTION
Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease.
DATA EXTRACTION
Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators.
RESULTS
13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain.
CONCLUSIONS
Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; B7-H1 Antigen; Humans; Immunity; Neoplasms; Nivolumab; Programmed Cell Death 1 Receptor
PubMed: 29540345
DOI: 10.1136/bmj.k793 -
Movement Disorders Clinical Practice Mar 2023There is overlap between movement disorders and neuroendocrine abnormalities. (Review)
Review
BACKGROUND
There is overlap between movement disorders and neuroendocrine abnormalities.
OBJECTIVES AND METHODS
To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed.
RESULTS
Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive.
CONCLUSIONS
In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed.
PubMed: 36949803
DOI: 10.1002/mdc3.13656 -
Lancet (London, England) Feb 2012Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium.
METHODS
We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity.
FINDINGS
We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders.
INTERPRETATION
Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment.
FUNDING
National Institute for Health Research Programme Grant for Applied Research.
Topics: Antipsychotic Agents; Humans; Lithium; Mood Disorders
PubMed: 22265699
DOI: 10.1016/S0140-6736(11)61516-X -
Nutrients Nov 2023Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The... (Meta-Analysis)
Meta-Analysis Review
Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "iron deficiency", "thyroid function", "thyroid disease", "thyroid dysfunction", and "hypothyroidism". A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran's Q testing and heterogeneity indices () were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: -0.24 mIU/L; 95% CI -0.41, -0.07; = 100%, = 0.005), FT4 (MD: -1.18 pmol/L; 95% CI -1.43, -0.94; = 99%, < 0.000001), and FT3 (MD: -0.22 pmol/L; 95% CI -0.32, -0.12; = 99%, < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.
Topics: Humans; Female; Pregnancy; Thyroxine; Thyroid Function Tests; Cross-Sectional Studies; Thyroid Hormones; Thyroid Diseases; Thyrotropin; Iron Deficiencies
PubMed: 38004184
DOI: 10.3390/nu15224790 -
Travel Medicine and Infectious Disease 2022COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the... (Review)
Review
COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the literature to assess the prevalence, clinical features and outcome of autoimmune thyroid disorders triggered by COVID-19. We reviewed case reports, case series, and observational studies of autoimmune thyroiditis including Graves' disease, Hashimoto thyroiditis, and silent thyroiditis developed in COVID-19 patients by searching PubMed, SCOPUS and Web of Science and included in the systematic review. Our search yielded no prevalence study. We noted 20 reported cases: Fourteen cases of Graves' disease, 5 cases of hypothyroidism due to Hashimoto's thyroiditis and one case of postpartum thyroiditis. The majority (16/20, 80%) were middle-aged (mean age: 40 years) female patients. Autoimmune thyroiditis was diagnosed either concomitantly or 7-90 days after the COVID-19 infection. Eight out of 14 cases with Graves' disease had a known thyroid disorder and they were stable in remission. One out of 5 cases with Hashimoto's thyroiditis had known prior hypothyroidism. The majority of the patients achieved remission within 3 months. One patient with thyroid storm due to Graves' disease and one patient with myxedema coma have died. Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission. It is reasonable to routinely assess the thyroid functions both in the acute phase and during the convalescence so as not to overlook a thyroid disorder and not to delay treatment especially in patients with preexisting autoimmune thyroid diseases.
Topics: Adult; COVID-19; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Middle Aged; Thyroiditis; Thyroiditis, Autoimmune
PubMed: 35307540
DOI: 10.1016/j.tmaid.2022.102314