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Frontiers in Immunology 2023Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between...
BACKGROUND
Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.
METHODS
Single nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves' disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran's Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy.
RESULTS
Forward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (OR=1.758, P=7.61×10). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (OR=1.274, P=3.88×10), GD (OR=1.269, P=8.15×10), and other types of hyperthyroidism (OR=1.141, P=1.80×10). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH.
CONCLUSION
Our results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction.
Topics: Humans; Mendelian Randomization Analysis; Hyperthyroidism; Hypothyroidism; Arthritis, Rheumatoid; Graves Disease; Genetic Predisposition to Disease; Thyrotropin
PubMed: 38090574
DOI: 10.3389/fimmu.2023.1238757 -
Advances in Therapy Jul 2020Hypothyroidism is one of the most common chronic endocrine conditions. However, as symptoms of hypothyroidism are non-specific, up to 60% of those with thyroid... (Review)
Review
Hypothyroidism is one of the most common chronic endocrine conditions. However, as symptoms of hypothyroidism are non-specific, up to 60% of those with thyroid dysfunction are unaware of their condition. Left untreated, hypothyroidism may contribute to other chronic health conditions. In the Arabian Gulf States, hypothyroidism is thought to be common, but is underdiagnosed, and management approaches vary. An advisory board of leading Saudi endocrinologists and policy advisers was convened to discuss and formulate recommendations for the diagnosis and management of hypothyroidism in Saudi Arabia based on their clinical expertise. The final document was shared with leading endocrinologists from the other Gulf Cooperation Council (GCC) and aconsensus report was generated and summerized in this article. While there is no consensus regarding population screening of hypothyroidism, current recommendations suggest screening patients with risk factors, including those with a history of head or neck irradiation, a family history of thyroid disease or pharmacological treatment that may affect thyroid function. Evidence from a cross-sectional study in Saudi Arabia suggests screening the elderly (> 60 years), at least in the primary care setting. In Saudi Arabia, the incidence of congenital hypothyroidism is approximately 1 in every 3450 newborns. Saudi nationwide population prevalence data are lacking, but a single-centre study estimated that the prevalence of subclinical hypothyroidism in the primary care setting was 10%. Prevalence rates were higher in other cross-sectional studies exclusively in women (13-35%). The recommendations included in this article aim to streamline the diagnosis and clinical management of hypothyroidism in the GCC, especially in the primary care setting, with the intention of improving treatment outcomes. Further study on the incidence, prevalence and risk factors for, and clinical features of, hypothyroidism in the GCC countries is required.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cross-Sectional Studies; Diagnostic Techniques and Procedures; Female; Humans; Hypothyroidism; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Practice Guidelines as Topic; Prevalence; Saudi Arabia; Symptom Assessment; Thyroxine; Young Adult
PubMed: 32488658
DOI: 10.1007/s12325-020-01382-2 -
Frontiers in Endocrinology 2020Pharmacological interference on L-thyroxine (L-T4) therapy can be exerted at several levels, namely from the hypothalamus/pituitary through the intestine, where the... (Review)
Review
Pharmacological interference on L-thyroxine (L-T4) therapy can be exerted at several levels, namely from the hypothalamus/pituitary through the intestine, where the absorption of exogenous L-T4 takes place. A number of medications interfere with L-T4 therapy, some of them also being the cause of hypothyroidism. The clinician should be aware that some medications simply affect thyroid function tests with no need of modifying the dose of L-T4 that the patient was taking prior to their prescription. Usually, the topic of pharmacological interference on L-T4 therapy addresses the patient with primary hypothyroidism, in whom periodic measurement of serum thyrotropin (TSH) is the biochemical target. However, this minireview also addresses the patient with central hypothyroidism, in whom the biochemical target is serum free thyroxine (FT4). This minireview also addresses two additional topics. One is the costs associated with frequent monitoring of the biochemical target when L-T4 is taken simultaneously with the interfering drug. The second topic is the issue of metabolic/cardiovascular complications associated with undertreated hypothyroidism.
Topics: Drug Interactions; Humans; Hypothyroidism; Thyroid Function Tests; Thyroid Hormones; Thyroxine
PubMed: 33414765
DOI: 10.3389/fendo.2020.607446 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2022To explore the effect of hypothyroidism (HT) on the ocular surface status of patients with primary Sjögren's syndrome-related dry eye (pSS-DED).
OBJECTIVE
To explore the effect of hypothyroidism (HT) on the ocular surface status of patients with primary Sjögren's syndrome-related dry eye (pSS-DED).
METHODS
The cross-sectional study included 36 patients with pSS-DED who were treated at the dry eye clinic of Peking University Third Hospital from December 2020 to June 2021, of whom 12 were pSS-DED patients combined with HT. In the same period, 24 patients with simple dry eye disease (DED) were served as a control group. All the patients filled out the Ocular Surface Disease Index (OSDI) questionnaire, and performed tear film break-up time (BUT), Schirmer test, tear meniscus height, corneal/conjunctival fluorescein staining, meibomian gland secretion capacity, meibum evaluation and confocal microscope examination.
RESULTS
(1) Compared with pSS-DED and simple DED patients, pSS-DED +HT patients had lower average BUT [(2.7±0.8) s], Schirmer test [(4.9±4.8) mm] and tear meniscus height [(0.13±0.03) mm], and the difference was statistically significant (=12.43, < 0.01; =6.96, < 0.01; =3.31, < 0.05). (2) Compared with DED and pSS-DED patients, the meibomian gland secretion capacity and meibomian trait scores of pSS-DED+HT patients were mainly distributed in the high division. There were statistically significant differences in the distribution of secretion capacity of meibomian glands (=10.72, < 0.05) and meibomian trait assessment scores (=8.34, < 0.05) among the three groups. (3) Serum total thyroxine and serum free thyroxine levels in the pSS-DED+HT patients showed positive correlation ( < 0.05, < 0.05) with their BUT (=0.60, 0.60), Schirmer's test (=0.64, 0.66) and tear river height (=0.61, 0.62), independent of lid gland secretory capacity; no significant correlation was found between thyroid-stimulating hormone, anti-thyroglobulin antibody and lid gland secretory capacity. Thyroid hormone, anti-thyroglobulin antibody, and thyroid peroxidase antibody were not found to be significantly correlated with ocular surface status. (4) Compared with pSS-DED, the fiber density of the subbasal nerve plexus in pSS-DED+HT group decreased (=2.06, < 0.05), and the curvature score increased (=2.13, < 0.05).
CONCLUSION
The ocular surface condition of pSS-DED patients with HT is worse than that of pSS-DED and DED patients. The main manifestations are that tear secretion, tear film stability, secretory function of the meibomian glands, meibum trait and fiber density of the subbasal nerve plexus decrease while the curvature increases. The mechanism might be related to the decrease in thyroid hormone production.
Topics: Cross-Sectional Studies; Dry Eye Syndromes; Humans; Hypothyroidism; Sjogren's Syndrome; Thyroxine
PubMed: 35950396
DOI: 10.19723/j.issn.1671-167X.2022.04.020 -
BMC Endocrine Disorders May 2023Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress,...
BACKGROUND
Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress, and inflammation may play roles in thyroid hypofunction. Thus, the present article aimed to determine the relationship between major dietary patterns and oxidative stress and inflammation in primary hypothyroid patients and healthy people in Iranian adults.
METHODS
This matched case-control study was conducted on 200 participants (100 cases and 100 controls). The presence of primary hypothyroidism was determined by endocrinologists based on American Thyroid Association (ATA) criteria. Dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). The principal component analysis (PCA) method was used to derive major dietary patterns. Statistical analysis was performed using logistic regression analysis, and the findings were reported using odds ratios (ORs) with 95% CIs.
RESULTS
We identified 2 major dietary patterns (i.e., healthy and Western dietary patterns). After adjusting for confounding variables, participants in the highest tertile of the healthy eating pattern had lower odds of primary hypothyroidism. Also, there was a significant relationship between total antioxidant capacity (TAC) levels and thyroid hypofunction; however, no significant correlation was seen between the Western dietary pattern and malondialdehyde (MDA) and C-reactive protein (CRP) with hypothyroidism.
CONCLUSIONS
There were statistically direct associations between healthy dietary patterns (loaded with vegetables, nuts and seeds, fruits, dried fruits, olives, garlic, black pepper, starchy vegetables, low-fat dairy, and legumes) and increased TAC levels with a decreased risk of thyroid hypofunction. However, Western dietary patterns and MDA and CRP levels did not associate with an underactive thyroid.
Topics: Humans; Adult; Case-Control Studies; Iran; Oxidative Stress; Inflammation; Antioxidants; Hypothyroidism
PubMed: 37161471
DOI: 10.1186/s12902-023-01348-9 -
Endocrine Regulations Oct 2022Cardiovascular diseases (CVD) and thyroid dysfunction are two of the most prevailing disorders in the world that are closely interlinked. Actions of thyroid hormones are... (Review)
Review
Cardiovascular diseases (CVD) and thyroid dysfunction are two of the most prevailing disorders in the world that are closely interlinked. Actions of thyroid hormones are mediated via thyroid receptors present in the myocardium and the vascular tissue. Primary mechanism that links thyroid dysfunction with CVD is the modification of cardiovascular risk factors (dyslipidemia, blood pressure, coagulation parameters, etc.) resulting in endothelial and left ventricular systolic and diastolic dysfunction. Both overt and subclinical hyperthyroidism and hypothyroidism may cause adverse alterations in cardiac function. Hyperthyroidism gives rise to palpitation, atrial fibrillation, systolic hypertension, and heart failure, whereas hypothyroidism increases diastolic hypertension, pericardial effusion, and the risk of ischemic heart disease via altering lipid and coagulation parameters. Early recognition and treatment of thyroid dysfunction may prevent adverse cardiovascular events in patients with or without pre-existing CVD. Certain cardiac conditions and medications can cause alterations in thyroid function that may predispose an individual to higher morbidity and mortality. In certain situations, thyroid dysfunction treatment may have cardiovascular benefits. This study deals with the interplay between cardiovascular and thyroid dysfunctions associated with clinical implications and management strategies.
Topics: Humans; Hyperthyroidism; Hypothyroidism; Thyroid Diseases; Thyroid Hormones; Cardiovascular Diseases; Hypertension; Lipids
PubMed: 36270343
DOI: 10.2478/enr-2022-0033 -
The Journal of Clinical Endocrinology... Nov 2023Clinical guidelines have recommended a trial of liothyronine (LT3) with levothyroxine (LT4) in select patients with hypothyroidism. However, little is known about the...
CONTEXT
Clinical guidelines have recommended a trial of liothyronine (LT3) with levothyroxine (LT4) in select patients with hypothyroidism. However, little is known about the real-world use of LT3 and desiccated thyroid extract (DTE) and the characteristics of patients treated with LT3 and DTE.
OBJECTIVES
(1) Determine national trends of new LT4, LT3, and DTE prescriptions in the United States; (2) determine whether sociodemographic, healthcare access, and dietary factors are associated with different thyroid hormone (TH) therapies.
METHODS
Parallel cross-sectional studies were conducted using 2 datasets: (1) a national patient claims dataset (2010-2020) and (2) the National Health and Nutrition Examination Study (NHANES) dataset (1999-2016). Included participants had a diagnosis of primary or subclinical hypothyroidism. Study outcomes included the impact of demographics and healthcare access on differences in the proportion of TH therapies consisting of LT4, LT3, and DTE (patient claims) and differences in dietary behaviors between DTE-treated participants and LT4-treated matched controls (NHANES).
RESULTS
On an average annual basis, 47 711 adults received at least 1 new TH prescription, with 88.3% receiving LT4 monotherapy, 2.0% receiving LT3 therapy, and 9.4% receiving DTE therapy. The proportion receiving DTE therapy increased from 5.4% in 2010 to 10.2% in 2020. In the analysis between states, high primary care and endocrinology physician densities were associated with increased use of LT4 monotherapy (odds ratio 2.51, P < .001 and odds ratio 2.71, P < .001). DTE-treated NHANES participants (n = 73) consumed more dietary supplements compared to LT4-treated participants (n = 146) (4.7 vs 2.1, P < .001).
CONCLUSIONS
The proportion of new TH therapies containing DTE for hypothyroidism doubled since 2010 while LT3 therapies remained stable. DTE treatment was associated with decreased physician density and increased dietary supplement use.
Topics: Adult; Humans; Nutrition Surveys; Cross-Sectional Studies; Hypothyroidism; Thyroxine; Triiodothyronine; Thyroid Hormones; Demography
PubMed: 37327351
DOI: 10.1210/clinem/dgad331 -
Frontiers in Endocrinology 2024Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have...
BACKGROUND
Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis.
METHODS
We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity.
RESULTS
Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships.
CONCLUSION
This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.
Topics: Humans; Mendelian Randomization Analysis; Alopecia Areata; Hypothyroidism; Odds Ratio
PubMed: 38562416
DOI: 10.3389/fendo.2024.1356832 -
Acta Veterinaria Scandinavica May 2016Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated...
BACKGROUND
Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome.
RESULTS
The results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal-distal and middle-distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I-V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal-distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I-V latencies decreased to normal values after a given time of the treatment.
CONCLUSIONS
The results indicate a demyelinating and axonal pattern of polyneuropathy in dogs with suspected hypothyroidism. Most of the patients without vestibular signs showed neither peripheral nor central auditory pathway impairment, concurrent to the generalized neuropathy. The follow-up examination showed a very good clinical outcome and only partial improvement in electrophysiological assessment.
Topics: Animals; Dog Diseases; Dogs; Electrodiagnosis; Female; Hormone Replacement Therapy; Hypothyroidism; Male; Polyneuropathies; Retrospective Studies
PubMed: 27209097
DOI: 10.1186/s13028-016-0212-9 -
Thyroid : Official Journal of the... Nov 2010Thyrotropin (TSH) changes in extreme primary hypothyroidism include increased secretion, slowed degradation, and diminished or absent TSH circadian rhythms. Diminished...
BACKGROUND
Thyrotropin (TSH) changes in extreme primary hypothyroidism include increased secretion, slowed degradation, and diminished or absent TSH circadian rhythms. Diminished rhythms are also observed in central hypothyroid patients and have been speculated to be a cause of central hypothyroidism. We examined whether TSH secretion saturation, previously suggested in extreme primary hypothyroidism, might explain diminished circadian rhythms in both disorders.
METHODS
We augmented and extended the range of our published feedback control system model to reflect nonlinear changes in extreme primary hypothyroidism, including putative TSH secretion saturation, and quantified and validated it using multiple clinical datasets ranging from euthyroid to extreme hypothyroid (postthyroidectomy). We simulated central hypothyroidism by reducing overall TSH secretion and also simulated normal TSH secretion without circadian oscillation, maintaining plasma TSH at constant normal levels. We also utilized the validated model to explore thyroid hormone withdrawal protocols used to prepare remnant ablation in thyroid cancer patients postthyroidectomy.
RESULTS
Both central and extreme primary hypothyroidism simulations yielded low thyroid hormone levels and reduced circadian rhythms, with simulated daytime TSH levels low-to-normal for central hypothyroidism and increased in primary hypothyroidism. Simulated plasma TSH showed a rapid rise immediately following triiodothyronine (T(3)) withdrawal postthyroidectomy, compared with a slower rise after thyroxine withdrawal or postthyroidectomy without replacement.
CONCLUSIONS
Diminished circadian rhythms in central and extreme primary hypothyroidism can both be explained by pituitary TSH secretion reaching maximum capacity. In simulated remnant ablation protocols using the extended model, TSH shows a more rapid rise after T(3) withdrawal than after thyroxine withdrawal postthyroidectomy, supporting the use of replacement with T(3) prior to (131)I treatment.
Topics: Carcinoma; Circadian Rhythm; Computer Simulation; Feedback; Humans; Hypothyroidism; Iodine Radioisotopes; Models, Biological; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 21062194
DOI: 10.1089/thy.2009.0349