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[Ultrasensitive TSH screening for detection of thyroid gland dysfunctions in women of a medical ambulatory care patient group].

This aim of the study was to identify the prevalence of unsuspected thyroid dysfunction in a female population attending a medical primary care unit (case-finding study). A TSH assay of the third generation was used as a screening test. The overall prevalence of unsuspected thyroid dysfunction in 1061 female patients was 2.5% (0.5% overt hyperthyroidism, 0.3% overt hypothyroidism, 0.5% subclinical hyperthyroidism, and 1.2% subclinical hypothyroidism). The prevalence of thyroid disease is clearly age dependent with 4.3% over the age of 40 and 5.9% for 50-60 year-olds. The ratio for females below 40 and over 40 was 10.75 (Odds ratio, p < 0.0001). We conclude from our study and from the literature that TSH screening as a case-finding strategy is indicated, and also seems cost-effective, in women over 40 years of age.

Adolescent↗

[Postpartum thyroid gland dysfunction--a prospective study].

In a prospective study the postpartum thyroid function was investigated in 120 healthy women in the department of obstetrics and gynecology of the Medical School Hannover. A physical examination was performed in the first week after delivery and two to five and five to eleven months later. Additionally blood was drawn for the determination of thyroid hormones, thyroid autoantibodies and thyroid-stimulating hormone. In 10% of the patients pathological titers for thyroid microsomal autoantibodies and thyroglobulin autoantibodies were found, in 2.5% pathological concentrations of thyroid hormones. In none of these patients clinical symptoms of thyroid dysfunction could be found. After delivery a immunologically mediated thyroid disease should be considered in patients with clinical symptoms. Then the thyroid function needs to be investigated.

Adolescent↗

Exacerbation of thyroid autoimmunity by interferon alpha treatment in patients with chronic viral hepatitis: our studies and review of the literature.

In the present studies, the long term effects of IFN alpha on thyroid function and thyroid autoantibodies were evaluated in 42 patients with chronic viral hepatitis type C treated with IFN alpha for at least 4 months. Before IFN treatment, 41 patients tested were all euthyroid. Five (12%) out of 24 patients tested had positive tests for thyroid autoantibodies. MCHA/TPOAb was detected in all 5 and TGHA/TGAb in 3 out of these 5 patients. Six to 10 x 10(6) units (U) of recombinant or natural IFN alpha were given intramuscularly daily for the first 2 to 4 weeks, followed by 3 to 10 x 10(6) U thrice weekly for the subsequent 14 to 22 weeks. Thyroid dysfunction and/or rises in titers of thyroid autoantibodies were observed in 6 patients during IFN alpha treatment; clinically overt thyroid dysfunctions, destructive thyroiditis and thyrotoxicosis of unidentified etiology, developed in 2 patients 4 to 5 months after start of IFN treatment, subclinical hypothyroidism with a slight increase in serum TSH concentrations but no serum thyroid hormone alternations was observed in 2 patients, and increases in titers of thyroid autoantibodies without thyroid dysfunction were found in 2 patients. Thus, IFN alpha exacerbated thyroid autoimmunity exclusively in all patients with positive tests for thyroid autoantibodies prior to treatment, but did not induce thyroid autoimmunity in thyroid autoantibody-negative patients. These data suggest that the prolonged IFN alpha therapy can lead to exacerbation of thyroid autoimmunity in susceptible (thyroid autoantibody-positive) patients.

Adult↗

Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction.

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na(+)/Ca(2+) exchanger, beta-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca(2+) cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload.

Animals↗

[Laboratory diagnosis before onset and prediction of Graves' disease].

Graves' thyrotoxicosis frequently occurs after delivery through immune rebound mechanism. We tried to establish a systematic method of predicting postpartum onset of Graves' thyrotoxicosis. We followed pregnant women with anti-thyroid microsomal antibody (MCAb) from their early pregnancy to the postpartum period, and analyzed the relation between activities of thyroid stimulating antibodies (TSAb) in early pregnancy and the postpartum occurrence of Graves' disease. Among 71 subjects with positive MCAb, 7 showed positive TSAb in their early pregnancy without any thyroid dysfunction. All 7 developed thyroid dysfunction in postpartum period. Five of seven (70% of TSAb positive subjects) developed Graves' disease. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction due to postpartum autoimmune thyroiditis. Graves' thyrotoxicosis also occurs after an attack of allergic rhinitis. A patient who developed Graves' thyrotoxicosis after an attack of allergic rhinitis showed positive TSAb before the attack of allergic rhinitis. These findings suggest that high risk of Graves' thyrotoxicosis onset can be predicted by the detection of TSAb.

Female↗

Infertility and thyroid disorders.

PURPOSE OF REVIEW: This review highlights the 'gap' in knowledge regarding the contribution of thyroid dysfunction in reproduction. Thyroid dysfunction, which is quite prevalent in the population affects many organs including the male and female gonads, interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. RECENT FINDINGS: Although menstrual irregularities are common, ovulation and conception can still occur in hypothyroidism, where thyroxine treatment restores a normal menstrual pattern and reverses hormonal changes. Subclinical hypothyroidism may be associated with ovulatory dysfunction and adverse pregnancy outcome. Thyroid autoimmunity increases the miscarriage rate, and thyroxine treatment does not seem to protect. Menstrual disturbances, frequent in thyrotoxicosis are restored following treatment. In males, thyrotoxicosis has a significant but reversible effect on sperm motility. Although radioactive Iodine (I) in ablation doses may transiently affect the gonads, it does not decrease fertility or increase genetic malformation rate in the offspring. SUMMARY: Awareness of the thyroid status in the infertile couple is crucial, because of its significant, frequent and often reversible or preventable effect on infertility. Many aspects of the role of thyroid disorders however in infertility need further research.

Autoimmune Diseases↗

Prediction of post-partum Graves' thyrotoxicosis by measurement of thyroid stimulating antibody in early pregnancy.

OBJECTIVE: Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting post-partum onset of Graves' thyrotoxicosis. DESIGN: We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post-partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post-partum occurrence of Graves' disease. PATIENTS: Seventy-one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb-positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years. MEASUREMENTS: MCAb was measured with a commercially available agglutination kit. For 71 MCAb-positive subjects, TSH-binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation. RESULTS: Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post-partum period. Five of them (70% of TSAb-positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of post-partum autoimmune thyroiditis. CONCLUSION: The individuals at high risk of post-partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post-partum Graves' disease in the general population is estimated above 0.54%, that is, one in 200 post-partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.

Autoantibodies↗

Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians.

PURPOSE: To review information on the benefits of screening with a sensitive thyroid-stimulating hormone (TSH) test for thyroid dysfunction in asymptomatic patients seeking primary care for other reasons. This paper focuses on whether screening should be aimed at detection of subclinical thyroid dysfunction and whether persons with mildly abnormal TSH levels can benefit. DATA SOURCES: A MEDLINE search for studies of screening for thyroid dysfunction and of treatment for complications of subclinical thyroid dysfunction. STUDY SELECTION: Studies of screening with thyroid function tests in the general adult population or in patients seen in the general office setting were selected (n=33). All controlled studies of treatment in patients with subclinical hypothyroidism or subclinical hyperthyroidism were also included (n=23). DATA EXTRACTION: The prevalence of overt and subclinical thyroid dysfunction, the evidence for the efficacy of treatment, and the incidence of complications in defined age and sex groups were extracted from each study. DATA SYNTHESIS: Screening can detect symptomatic but unsuspected overt thyroid dysfunction. The yield is highest for women older than 50 years of age: In this group, 1 in 71 women screened could benefit from relief of symptoms. Evidence of the efficacy of treatment for subclinical thyroid dysfunction is inconclusive. CONCLUSIONS: Even though treatment for subclinical thyroid dysfunction is controversial, office-based screening to detect overt thyroid dysfunction may be indicated in women older than 50 years of age. Large randomized trials are needed to determine the likelihood that treatment will improve quality of life in otherwise healthy patients who have mildly elevated TSH levels.

Adult↗

[Dementia and disorders of the thyroid gland].

Cognitive deficits pretending dementia can be caused by thyroid dysfunction. The literature addressing pathophysiology and therapy of thyroid dysfunction is reviewed. A shorter duration and less severe course of thyroid dysfunction seem to indicate a better response to therapy. There are not studies on the latency between therapy and response. It is recommended to measure at least TSH in the differential diagnosis of dementive syndromes. Degenerative dementia can occur in coincidence with thyroid dysfunction. Therapy would improve at least symptoms caused by the thyroid dysfunction.

Dementia↗

Optic nerve dysfunction in thyroid eye disease: CT.

Optic nerve dysfunction in thyroid eye disease is thought to be due to compression of the optic nerve by enlarged extraocular muscles near the orbital apex. High-resolution computed tomography (CT) scans of 78 orbits of 31 patients with thyroid eye disease were reviewed. Axial scans alone were inadequate for demonstrating compression of the optic nerve. With a coronal reformatted scan from the axial scans, a muscular index was devised and measured to reflect extraocular muscle impingement on the optic nerve. Orbits with optic nerve dysfunction had significantly higher muscular indices than those without optic nerve dysfunction, supporting the hypothesis that optic nerve dysfunction is usually secondary to compression by enlarged extraocular muscles. Muscular indices of 67% or greater in patients with optic nerve dysfunction were diagnostic of compressive optic neuropathy, while muscular indices of less than 50% appeared to exclude optic nerve compression. A single case of optic nerve dysfunction without muscular compression is also discussed.

Exophthalmos↗

Thyroid function in Kuwaiti subjects with Down's syndrome.

OBJECTIVE: To investigate the thyroid function of individuals with Down's syndrome (DS). METHODS: Thyroid function and antithyroid antibodies were measured in 58 Kuwaitis with DS who resided at a residential facility or attended rehabilitation centers. RESULTS: Twenty-six subjects (45%) were euthyroid and 32 (55%) had thyroid dysfunction. One patient had previously been diagnosed with thyroid failure whereas the other 31 patients had newly discovered disease: 9 patients had primary hypothyroidism (T(4) 9.95 +/- 1.1 pmol/l and TSH 15.15 +/- 11.93 mU/l), 19 subclinical hypothyroidism (TSH 6.47 +/- 2.57 mU/l), 1 secondary hypothyroidism, 1 hyperthyroidism, and the remaining 1 subclinical hyperthyroidism. Antithyroid antibodies were found in 52% of the total subjects and in 59% of those with thyroid dysfunction. CONCLUSIONS: Thyroid dysfunction is common in Kuwaiti subjects with DS and is presumably the consequence of autoimmune thyroid disease. Periodic thyroid function testing is recommended in individuals with DS, which is best done through a national program.

Adolescent↗

Assessment of anxiety in subclinical thyroid disorders.

It is well known that manifest thyroid dysfunction causes mood disorders. In the literature there are few studies related with subclinical thyroid dysfunction and anxiety. We aimed to determine if there exists a relation between the anxiety and subclinical thyroid dysfunction. This study was carried out in the Meram Medical Faculty of Selçuk University, Department of Endocrinology and Metabolism. Eighty-five outpatients were enrolled into the study. In the presence of normal fT(3) and fT(4), patients were grouped as subclinical hyperthyroid with TSH lower than 0.1 mU/L (n = 24), subclinical hypothyroid with TSH higher than 4.5 mU/L (n = 32) and euthyroid subjects (n = 29). Beck's Anxiety Inventory (BAI) was administered to all patients. There was no any statistically significant difference between euthyroid and study groups in terms of age, gender, weight and height (p<0.05). One-way ANOVA showed that both of the subclinical hypothyroid and subclinical hyperthyroid groups had significantly higher anxiety scores than euthyroid group (F: 11.4, p<0.001). Manifest hypothyroidism and hyperthyroidism, as causes of mental and neurological dysfunction have been known for a long time, but the relation between subclinical thyroid dysfunction and anxiety is less well studied. We have found that subclinical thyroid dysfunction increases the anxiety of patients whether hyperthyroid or hypothyroid. Overlap of symptoms common to both thyroid dysfunction and anxiety is an important limitation in this study. Mood changes especially anxiety due to subclinical thyroid dysfunction may have an important impact on the patient's quality of life. Negative effect on quality of life may be an indication of treatment in these patients. It is the first study evaluating anxiety in subclinical hypothyroidism in the literature.

Adult↗

Screening for thyroid disease in children with IDDM.

The aim of this study was to evaluate the usefulness of screening for thyroid disease by performing thyroid function tests and measuring thyroid autoantibodies in 371 children and adolescents with insulin-dependent diabetes mellitus (IDDM). We analyzed clinical data and results of serum thyroxine, triiodothyronine uptake, thyroid-stimulating hormone, and antibodies to thyroid microsomal antigen and thyroglobulin. Goiter was noted in 20% of subjects. Thyroid-specific autoantibody was positive in 19% of subjects. Twenty-seven subjects (7%) had thyroid dysfunction. Autoantibody testing identified subjects with thyroid dysfunction with a sensitivity of 50%, a specificity of 84%, a degree of misclassification of 17%, a positive predictive value of 13%, and a negative predictive value of 97%. We recommend that all children and adolescents be screened shortly after diagnosis of IDDM by determination of thyroid-stimulating hormone (measured by high-sensitivity assay) to identify thyroid dysfunction and by testing for antibody to thyroid microsomal antigen to characterize both risk of future thyroid dysfunction and the need for future testing.

Adolescent↗

[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)].

The right number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made: 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticiably changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appearance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal wether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor.

Animals↗

[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)].

The hight number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made : 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticialy changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appareance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal whether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor.

Animals↗

Autoimmune hypothyroidism and hyperthyroidism in patients with Turner's syndrome.

A high prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS) but the extent of this association is controversial for the prevalence of thyroid autoantibody and the clinical impact of thyroid dysfunction. In this study we searched for thyroid disease and thyroid autoantibodies in patients with TS. Seventy-five unselected TS patients (age range 3-30 years) were studied. Sera were tested for thyroid hormones, thyrotropin (TSH), thyroglobulin (TG-ab) and thyroperoxidase (TPO-ab) antibodies. The TSH-receptor antibodies with thyroid-stimulating (TS-ab) or TSH-blocking activity (TSHB-ab) were measured in the IgG fraction using a bioassay. Ten out of 75 (13.3%) TS patients had AITD: eight had autoimmune thyroiditis (AT) (six with subclinical and two with overt hypothyroidism and one with euthyroidism) and one had Graves' disease. The prevalence of AITD increased significantly (p < 0.05) from the first (15%) to the third (30%) decade of life. The prevalence of TPO-ab and/or TG-ab (20%) was higher (p < 0.05) in TS than in age-matched female controls and increased from the first (15%) to the third (30%) decade of life. Clinical AITD was diagnosed in 46% of TS patients with TPO-ab and/or TG-ab. Thyroid-stimulating antibody was detected in the hyperthyroid patient, and TSHB-ab was found in one of eight patients with hypothyroid AT. It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.

Adolescent↗

Residual goitre in the postiodization phase: iodine status, thiocyanate exposure and autoimmunity.

OBJECTIVE: This study was done to assess goitre prevalence, thyroid functional status and cause of residual goitre among school children in the postsalt iodization phase in India. DESIGN: A cross-sectional study in which, 14762 school children in the age group of 6-18 years, from different States and Union territories of India, were evaluated for goitre prevalence, urinary iodine and thiocyanate excretion, functional status of the thyroid as well as serological and cytopathological markers for thyroid autoimmunity. MEASUREMENTS: Urinary iodine (wet ashing method), urinary thiocyanate (colourimetric method), serum thyroxine [in-house radioimmunoassay (RIA)], serum TSH (IRMA), antithyroid microsomal and antithyroglobulin antibodies (haemagglutination method) were estimated. Fine-needle aspiration cytology was performed in all goitrous subjects giving consent. RESULTS: The overall goitre prevalence was 23% (27.1% girls; 17.8% boys, P < 0.001). Subjects belonging to poor socio-economic strata had significantly higher goitre prevalence. Median urinary iodine excretion (UIE) in goitrous subjects (2-53 micromol/l) was significantly higher than in controls (2-24 micromol/l; P < 0.001). Levels of UIE observed among goitrous subjects showed no relationship with the presence or absence of thyroid dysfunction or with thyroid antibody status. High titres (> or = 1:1600) of TMA were present more often in goitrous subjects (6.08%) than nongoitrous controls (0.34%; P < 0.001) and in girls (7.3%) than boys (2.35%; P < 0.001). TMA positivity were significantly more among goitrous subjects with thyroid dysfunction than in euthyroid subjects. Significantly higher median urinary thiocyanate (USCN) excretion was observed in goitrous subjects (0.75 mg/dl) compared to controls (0.64 mg/dl; P < 0.001) and goitrous girls compared to goitrous boys. USCN excretion of goitrous subjects and controls showed no relationship with functional or thyroid antibody status in various groups. CONCLUSIONS: Persistent, albeit reduced prevalence of goitre, despite adequate iodine prophylaxis, suggests existence of additional factors in goitrogenesis in India. Thyroid autoimmunity can explain only a part of the goitre prevalence. The role of goitrogens in residual goitre prevalence is brought forth.

Adolescent↗

Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness.

On the basis of low specificity, poor positive predictive value, and cost, there is at present no basis for routine assessment of thyroid function in acutely hospitalized patients, unless clinical features suggest the possibility of thyroid dysfunction, or a patient's background increases the likelihood of thyroid dysfunction. When used in severely ill patients, estimates of both thyroxine (T4) and thyrotropin (TSH) show a high prevalence of abnormal results, but lack specificity and have poor positive predictive value for true thyroid disease. When thyroid function is tested in the critically ill, the positive predictive value for true thyroid disease of both free T4 and TSH measurements could be improved by using wider reference intervals than for unselected populations. The knowledge of nonspecific disease-related abnormalities of triiodothyronine, T4, and TSH is not currently likely to yield useful prognostic information or to alter management for individual patients. Thyroid testing should be readily available for any acutely ill patient with any clinical features that suggest thyroid dysfunction, and for groups at increased risk of thyroid dysfunction. An initial abnormal result for either TSH or free T4 estimate should be followed by combined analysis of free T4 and TSH with the best available methodology. Diagnosis of thyroid dysfunction should be based on the T4-TSH relation rather than either value alone. Persistence of an apparent diagnostic abnormality should be confirmed before therapy is commenced.

Humans↗