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PubMed1991

Relationships between serum thyroid stimulating hormone levels and development of thyroid tumors in rats treated with N-bis-(2-hydroxypropyl)nitrosamine.

Relationships between serum thyroid stimulating hormone (TSH) levels, carcinogen dose and development of thyroid tumors were studied in Wistar rats of both sexes treated with N-bis-(2-hydroxypropyl)nitrosamine (DHPN). DHPN (210 mg/100 g body wt) was injected i.p. weekly. Wistar rats were used, divided into five groups of males (M1-M5) and five groups of females (F1-F5). M1 and F1 received one injection of DHPN, M2 and F2 two injections of DHPN, M3 and F3 three injections of DHPN, M4 and F4 four injections, and M5 and F5 as control rats received saline vehicle. The resultant incidences of total thyroid tumors were 4% in group M1, 24% in M2, 80% in M3, 76% in M4, 0% in F1, 4% in F2, 20% in F3, 17% in F4 and 0% in M5 and F5. Thus dose dependence for DHPN carcinogenesis was found in both sexes for up to at least three injections of DHPN and in all cases males proved more susceptible than females. Similar results were gained for carcinomas treated separately. A sex difference in DHPN induction of thyroid tumor was thus shown for Wistar rats opposite to that reported to exist in humans. However, no clear relationship between dose of DHPN or incidence of thyroid tumors and serum TSH concentration was evident at the end of the experiment (week 30).

Adenoma↗
PubMed2003

Cloning of a partial cDNA for Japanese quail thyroid-stimulating hormone and effects of methimazole on the thyroid and reproductive axes.

The purposes of this study were to develop a probe for the detection of thyroid-stimulating hormone (TSH) beta subunit mRNA, to validate the usefulness of that probe in measuring TSH, and to use it to investigate the effects of thyroid suppression on TSH and the reproductive axis in Japanese quail. The objectives of experiment 1 were to isolate and characterize a partial cDNA for quail TSH and validate a riboprobe transcribed from this cDNA. This riboprobe was then used to assess changes in TSHbeta mRNA levels in Japanese quail. We isolated a cDNA of 168 bp with 94% identity to the corresponding sequence in chicken TSHbeta. The transcribed riboprobe was shown to be pituitary gland specific, and differences in TSHbeta mRNA levels were detectable with 2.5 microg of total RNA in Northern blot analysis. In experiment 2, our objective was to determine if thyroid inhibition would result in a detectable change in TSHbeta mRNA and alterations in the pituitary luteinizing hormone (LH) or indices of gonadal function. We used adult, reproductively active, male Japanese quail on a long-day photoperiod. Treatment with a goitrogen, methimazole (MMI), increased (P < 0.05) thyroid gland and liver weights and decreased (P < 0.05) serum thyroxine (T4) concentrations compared to control birds. We detected increased TSHbeta mRNA in the pituitaries of MMI-treated birds compared to controls. There was no effect of MMI treatment on the reproductive variables measured, including LHbeta mRNA levels, serum androgen and estradiol concentrations, gonad weight, or cloacal gland area. Therefore, it appears that thyroid axis inhibition and the consequent increase in TSHbeta mRNA did not have direct effects on reproductive axis function in male Japanese quail.

Amino Acid Sequence↗
PubMed2001

Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases.

BACKGROUND: Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil cytoplasmic antibodies (ANCA) antigens. The objective of the present study was to investigate the presence of cross-reactivity to MPO of TMA. METHODS: We studied sera from 51 patients with autoimmune thyroid diseases, all of them TMA-positive. The presence of ANCA was investigated by indirect immunofluorescence and by capture enzyme-linked immunosorbent assay. RESULTS: ANCA were positive in 3.9% of the TMA-positive sera and none of them reacted with MPO. In contrast, the ANCA-positive sera revealed antielastase activity. None of the ANCA-positive cases presented clinical signs of vasculitis. However, these 2 patients had been on prolonged treatment with propylthiouracil. CONCLUSIONS: We conclude that there is no cross-reactivity to MPO of TMA in patients with autoimmune thyroid diseases, possibly because of difference in the spatial configuration of the immunodominant region. The presence of ANCA in patients with autoimmune thyroid diseases without evidence of vasculitis might result from propyIthiouracil-induced polyclonal activation.

Adult↗
PubMed1982

Radiation and risk for thyroid cancer: atypical findings of a community thyroid recall program.

Screening of 553 persons for thyroid disease by scan and physical exam was performed. Group I (245) had documented irradiation, with most (85%) receiving 300 R for lymphoid hyperplasia. Group II (308) had only a history of prior irradiation. Abnormal glands were found in 17 of 245 (7%) of Group I with 7 of 245 (3%) having nodular disease. No cancers were found in six of eight (75%) persons with nodular disease having surgery. Abnormal glands were found in 45/308 (14.6%) of Group II with 16/308 (5.2%) having nodular disease. Twelve of 16 (75%) with nodular disease from Group II had surgery and three thyroid cancers were found; in addition, one person from this group had a history of prior surgery for thyroid cancer. The incidence of thyroid cancer in Group I was 0%, Group II was 1.3%, and the combined incidence was 0.7%. The relatively low incidence of thyroid cancer observed is attributed to the relatively late average age at time of irradiation; 22 years for Group 1, 13 years for Group II.

Acne Vulgaris↗
PubMed1987

Improved prediction of thyroid lobar mass from parameters obtained by routine thyroid scintigraphy.

Estimation of thyroid mass both from parameters derived from thyroid scintigraphy and clinical palpation for purposes of therapeutic dosimetry has not been tested for accuracy. To more precisely determine thyroid mass 90 thyroid lobes from 45 autopsies without history of thyroid disease were studied. Specimens were dissected free of nonthyroidal tissue and assessed for volume, maximum depth (D), width (W), length (L) and mass (M). Using a linear regression model and applying known lobar depth, the most accurate formula to predict true lobar mass (in grams) was 4.9D + 0.07L2W-2.3 (in cms). Length and width would be obtainable in vivo from routine scintigraphic measurements (in cm) and depth would be most accurately determined by ultrasound. For most clinical circumstances where lobar depth is unknown we found the best formula for mass (g) to be 0.1L2W (in cm).

Humans↗
PubMed2000

Assessing the effects of thyroid suppression on benign solitary thyroid nodules. A model for using quantitative research synthesis.

Systematic review of the available information with a modified, largely quantitative method of research synthesis disclosed that an initial trial of thyroid hormone suppression therapy leads to clinically significant (> or = 50%) reduction of nodule size or arrest of nodule growth in a subset of patients with benign solitary thyroid nodules. In fact, in addition to objective improvements due to decreasing nodule size, L-T4 suppression therapy may benefit patients by reducing perinodular thyroid volume. Consequently, both pressure symptoms and cosmetic complaints may improve (9, 68). Additional studies for the assessment of the risks versus benefits of supraphysiologic doses of L-T4, the optimal level of thyroid suppression and the dose needed to achieve this magnitude of reduction, the optimal length of the initial trial, and the conditions for the continuation of L-T4 thyroid suppression therapy, as well as the identification of markers for patients most likely to respond to this therapy, are warranted. Finally, quantitative assessment of available evidence as described here may be applicable to the review of other controversial issues as well.

Adult↗
PubMed2003

Thyroid abscess due to Acinetobacter calcoaceticus: case report and review of the causes of and current management strategies for thyroid abscesses.

Thyroid abscess was a common condition in the era before antibiotics. In the current medical environment, however, it is a clinical entity that is seldom encountered. We report the case of a unique cause of thyroid abscess, the environmental Gram-negative bacterium Acinetobacter calcoaceticus. Review of the published causes of thyroid abscess since 1980 demonstrated that although Gram-positive bacteria (Staphylococcus and Streptococcus species) remain the most common causes, there has been a marked decrease in the number of cases caused by mycobacteria, Salmonella species, and anaerobes when compared with the early part of the 20th century. Patients infected with the human immunodeficiency virus, however, still develop mycobacterial and fungal thyroid infections with some regularity. Reported modes of management of thyroid abscess vary, but drainage remains an integral component of therapy for resolution of the infection.

AIDS-Related Opportunistic Infections↗
PubMed1990

Anti-thyroglobulin autoantibodies in sera from patients with chronic thyroiditis and from healthy subjects: differences in cross-reactivity with thyroid peroxidase.

A significant portion (about 12.7%) of healthy subjects was found to contain anti-thyroglobulin (anti-Tg) antibodies in their sera. We compared the binding activities of these antibodies and of anti-Tg autoantibodies from sera of patients with chronic thyroiditis with human thyroid peroxidase (TPO). The results obtained by ELISA indicated that out of 10 healthy subjects with anti-Tg antibodies, only four had anti-Tg antibodies capable of binding to TPO, whereas anti-Tg autoantibodies from almost all patients with chronic thyroiditis possessed high binding activities to TPO. By use of the immunoprecipitation method, it was also shown that although all anti-Tg autoantibodies from patients precipitated TPO, a majority of anti-Tg antibodies from healthy subjects could not precipitate TPO. Such findings cannot be ascribed to the differences in levels of anti-Tg autoantibodies and anti-TPO autoantibodies in sera and the differences in avidities of anti-Tg antibodies in sera between healthy subjects and patients with chronic thyroiditis. Thus, it can be concluded that anti-Tg antibodies from healthy subjects differ from those of patients with chronic thyroiditis with respect to TPO binding, probably due to difference in fine specificities of these anti-Tg antibodies.

Adolescent↗
PubMed1983

Natural history of thyroid function in diabetics with impaired thyroid reserve: a four year controlled study.

An attempt was made to compare the natural history of thyroid function in 80 diabetics having raised serum TSH concentrations (median 8.9 mU/l, range 5.8-46.3 mU/l) but serum T4 concentrations within the normal range (Group 1), and in 59 diabetics having normal serum TSH (median 1.9 mU/l, range 0.8-4.7 mU/l) and T4 concentrations (Group 2). Thyroid microsomal antibodies were present initially in 65% of patients in Group 1 and 15% of patients in Group 2. By 1981, 59 patients (74%) in Group 1 and 47 patients (80%) in Group 2 had been followed for a mean +/- SD duration of 4.2 +/- 1.8 and 4.2 +/- 1.5 years, respectively. Hypothyroidism developed in 9 patients in Group 1, but none from Group 2. Of patients in Group 1, hypothyroidism developed at a rate of 5% per annum in those with thyroid microsomal antibodies, but only 1% per annum in those without antibodies. Therefore, the risk of development of hypothyroidism is greatest in diabetics having both elevated serum TSH concentrations and thyroid microsomal antibodies and such patients should have regular review of thyroid function. Either risk factor alone appears to be a poor predictor of development of hypothyroidism.

Antibodies↗
PubMed2005

The significance of thyroid blood flow at the inferior thyroid artery as a predictor for early Graves' disease relapse.

OBJECTIVE: We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse. MEASUREMENT: Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated. PATIENTS: ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17). RESULTS: In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF). CONCLUSION: ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.

Adolescent↗
PubMed2005

Thyroid cancer review 2: management of differentiated thyroid cancers.

This is the second review article on thyroid cancer dealing with the common differentiated types that comprise 90% of thyroid cancers. Despite clinical management guidelines offered by a number of organisations including the British Association of Otolaryngologists and Head and Neck Surgeon, The British Thyroid Association, The American Association Of Endocrinologists, The American Thyroid Association and the National Cancer Centre Network, debate regarding the management of differentiated thyroid cancer continues. This is because of the absence of good quality research evidence as a consequence of the natural history of this disease.

Carcinoma, Papillary↗
PubMed2004

Gastric emptying function changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy.

BACKGROUND: Hypothyroidism is commonly thought to cause decreased gastric emptying but is mostly associated with autoimmune disease. In the present study the gastric emptying function of thyroid cancer patients with severe hypothyroidism of short duration was evaluated with a radionuclide solid meal gastric emptying study. METHODS: Twenty-two patients who had undergone surgical operation and (131)I ablation for thyroid cancer participated in solid meal gastric emptying studies before the withdrawal of thyroxine and then again 4 weeks after the withdrawal of thyroxine. Eleven patients had an additional gastric emptying study at 6 weeks after withdrawal of thyroxine. Gastric emptying curves and emptying parameters were calculated. Student's paired t-test was used for statistical analysis of data for all cases between the baseline and at 4 weeks after withdrawal. An additional repeated measure anova with multiple comparisons was performed on data between baseline, 4 weeks and 6 weeks after withdrawal for the other 11 patients. All P values presented are two-tailed and the significance level is 0.05. RESULTS: Hypothyroidism status was confirmed by the marked change of the serum thyroxine and thyroid-stimulating hormone 4 weeks and 6 weeks after withdrawal of the thyroxine replacement (P < 0.001). The gastric half-emptying time and emptying rate changed significantly after short-term severe thyroid hormone deficiency (P < 0.005). However, the length of the lag phase did not have a statistically significant change at 4 weeks or 6 weeks after withdrawal of the thyroxin replacement (P = 0.219 and 0.142). CONCLUSIONS: Hypothyroidism following the withdrawal of the thyroxine replacement in thyroid cancer patients preparing for (131)I cancer work-up can significantly prolong gastric half-emptying time and emptying rate.

Acute Disease↗
PubMedDate not supplied

Using recombinant human thyroid-stimulating hormone for the diagnosis of recurrent thyroid cancer.

BACKGROUND: Recombinant human thyroid-stimulating hormone (rhTSH) has been suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer, instead of the current practice of thyroid hormone (THT) withdrawal. METHODS: An evidenced-based literature review was used as the basis for a cost-utility, decision-analytic model. Outcome measures were safety, efficacy (diagnostic performance and quality of life) and cost effectiveness of rhTSH. RESULTS: The literature search identified six comparative studies of rhTSH versus THT withdrawal. The most common adverse events associated with the use of rhTSH were headache (3.5-11.1%) and nausea (7.7-17%). When used as a diagnostic agent, the unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively. Thus the use of rhTSH instead of THT withdrawal would result in a reduction in diagnostic accuracy, with 11% of patients' disease status being misclassified. Use of rhTSH resulted in a higher quality of life in the period prior to diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic performance, patient compliance to follow-up and modified quality of life were modelled over a 5 year time-frame, the incremental cost per QALY of rhTSH relative to THT withdrawal was $51 344.42. CONCLUSIONS: The use of rhTSH as a diagnostic agent appears to be safe but less diagnostically accurate and less cost-effective (on whole of healthcare cost basis) when used in the follow-up of patients with thyroid cancer who have had a previous negative radioiodine scan after thyroid hormone withdrawal.

Decision Support Techniques↗
PubMed2006

Thyroid cancer review 3: management of medullary and undifferentiated thyroid cancer.

This is the last of the three review articles dealing with thyroid cancer. Over 90% of thyroid cancer is of the differentiated type associated with a very good 10-year disease-free survival rate. In contrast, the rare forms of thyroid cancer which comprise medullary thyroid cancer arising from parafollicluar C cells, Hurthle cell carcinoma, anaplastic carcinoma, thyroid lymphoma and squamous cell carcinoma are typically associated with a poorer survival rate. Management is based upon small retrospective cohort studies.

Carcinoma↗
PubMed1969

Thyroid-stimulating hormone and prostaglandin E1 stimulation of cyclic 3',5'-adenosine monophosphate in thyroid slices.

Thyroid-stimulating hormone increased the cyclic 3',5'-adenosine monophosphate concentration in dog thyroid slices during a 1-minute incubation period and produced a maximum effect soon thereafter. The elevation persisted for at least 30 minutes. The concentrations of the cyclic 3',5'-adenosine monophosphate increased as the TSH concentration was increased from 0.125 to 50 milliunits per milliliter. Prostaglandin E(1), which increases glucose oxidation in dog thyroid slices, also increased the concentration of cyclic 3',5'-adenosine monophosphate. Although sodium fluoride stimulates thyroid adenyl cyclase, it did not increase concentration of cyclic 3',5'-adenosine monophosphate. Carbamylcholine and menadiol sodium diphosphate augment glucose oxidation in dog thyroid slices but do not change concentrations of cyclic 3',5'-adenosine monophosphate.

Adenine Nucleotides↗
PubMed2005

Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter.

The prohormone convertases (PCs) PC1 and PC2 are involved in the tissue-specific endoproteolytic processing of neuropeptide precursors within the secretory pathway. We previously showed that changes in thyroid status altered pituitary PC2 mRNA and that this regulation was due to triiodothyronine-dependent interaction of the thyroid hormone receptor (TR) with negative thyroid hormone response elements (nTREs) contained in a large proximal region of the human PC2 promoter. In the current study, we examined the in vivo regulation of brain PC2 mRNA by thyroid status and found that 6-n-propyl-2-thiouracil-induced hypothyroidism stimulated, whereas thyroxine-induced hyperthyroidism suppressed, PC2 mRNA levels in the rat hypothalamus and cerebral cortex. To address the mechanism of T3 regulation of the PC2 gene, we used human PC2 (hPC2) promoter constructs transiently transfected into GH3 cells and found that triiodothyronine negatively and 9-cis-retinoic acid positively regulated hPC2 promoter activity. EMSAs, using purified TRalpha1 and retinoid X receptor-beta (RXRbeta) proteins demonstrated that TRalpha bound the distal putative nTRE-containing oligonucleotide in the PC2 promoter, and RXR bound to both nTRE-containing oligonucleotides. EMSAs with oligonucleotides containing deletion mutations of the nTREs demonstrated that the binding to TR and RXR separately is reduced, but specific binding to TR and RXR together persists even with deletion of each putative nTRE. We conclude that there are two novel TRE-like sequences in the hPC2 promoter and that these regions act in concert in a unique manner to facilitate the effects of thyroid hormone and 9-cis-retinoic acid on PC2.

Alitretinoin↗
PubMedDate not supplied

[Comparison of administration of rhTSH with withdrawal of thyroid hormone. Follow-up of patients with differentiated thyroid carcinoma].

UNLABELLED: Recombinant human thyrotropin (rhTSH) has been introduced recently in follow up of differentiated thyroid cancer (DTC) patients, as an alternative of thyroid hormone withdrawal. The aim of this retrospective study is to compare recombinant human thyrotropin versus endogenous stimulation. MATERIAL AND METHODS: Thirty-three patients with DTC with previous thyroidectomy and thyroid ablation were selected. All patients underwent whole-body radioiodine scanning and third day serum thyroglobulin (TG) measurement by two techniques, the first one after conventional thyroid hormone withdrawal (TSHe, TGe), and the second one after rhTSH stimulation (TSHr, TGr). Measurement of TG was performed on the third day due to the infrastructure. We only included patients with stable disease, without therapeutic interventions between two consecutive controls in an interval inferior to one year. Two qualitative categories were defined for TG (positive TG > 2 ng/ml or negative TG<2 ng/ml) and whole-body radioiodine scan (positive or negative). RESULTS: TSHe: 62.9 +/- 55.48; TSHr: 113.16 +/- 50.6; (p: ns); TGe: 62.5 +/- 115.7; TGr: 54.6 +/- 111.1; (p: 0.044). Quantitative data analysis showed significant differences between two techniques. Qualitative data analysis showed no significant differences in clinical setting based in TG and radioiodine scan. CONCLUSIONS: Administration of rhTSH produces a significantly higher increase of TSH than thyroid hormone withdrawal and lower increase in TG levels. There were no significant differences in the stage of disease (TG and whole-body radioiodine scan).

Adenocarcinoma, Follicular↗
PubMed1987

Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase.

The thyroid microsomal antigen (MSA) in autoimmune thyroid disease is a protein of approximately 107 kD. We screened a human thyroid cDNA library constructed in the expression vector lambda gt11 with anti-107-kD monoclonal antibodies. Of five clones obtained, the recombinant beta-galactosidase fusion protein from one clone (PM-5) was confirmed to react with the monoclonal antiserum. The complementary DNA (cDNA) insert from PM-5 (0.8 kb) was used as a probe on Northern blot analysis to estimate the size of the mRNA coding for the MSA. The 2.9-kb messenger RNA (mRNA) species observed was the same size as that coding for human thyroid peroxidase (TPO). The probe did not bind to human liver mRNA, indicating the thyroid-specific nature of the PM-5-related mRNA. The nucleotide sequence of PM-5 (842 bp) was determined and consisted of a single open reading frame. Comparison of the nucleotide sequence of PM-5 with that presently available for pig TPO indicates 84% homology. In conclusion, a cDNA clone representing part of the microsomal antigen has been isolated. Sequence homology with porcine TPO, as well as identity in the size of the mRNA species for both the microsomal antigen and TPO, indicate that the microsomal antigen is, at least in part, TPO.

Amino Acid Sequence↗