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PubMed1997

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

Adult↗
PubMed2001

Radiopeptide transmitted internal irradiation of non-iodophil thyroid cancer and conventionally untreatable medullary thyroid cancer using.

AIM: Differentiated thyroid carcinomas (DTC) and medullary thyroid carcinomas (MTC) overexpress somatostatin receptor subtypes (sstr). The aim of this pilot study was to evaluate the tumour response of thyroid carcinomas to targeted irradiation with the radiolabelled somatostatin analogue [90Y]-1,4,7,10-tetra-azacyclododecan-4,7,10-tricarboxy-methyl-1-yl-acetyl-D-Phe1-Tyr3-octreotide ([90Y]-DOTA-D-Phe1-Tyr3-octreotide, or 90Y-DOTATOC) which has a high affinity to subtype 2 and a low affinity to subtype 5. It shows no affinity to sstr1, sstr3 and sstr4. PATIENTS AND METHODS: Twenty patients (mean age 58 years; 50% female, 50% male) with thyroid cancer were included (medullary thyroid cancer (MTC), 12 patients; differentiated thyroid cancer (DTC), seven patients; papillar carcinoma (PC), four patients; follicular carcinoma (FC), three patients; anaplastic carcinoma (AC), one patient). All patients had been therapy resistant and had progressive disease before 90Y-DOTATOC therapy. The dose applied was between totals of 1700 MBq x m(-2) to 7400 MBq x m(-2) 90Y-DOTATOC, administered in one to four injections at intervals of 6 weeks. In the case of tumour progression under therapy, treatment was terminated. RESULTS: The overall antitumour effect (objective response and stable disease) was 35%; in MTC 42%, in DTC 29%, and in AC 0%. The objective overall response rate was 0%. A stable disease was achieved in 35% (7/20), and progressive disease was found in 65% (13/20). The median time to progression was 8 months, with a median follow-up of 15 months. The treatment was very well tolerated. There were no grade III/IV haematological or renal toxicities. CONCLUSION: Targeted radiotherapy using 90Y-DOTATOC is able to stop tumour progression in a small number of patients and therefore may be an alternative treatment option for resistant disease. More significant tumour responses in thyroid and medullary thyroid cancer may be obtained by using radiopeptides with pan-somatostatin characteristics.

Adult↗
PubMed2006

Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals.

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.

Female↗
PubMed2006

Hyalinizing trabecular adenoma of the thyroid revisited: a histologic and immunohistochemical study of thyroid lesions with prominent trabecular architecture and sclerosis.

BACKGROUND: Since its description, hyalinizing trabecular adenoma (HTA) of the thyroid has been a controversial entity. Some have considered it a unique entity, some have considered it a variant of papillary carcinoma (PC), and still others have considered it a nonspecific pattern that may be seen with a variety of thyroid lesions. Complicating the matter, studies demonstrating metastases have shown entities that do not appear to be HTAs as originally described, and molecular studies showing changes of PC have used methods that are not specific. This study reviews our experience with thyroid lesions that showed at least some histologic features of HTA and presents the immunohistochemical findings for these lesions using antibodies employed for the diagnosis of PC. DESIGN: Our files were reviewed for all thyroid resection reports describing lesions with hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis or diagnostic comment. All cases were reviewed and classified as either HTA or as different lesions based upon histologic features. Immunohistochemistry with antibodies to HBME1, CK19 and p63 was performed with all lesions and with a series of controls. RESULTS: Eighteen thyroid lesions with prominent sclerosis or hyalinization and trabecular architecture were identified. Only 4 of these were found to completely match the histologic and cytologic descriptions of HTA by HE review. The other cases showed histologic features more compatible with other diagnoses including cellular adenomatoid nodule (5), follicular adenoma (4), follicular variant of PC (FVPC) (3), and epithelial neoplasm with features of FVPC (2). All HTAs lacked immunoreactivity for HBME1, CK19 and p63. All cases deemed to be adenomatoid nodules, follicular adenomas and epithelial neoplasms showed no immunoreactivity for HBME1 and CK19 and, of these, only a single AN showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse immunoreactivity for HBME1 and CK19 and 1 reacted with antibodies to p63. Of control PCs and other thyroid lesions, reactivity for HBME1, CK19, and p63 was observed in 8/8, 7/7, and 7/8 and 3/27, 7/27, and 7/27 cases, respectively. CONCLUSIONS: A sclerotic or hyalinized stroma with a trabecular growth pattern may be seen in a number of different thyroid lesions and, when seen, is usually a focal feature of a lesion other than HTA. Immunohistochemistry may be of assistance as cases of FVPC with prominent hyalinization and trabeculation will show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions with hyalinization and trabeculation will not.

Adenoma↗
PubMed2006

Immunogenetic association and thyroid autoantibodies in juvenile autoimmune thyroiditis in North India.

OBJECTIVES: Autoimmune thyroid diseases (AITD) encompass a number of conditions that have in common cellular and humoral responses targeting the thyroid gland. Interactions between susceptibility genes and environmental triggers are thought to initiate an autoimmune response to thyroid antigens leading to disease manifestation. Commencement of the disease in childhood leads to the presumption that genetics may have an important role in the causation of the disease. DESIGN: The present study was aimed at evaluating the human leucocyte antigen (HLA) encoded susceptibility to develop juvenile autoimmune thyroiditis (JAT) in patients from North India. PATIENTS: We studied 48 consecutive patients of JAT along with 176 first-degree relatives for their thyroid function (FT4, TSH) and anti-thyroid peroxidase antibody status (AbTPO). MEASUREMENTS: HLA studies were carried out using serology for HLA-class I antigens and DNA analysis of HLA-class II alleles. The data were compared with a cohort of 308 ethnically matched healthy individuals. RESULTS: We observed overt hypothyroidism in 50% and AbTPO positivity in 70.8% of the index cases. Among the first-degree relatives, goitre was observed in 51.7%, thyroid dysfunction in 28.4% and AbTPO in 29.5% of individuals. Of the 37 relatives who underwent fine-needle aspiration cytology (FNAC), 60% had evidence of chronic lymphocytic thyroiditis (CLT). A strong positive association of HLA-DRB1*1404 was observed with the JAT (35.4%vs. 10.4%, chi2 = 19.8, Pc = 0.0001). We also observed a higher (72%, P = 0.03) paternal transmission of HLA-DRB1*1404 to affected offspring in comparison to unaffected offspring. HLA-DRB1*03 was also increased among JAT patients but did not reach statistical significance. CONCLUSION: These studies point towards an important role of immune modifying genes, such as HLA, in influencing susceptibility to juvenile-onset AITD.

Adolescent↗
PubMed1986

Age-related anti-thyroid antibodies and thyroid abnormalities in Turner syndrome.

One hundred pediatric patients with Turner syndrome were studied to determine the correlation between the presence of anti-thyroid antibodies with age and karyotype, and the value of anti-thyroid antibody titers as predictors of subsequent thyroid abnormalities. (54 patients = 45,X; 46 = other karyotypes.) The frequency of positive titers of anti-thyroid antibodies increased linearly with cumulative age. Anti-parietal cell and anti-adrenocortical cell antibodies were not increased in these patients (1.3 and 2.6% respectively). The ability to use positive anti-thyroid antibody titers to predict the development of thyroid abnormalities increased from age 10 years and became statistically significant at ages 13-17 years for the whole group as well as 45,X patients. None of the patients had clinical symptoms of thyroid dysfunction although 22% developed thyroid abnormalities, which included elevated TSH, low T4, and/or goiter.

Adolescent↗
PubMed1990

Characterization of a thyroid-specific enhancer located 5.5 kilobase pairs upstream of the human thyroid peroxidase gene.

A 6.3-kbp segment of DNA, upstream of the human thyroid peroxidase gene, and various deletions thereof were linked to a promoterless bacterial chloramphenicol acetyltransferase reporter gene. These constructs were analyzed by transfection and expression in rat FRTL-5 thyroid cells and in human hepatoma HepG2 cells to localize sequences that are important for thyroid cell-specific expression of the thyroid peroxidase gene. A thyroid-specific enhancer element, capable of activating enhancerless simian virus 40 promoter expression in FRTL-5 cells, was localized to a 230-bp region approximately 5.5 kbp upstream of the human thyroid peroxidase gene transcription start site. DNase I footprinting, using nuclear extracts prepared from FRTL-5 cells, revealed three regions within the 230-bp fragment; none of these regions were protected by nuclear extracts from HepG2 cells. Gel mobility shift assays, using double-stranded oligonucleotides corresponding to the three protected regions, further confirmed the existence of factors in FRTL-5 cells, but not HepG2 cells, able to specifically bind to the enhancer sequences. These results suggest the presence of three cis-acting DNA elements in the human thyroid peroxidase gene enhancer that interact with thyroid-specific trans-acting factors.

Animals↗
PubMed2005

Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation.

The BRAFT1799A mutation is the most common genetic alteration in papillary thyroid carcinomas (PTC). It is also found in a subset of papillary microcarcinomas, consistent with a role in tumor initiation. PTCs with BRAFT1799A are often invasive and present at a more advanced stage. BRAFT1799A is found with high prevalence in tall-cell variant PTCs and in poorly differentiated and undifferentiated carcinomas arising from PTCs. To explore the role of BRAFV600E in thyroid cancer pathogenesis, we targeted its expression to thyroid cells of transgenic FVB/N mice with a bovine thyroglobulin promoter. Two Tg-BRAFV600E lines (Tg-BRAF2 and Tg-BRAF3) were propagated for detailed analysis. Tg-BRAF2 and Tg-BRAF3 mice had increased thyroid-stimulating hormone levels (>7- and approximately 2-fold, respectively). This likely resulted from decreased expression of thyroid peroxidase, sodium iodine symporter, and thyroglobulin. All lines seemed to successfully compensate for thyroid dysfunction, as serum thyroxine/triiodothyronine and somatic growth were normal. Thyroid glands of transgenic mice were markedly enlarged by 5 weeks of age. In Tg-BRAF2 mice, PTCs were present at 12 and 22 weeks in 14 of 15 and 13 of 14 animals, respectively, with 83% exhibiting tall-cell features, 83% areas of invasion, and 48% foci of poorly differentiated carcinoma. Tg-BRAF3 mice also developed PTCs, albeit with lower prevalence (3 of 12 and 4 of 9 at 12 and 22 weeks, respectively). Tg-BRAF2 mice had a 30% decrease in survival at 5 months. In summary, thyroid-specific expression of BRAFV600E induces goiter and invasive PTC, which transitions to poorly differentiated carcinomas. This closely recapitulates the phenotype of BRAF-positive PTCs in humans and supports a key role for this oncogene in its pathogenesis.

Animals↗
PubMed2006

C8orf4/TC-1 (thyroid cancer-1) gene expression in thyroid cancer and goiter.

BACKGROUND: The expression of the thyroid cancer-1(TC-1) gene seems to be related with malignant transformation in the thyroid tissue. OBJECTIVE: We evaluated the potential use of TC-1 gene expression as a marker of malignancy in thyroid nodules. METHODS: A total of 92 frozen thyroid samples were studied, including 46 samples from thyroid nodules (19 papillary carcinomas, 1 follicular carcinoma, 24 adenomatous goiters, and 2 follicular adenomas) and 46 samples from normal surrounding thyroid tissue. Total RNA was extracted and TC-1 expression was assessed by semiquantitative Multiplex PCR. Results were verified using real-time RT-PCR in some of the samples. RESULTS: Overall mean TC-1 gene expression (normalized by the ABL gene) was 1.73 +/- 1.67 (0.33-9.33). There was a significant difference (p < 0.001) between TC-1 gene expression in benign thyroid lesions (1.07 +/- 0.10) and carcinomas (2.73 +/- 0.51). CONCLUSION: Our results suggest that TC-1 gene expression may be useful in the differential diagnosis of goiters and thyroid papillary carcinomas.

Adenoma↗
PubMed2005

Thyroid hemiagenesis is a rare variant of thyroid dysgenesis with a familial component but without Pax8 mutations in a cohort of 22 cases.

Thyroid hemiagenesis is a rare form of thyroid dysgenesis of which some familial cases have been reported, including one associated with a heterozygous mutation in the Pax8 gene. However, the physiopathology remains not well known. The objectives of this study were 1) to describe the clinical features, 2) to look for familial clustering, and 3) to search for Pax8 mutations in a relatively large cohort of affected patients. A family history of thyroid dysgenesis was found in nine patients (40%), whose affected relatives had ectopic thyroid (n = 4), athyreosis (n = 1), thyroid hemiagenesis (n = 2), or thyroglossal duct cysts (n = 2). Screening for Pax8 mutations identified abnormal migration profiles by SSCP analysis in 3 patients, but direct sequencing did not show coding region mutations in any of the 22 patients. In conclusion, this study provides the first evidence that thyroid hemiagenesis can occur as a familial disorder associated with any form of thyroid dysgenesis. This finding supports both a common underlying mechanism to the various abnormalities in thyroid development and a role for genetic factors; however, our results from Pax8 analysis suggest that this gene may not be a key factor.

Abnormalities, Multiple↗
PubMed1976

Effects of excess iodide and other anions on thyroid hormone secretion in normal or hypophysectomized rats treated with graded doses of thyroid hormone.

In order to obtain further information about the stimulatory action of excess iodide on thyroid hormone secretion in thyroxine (T4)-treated rats, experiments were performed in hypophysectomized rats, or rats treated with graded doses of T4 or triiodothyronine (T3).T3 as well as T4 played a permissive role in the production of the iodide effect in normal animals, but T3 was more effective than T4. Excess iodide stimulated thyroid hormone secretion in hypophysectomized animals, this finding being compatible with the hypothesis that, by inhibiting TSH secretion, T3 and T4 produced a condition in which excess iodide stimulated thyroid hormone secretion in intact rats. However, T4 played an additional role in thyroid hormone secretion by acting directly on the thyroid. In hypophysectomized animals, small doses of T4 stimulated thyroid hormone secretion, and this action was additive to that of excess iodide, whereas large doses of T4 were inhibitory and reduced the effectiveness of excess iodide. The stimulatory action on thyroid hormone secretion was specific for iodide and was not shared by other anions. The action of excess iodide was blocked by methimazole. We suggest that excess iodide stimulates thyroid hormone secretion by increasing intrathyroidal concentrations of cyclic AMP in the absence of TSH, and that this increase in cyclic AMP concentration is blocked by methimazole.

Animals↗
PubMed1992

Regulation of thyroid hormone synthesis in cultured ovine thyroid follicles.

Primary cultures of sheep thyroid follicles were used to study the regulatory control mechanisms of thyroid hormone production. When maintained under serum-free conditions in vitro these follicles exhibit hormone-dependent iodide transport, iodine organification, and physiological de novo thyroid hormone formation. In previous studies we have also shown that thyroid follicles condition their culture media with insulin-like growth factors (IGFs) and IGF-binding proteins which are of potential autocrine or paracrine significance in thyroid hormonogenesis. TSH (100 microU/ml) alone modestly stimulated iodine uptake and organification, which was further potentiated by pharmacological or physiological concentrations of insulin and by physiological concentrations of IGF-I or IGF-II. A combination of TSH and cortisol (10 nM) optimally stimulated iodine uptake and organification without additive or synergistic effects among combinations of cortisol with insulin or IGFs. Insulin, IGF-I, IGF-II, or cortisol alone were without effect on iodine uptake and organification. The effect of TSH was mimicked by forskolin or (Bu)2cAMP, and the synergistic effect of cortisol with TSH was duplicated in incubations of dexamethasone with TSH. In long term studies of the same experimental conditions, with 10(-6) M NaI added to the culture medium, an increase in radioimmunoassayable T4 and T3 in conditioned cell culture media and cell layer extracts was confirmed for all conditions, with the exception of physiological concentrations of insulin. IGF-I and IGF-II were equipotent in their stimulation of thyroid hormonogenesis in the presence of TSH. The effect of high concentrations of insulin may be explained by a combined action through insulin and type I IGF receptors. We have previously reported that the stimulation of iodine uptake and organification (de novo thyroid hormone formation here) by TSH and cortisol is inversely correlated with their inhibition of IGF-binding proteins released by the cells while IGF release is unchanged. Overall, these data suggest that the regulation of thyroid hormonogenesis involves the endocrine hormones TSH and cortisol, acting in synergy with locally produced IGFs.

Analysis of Variance↗
PubMed2003

Color Doppler ultrasonography: diagnosis of ectopic thyroid gland in patients with congenital hypothyroidism caused by thyroid dysgenesis.

The etiology of congenital hypothyroidism (CH) may play an important role in determining disease severity, outcome, and, therefore, its treatment schedule. Radionuclide imaging (RI) is currently the most precise diagnostic technique to establish the etiology of CH. Conventional ultrasound can identify an athyrotic condition at the normal neck position and has gained acceptance for the initial evaluation of CH; however, its ability in delineating ectopic thyroid is limited. We used color Doppler ultrasonography (CDU) to assess blood flow and morphology in the detection of ectopic thyroid in 11 CH patients disclosed by neonatal screening; thyroid glands were undetectable at the normal location by gray-scale ultrasonography (GSU). The patients studied consisted of two infants for initial investigation and nine children for reevaluating the cause of CH. All of the patients underwent GSU, CDU, RI, and magnetic resonance imaging (MRI) investigation. We set RI as the defining diagnostic test for detecting ectopic thyroid and compared the imaging of CDU with those of GSU and MRI. The results of RI showed 10 ectopic thyroids and one athyreosis. In the patients with ectopic thyroid, the sensitivity of CDU, GSU, and MRI for detecting ectopic thyroid was 90, 70, and 70%, respectively. We conclude that CDU is superior to GSU and MRI for detecting ectopic thyroid and that CDU may be adopted as the diagnostic tool for the initial investigation of suspected CH.

Adolescent↗
PubMed2004

Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer.

Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker. We measured circulating TSHR-mRNA by RT-PCR in 51 normal controls, 27 patients with benign thyroid disease, 67 patients with treated differentiated thyroid cancer (DTC), and eight patients with newly diagnosed DTC, preoperatively. Results were compared with thyroglobulin (Tg) mRNA and serum Tg levels. TSHR-mRNA signals were not detected in normal controls and in 24 of 27 (89%) patients with benign thyroid disease. All 19 patients with treated DTC with evidence of distant or local disease tested positive for TSHR-mRNA (sensitivity 100%). Among patients with no evidence of disease, TSHR-mRNA was detected in 1 in 48 (specificity 98%). Six of the eight newly diagnosed DTC patients tested preoperatively were positive for TSHR-mRNA. The concordance between TSHR-mRNA and Tg-mRNA and between TSHR-mRNA and serum Tg was 95%. Fourteen patients with DTC (21%) had Tg antibodies, three with local disease (all positive for TSHR-mRNA), and 11 with no evidence of disease (all negative for TSHR-mRNA). Our results indicate that TSHR-mRNA and/or Tg-mRNA in peripheral blood are both equally sensitive and specific markers for monitoring thyroid cancer patients. Their principal value resides in the Tg antibody-positive patients in whom a positive or a negative mRNA value might have indicated or obviated the need for a whole-body scan. Furthermore, the high specificity combined with their ability to predict thyroid cancer preoperatively suggests a potential role in detecting thyroid cancer in patients with thyroid nodules.

Adult↗
PubMed2004

Impact of ovarian hyperstimulation on thyroid function in women with and without thyroid autoimmunity.

Pregnancy is accompanied by changes in thyroid function, but limited data are available on these changes in the very first weeks of pregnancy. Yet, T(4) plays a major role in implantation and early fetal development. We sought to determine thyroid function during this period and during the first trimester, in pregnancies achieved by assisted reproductive technology. Furthermore, the thyroid hormone profile was compared between euthyroid women with (TAI+) and without (TAI-) thyroid autoimmunity. We prospectively analyzed data from 35 women who received ovarian hyperstimulation (OH) and presented clinical pregnancies. The mean age of the women was 32 +/- 5 yr. Thyroid function tests [serum TSH and free T(4) (FT(4))] and thyroid antibody status were determined before OH (baseline values) and every 20 d after ovulation induction during the first trimester of pregnancy. Serum TSH and FT(4) increased significantly at d 20, compared with baseline values (3.3 +/- 2.4 vs. 1.8 +/- 0.9 mU/liter; P < 0.0001 and 13.2 +/- 1.7 vs. 12.4 +/- 1.9 ng/liter; P = 0.005). During the first trimester of pregnancy, there was a significant change over time for TSH and FT(4) (P < 0.001 and P = 0.005, respectively). Nine women (27%) were TAI+. The TSH curve among these TAI+ women was significantly higher compared with TAI- women (P = 0.010). The opposite was observed for the FT(4) curve (P = 0.020). In conclusion, the present study showed a significant increase of serum TSH and FT(4) levels after OH in the very first period of pregnancy compared with pre-OH levels and a significant impact of TAI on the thyroid hormone profile during the first trimester. This provides evidence for an altered thyroid function in euthyroid TAI+ patients.

Adult↗
PubMed1985

The effect of carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes.

Thyroid autoantibody synthesis was investigated in cultures of lymphocytes isolated from several sources, including thyroid and lymph nodes from patients with hyperthyroid Graves' disease treated preoperatively with carbimazole or propranolol. The ability of thyroid lymphocytes to secrete immunoglobulins, including thyroid microsomal or thyroglobulin autoantibodies, was markedly reduced in lymphocyte suspensions obtained from patients treated with carbimazole compared with suspensions from patients treated with propranolol. This effect (which was greater in individuals treated with carbimazole for longer periods) was attributable to a significant reduction in the number of viable lymphocytes present after the 14-day culture interval. In contrast, the type of preoperative therapy had little effect on cultures of lymphocytes obtained from lymph nodes draining the thyroid. Although it is not yet clear whether carbimazole exerts its effects in vivo by direct immunosuppression or indirectly by altering the thyroid microenvironment, our observations indicate that the fall in serum levels of thyroid autoantibodies that occurs during carbimazole therapy is related to an effect of the drug on lymphocytes within the thyroid.

Antibody Formation↗
PubMed1990

Characterization, by molecular cloning, of smaller forms of thyroid peroxidase messenger ribonucleic acid in human thyroid cells as alternatively spliced transcripts.

The mRNA for human thyroid peroxidase (hTPO) is 3.1 kilobases (kb) in size, coding for a protein of 933 amino acids. However, there is controversy as to whether other hTPO mRNA transcripts exist in thyroid cells. There is one report of the existence of 2.1- and 1.7-kb transcripts (hTPO mRNA species I and II), representing up to half of the hTPO mRNA in TSH-stimulated human thyroid cells. On the other hand, numerous other studies have only observed 3.1-kb hTPO mRNA transcripts. The nature of these putative 2.1- and 1.7-kb mRNA transcripts, if present, is unknown. We now report the isolation and characterization of two smaller hTPO cDNA species, designated hTPO cDNA I and II. cDNA I and II are 1753 and 1044 basepairs (bp) in size, with open reading frames of only 225 and 174 amino acids, respectively. Comparison of the nucleotide sequences of cDNA I and II with available hTPO genomic sequence reveals that cDNA I consists of exons 1-6 (654 bp) and the 5'-end of intron 6 (1099 bp); cDNA II contains exons 1-5 (486 bp) and an unidentified DNA tract of 558 bp further down-stream, presumably an intron. Confirmation that cDNA I and II correspond to mRNA transcripts I and II, respectively, was provided by Northern blot analysis with DNA probes specific for cDNA I and II. hTPO mRNA transcripts I and II are present in TSH-stimulated and TSH-deprived human thyroid cells in culture as well as in intact thyroid tissue. In summary, the present data 1) demonstrate directly that hTPO mRNA transcripts I and II exist in human thyroid cells, 2) explain the discrepant data in the literature regarding their existence, 3) elucidate their molecular structure, 4) indicate that they are generated by alternative splicing, and 5) demonstrate that hTPO mRNA I and II exist in the thyroid gland in vivo as well as in thyroid cells in culture.

Base Sequence↗
PubMed1991

Erythrocyte carbonic anhydrase-I concentrations in patients with Graves' disease and subacute thyroiditis reflect integrated thyroid hormone levels over the previous few months.

We have recently reported that in patients with hyperthyroidism, red blood cell (RBC) zinc (Zn), most of which is present as the metal of carbonic anhydrase-I isozyme (CAI), reflects a patient's integrated thyroid hormone level over the previous few months. In the present report the RBC CAI concentration was measured by RIA in 26 healthy controls, 25 patients with hyperthyroid Graves' disease, 5 patients with primary hypothyroidism, and 10 subjects with subacute thyroiditis with elevated thyroid hormone levels. The mean (+/- SD) RBC CAI concentration in euthyroid controls was 380 +/- 70 nmol/g hemoglobin (Hb), and the normal range defined as the mean +/- 2 SD, was 240-520 nmol/g Hb. The mean RBC CAI in Graves' disease was decreased (180 +/- 53 nmol/g Hb), and 22 patients (88%) had subnormal values. The mean RBC CAI concentrations in hypothyroidism and subacute thyroiditis were not different from the control values. After treatment with antithyroid drugs, both mean the plasma T4 and T3 levels in 11 Graves' patients became normal within 4 weeks, but the normalization of RBC CAI lagged behind by about 2 months. Furthermore, the highest correlation was observed between the RBC CAI and plasma T4 and T3 levels measured 8 weeks earlier. During prednisolone therapy the RBC CAI in patients with subacute thyroiditis remained at a normal level. These results suggest that 1) not only RBC Zn but also the RBC CAI concentration in patients with Graves' disease reflect the patient's mean thyroid hormone level over the preceding several months; and 2) in patients with subacute thyroiditis, elevation of plasma thyroid hormone concentrations is transient and causes little change in the RBC CAI concentration.

Adolescent↗