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PubMed1999

[Simultaneous operations in patients with thyroid diseases].

Twenty-four cases of simultaneous surgical treatment for coexisting diseases of the thyroid gland and other organs are discussed. Such operations were mainly performed for associated nodular goiter (including thyroid cancer) and benign or malignant tumours of other localisations. As a rule surgical interventions were planned beforehand. Only in 2 cases there were urgent operations for coexisting diffuse toxic goiter and complicated ulcer disease. In 4 cases thyroid resection and laparoscopic cholecystectomy were made simultaneously. Immediate and long-term outcomes were good. The indications and conditions of performing the operations are discussed.

Adult↗
PubMed2000

Subclinical thyroid disease after radiation therapy detected by radionuclide scanning.

PURPOSE: The actuarial risk for developing benign or malignant thyroid disease following radiation therapy (RT) is controversial, but may be as high as 50% at 20 years. An effective screening modality should be specific but not overly sensitive, a limitation of ultrasound. We questioned whether Technetium-99 m pertechnetate ((99m)Tc TcO(4)(-)) scanning could detect clinically significant disease in ostensibly disease-free cancer survivors. METHODS AND MATERIALS: Eligibility criteria included an interval of at least 5 years after RT to the cervical region, a thyroid gland that was normal to palpation, euthyroid status determined by clinical examination, free T4 and TSH. The 34 patients scanned included 16 children (<18 years old) and 18 adults at the time of RT, 16 females and 18 males. The mean age at RT was 20 years (range, 2.1-50.3 years), and the mean age at (99m)Tc TcO(4)-scanning was 33 years (range, 13.6-58 years), providing a mean interval of 13 years (range, 5.3-26.6 years). The mean RT dose to the thyroid was 36.4 Gy (range, 19.5-52.5). Thyroid scanning was performed with a 5 mCi dose of (99m)Tc TcO(4)(-) obtaining flow, immediate and delayed static, and pinhole collimator images. RESULTS: Seven patients (21.6%) had abnormal scans, and the percentage was higher among children (25%) and females (25%) compared to adults (16.7%) and males (16.7%), respectively. Two of 34 patients (5.9%) were discovered to have a thyroid cancer; histopathologies were papillary and follicular carcinoma. CONCLUSION: In this population of clinically normal cancer survivors who had been irradiated to the cervical region, subclinical thyroid disease, of potential clinical significance, was detected by (99m)Tc TcO(4)(-) in about 20%. Children may be more commonly affected. Although the cost effectiveness of screening will require a larger sample number, we propose a surveillance schema for this patient population.

Adolescent↗
PubMed1993

Deregulated production of interleukin-4 (IL4) in autoimmune thyroid disease assayed with a new radioimmunoassay.

A sensitive, reproducible and specific radioimmunoassay for human interleukin-4 (IL4) has been developed. Using 125I-labeled IL4 and polyclonal rabbit antisera raised against recombinant human IL4, a competitive inhibition assay was developed which could detect 5 pg/ml of human IL4. Other interleukins, growth factors, hormones, peptides and lectins did not affect the assay. IL4 was measured in supernatants of culture media of stimulated human peripheral blood mononuclear cells (PBMC). Kinetics of IL4 production in PHA-stimulated PBMC from seven normal subjects revealed that the peak levels of IL4 were seen at 24 h and then declined. Peak IL4 levels in PHA stimulation of PBMC from untreated patients with autoimmune thyroid diseases (Graves' disease and chronic thyroiditis) were significantly higher than normal controls. However, after treatment, IL4 production decreased to normal. The present study demonstrates the usefulness of quantitating human IL4 produced by PBMC and that there exists a deregulated production of IL4 in autoimmune thyroid diseases.

Antibody Specificity↗
PubMed1993

Deregulated production of interleukin-8 (IL-8) in autoimmune thyroid disease studied by newly developed IL-8 radioimmunoassay.

We have developed a sensitive, reproducible and specific radioimmunoassay for human interleukin-8 (IL-8). Using 125I-labelled IL-8 and polyclonal rabbit antisera raised against recombinant human IL-8, a competitive inhibition assay was developed which could detect 5 pg/ml of human IL-8. Other interleukins, growth factors, hormones, peptides and lectins did not affect the assay. IL-8 measured in supernatants of culture media of stimulated human peripheral blood mononuclear cells (PBMC). Kinetics of IL-8 production in SAC-stimulated PBMC from seven normal subjects revealed that the production of IL-8 was detectable within 12 h and reached a plateau at 24 h. IL-8 levels in SAC-stimulation of PBMC from untreated patients with autoimmune thyroid diseases (Graves' disease and chronic thyroiditis) were significantly higher than in normal controls. However, after treatment, IL-8 production decreased to normal. The present study demonstrates the usefulness of quantitating human IL-8 produced by PBMC and the presence of a deregulated production of IL-8 in autoimmune thyroid diseases.

Antibody Specificity↗
PubMed2000

Thyroid disease.

In summary, disease of the thyroid gland is common. Anaesthetists will be required to manage patients with hypothyroidism and hyperthyroidism and those requiring thyroidectomy. Since anaesthesia for thyroidectomy provides many challenges of airway management, the anaesthetist should pay particular attention to preoperative assessment of the airway and should be able to deal with acute airway complications in the perioperative phase.

Anesthesia↗
PubMed1977

[Therapy of thyroid diseases].

A survey is given on the therapy of hyperthyroidism, hypothyroidism and the bland struma including the thyrogenic crises. Indications and contraindications of the therapeutic measures available are described. During the therapy of hyperthyroidism the suppression test for the control of the course is recommended. Furthermore it is shown that the thyroxine is more favourable for the long-term treatment than triiodine thyronine or the combination preparations offered at present. But the rules described for the treatment of diseases of the thyroid gland must always be adapted to the individual case.

Female↗
PubMed1986

Cutaneous signs of thyroid disease.

Hyperactivity of the sympathetic nervous system produces many of the skin changes of hyperthyroidism, while the hypometabolic state and the accumulation of mucopolysaccharides in the dermis are responsible for hypothyroid cutaneous manifestations. Acropachy, atopic eczema, localized myxedema and nail changes are associated with thyrotoxicosis. Vitiligo may be seen in all three thyroid diseases of autoimmune origin. Hyperpigmentation, pruritus and urticaria are associated with hyperthyroidism.

Dermatitis, Atopic↗
PubMed2005

Putative association between anti-Borrelia IgG and autoimmune thyroid disease?

An association between borreliosis and autoimmune thyroid disease (AITD) has previously been discussed. We undertook the present analyses to explore associations between anti-Borrelia immunoglobulin G (IgG) and AITD using data from the population-based Study of Health in Pomerania (SHIP), which was conducted in a region with endemic Borreliosis. Data of 4,256 persons were available for the present analyses. IgG antibodies to Borrelia were determined by enzyme-linked immunosorbent assay (ELISA). AITD was defined as the combined presence of a hypoechogenic thyroid pattern in thyroid ultrasound and positive anti-thyroperoxidase levels. An association between anti-Borrelia IgG and AITD was neither present in bivariate nor in multivariate statistical analyses. This result was not affected by using different definitions of the exposure and the end points. There is no association between the exposure to Borrelia as defined by anti-Borrelia IgG and the risk of AITD. It seems unlikely that Borrelia species represent a relevant causal factor for AITD.

Adult↗
PubMed1995

[Molecular endocrinology of thyroid diseases].

Over the last decade it has become possible to investigate the molecular basis of functional and neoplastic thyroid diseases, leading to the elucidation of various genetic defects at the level of the pituitary, thyroid and target organs. Mutations in either the pituitary-specific transcription factor Pit-1 or its target gene, TSH beta, lead to rare forms of hereditary congenital hypothyroidism. However, somatic mutations in thyroid epithelial cells causing an increase in hormone production and/or cellular proliferation are much more frequent. Nearly 50% of all toxic adenomas were shown to harbour activating mutations in either the TSH-receptor or certain G-proteins. In contrast, follicular and papillary thyroid malignancies are associated with mutations in the ras and ret genes respectively. Intriguingly, different mutations and rearrangements in the ret gene were shown to cause medullary thyroid cancer and MEN2 as well as to be specifically associated with papillary thyroid cancer. In contrast, mutations in thyroid-specific genes, such as thyroid peroxidase and thyroglobulin, causing congenital hypothyroidism are extremely rare. Besides the molecular abnormalities at the pituitary and thyroidal level leading to altered hormone secretion, genetic defects impairing thyroid hormone action at the target level also occur. Specifically, mutations in one of the thyroid hormone receptor genes (the proto-oncogene c-erbA beta) were shown to cause the autosomal dominant syndrome of resistance to thyroid hormone. The quest for a better understanding of the molecular defects in the pituitary-thyroid axis has led to the cloning of some of the key proteins, which can now be used for diagnostic purposes in vivo and in vitro. The use of recombinant thyroid peroxidase and TSH-receptor proteins has made possible the development of more sensitive and specific in vitro assays for autoantibodies. In addition, recombinant TSH was recently shown to be effective in stimulating radioiodine uptake in patients with residual differentiated thyroid cancer who remained on suppressive thyroid hormone therapy. Recombinant human TSH may therefore become a convenient diagnostic tool in the follow-up of patients with thyroid cancer by allowing for thyroglobulin measurements and radioiodine scanning without the need for the patient to become hypothyroid.

DNA-Binding Proteins↗
PubMed2002

Apoptosis: life through planned cellular death regulating mechanisms, control systems, and relations with thyroid diseases.

Apoptosis is an active biologic process that represents a form of programmed cellular suicide, activated either by genetic factors or by cellular lesions caused by various extracellular traumatic agents. The alterations of its functional mechanisms control cellular homeostasis are involved in the genesis of many illnesses. There are different control systems that can both stimulate and inhibit apoptosis, such as the p53 and Bcl-2 proteins. Different injuries may cause a rapid increase in the levels of p53 and the activation of the complex mechanism which leads either to damage repair or cellular apoptosis. The concept of tumor growth as a dynamic balance between cellular development and death is well applicable to differentiated thyroid carcinomas, which are generally not highly invasive and present excellent prognosis. On the contrary, in aggressive anaplastic thyroid carcinoma there is an increase in p53, whereas in normal thyroid cells there is a high expression of Bcl-2, so as to interfere with apoptosis when physiologic hormone levels are normal. However, only some of the biomolecular mechanisms behind the genesis of thyroid tumors have been explained, and the role of apoptosis in thyroid diseases has not been well defined. This review provides information about relationship between apoptosis and thyroid diseases.

Apoptosis↗
PubMed1996

TSH-receptor expression and human thyroid disease: relation to clinical, endocrine, and molecular thyroid parameters.

Thyrotropin receptor (TSH-R) gene expression can be positively or negatively regulated by TSH and stimulating TSH-R antibodies (TSAbs) in immortalized thyroid cell lines such as rat FRTL-5 cells. However, regulation is less clear in other mammalian cells including cultures of human thyroid cells. Additionally, it has been suggested, based on FRTL-5 cell data, that TSH-R gene negative regulation by TSH or TSAbs might be lost in Graves' disease. The present study evaluated TSH-R gene transcript levels in thyroids from patients with Graves' disease to correlate in vivo data with in vitro observations or hypotheses. TSH-R mRNA levels were characterized in a total of 66 human thyroid glands with particular concern to levels in Graves' patients. Results were related to clinical parameters, transcript levels of thyroglobulin (TG), and thyroid peroxidase (TPO), as well as transcript levels of thyroid transcription factor 1 (TTF-1) which regulates the expression of all three genes and paired box-gene 8 (Pax-8) which regulates TG and TPO gene expression. Northern blot analyses showed that TSH-R expression was significantly increased, 2.2-fold, in Graves' thyroids (p = 0.0098, n = 35) by comparison to normals (n = 6). TSH-R mRNA levels were decreased to 30% and 7% of normal levels in Hashimoto's thyroids (p = 0.0281, n = 5) and anaplastic carcinomas (p = 0.0033, n = 6), respectively. No significant changes were seen in endemic goiters (n = 8) and in thyroid autonomy (n = 6). TSH-R RNA levels were higher, 3.6-fold, in thyroids of a subgroup of Graves' patients that had not been pretreated with iodide before surgery (n = 10) by comparison to thyroids from those that had been treated before surgery, 1.7-fold (n = 25). TSH-R antibodies exhibited a nonsignificant tendency toward a negative correlation. All other clinical or endocrine parameters showed no clear relation to TSH-R mRNA levels. Pax-8 and TTF-1 transcripts were detectable in normal thyroids; however, Pax-8 expression was increased in Graves' thyroids (3.8-fold), whereas TTF-1 expression was only minimally changed in all thyroids investigated. Changes of the two did not correlate. Pax-8 expression correlated with TG and TPO expression (in all cases, p = 0.0001); TTF-1, despite its minimal change, still correlated with TG (p = 0.0471) but not with TPO expression (p = 0.0984). TTF-1, again despite its minimal changes, correlated positively with TSH-R gene expression (p = 0.0251); however, surprisingly, Pax-8, which does not regulate TSH-R gene expression, correlated even better with TSH-R transcript levels (p = 0.0001). We conclude that augmentation of TSH-R expression levels, and thus potential ligand binding sites, may indicate an important regulatory principle in the pathogenesis of autoimmune hyperthyroidism in vivo: the responsiveness of the TSH-R to TSH and TSAb induced negative regulation is lost. This increase of TSH-R expression levels is not due to an ongoing transcriptional activation of the TTF-1 gene. Pax-8, though positively correlated with TSH-R RNA levels, cannot be the factor either, because Pax-8 does not upregulate TSH-R expression. This predicts that other factors involved in TSH-R induced negative regulation are abnormal and must be searched for and evaluated.

Adolescent↗
PubMed2006

Does frozen section alter surgical management of multinodular thyroid disease?

BACKGROUND: Frozen section (FS) evaluation during thyroid surgery is often used to guide intraoperative management. We sought to determine the utility of FS in patients undergoing thyroidectomy for multinodular thyroid disease. METHODS: From May 1994 through November 2004, 236 patients with multinodular goiter underwent thyroidectomy at our institution. Patient data were retrospectively analyzed to see if a frozen section was performed during the procedure and whether it changed the patient's outcome. RESULTS: Of the 236 patients, 135 (57%) had intra-operative FS. There were no differences between patients who had FS analysis and those who did not with regard to age, gender, and the incidence of malignancy. Of the patients who had FS, 4/135 (3%) were subsequently diagnosed with thyroid cancer on permanent histology. Three of these FS were misread as benign. Therefore, the sensitivity of FS for the diagnosis of thyroid cancer was only 25%. Importantly, in none of the 135 patients did FS alter the intraoperative management. CONCLUSION: While FS was commonly used in patients undergoing thyroidectomy at our institution, in no patient over the last decade did FS correctly alter the intraoperative management. Given the time required to perform FS and the cost associated with it, we believe that routine FS should not be performed in these patients.

Adult↗