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PubMed2006

The adaptation of TSH secretion to autonomy in non-toxic goiter may be based-on active regulation of set-point and sensitivity of central TSH-receptors, perhaps by the microRNA (MIR) gene.

The hypothalamic-pituitary-thyroid (HPT) feedback system is one of the most complex regulatory systems and it has intrigued researchers for more than 50 years. One of the unsolved problems of this regulation in humans is the hypothalamic and pituitary adaption to autonomous function of the thyroid gland in non-toxic goiter (NTG). A new hypothesis, that TSH secretion is actively regulated in NTG in response to changes in thyroid autonomy in order to keep the patient euthyroid, was discussed in the present study on basis of previous experimental data in NTG patients with different degree of autonomous function. The patients were submaximally suppressed for one month with a fixed daily dose of T3. Group data suggested an inverse correlation between TSH suppression and suppression of thyroid function. Group data also suggested that TSH suppression was significantly correlated to basal TSH. This means that a NTG patient with a low normal TSH in blood before suppression (basal TSH) and a high degree of autonomous function may exhibit a relatively high TSH suppression. This ensures a minimal stimulation of the thyroid gland thereby protecting the gland from developing hyperthyroidism. A patient with a high normal TSH in blood before suppression (basal TSH) and a low degree of autonomous function, may exhibit a relatively low TSH suppression, indicating a high stimulation of the thyroid gland thereby protecting the patient from developing hypothyroidism. It is hypothesized that this adaption of TSH secretion to autonomy in NTG patients may be based on active regulation of both the set- point of the central TSH-receptors and the sensitivity of these receptors as well. Such an active regulation of the HPT axis may be controlled by one of the newly found post-transcriptional genes called MIR (microRNA).

Adaptation, Physiological↗
PubMed2002

Intraoperative neuromonitoring of surgery for benign goiter.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy is one of the most serious complications in thyroid surgery. No prospective studies are available that evaluate if the additional use of intraoperative neuromonitoring reduces the rate of RLN palsy. METHODS: Between January 1 and December 31, 1998, surgery for histologically benign goiter with intraoperative identification with and without additional intraoperative RLN neuromonitoring was performed on 4,382 patients in 45 hospitals. Data were collected prospectively by questionnaire. RESULTS: The rate of transient and permanent RLN palsy based on nerves at risk were 1.4% and 0.4% with intraoperative neuromonitoring. These rates were significantly lower (P <0.05) compared with intraoperative visual RLN identification without intraoperative neuromonitoring which resulted in rates of 2.1% and 0.8%, respectively. A multivariate logistic regression analysis confirmed that the use of intraoperative neuromonitoring decreases the rate of postoperative transient (P <0.008) and permanent (P <0.004) RLN palsies as an independent factor by 0.58 and 0.30, respectively. CONCLUSIONS: Intraoperative neuromonitoring of the RLN in thyroid surgery is recommended because of significantly lower rates of transient and permanent RLN palsy rates in comparison with conventional RLN identification.

Female↗
PubMed2006

[Hemithyroidectomy in a unilateral goiter: a valid therapeutic option. Review of the contralateral hemithyroid ten years after treatment].

INTRODUCTION: Nodular goiter (NG) is frequent among the general population and is considered a diffuse disease. Although NGs are rarely unilateral, they pose a dilemma in terms of the extent of the thyroidectomy. The aim of the present study was to evaluate the remaining thyroid in patients with NG compared with those with follicular adenoma who underwent hemithyroidectomy. PATIENTS AND METHODS: Patients who underwent surgery for unilateral NG with over 10 years of postoperative follow-up and normal findings on ultrasonography of the contralateral thyroid lobe were selected to form the study group (SG). Patients with follicular adenoma (with normal contralateral ultrasonography) who underwent hemithyroidectomy during the same period were selected to form the control group (CG). The selected patients underwent clinical, laboratory and ultrasound examinations. Both groups were compared statistically. No significant differences were found in age, gender, anesthetic risk, side, postoperative complications, length of hospital stay, or postoperative outcome. RESULTS: Less than 10% of the patients reported symptoms, and all symptoms were of little significance. Ultrasonographic nodules were found in the remaining thyroid lobe in 70% of patients in the SG and in 60% of those in the CG, with no statistically significant differences. The mean size of the largest nodule was 13.58 +/- 8.01 in the SG and 9.15 +/- 5.93 in the GC (p = 0.048). No differences were found in the anterior-posterior, transverse or longitudinal diameters of the remaining lobe. None of the patients underwent reintervention for nodular disease. CONCLUSIONS: After hemithyroidectomy, both groups of patients developed nodules in the remaining thyroid lobe, with no statistically significant differences. Hemithyroidectomy due to unilateral NG involves less risk to the patient and therefore we consider it to be a valid option. Long-term ultrasonographic follow-up seems advisable.

Adult↗
PubMed2006

[Development and outcomes of the surgical management of multinodular goiter].

OBJECTIVES: The aims of this study were to: 1. Define our criteria and the results obtained in the surgical management of multinodular goiter (MNG); 2. Compare the results of partial thyroidectomies with those of total thyroidectomies; 3. Determine the incidence of "hidden" carcinomas diagnosed as MNG; 4. Define the most suitable treatment of MNG. MATERIAL AND METHODS: We performed a retrospective study (1999-2005) of 190 patients with MNG. Clinical characteristics, the diagnostic procedures used, surgical indications, the strategy employed, and biopsy results were analyzed. Overall morbidity and mortality were evaluated and statistical comparison of the morbidity-mortality rate between partial and total thyroidectomies was performed. RESULTS: Depending on the patients, diagnostic procedures consisted of ultrasonography, gammagraphy, computed tomography, and fine-needle aspiration (FNA). Surgical indication was established by compressive syndrome, endothoracic prolongation, rapid growth, suspected malignancy, nodular hyperthyroidism, the endocrinologist's criteria, and the patient's wishes. The surgical strategy showed a change in favor of radical surgery. The most common histologic diagnosis was nodular hyperplasia, but 16 carcinomas were "hidden" under a diagnosis of MNG (8.5%). There was no mortality. Morbidity, however, did exist, with the poorest results, showing statistically significant differences, occurring in total thyroidectomies. CONCLUSIONS: 1. Ultrasonography and FNA were routinely used for diagnosis. Surgical treatment tended to be radical. We believe that identification of recurrences and parathyroid disease is mandatory; 2. Morbidity was greater with total thyroidectomy; 3. Of patients who underwent surgery for MNG, 8.5% had a hidden thyroid carcinoma; 4. With certain limitations, total thyroidectomy is the most suitable therapy.

Adult↗
PubMed2004

[Hypoparathyroidism and hypocalcemia following thyroid surgery of multinodular goiter. Multivariant study of the risk factors].

BACKGROUND AND OBJECTIVE: The hypoparathyroidism is one of the most important complications in the patients submitted to thyroid surgery. The aim is to analyze across a multivariate statistical analysis the risks factors for the development of transient and permanent hypoparathyroidism following the multinodular goiter (MG) surgery. PATIENTS AND METHOD: Between 1970 and 1999, 672 thyroidectomies by MG were reviewed. It was considered transient hypoparathyroidism when the calcemia was minor of 7.5 mg/dl or when being minors of 8.5 mg/dl the patient was presenting symptomatology for the hipocalcemia. The hypoparathyroidsm was considered permanent when the calcemia was minor of 8.5 mg/dl to the year of the surgery. RESULTS: The hypoparathyroidism appeared in 75 patients (11.2%), 20 with symptomatology (3%), persisting like permanent 6 cases (0.9%). The risk factors for the development of this were the hyperthyroidism (p = 0.0370), and the surgical technique (p < 0.00001) (unilateral versus bilateral surgery), persisting in the multivariate analysis both variables. With respect to the permanent hypoparathyroidism, the risk factor was the toxic MG (p = 0.0109), persisting as independent risk factor in the multivariate analysis (RR = 2.3). CONCLUSIONS: The principal risk factor of permanent hypoparathyroidism in the MG surgery is the presence of hyperthyroidism.

Adolescent↗
PubMed2000

Multinodular goiter: the surgical procedure of choice.

Surgical management of multinodular goiter (MNG) poses an ongoing dilemma between radical resection with its associated complications and partial resection, which carries the risk of recurrence and increased morbidity and difficulty for rethyroidectomy. This study was designed to evaluate the recurrence rate and need for reoperation in a carefully selected population of MNG patients, after nontotal thyroidectomy. The study addressed a highly selected population of patients who were treated and thoroughly evaluated at one surgical department for several years. We analyzed the recurrence rate of MNG in 124 patients. The follow-up duration extended from 6 to 516 months (mean 93 months). The general recurrence rate for all nontotal bilateral thyroidectomies was 21% (21/100 patients), increasing from 13.4% to 60% according to the extent of resection. The average time for recurrence was 105 months (8.75 years). Among the patients with recurrent MNG, only 4 (4% of the patients with nontotal bilateral thyroidectomy) required secondary surgical interventions with no resultant morbidity. In our series of very highly selected patients, the recurrence rate for nontotal thyroidectomy was high (21%); however, the need for secondary surgical intervention was low (4%). Thus nontotal thyroidectomy for MNG is legitimate. However, we suggest that the surgical procedure of choice be tailored according to the severity of the disease and the patient's general condition.

Adult↗
PubMed1994

[Surgery in goiter with a primary mediastinal manifestation].

Eight patients with mediastinal masses and occupational syndrome were presented. Seven were diagnosed prior to surgery, allowing the staff to plan the procedure. The cervical route is advisable. It provides the best exposure that provides the safest surgery, but the incision must often be enlarged for the patient's safety. Results of surgery are excellent, with immediate relief of compressive symptoms. Postoperative infection of the wound is a possible complication. Results of medium- and long-term follow-up lead us to advise concomitant medical treatment along with surgery, given the risk of recurring goiter.

Adult↗
PubMed2000

[Sarcoidosis and goiter. A case report in an adolescent].

UNLABELLED: Sarcoidosis is a systemic granulomatous disease of uncertain etiology which can affect different organs in the body. In this study, we report a case with both lung and thyroid involvement. CASE REPORT: A 12-year-old girl with goiter was referred for dyspnea. Lung CT scan showed diffuse interstitial disease. The diagnosis of sarcoidosis was made following a histological study of lung specimens obtained via video-assisted thoracoscopy. CONCLUSION: Lung biopsy is important in establishing the diagnosis of interstitial lung disease. In this study, the various forms of granulomatous lesions in the thyroid gland and in the lung have been described. However, it should be emphasized that the association of thyroid gland disorder and lung involvement in cases of sarcoidosis is a rare occurrence in children and adolescents. The necessity of establishing a certain diagnosis justifies the use of these invasive procedures.

Biopsy↗
PubMed1989

Relationship between T4, T3 and T4/T3 ratio in thyroid tissue, thyroid and peripheral veins in patients with nontoxic nodular goiter.

The relationship between T4, T3 and T4/T3 ratio in thyroid nodules/paranodular tissues, thyroid and peripheral veins has been investigated in 26 patients with nontoxic nodular goiters; eleven of them were treated with l-thyroxine 150 micrograms daily. A significant correlation between iodothyronine concentrations and T4/T3 [corrected] ratio in paranodular thyroid tissues and thyroid effluents was found in both groups of patients. By contrast, the correlation between these parameters in the nodule and thyroid veins was poor, which implies that the thyroid hormone pattern in the thyroid veins on the side of nodular lesion is predominantly controlled by the release of the hormones from paranodular healthy tissue. A close dependence of the serum T4/T3 ratio on the values of iodothyronines and their ratio in thyroid tissues and thyroid veins was observed in nontreated, but not in treated patients. Conversely, in the latter group, the thyroidal T4/T3 ratio in paranodular tissue, but not in the nodule, was found to be dependent on the serum T4/T3 ratio, suggesting that paranodular thyroid tissue more readily responds to 1-thyroxine-inhibited TSH secretion. The results demonstrate that 1. the serum thyroid hormone pattern under physiological conditions is dependent on the intrathyroidal T4/T3 ratio, and 2. minor alterations in the serum thyroid hormones may secondarily change the thyroidal T4/T3 ratio, presumably by their effect on TSH secretion.

Goiter, Nodular↗
PubMed1996

Role of basic fibroblast growth factor in the pathogenesis of nodular goiter.

Thyroid epithelial cells are known to produce several growth factors and cytokines which influence thyroid cell growth and function in an autocrine and/or paracrine manner. It is already known that insulin-like growth factor I (IGF I) is overexpressed in toxic adenomas whereas epidermal growth factor (EGF) is found predominantly in thyroid neoplasia. We now investigated the expression of bFGF by immunohistochemistry in thyroid tissue of patients with toxic adenoma (n = 27), cold nodules (n = 27) and for comparison in Graves' disease (n = 5). In addition bcl-2-oncoprotein expression in these tissues were also detected by immunohistochemistry. Most of bFGF immunostaining was found in the connective tissue of all thyroid tissues with a predominance in adenomas and in Graves' diseases. The collagen surrounding the thyroid follicles close to their basal membrane were homogeneously and intensively stained. All the cytoplasm of fibroblast in the connective tissue were strongly positive. Within the cytoplasm of only 2-10% thyroid epithelial cells bFGF immunostaining was found without any difference between toxic adenomas or cold nodules. In the tissue of patients with Graves' disease, less than 2% of thyrocytes were stained. All thyroid epithelial cell showed clearly an immunostaining for bcl-2-oncoprotein in nodular goiter as well as Graves' disease.

Adenoma↗
PubMed1996

Constitutively activating TSH receptor mutations as the cause of toxic thyroid adenoma, multinodular toxic goiter and autosomal dominant non autoimmune hyperthyroidism.

cAMP stimulates both the growth and differentiated thyroid function of the thyroid gland. In toxic nodules the clinical observation of hyperthyroidism together with TSH independent growth of the hot nodule suggests a chronic activation of the cAMP cascade. Somatic mutations in a gene of the cAMP regulatory cascade leading to constitutive activation of this cascade in toxic nodules were first detected in the G protein Gs alpha. Thereafter constitutively activating TSH receptor mutations were identified in 20-80% of toxic thyroid nodules and in 3 of 6 toxic multinodular goiters. Constitutively activating TSH receptor germline mutations are expected to lead to toxic hyperplasia. Sequencing of the TSH receptor gene in families with hereditary non autoimmune hyperthyroidism led to the identification of constitutively activating TSH receptor mutations in 7 families. Moreover, sporadic TSH receptor germline mutations have been identified in 3 children with severe congenital nonautoimmune hyperthyroidism. Therefore, in cases of clustering of non autoimmune hyperthyroidism in families and in cases of sporadic congenital hyperthyroidism with thyroid hyperplasia and no evidence for an autoimmune etiology a search for TSH receptor gene mutations is necessary to appropriately direct the therapy of these patients.

Adenoma↗
PubMed1998

Cost analysis of surgical procedures for toxic nodular goiter.

Effective by January 1, 1993, the Federal Care Rate Regulation (Bundespflegesatzverordnung; BPflV) has started increased competition between hospitals by introducing performance related reimbursements. All three categories of flat payments, Fallpauschale (FP), Sonderentgelt (SE) and Budget-patient (BP), apply to toxic nodular goiter surgery, governed solely by the extent of thyroid resection. Unlike FP 2.01 and FP 2.02 which do not cover all surgical expenses, the BP flat rate provides a comparatively generous refund for total thyroidectomy. With the oncoming reduction of upper values for residual radioactivity, hospitalization will fall after radioiodine therapy, resulting in lower overall refunds. With this anticipated fall in reimbursement, refunds for radioactive therapy must be increased in the near future to ensure adequate financial compensation. Economic arguments for either therapeutic option will then cease to play a major role, allowing medical therapeutic considerations to prevail.

Costs and Cost Analysis↗
PubMed2001

Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter.

Distinguishing Graves' disease (GD) from a toxic multinodular goiter (TMG) subgroup with a diffuse but uneven Tc-distribution depends on the diagnostic power of the TSH-receptor antibody (TRAb) determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay, which uses the hTSH-receptor as an antigen (DYNOTEST TRAK human, Brahms, Germany), showed a higher sensitivity for the detection of TRAbs in patients with GD than assays using solubilized porcine epithelial cell membranes. The aim of this study was to investigate whether the new Dynotest TRAK human assay has an increased sensitivity to distinguish GD from non-autoimmune hyperthyroidism. Therefore, we examined 21 consecutive patients with the initial diagnosis of TMG for thyroid-stimulating antibodies (TSAbs, JP26 cell assay) and TBII with the new highly sensitive Dynotest TRAK human (Brahms, Germany). The initial diagnosis of TMG was based on suppressed TSH and a patchy Tc-uptake of more than 1 % and less than 7 % or TSH of more than 0.3 mIE/l with a patchy Tc-uptake of more than 1.5 % and less than 7 % and negative TBII values in a displacement assay using solubilized porcine epithelial cell membranes (TRAK, Brahms, Germany). 11 sera from these 21 patients showed TSAb activity. Furthermore, 10 of these 11 TSAb-positive sera were also positive in the Dynotest TRAK human assay, whereas one serum sample was borderline positive. TSAb activity and inhibition of (125)I-bTSH binding in the Dynotest TRAK human assay correlated well (r = 0.7). Therefore, 11 of the 21 investigated patients initially classified as TMG actually had GD, which was undetectable using the porcine TBII assay. In conclusion, TSAbs or TRAbs detected with the Dynotest TRAK human have the highest diagnostic power to differentiate GD from TMG. Because of the less cumbersome assay technique, the Dynotest TRAK human measurements should be obtained for all patients with non-typical TMG to differentiate GD from non-autoimmune hyperthyroidism in order to select the appropriate therapy for these patients.

Adult↗
PubMed2002

[Resistance to thyroid hormone - goiter and attention deficit-hyperactivity disorder as main manifestation].

HISTORY AND CLINICAL FINDINGS: Two siblings with goiter and attention deficit-hyperactivity disorder were presented. Earlier laboratory tests showed increased serum levels of thyroid hormones in association with non-suppressed serum levels of thyrotropin (TSH) in both children. Because hyperthyroidism caused by inappropriate secretion of thyrotropin was suspected, a cerebral MRI was performed. A pituitary adenoma was excluded in both children. Before antithyroid drug treatment was initiated, both patients were referred to our hospital. Careful medical history, clinical examination of the patients and careful interpretation of the laboratory results finally led to the diagnosis resistance to thyroid hormone (RTH). INVESTIGATIONS: Thyroid hormone serum levels were elevated in both children, while serum TSH was within the normal range. Molecular analysis confirmed the diagnosis of RTH. COURSE: Thyrostatic treatment was not initiated. CONCLUSION: Careful medical history, correct interpretation of laboratory results, comprehensive clinical examination and molecular genetic analysis are important in the diagnosis of RTH.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation.

Serum calcitonin (CT) has become a very specific and sensitive marker for human medullary thyroid carcinoma (MTC), a neuroendocrine tumor affecting about 1 % of patients with nodular thyroid disease. MTC is characterized by early micrometastasis and a lack of curative non-surgical treatment, so that early diagnosis is desirable. Based on a systematic review of scientific evidence, we propose multidisciplinary consensus recommendations for the clinical use of CT in patients with nodular goiter. To exclude MTC, serum CT should be determined in patients with nodular thyroid disease, using a two-site CT immunoassay. If basal serum CT exceeds 10 pg/ml, CT should be analysed by pentagastrin stimulation testing, after renal insufficiency and proton pump inhibitor medication have been ruled out. As the risk for MTC is higher than 50 % in patients with stimulated CT values > 100 pg/ml, thyroidectomy is advised in these individuals. If stimulated CT exceeds 200 pg/ml, thyroidectomy and lymphadenectomy is strongly recommended. Pentagastrin-stimulated CT values < 100 pg/ml are associated with a low risk of MTC, or very rarely, non-metastasizing micro-MTC (size < 10 mm). Therefore, regular clinical and biochemical follow-up is the preferred treatment in such patients, unless thyroid malignancy is suspected otherwise.

Calcitonin↗