German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease.

INTRODUCTION: Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines. METHODS: Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations. RESULTS: The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes. CONCLUSIONS: Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines.

Real-time ultrasound elastography--a noninvasive diagnostic procedure for evaluating dominant thyroid nodules.

PURPOSE: Ultrasound elastography (USE) is a newly developed technique for the evaluation of tissue stiffness. It is known that malignancies often show a low-strain value. So far, only limited data for thyroid nodules is available. METHODS: This study included 309 prospective evaluated patients with dominant, nontoxic thyroid nodules. All patients were referred to surgery. USE was performed preoperatively. Three measuring groups were formed: hard (< 0.15), intermediate (0.16-0.3), and soft (> 0.31). The measurements were correlated to the final histological findings. RESULTS: The strain rated from 0.01 to 0.84 (mean 0.26 ± 0.13). A total of 50 thyroid malignancies (35 papillara carcinoma, 9 medullary carcinoma, and 6 follicular carcinoma) were observed. Patients (81) were within the hard group, 35 of them (43.2%) had thyroid cancer (TC) in final histology. Out of 132 patients in the intermediate group, 15 patients had TC (11.4%). All 96 patients from the soft group showed benign histological results (NPV 100%). Seventy percent of patients with TC were within the hard group (PPV 42%). These results were highly significant (p < 0.001). Coarse calcifications and cystic nodules were not connected with reliable measurements and therefore are not suitable for USE. CONCLUSION: USE is a useful adjunctive tool in the workup of thyroid nodules. A low strain value needs surgical intervention, whereas a high strain value predicts a benign histology. It might substitute fine-needle aspiration cytology in the future.

Vitamin D receptor polymorphisms in differentiated thyroid carcinoma.

BACKGROUND: Vitamin D receptor (VDR) expression has been shown to be upregulated in several tumors and is supposed to represent an important endogenous response to tumor progression. To investigate the role of the VDR gene and its influence on 25(OH)D(3) and 1,25(OH)(2)D(3) plasma levels in thyroid carcinoma, we analyzed four VDR polymorphisms in patients and healthy controls (HC). METHODS: Patients with thyroid carcinoma (n = 172) (n = 132 for papillary and n = 40 for follicular) and HC (n = 321) were genotyped for the ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410), and FokI (rs10735810) polymorphisms within the VDR gene and correlated with 25(OH)D(3) and 1,25(OH)(2)D(3) plasma levels. RESULTS: The genotypes AA of the ApaI (rs7975232) and FF of the FokI (rs10735810) polymorphisms were significantly less frequent (12.5% vs. 35.2% and 25% vs. 42.1%, respectively, both corrected p [p(c)] = 0.04) in patients with follicular thyroid cancer (FTC) than in HC. Additionally, the haplotypes, Ta (57.5% vs. 41.4%; p(c) = 0.0207), af (24.6% vs. 14.3%; p(c) = 0.0116), Tab (51.1% vs. 36.8%; p(c) = 0.0495), and Tabf (18.7% vs. 13.6%; p(c) = 0.0240) were more frequent, whereas the haplotypes AF (17.1% vs. 37.2%; p(c) = 0.0008), BF (11.4% vs. 31.9%; p(c) = 0.012), tF (7.9% vs. 25.5%; p(c) = 0.0016), and tABF (7.6% vs. 23%; p(c) = 0.0115) were less frequent in the FTC patients compared to HC. Neither genotype nor haplotype frequencies differed between patients with papillary thyroid cancer (PTC) and HC. Further, individuals with PTC and FTC had a significantly lower level of circulating 1,25(OH)(2)D(3) compared to controls. In contrast, no differences of the 25(OH)D(3) concentration between patients and HC were observed. VDR polymorphisms were not associated with 25(OH)D(3) and 1,25(OH)(2)D(3) plasma levels. CONCLUSIONS: Lower circulating levels of 1,25(OH)(2)D(3) are observed in patients with differentiated thyroid carcinoma. Further, while the alleles AA and FF of the ApaI (rs7975232) and FokI (rs10735810) VDR polymorphisms and the haplotype tABF confer to protection from follicular carcinoma, the haplotype Tabf appeared to be associated with an increased FTC risk. Since this is the first report associating VDR polymorphisms with thyroid carcinoma, these findings need to be confirmed in studies with larger numbers of patients.

Differentiated operative strategy in minimally invasive, video-assisted thyroid surgery results in 196 patients.

To date, experience in minimally invasive thyroid surgery has been limited to unilateral lobectomy and total thyroidectomy. There are no reports regarding selective operative strategy, guided by morphology and function, which is widely accepted in endemic goiter regions. To analyze the efficiency and outcome of tissue-preserving thyroid surgery using a minimally invasive video-assisted technique (MIVA-T), a total of 196 patients were operated on for thyroid nodules between February 1999 and October 2003. Concurrent primary hyperthyroidism was treated in 22 (11%) cases. Indications for operation were solitary, multiple unilateral, or bilateral nodules with a maximum diameter of 30 mm and a maximum lobe volume of 15 ml. Contraindications for minimally invasive operation were thyroid malignancy diagnosed by fine-needle aspiration (FNA), recurrent goiter, and Hashimoto's thyroiditis. Nodule excision was performed in 6% of these cases; subtotal lobectomy, in 6%; selective resection, in 48%; and total lobectomy, in 39%. Histological examination revealed follicular adenoma in 82%, colloid and cystic lesions in 11%, thyroiditis in 1%, and differentiated thyroid carcinoma in 6%. Conversion to open surgery was necessary in 7.7% of the patients (secondary to malignancy demonstrated on frozen section in 3% and to technical difficulties in 4.7%). Transient and permanent laryngeal nerve palsy occurred in 2.0% and 0.5% of patients, respectively. Temporary hypoparathyroidism occurred in 5.6% of patients exclusively after conversion to open total thyroidectomy or in those patients ( n = 22) with additional primary hyperparathyroidism. Given a correct indication, MIVA-T technique can be performed with low conversion and complication rates. Selective operative strategy, guided by morphology and thyroid function, with a variety of operative procedures fitting the individual situation may be performed by this minimally invasive technique.

Thyroid fetal male microchimerisms in mothers with thyroid disorders: presence of Y-chromosomal immunofluorescence in thyroid-infiltrating lymphocytes is more prevalent in Hashimoto's thyroiditis and Graves' disease than in follicular adenomas.

The presence of fetal cells in a maternal compartment is defined as fetal-maternal microchimerism, which has been detected in thyroids of mothers suffering from autoimmunity. We analyzed the immunohistology of paraffin-embedded thyroid specimen taken at surgery from 49 women with Hashimoto's thyroiditis (n = 25), Graves' disease (n = 15), or nodular or diffuse follicular adenomas (n = 9), whose childbirth history was positive for sons. By fluorescence in situ hybridization we screened for X-chromosome- and Y-chromosome-specific staining and compared the finding with human leukocyte antigen (HLA) DQ types of the mothers and, where available, their offspring. In 23 thyroids we found Y-chromosome-specific staining, which was more frequent in thyroid autoimmune disease (60% Hashimoto's thyroiditis and 40% Graves' disease) than in follicular adenomas (22.2%). There was no significant difference for HLA DQ alleles among women whose thyroids showed Y-chromosome staining and those without. However, a subgroup of all investigated microchimerism-positive mother-child pairs and women with Hashimoto's thyroiditis and Graves' disease more often had the susceptibility alleles HLA DQA1*0501-DQB1*0201 or DQB1*0301. In conclusion, fetal microchimerism is observed in thyroids of mothers with sons, and this is found more frequently in thyroid autoimmune diseases.

Early malignant progression of hereditary medullary thyroid cancer.

BACKGROUND: An age-related progression from C-cell hyperplasia to medullary thyroid carcinoma is associated with various germ-line mutations in the rearranged during transfection (RET) proto-oncogene that could be used to identify the optimal time for prophylactic surgery. METHODS: In this European multicenter study conducted from July 1993 to February 2001, we enrolled patients who had a RET point mutation in the germ line, were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Exclusion criteria were medullary thyroid carcinomas of more than 10 mm in greatest dimension and distant metastasis. RESULTS: Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C-cell hyperplasia to medullary thyroid carcinoma and, ultimately, nodal metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with the codon 634 genotype. No lymph-node metastases were noted in patients younger than 14 years of age. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggest that the risk of progression was based on the transforming potential of the individual RET mutation. CONCLUSIONS: These data provide initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations.