[Clinical features of patients with Basedow Graves disease seen at a university hospital]. / Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario.

BACKGROUND: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. AIM: To describe the clinical features of patients with BGD seen at a university hospital. MATERIAL AND METHODS: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. RESULTS: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. CONCLUSIONS: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

[Study and management of thyroid nodes by non specialist physicians: SOCHED consensus]. / Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED.

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Clinical and histopathological features of follicular thyroid cancer in Chile.

Objective: Follicular thyroid carcinoma (FTC) is less frequent but has a worse prognosis than papillary carcinoma. The available evidence on pre-operative characteristics of FTC is controversial. Our objective was to characterize the clinical, ultrasound and histopathological presentation of FTC patients treated Chile. Subjects and methods: Retrospective analysis of 97 patients treated for FTC in 6 large centers in Chile. We analyzed their ultrasonographic features and classified the nodules according to ATA risk of malignancy and TI-RADS score, as well as the cytological findings according to the Bethesda system. We described their clinical and histopathological findings at diagnosis and classified their risk of recurrence and mortality according to ATA 2015 recurrence risk category and the eighth edition of the AJCC/UICC staging system, respectively. Results: Median age was 48 years and 73.2% were females. The median diameter was 38.8 mm; only 9.5% of them were microtumors. According to ATA risk of malignancy, 86% of the nodules were low or intermediate suspicious, while 78% were category 3 or 4A nodules according to the TI-RADS. Regarding the Bethesda system, 65.9% had indeterminate cytology (20.6% category III and 45.3% category IV). At histological examination, most were minimally-invasive and angio-invasive tumors with less than 4 foci (54.7% and 28.4% respectively). More than 90% of FTC were unifocal and there was no lymphovascular or extrathyroidal invasion or lymph node involvement. Four patients (4.1%) had distant metastases at diagnosis. Most patients (95%) had stage I or II disease according to the AJCC/UICC staging system, while the risk of recurrence was low at 51.5% when using the ATA risk of recurrence scale. Conclusion: At diagnosis, most FTCs were nodules of low or intermediate suspicion at ultrasound, nearly two thirds had indeterminate cytology according to the Bethesda system, and nearly 50% of them were of low risk of recurrence.

A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials.

Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and -2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and -2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and -2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.

Clinical and histopathological features of follicular thyroid cancer in Chile

ABSTRACT Objective: Follicular thyroid carcinoma (FTC) is less frequent but has a worse prognosis than papillary carcinoma. The available evidence on pre-operative characteristics of FTC is controversial. Our objective was to characterize the clinical, ultrasound and histopathological presentation of FTC patients treated Chile. Subjects and methods: Retrospective analysis of 97 patients treated for FTC in 6 large centers in Chile. We analyzed their ultrasonographic features and classified the nodules according to ATA risk of malignancy and TI-RADS score, as well as the cytological findings according to the Bethesda system. We described their clinical and histopathological findings at diagnosis and classified their risk of recurrence and mortality according to ATA 2015 recurrence risk category and the eighth edition of the AJCC/UICC staging system, respectively. Results: Median age was 48 years and 73.2% were females. The median diameter was 38.8 mm; only 9.5% of them were microtumors. According to ATA risk of malignancy, 86% of the nodules were low or intermediate suspicious, while 78% were category 3 or 4A nodules according to the TI-RADS. Regarding the Bethesda system, 65.9% had indeterminate cytology (20.6% category III and 45.3% category IV). At histological examination, most were minimally-invasive and angio-invasive tumors with less than 4 foci (54.7% and 28.4% respectively). More than 90% of FTC were unifocal and there was no lymphovascular or extrathyroidal invasion or lymph node involvement. Four patients (4.1%) had distant metastases at diagnosis. Most patients (95%) had stage I or II disease according to the AJCC/UICC staging system, while the risk of recurrence was low at 51.5% when using the ATA risk of recurrence scale. Conclusions: At diagnosis, most FTCs were nodules of low or intermediate suspicion at ultrasound, nearly two thirds had indeterminate cytology according to the Bethesda system, and nearly 50% of them were of low risk of recurrence.

A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study.

BACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.

Determinación de niveles de vitamina D en pacientes con fibromialgia: estudio de casos y controles / Vitamin D levels in patients with fibromyalgia: case control study

Introduction: fibromyalgia (FM) is characterized by diffuse chronic muscle pain, fatigue and disability, affecting quality of life. In recent years there are many reports that show a high prevalence of vitamin D deficiency in different populations. In patients with FM there are conflicting results about the associations with vitamin D deficiency. Method: Case control study matched controls by age and sex. A clinical interview, measurement of 25-OH vitamin D, calcium, phosphorus and intact PTH was measured. The definitions of the American Society of Endocrinology were used: Insufficient vitamin D levels of 21-29 ng/ml and deficiency when they are less than 20 ng/ml. Results: 39 female patients were included in each group. The average age was 46.33 years (SD 10.6) in patients with FM and 45.92 years (SD 11.9) in controls. VD average levels in women with FM was 26.13 ng/ml (SD 8.3) and the controls of 28.45 ng/ml (SD 8.7) p = 0.082. No group differences were found when using cutoffs of 30 ng/dl (OR 2.75 with p = 0.35 [95 percent CI 0.96 to 8.06]) or 20 ng/dl (OR 0,6 p = 0.38 [95 percent CI 0.15 to 2.18]). No VD patients with levels below 10 ng/dl were presented. Conclusions: We found no differences between groups in VD levels when considering the average levels of VD or using different cutoffs.

Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario / Clinical features of patients with Basedow Graves disease seen at a university hospital

Background: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. Aim: To describe the clinical features of patients with BGD seen at a university hospital. Material and Methods: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. Results: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. Conclusions: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Expression of cytokeratin 19 in the diagnosis of thyroid papillary carcinoma by quantitative polymerase chain reaction.

OBJECTIVE: To examine cytokeratin 19 (CK19) expression levels by immunostaining for protein and quantitative reverse-transcription polymerase chain reaction (qPCR) for messenger RNA in thyroid surgical specimens from patients with papillary carcinoma (PC) and other types of thyroid lesions. METHODS: A total of 54 randomly selected postoperative thyroid tissue samples were collected for formalin-fixed paraffin-embedded sectioning or flash-frozen total RNA extraction for complementary DNA synthesis (or both). Tissue sections were stained for CK19 expression with use of a specific monoclonal antibody. qPCR was performed on synthesized complementary DNA with sequence-specific primers for human CK19 in conjunction with ribonucleoprotein S18 for normalization. RESULTS: CK19 immunostaining was diffuse and intense in all PC lesions and considerably less in specimens that harbored both Hashimoto thyroiditis (HT) and PC. CK19 immunostaining was mostly absent in areas of multinodular goiter (MNG), with occasional focal staining. HT and Hürthle cell adenoma were essentially negative for CK19 immunostaining, except for weak staining in focal areas. Analysis of CK19 gene expression by qPCR revealed that the PC samples tested (n = 21) had significantly higher levels in comparison with all other groups (P < 0.0001). Furthermore, PC had a 32-fold mean level increase in CK19 expression in comparison with CK19 expression in MNG. Hürthle cell adenoma (n = 5) and HT (n = 7) lesions were similar to MNG in CK19 expression, with some overlap of CK19 between HT and PC. CONCLUSION: The data indicate that expression of CK19 by qPCR is a quantitative method for distinguishing PC lesions from other types of thyroid lesions, in contrast to the more qualitative immunohistochemistry. Moreover, qPCR of CK19 is a valid method that could be used as an ancillary tool in diagnosing thyroid cancer. The expression of CK19 by qPCR may be adopted, in combination with other markers, for molecular definition of the various subtypes of thyroid lesions assessed by fine-needle aspiration biopsy in the preoperative diagnosis of thyroid lesions.

[Detection of malignancy markers in thyroid nodules by reverse transcriptase polymerase chain reaction (RT-PCR)]. / Detección de marcadores de malignidad en nódulos tiroideos por transcripción reversa y reacción en cadena de la polimerasa (RT-PCR).

BACKGROUND: Nodular thyroid disease is a very common disorder with a low frequency of malignancy. The most accurate diagnostic test is fine needle aspiration biopsy (FNAB) of nodules with cytological analysis of the sample. However, this procedure has some limitations in the diagnosis of follicular and papillary thyroid carcinoma. AIM: To detect mRNA from specific malignancy markers in thyroid nodules and to evaluate their potential correlation with cytological and pathological diagnosis. PATIENTS AND METHODS: In 20 patients with thyroid nodules FNAB was performed prior to surgery. The main part of the FNAB sample was used to perform classical cytology. In the remaining of the sample were detected MUC-1, CD26, galectin-3 and TSH receptor mRNAs by RT-PCR technique. RESULTS: Eight patients had positive cytology for papillary cancer, which was confirmed by pathology. Nine had suspicious or non conclusive cytological findings and 3 were negative for neoplastic cells; all 12 were pathologically benign. We detected TSH receptor and galectin-3 mRNA in almost all benign and malignant nodules. MUC-1 was present in 5/8 papillary carcinoma (62.5%), and 1/12 benign nodules (8.3%). CD26 was detected in 7/8 papillary carcinomas but also in 8/12 benign nodules. CONCLUSIONS: RT-PCR can be performed in very small samples of thyroid tissue to detect several mRNA markers. MUC-1 can be a potentially useful marker of malignancy in thyroid nodules. It can be detected by RT-PCR as a complementary technique in the diagnostic evaluation of thyroid nodules.

[Prader-Willi Syndrome (PWS) associated to morbid obesity: surgical treatment]. / Síndrome Prader-Willi asociado a obesidad mórbida: tratamiento quirúrgico.

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypothalamic hypogonadism, mental retardation and compulsive hyperphagia associated with early and severe obesity. Complications of overweight, such as type-2 diabetes Mellitus, dyslipidemia and diffuse atheromatosis are common. We report a 15 years old morbid obese male with PWS, with a body mass index of 57.7 kg/m2, refractory to weight-lowering treatments. He underwent preoperative evaluation and treatment by a multidisciplinary team, and subjected to a 95% gastrectomy, leaving a 50 ml remnant pouch and a long limb (120 cm) Y-Roux gastro-jejuno anastomosis. There were no surgical complications, oral feeding was initiated at the 5th day with an hypocaloric diet. During the first postoperative year, the patient lost 70 kg, achieving a body mass index of 30 kg/m2. Surgical treatment can become a therapeutic choice for obesity in PWS patients.