Improving the Efficacy of ACR TI-RADS Through Deep Learning-Based Descriptor Augmentation.

Thyroid nodules occur in up to 68% of people, 95% of which are benign. Of the 5% of malignant nodules, many would not result in symptoms or death, yet 600,000 FNAs are still performed annually, with a PPV of 5-7% (up to 30%). Artificial intelligence (AI) systems have the capacity to improve diagnostic accuracy and workflow efficiency when integrated into clinical decision pathways. Previous studies have evaluated AI systems against physicians, whereas we aim to compare the benefits of incorporating AI into their final diagnostic decision. This work analyzed the potential for artificial intelligence (AI)-based decision support systems to improve physician accuracy, variability, and efficiency. The decision support system (DSS) assessed was Koios DS, which provides automated sonographic nodule descriptor predictions and a direct cancer risk assessment aligned to ACR TI-RADS. The study was conducted retrospectively between (08/2020) and (10/2020). The set of cases used included 650 patients (21% male, 79% female) of age 53 ± 15. Fifteen physicians assessed each of the cases in the set, both unassisted and aided by the DSS. The order of the reading condition was randomized, and reading blocks were separated by a period of 4 weeks. The system's impact on reader accuracy was measured by comparing the area under the ROC curve (AUC), sensitivity, and specificity of readers with and without the DSS with FNA as ground truth. The impact on reader variability was evaluated using Pearson's correlation coefficient. The impact on efficiency was determined by comparing the average time per read. There was a statistically significant increase in average AUC of 0.083 [0.066, 0.099] and an increase in sensitivity and specificity of 8.4% [5.4%, 11.3%] and 14% [12.5%, 15.5%], respectively, when aided by Koios DS. The average time per case decreased by 23.6% (p = 0.00017), and the observed Pearson's correlation coefficient increased from r = 0.622 to r = 0.876 when aided by Koios DS. These results indicate that providing physicians with automated clinical decision support significantly improved diagnostic accuracy, as measured by AUC, sensitivity, and specificity, and reduced inter-reader variability and interpretation times.

Diagnostic Performance Evaluation of a Computer-Assisted Imaging Analysis System for Ultrasound Risk Stratification of Thyroid Nodules.

OBJECTIVE. Ultrasound-based stratification of the malignancy risk of thyroid nodules has potential variability. The purpose of this study is to evaluate the diagnostic effectiveness of the first commercially available system for computer-aided diagnosis (CADx) imaging analysis. MATERIALS AND METHODS. Ultrasound images of 300 thyroid nodules (135 of which were malignant) acquired before surgical treatment were retrospectively reviewed by a thyroid expert, and his classification of each image was then compared with the classification rendered by an image analysis program (AmCAD-UT, AmCAD Biomed). The American Thyroid Association (ATA) classification system, the European Thyroid Imaging Reporting and Data System (EU-TIRADS), and the classification system jointly proposed by American and Italian associations of clinical endocrinologists (the American Association of Clinical Endocrinologists [AACE], the American College of Endocrinology [ACE], and Associazione Medici Endocrinologi [AME]) were used for risk stratification. RESULTS. The diagnostic performance of the thyroid expert when the ATA system was used was as follows: sensitivity, 87.0%; specificity, 91.2%; positive predictive value, 90.5%; and negative predictive value, 90.9%. Compared with the expert, the CADx program, when used with the three classification systems, had a similar sensitivity but a lower specificity and positive predictive value. Regarding the negative predictive value, the results of the expert did not differ from those of the CADx program when it applied the ATA classification system (90.9% vs 86.3%; p = 0.07). The ROC AUC value was 0.88 for the expert clinician and 0.72 for the CADx program when the ATA classification system was used. CONCLUSION. The CADx ultrasound image analysis program described in the present study is useful for risk stratification of thyroid nodules, but it does not perform better than a sonography expert.

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population.

BACKGROUND: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D). AIM: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers. METHODS: Concentrations of YKL-40, adiponectin, IL-6, IL-1ß, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS). RESULTS: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008). CONCLUSIONS: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.

Evaluation of efficacy, safety, pain perception and health-related quality of life of percutaneous ethanol injection as first-line treatment in symptomatic thyroid cysts.

BACKGROUND: To evaluate the efficacy, safety, pain perception and health-related quality of life (QoL) of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. METHODS: Thirty consecutive patients (46 ± 10 years; 82% women) with symptomatic benign thyroid cysts relapsed after drainage were included. In all cases, cytology prior to treatment, maximum cyst diameter and volume were determined. PEIT was conducted using the established procedure, and the volume of fluid removed and pain perceived by the patient were assessed. In each procedure, the volume of alcohol instilled was <2 ml. After follow-up, final cyst diameter and volume were determined and the persistence of symptoms and QoL were assessed by a questionnaire (SF-36). RESULTS: Mean symptom duration was 10 ± 20 months. A single session of PEIT was required to complete the procedure in 45% of patients, two in 31% and three in 13%. Mean initial maximum cyst diameter was 3.5 ± 1.0 cm and mean extracted liquid volume 61 ± 36 ml. During PEIT, 39% of patients experienced virtually no pain, 43% mild pain and 17% moderate pain. No complications of PEIT were observed. After 12.1 ± 1.4 months of follow-up, cysts were reduced more than 70% in volume in 86.3% of patients, more than 80% in 61.9% and more than 90% in 42%. On the health-related QoL SF-36 questionnaire, patient scores 6 months post-PEIT did not differ significantly from those of the healthy Spanish population. With respect to cosmetic complaints or local symptoms of compression, PEIT-treated patients presented an initial score of 22 ± 8 and 13 ± 5 after treatment (p < 0.05). CONCLUSIONS: In our experience, percutaneous ethanol injection has prove to be an effective, safe and well-tolerated first-line treatment of symptomatic thyroid cysts.

Adrenal Solitary Fibrous Tumor: A Case Report.

Solitary fibrous tumor is a mesenchymal neoplasm that first appeared in the literature as a pleural lesion, but over the last decades, it has been reported in many extrathoracic sites. Primary solitary fibrous tumor in the adrenal gland is very uncommon. Its biological behavior is variable but mostly benign. We report here a case of an apparently healthy woman who, in the context of the study of limb paresthesias, was diagnosed with an adrenal incidentaloma. Laboratory tests were performed, and no hormone hyperfunction was detected. Subsequently, a right adrenalectomy was performed, and the pathological study confirmed a solitary fibrous tumor. To the best of our knowledge, this is the 19th case reported in the literature of a primary solitary fibrous tumor originating from the adrenal gland and, notably, the first documented instance in Spain.

Diabetic Retinopathy Is Associated with Decreased Tyrosine Nitrosylation of Vitreous Interleukins IL-1α, IL-1ß, and IL-7.

OBJECTIVE: To simultaneously evaluate tyrosine nitrosylation and phosphorylation levels of vitreous interleukins of patients with diabetic retinopathy, in which abnormal tyrosine phosphorylation has been previously described. RESEARCH DESIGN AND METHODS: Specific immunoprecipitation of interleukins IL-1α, IL-1ß, IL-2 and IL-7 was carried out in samples obtained during vitrectomy performed for proliferative diabetic retinopathy in patients (n=12) and for macular hole in controls (n=12). Tyrosine nitrosylation and phosphorylation levels of the immunoprecipitated interleukins were analysed by Western blot with the respective specific antibodies and correlated. The results were also correlated with the total amount of immunoprecipitated interleukin protein. The mean phosphorylation/nitrosylation ratios of these proteins in vitreous humour of both the control group and diabetic patients were determined. RESULTS: Diabetes was associated with decreased tyrosine nitrosylation of IL-1α, IL-1ß and IL-7 and an increased tyrosine phosphorylation/nitrosylation ratio with respect to controls in IL-1α (1.58±0.22 vs. 2.74±0.39, respectively; p<0.05) and IL-7 (2.15±0.01 vs. 3.26±0.57, respectively; p<0.05). No significant changes were observed in nitrotyrosine or in the tyrosine phosphorylation/nitrosylation ratio of IL-2. CONCLUSIONS: Proliferative diabetic retinopathy is associated with concomitant and simultaneous changes in both tyrosine phosphorylation and tyrosine nitrosylation status of specific pro-inflammatory interleukins present in the vitreous fluid such as IL-1α, IL-1ß and IL-7. These changes could be related to the increase in pro-inflammatory activity detected in diabetes-induced retinopathy.

Long-term efficacy evaluation of a protocol for the management of symptomatic thyroid cysts with ultrasound-guided percutaneous ethanol injection.

AIM: To evaluate the long-term efficacy of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. PATIENTS AND METHODS: 100 subjects (48±12 years; 58% women) with symptomatic thyroid cysts relapsing after drainage were prospectively included. PEIT was conducted using an established procedure, and the initial cyst volume, symptoms and pain perceived by the patient were assessed. The volume of instilled alcohol was ≤2ml without re-extraction in all cases. Patients were followed-up for more than 3 years and final cyst volume and symptom improvement were assessed. RESULTS: Mean maximum cyst diameter before drainage was 3.1±1.2cm. In 71% of patients ≤2 PEIT sessions were required. Median maximum cyst volume was 12.7 (5.4-21.7)ml before the first drainage and median total volume extracted from the cysts was 13.0 (6.2-37.0)ml. After a mean follow-up period of 52±10 months, 98% of patients reported a complete absence of symptoms. The final median volume for the whole group was 0.8 (0.1-2.0)ml with a median volume reduction of 94 (81-99)%. A final volume reduction greater than 65% was observed in 90% of cases. Reported pain during the procedure was absent or mild in 76.4% of cases. CONCLUSIONS: PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.

Long-term efficacy evaluation of a protocol for the management of symptomatic thyroid cysts with ultrasound-guided percutaneous ethanol injection.

AIM: To evaluate the long-term efficacy of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. PATIENTS AND METHODS: 100 subjects (48±12 years; 58% women) with symptomatic thyroid cysts relapsing after drainage were prospectively included. PEIT was conducted using an established procedure, and the initial cyst volume, symptoms and pain perceived by the patient were assessed. The volume of instilled alcohol was ≤2ml without re-extraction in all cases. Patients were followed-up for more than 3 years and final cyst volume and symptom improvement were assessed. RESULTS: Mean maximum cyst diameter before drainage was 3.1±1.2cm. In 71% of patients ≤2 PEIT sessions were required. Median maximum cyst volume was 12.7 (5.4-21.7)ml before the first drainage and median total volume extracted from the cysts was 13.0 (6.2-37.0)ml. After a mean follow-up period of 52±10 months, 98% of patients reported a complete absence of symptoms. The final median volume for the whole group was 0.8 (0.1-2.0)ml with a median volume reduction of 94 (81-99)%. A final volume reduction greater than 65% was observed in 90% of cases. Reported pain during the procedure was absent or mild in 76.4% of cases. CONCLUSIONS: PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.

[Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus]. / Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. SUBJECTS AND METHODS: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO(2) of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO(2) of >2% of the finger compared to foot or to 30cm foot elevation. RESULTS: 60 patients were men (age of 62+/-7 years, HbA(1c) of 6.9+/-1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. CONCLUSION: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM.

Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer.

To date, the genes involved in familial non-medullary thyroid cancer (FNMTC) remain poorly understood, with the exception of syndromic cases of FNMTC. It has been proposed that germline mutations in telomere-related genes, such as POT1, described in familial melanoma might also predispose individuals to thyroid cancer, requiring further research. We aimed to identify germline mutations in POT1 in selected FNMTC families (with at least three affected members) without a history of other cancers or other features, and to describe the clinical characteristics of these families. Sequencing of the 5'UTR and coding regions of POT1 was performed in seven affected people (index cases) from seven families with FNMTC. In addition, we performed whole-exome sequencing (WES) of DNA from 10 affected individuals belonging to four of these families. We did not find germline variants of interest in POT1 by Sanger sequencing or WES. We neither found putative causative mutations in genes previously described as candidate genes for FNMTC in the 4 families studied by WES. In our study, no germline potentially pathogenic mutations were detected in POT1, minimizing the possibilities that this gene could be substantially involved in non-syndromic FNMTC.

Prognostic Significance of Thyroglobulin Antibodies in Differentiated Thyroid Cancer.

OBJECTIVE: To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods. We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%. RESULTS: In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in (n = 35) or disappearance of (n = 30) TgAb. CONCLUSIONS: Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign.

Kallikreins Stepwise Scoring Reveals Three Subtypes of Papillary Thyroid Cancer with Prognostic Implications.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Unlike most cancers, its incidence has dramatically increased in the last decades mainly due to increased diagnosis of indolent PTCs. Adequate risk stratification is crucial to avoid the over-treatment of low-risk patients, as well as the under-treatment of high-risk patients, but the currently available markers are still insufficient. Kallikreins (KLKs) are emergent biomarkers in cancer, but their involvement in PTC is unknown. METHODS: This study analyzed DNA methylation (HumanMethylation arrays) and gene expression (RNA-Seq) of KLKs, BRAF and RAS mutations, and clinical data from four published thyroid cancer data sets including normal and tumor tissues (n = 73, n = 475, n = 20, and n = 82) as discovery, training, and validation series. The C4.5 classification algorithm was used to generate a decision tree. Disease-free survival was estimated using Kaplan-Meier and Cox approaches. Specific analyses were performed using real-time polymerase chain reaction and immunohistochemistry. RESULTS: The entire KLK family was deregulated in PTC, displaying a specific epigenetic and transcriptional profile strongly associated with BRAFV600E or RAS mutations. Thus, a decision-tree algorithm was developed based on three KLKs with >80% sensitivity and >95% specificity, identifying BRAF- and RAS-mutated tumors. Notably, tumors lacking these mutations were classified as BRAF- or RAS-like. Most importantly, the KLK algorithm uncovered a novel PTC subtype showing favorable prognostic features. CONCLUSIONS: The KLK algorithm could lead to a new clinically applicable strategy with important implications for the risk stratification of PTC and the management of patients.

Increased Global DNA Hypomethylation in Distant Metastatic and Dedifferentiated Thyroid Cancer.

Context: Global DNA hypomethylation is a major event for the development and progression of cancer, although the significance in thyroid cancer remains unclear. Therefore, we aimed to investigate its role in thyroid cancer progression and its potential as a prognostic marker. Methods: Global hypomethylation of Alu repeats was used as a surrogate marker for DNA global hypomethylation, and was assessed using the Quantification of Unmethylated Alu technique. Mutations in BRAF and RAS were determined by Sanger sequencing. Results: Ninety primary thyroid tumors were included [28 low-risk differentiated thyroid cancer (DTC), 13 pediatric DTC, 33 distant metastatic DTC, 7 poorly differentiated thyroid cancer (PDTC), and 9 anaplastic thyroid cancer (ATC)], as well as 24 distant metastases and 20 normal thyroid tissues. An increasing hypomethylation was found for distant metastatic DTC [median, 4.0; interquartile range (IQR), 3.1 to 6.2] and PDTC/ATC (median, 9.3; IQR, 7.0 to 12.1) as compared with normal thyroid tissue (median, 2.75; IQR, 2.30 to 3.15), whereas low-risk and pediatric DTC were not affected by hypomethylation. Alu hypomethylation was similar between distant metastases and matched primary tumors. Within distant metastatic DTC, Alu hypomethylation was increased in BRAF vs RAS mutated tumors. Kaplan-Meier and Cox regression analyses showed that thyroid cancer-related and all-cause mortality were associated with tumor hypomethylation, but this association was lost after adjustment for thyroid cancer risk category. Conclusion: Distant metastatic DTC, PDTC, and ATC were increasingly affected by global Alu hypomethylation, suggesting that this epigenetic entity may be involved in thyroid cancer progression and dedifferentiation.

Quantification of unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples.

Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings.

Serum pepsinogen I: an early marker of pernicious anemia in patients with type 1 diabetes.

CONTEXT: Pernicious anemia (PA) is an autoimmune organ disease much more common in type 1 diabetic patients (DM1) than in nondiabetic subjects, but it is clinically silent until its end stage. OBJECTIVE: This study aimed to determine biochemical markers of latent PA in a population of DM1 patients attending the endocrinology outpatient clinic of a university hospital. STUDY SUBJECTS: The population studied consisted of 186 unselected patients (32.4 +/- 8.7 yr) and 118 healthy controls (30.9 +/- 9.4 yr). MEASUREMENTS AND INTERVENTIONS: Plasma gastrin and pepsinogen I were determined in patients and controls, whereas hemoglobin A1c, serum cobalamin, hemoglobin, and organ-specific antibodies were determined only in patients. Latent PA was defined as serum pepsinogen I less than 30 microg/liter. In patients with low pepsinogen I concentrations and hypergastrinemia, esophagogastroduodenoscopy (EGD) was performed. RESULTS: DM1 patients showed significantly lower pepsinogen I concentrations (P < 0.001) and higher gastrinemia than controls. Latent PA was present in 12.4% of patients vs. 0.9% of controls. Among patients, more women than men showed low plasma pepsinogen I concentrations (P = 0.002) and thyroperoxidase antibody positivity (P < 0.001). Only the highest parietal cell antibody titers (> or =1:640) identified patients with significantly higher levels of plasma gastrin (P < 0.001) and lower levels of pepsinogen I (P < 0.001). The histopathological EGD findings confirmed different degrees of gastric body mucosa atrophy in all cases. CONCLUSION: The high prevalence of latent PA found in our DM1 patients leads us to recommend its screening using serum pepsinogen I concentrations. In patients with hypergastrinemia and high parietal cell antibody titers, EGD should be considered to confirm gastric mucosa atrophy.

Frequency of antineutrophil cytoplasmic antibody in Graves' disease patients treated with methimazole.

Retrospective studies have shown antineutrophil cytoplasmic antibody (ANCA) positivity in patients treated for Graves' hyperthyroidism; ANCA has been attributed to either antithyroid drugs or to the disease itself. The aim of this study was to determine ANCA in Graves' disease patients at diagnosis and after treatment with methimazole and to evaluate the relationship between ANCA and hyperthyroidism evolution. Thirty patients recently diagnosed with Graves' hyperthyroidism were prospectively studied. ANCA were determined by indirect immunofluorescence. ANCA autoantibodies against specific antigens (proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein (BPI), cathepsin, lysozyme, elastase, and lactoferrin) were detected by ELISA. The median observation period was 22 months. Kaplan-Meier analysis was performed to identify ANCA as an outcome variable. Twenty patients (67%) were ANCA positive before the onset of treatment, and four (19%) remained positive after 1 yr of antithyroid drug treatment. No differences were observed in any clinical or analytical features between patients with or without positive ANCA. Before treatment, BPI-positive patients required radioiodine treatment or presented relapse more rapidly than BPI-negative patients (log-rank test P < 0.0002). Patients with Graves' hyperthyroidism show positive ANCA before medical treatment, which points to a relationship with the autoimmune disease itself. Our results suggest that BPI-positive patients tend to relapse with antithyroid medication.

Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable?

Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.

The truncated isoform of somatostatin receptor5 (sst5TMD4) is associated with poorly differentiated thyroid cancer.

Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3-6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment.

Non-detectable Chlamydophila pneumoniae DNA in peripheral leukocytes in type 2 diabetes mellitus patients with and without carotid atherosclerosis.

BACKGROUND AND OBJECTIVE: To study Chlamydophila pneumoniae DNA (CP-DNA) in leukocytes measured by real-time polymerase chain reaction (PCR) in patients with type 2 diabetes mellitus (DM2) with different degrees of atherosclerosis, a cross-sectional protocol was performed. PATIENTS AND METHODS: We included 135 patients with DM2. Clinical, metabolic and inflammatory variables were measured. Previous clinical macrovascular disease was recorded and carotid ultrasound and real-time PCR for CP-DNA were performed. RESULTS: Mean age was 62 (7) years and mean diabetes duration 16 (9) years; 40.7% of patients presented clinical atherosclerosis, 32.5% subclinical atherosclerosis and 26.6% no evidence of atherosclerosis. Anthropometric data were homogeneous in the three groups. Patients with clinical atherosclerosis had greater carotid intima-media thickness compared to the other two groups. No CP-DNA was detected in any patient. CONCLUSIONS: The lack of detection of CP-DNA in blood leukocytes suggests that C. pneumoniae plays no active, systemic role in the pathogenesis of atherosclerosis in DM2 patients and is not a reliable marker of atherosclerosis in high-risk patients.