European experience with the Afirma Gene Expression Classifier for indeterminate thyroid nodules:A clinical utility study in the Netherlands

Background: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup. Methods: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules. Diagnostic surgical rates for Bethesda III and IV nodules were compared to a historical cohort of 171 indeterminate nodules. Samples were post hoc tested with the GSC. Results: The GEC classified 26% as benign. Surgical rates between the prospective and historical cohort did not differ (72.1% vs. 76.6%). The GSC classified 59% as benign, but misclassified six malignant lesions as benign. Conclusion: Implementation of GEC in management of indeterminate nodules in a European country with restrictive diagnostic workup is currently not supported, especially in oncocytic nodules. Prospective studies with the GSC in European countries are needed to determine the clinical utility.</p

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy

BackgroundLevothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone.ObjectiveTo study if serum miRNA profiles are changed in different thyroid states.Design and methodsWe studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification.ResultsMean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/I during levothyroxine withdrawal and 0.006 mU/I during LT4 treatment with a median dosage of 2.1 fag/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment.ConclusionAlthough we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans

A symptom-based algorithm for calcium management after thyroid surgery: a prospective multicenter study

Objective: Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed symptom-based treatment algorithm including a protocolized attempt to phase out supplementation. Methods: In a prospective multicenter study, patients were treated according to the new algorithm and compared to a historical cohort of patients treated with a biochemically based approach. The primary outcome was the proportion of patients receiving calcium and/or alfacalcidol supplementation. Secondary outcomes were calcium-related complications and predictors for supplementation. Results: One hundred thirty-four patients were included prospectively, and compared to 392 historical patients. The new algorithm significantly reduced the proportion of patients treated with calcium and/or alfacalcidol during the first postoperative year (odds ratio (OR): 0.36 (95% CI: 0.23–0.54), P < 0.001), and persistently at 12 months follow-up (OR: 0.51 (95% CI: 0.28–0.90), P < 0.05). No severe calcium-related complications occurred, even though calcium-related visits to the emergency department and readmissions increased (OR: 11.5 (95% CI: 4.51–29.3), P <0.001) and (OR: 3.46 (95% CI: 1.58–7.57), P < 0.05), respectively. The proportional change in pre- to post operative parathyroid hormone (PTH) was an independent predictor for supplementation (OR: 1.04 (95% CI: 1.02–1.07), P < 0.05). Conclusions: Symptom-based management of postthyroidectomy hypocalcemia and a protocolized attempt to phase out supplementation safely reduce d the proportion of patients receiving supplementation, although the number of calcium-related hospital visits increased. For the future, we envision a more individualized treatment approach for patients at risk for delayed symptomatic hypocalcemia, including the proportional change in pre- to post- operative PTH

Appetite suppression through smelling of dark chocolate correlates with changes in ghrelin in young women

Cephalic effects on appetite are mediated by vagal tone and altered gastrointestinal hormones. The objective of this study is to explore the relationship between appetite and levels of gastrointestinal hormones after smelling chocolate and after melt-and-swallow 30 g chocolate (1.059 oz, 85% cocoa, 12.5 g of sugar per 100 g product). Twelve female residents (BMI between 18 and 25 kg/m(2)) all participated in two 60-minute study sessions. In the first session, all 12 women ate chocolate; for the second session, they were randomized either to smell chocolate (n = 6) or to serve as a control (no eating or smelling; n = 6). At the start of the sessions, levels of insulin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), but not glucose, correlated with appetite scored on a visual analogue scale (VAS). In contrast, ghrelin levels correlated inversely with scored appetite. Chocolate eating and smelling both induced a similar appetite suppression with a disappearance of correlations between VAS scores and insulin, GLP-1 and CCK levels. However, while the correlation between VAS score and ghrelin disappeared completely after chocolate eating, it reversed after chocolate smelling, that is, olfactory stimulation with dark chocolate (85%) resulted in a satiation response that correlated inversely with ghrelin levels. (C) 2010 Elsevier B.V. All rights reserved

European experience with the Afirma Gene Expression Classifier for indeterminate thyroid nodules:A clinical utility study in the Netherlands

Background: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup. Methods: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules. Diagnostic surgical rates for Bethesda III and IV nodules were compared to a historical cohort of 171 indeterminate nodules. Samples were post hoc tested with the GSC. Results: The GEC classified 26% as benign. Surgical rates between the prospective and historical cohort did not differ (72.1% vs. 76.6%). The GSC classified 59% as benign, but misclassified six malignant lesions as benign. Conclusion: Implementation of GEC in management of indeterminate nodules in a European country with restrictive diagnostic workup is currently not supported, especially in oncocytic nodules. Prospective studies with the GSC in European countries are needed to determine the clinical utility.</p

Comparison of growth and differentiation factors between healthy controls and subjects.

<p>Comparison of growth and differentiation factors between healthy controls and subjects.</p

Change in Thyroid Hormone Metabolite Concentrations Across Different Thyroid States

Background: In contrast to the thyroid hormones (TH) 3,3′,5-triiodothyronine (T3) and thyroxine (T4), current literature on thyroid hormone metabolite concentrations in the hypothyroid and hyperthyroid states is inconclusive. It is unknown how thyroidectomy affects thyroid hormone metabolite concentrations and if levothyroxine (LT4) replacement therapy after thyroidectomy restores thyroid hormone metabolite concentrations in those without a thyroid gland. The treatment of patients with differentiated thyroid cancer (DTC) covers the euthyroid, hypothyroid, and (subclinical) hyperthyroid states and therefore provides a unique model to answer this. Here, we prospectively studied nine TH and its metabolites (THM) across different thyroid states in a cohort of patients treated for DTC. Also, three potentially important determinants for THM concentrations were studied. Methods: We prospectively included patients aged 18 to 80 years who were scheduled for DTC treatment at the Erasmus MC. Peripheral blood samples were obtained before surgery (euthyroid, endogenous TH production), after surgery just before radioactive iodine therapy (hypothyroid), and six months later on LT4 therapy ([subclinically] hyperthyroid, exogenous T4 supplementation). Nine THMs were quantified in serum with an established liquid chromatography/tandem mass spectrometry method. Repeated measurement analysis was used to compare the three different thyroid states with each other for each THM, while linear regression was used to determine the association between THM concentrations and age, sex, and kidney function. Results: In total, 77 patients (mean age 49 years; 65% women) were eligible for the study. 3,5-diiodothyronine and 3,3′,5-triiodothyroacetic acids were below the lower limit of detection. Compared with the euthyroid state, all THMs were significantly decreased in the hypothyroid state and significantly increased in the (subclinically) hyperthyroid state, with T3 concentrations remaining within the reference interval. Higher age was associated with higher 3-monoiodothyronine (3-T1) concentrations (p < 0.001). Women had higher L-thyronine concentrations than men (p = 0.003). A better kidney function was associated with lower 3-T1 concentrations (p < 0.001). Conclusions: All THMs decrease after a thyroidectomy and increase under thyrotropin (TSH)-suppressive LT4-therapy, suggesting that formation of thyroid hormone metabolites is dependent on peripheral extrathyroidal metabolism of T4. This is also reflected by T3 concentrations that remained within the reference interval in patients receiving TSH-suppressive LT4-therapy as T3 has some thyroidal origin

Serum levels of growth and differentiation factors in healthy controls (C), Seroconverting (SC) and Non-Seroconverting (NSC) family members.

<p>Serum levels of growth and differentiation factors in healthy controls (C), Seroconverting (SC) and Non-Seroconverting (NSC) family members.</p

Maternal and obstetrical outcome in 35 cases of well-differentiated thyroid carcinoma during pregnancy

Thyroid cancer, with 6% to 10% of cancer diagnoses, is one of the most common malignancies during pregnancy. Its treatment poses a risk for the pregnancy, as the thyroid gland plays a crucial role in the evolution of pregnancy. The aim of this study is to evaluate treatment of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes.status: publishe

Patterns of expression levels of cytokines, chemokines and growth and differentiation factors, assessed in the previous study of Beumer <i>et al</i>. and in the current study [7].

<p>Patterns of expression levels of cytokines, chemokines and growth and differentiation factors, assessed in the previous study of Beumer <i>et al</i>. and in the current study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153892#pone.0153892.ref007" target="_blank">7</a>].</p