TSH-CHECK-1 test: diagnostic accuracy and potential application to initiating treatment for hypothyroidism in patients on anti-tuberculosis drugs.

Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed

Aldosterone, atherosclerosis and vascular events in patients with stable coronary artery disease

AbstractBackground and aimsPlasma aldosterone has been associated with all-cause and cardiovascular mortality in high-risk cardiovascular populations, including patients with heart failure, myocardial infarction and high-risk coronary artery disease (CAD) patients. In the present study, we evaluated the association of plasma aldosterone levels with vascular events in a large prospective cohort of stable CAD patients recruited in an outpatient setting. Moreover, we investigated the relationship between aldosterone and atherosclerotic burden.Methods and resultsBaseline plasma aldosterone levels were measured in 2699 subjects with CAD (mean age 60±10years, 82% male). During a median follow-up of 4.7years, 308 (11%) patients died, of which 203 were from a vascular cause. Vascular endpoints of myocardial infarction, ischemic stroke or vascular death occurred in 355 (13%) patients. Multivariable Cox regression analysis was performed, adjusting for multiple confounders. Aldosterone (median 96pg/mL, interquartile range 70–138pg/mL, normal range 58–362pg/mL) was independently associated with major vascular events (hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.13–2.15) and vascular mortality (HR 1.95, 95% CI 1.27–3.00). By multivariable regression analysis, aldosterone was also associated with the presence of atherosclerosis in additional vascular territories (cerebrovascular disease and/or peripheral artery disease) (p=0.026).ConclusionsIn patients with stable coronary artery disease, plasma aldosterone is independently associated with the risk of major vascular events and vascular mortality and with atherosclerotic burden

Changes in thyroid function parameters 3 months after allogeneic and autologous hematopoietic stem cell transplantation in children

Background: Thyroid dysfunction (hypo- and hyperthyroidism) has been reported as a late effect after hematopoietic stem cell transplantation (HSCT) in children. Short-term effects of HSCT on thyroid function parameters are, however, unclear. Methods: We prospectively evaluated thyroid function parameters before and 3 months after HSCT in all children (&lt;21 years) who underwent HSCT during a 2-year period in the Princess Máxima Center, the Netherlands. Results: Among 72 children, none had thyroidal hypothyroidism or hyperthyroidism 3 months after HSCT. Changes in thyroid function parameters (either aberrant thyroid-stimulating hormone [TSH] or free thyroxine [FT4] concentrations) were found in 16% before and in 10% 3 months after HSCT. Reverse triiodothyronine (rT3) was found elevated in 9.3% before and in 37% 3 months after HSCT, which could be related to poor physical condition. An individual decline in FT4 concentration of ≥20% was found in 10.5% (6/57) 3 months after HSCT. Conclusion: In conclusion, thyroidal hypo- and hyperthyroidism are very rare 3 months after HSCT. These results indicate that surveillance for hypo- and hyperthyroidism may start later in time. The changes in thyroid function parameters found 3 months after HSCT might reflect euthyroid sick syndrome.</p

Prediagnostic Serum Vitamin D Levels and the Risk of Crohn’s Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study

Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings

Recurrent differentiated thyroid cancer: Towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): Study protocol of a multicenter observational cohort study

Background: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.Discussion: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registration: Clinicaltrials.gov identifier: NCT01641679

Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall

Clinical interpretation of prostate-specific antigen values: type of applied cut-off value exceeds methods bias as the major source of variation

Background: Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods: The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results: In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions: This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making

Decreased nocturnal growth hormone secretion and sleep fragmentation in combat-related posttraumatic stress disorder; potential predictors of impaired memor consolidation

Background Healthy sleep facilitates the consolidation of newly acquired memories. Although patients with posttraumatic stress disorder (PTSD) often complain of sleep disturbances and memory deficits, the interrelatedness of these symptoms is not well understood. Sleep may be disturbed in PTSD by increased awakenings during sleep, which has been associated with decreased growth hormone (GH) secretion. We conducted a controlled study in which we assessed sleep fragmentation, nocturnal secretion of GH, and memory consolidation in patients with PTSD. Methods While sleep EEG was being monitored, 13 veterans with PTSD, 15 trauma controls (TC) and 15 healthy controls (HC) slept with an iv catheter, through which blood was collected every 20 min from 23:00 h to 08:00 h. Declarative memory encoding was assessed with the 15 word task before sleep, and consolidation was assessed the next morning by a free recall. Results Sleep was more fragmented in patients with PTSD, with more awakenings in the first half of the night (p &lt;0.05). Plasma levels of GH during the night were significantly decreased in PTSD compared with HC (p &lt;0.05). Furthermore, GH secretion and awakenings were independent predictors for delayed recall, which was lower in PTSD compared to HC (p &lt;0.05). Conclusions These data show that PTSD is associated with increased awakenings during sleep and decreased nocturnal GH secretion. Furthermore, decreased GH secretion may be related to sleep fragmentation and both variables may exert a negative effect on sleep dependent memory consolidation