Biospecific nanoparticles for multiplex phosphorescence analysis (PHOSPHAN)

We have developed a technology for the production of polymeric nanoparticles containing the incorporated phosphorescent label (europium ions–naphthoyltrifluoroacetone complexes) and streptavidin that is covalently bound on the surface. The aggregation-stable biospecific nanoparticles (40–60 nm in diameter) include up to 2000 molecular tags/particle and retain biological activity and stable phosphorescence for at least 20 months. They can be used in phosphorescence analysis (PHOSPHANTM)-based biochip technology as an effective detector system to record phosphorescence from microzones (microarrays) printed on the well bottoms of standard polystyrene microplates. The creation of a dense monolayer on the surface of a microzone requires up to 10⁸ particles/microarray, or 10⁹ particles/mm² of area; this is in good agreement with theoretical estimates. The detection limit is as low as 300–400 phosphorescent nanoparticles per a microzone with an area of ~0.1 mm². It has been demonstrated in the model of thyroid stimulating hormone (TSH) detection in filter paper dried blood that the newly developed detector system is five times more sensitive than the conventional methods of multiplex PHOSPHAN (with Pt-coproporphyrin phosphorescent label) and lanthanide immune fluoroassay (with fluorescent Eu³⁺ chelate complexes registered in the enhancement solution). The sensitivity of phosphorescent nanoparticle-based detector system is as low as 6.8 × 10⁵ molecules/1.5 μL sample, which corresponds to a TSH concentration of 1.5 × 10^–14 M.     

Neonatal thyroid-stimulating hormone level and perchlorate in drinking water

BACKGROUND: The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotropin; TSH) levels was examined for Las Vegas and Reno, Nevada. METHODS: The neonatal blood TSH levels in Las Vegas (with up to 15 microg/L (ppb) perchlorate in drinking water) and in Reno (with no perchlorate detected in the drinking water) from December 1998 to October 1999 were analyzed and compared. The study samples were from newborns in their first month of life (excluding the first day of life) with birth weights of 2, 500-4,500 g. A multivariate analysis of logarithmically transformed TSH levels was used to compare the mean TSH levels between Las Vegas and Reno newborns, with age and sex being controlled as potential confounders. RESULTS: This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of 相似文献   

Sensitive time-resolved fluoroimmunoassay for simultaneous detection of serum thyroid-stimulating hormone and total thyroxin with Eu and Sm as labels

Based on a novel cocoating strategy and dissociation enhancement lanthanide fluorescence immunoassay technique, a sensitive time-resolved fluoroimmunoassay (TRFIA) has been developed for simultaneous quantification of human serum thyroid-stimulating hormone (TSH) and thyroxin (T4) in a one-and-the-same assay procedure. The new cocoating strategy for preparing highly active surface anti-TSH and anti-T4 monoclonal antibodies (McAbs) was performed by a three-step protocol. Namely, anti-TSH McAb at high concentration (10 micro g/ml) and extensively biotinylated bovine serum albumin (BSA) at low concentration (0.5 micro g/ml) were coated on microwells by passive adsorption, then streptavidin was captured by the surface BSA-biotin, and finally biotinylated anti-T4 McAb was immobilized by the remnant binding sites of the bound streptavidin. In the present TSH/T4 TRFIA, both sandwich- and competitive-type configurations were involved, and Eu(3+) and Sm(3+) were used as labels for TSH and T4 detection, respectively. The method showed rapid kinetics; the equilibrium was reached within 30min at 37 degrees C due to the use of high concentrations of reaction reagents, rapid agitation, and small reaction volume. The lower limits of detection of the method were 0.028 mIU/L for TSH and 4.1 nmol/L for T4 with 20 micro L of sample volume. The assay ranges for TSH and T4 were 0.21-80.00 mIU/L and 20-300 nmol/L, respectively. The correlation between the TSH/T4 values obtained by the present TSH/T4 TRFIA and those obtained by commercial chemiluminescence immunoassay was satisfactory.     

术前血清促甲状腺激素水平与甲状腺结节相关性的研究

目的:探讨术前血清促甲状腺激素(TSH)水平与甲状腺结节良恶性的关系。方法:回顾性分析了1499例甲状腺结节手术切除患者术前血清TSH、甲状腺B超,手术记录、术后病理诊断报告。根据术后病理报告判定甲状腺结节良恶性,分析术前血清TSH水平在甲状腺良恶性结节中的不同分布。结果:分化型甲状腺癌(DTC)患者术前血清TSH水平明显高于甲状腺良性结节组(2.179±2.017vs1.259±0.884μIU/mL),P<0.001;在DTC患者中,有淋巴结转移较无淋巴结转移、TNM分期III、IV期较I、II期以及肿瘤直径≥1cm较<1cm的患者术前血清TSH明显升高(均P<0.001)。结论:术前血清TSH水平是预测甲状腺结节良恶性的重要指标。     

Effect of Proton Pump Inhibitors on Serum Thyroid-Stimulating Hormone Level in Euthyroid Patients Treated with Levothyroxine for Hypothyroidism

ObjectiveTo examine retrospectively the effect of proton pump inhibitors (PPIs) on thyrotropin (thyroid-stimulating hormone or TSH) values in patients with hypothyroidism and normal TSH levels receiving levothyroxine (LT₄) replacement therapy.MethodsThe data collection was done by retrospective review of electronic medical records from the period of December 2002 to August 2005 from patients with hypothyroidism who were receiving at least 25 μg of LT₄ replacement daily at Queens Hospital Center. The first 92 patients meeting all inclusion and exclusion criteria were included in the study. The study group (N = 37) patient data were collected by selecting euthyroid patients who had received stable LT₄ replacement for at least 6 months and in whom PPI therapy (lansoprazole) was later initiated. TSH levels were collected before and at least 2 months after the PPI treatment was started. The control group (N = 55) patient data were collected by reviewing TSH levels among euthyroid patients with a history of hypothyroidism receiving stable LT₄ therapy and not receiving a PPI during the period of data collection. The statistical analysis was done by comparing the mean change in TSH level in each group with use of the Student t test.ResultsIn the study group, the mean change in the TSH level from before to at least 2 months after initiation of PPI therapy, 0.69 ± 1.9 μIU/mL, was statistically significant (P = 0.035). In the control group, the mean change in the TSH level during the study period, 0.11 ± 1.06 μIU/mL, was not statistically significant (P = 0.45).ConclusionTo our best knowledge, this is the first study in humans with hypothyroidism demonstrating the effect of PPIs on serum TSH levels. PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT₄ replacement. Patients with hypothyroidism and normal TSH values during LT₄ replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT₄ dose. (Endocr Pract. 2007;13:345-349)     

Pre-Operative Ultrasound Identification of Thyroiditis Helps Predict the Need for Thyroid Hormone Replacement After Thyroid Lobectomy

ObjectiveTo evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy.MethodsData from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had >1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR.ResultsDuring follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001).ConclusionA pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months). (Endocr Pract. 2013;19:1015-1020)     

Simultaneous quantification of 17α-OH progesterone, 11-deoxycortisol, Δ4-androstenedione, cortisol and cortisone in newborn blood spots using liquid chromatography-tandem mass spectrometry

Adrenal steroid profiling, including 17α-OH progesterone (17OHP), 11-deoxycortisol (S), Δ4-androstenedione (Δ4-A) and cortisol (F) in blood spots by tandem mass spectrometry, is used for newborn screening to detect congenital adrenal hyperplasia (CAH). Pre-analytical sample processing is critical for assay specificity and accuracy; however, it is laborious and time-consuming. This study describes the development and validation of a new Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of five steroids: 17OHP, S, Δ4-A, F and cortisone (E) in blood spots from newborns. Whole blood was eluted from a 5.00 mm dried blood spot by an aqueous solution containing the deuterium-labeled internal standards d8-17OHP and d4-cortisol. The steroids extracted from blood spot into aqueous solution were subsequently purified via Extelut mini NT1 column using diethylether. The extracts were evaporated and quantified using LC-MS/MS. The detection limit was 0.25 ng/mL for 17OHP and S, 0.4 ng/mL for Δ4-A and 0.5 ng/mL for F and E. The limit of quantification was 0.5 ng/mL for 17OHP, S and Δ4-A and 1 ng/mL for F and E. Precision for 17OHP, S, Δ4-A at concentrations of 0.5, 2, and 8 ng/mL (n=5) in fortified steroid free serum samples was 1.3-3.5% (intra-assay CV) and 7-14.8% (inter-assay CV). Precision for F and E at concentrations of 5 and 20 ng/mL was 1.5-4.8% (intra-assay, CV%) and 6-15% (inter-assay, CV%). Accuracy was calculated at concentrations of 0.5, 2, and 8 ng/mL for 17OHP, S and Δ4-A and ranged from -0.3 to 0.2%, while for F and E it ranged from -3.2 to 0.2%. Relative recoveries at concentration 2 ng/mL and 8 ng/mL for 17OHP, S, Δ4-A and at 5 ng/mL and 20 ng/mL for F and E ranged from 55% to 80%. Reference intervals were estimated for all steroids in newborns (on day 3). The steroid profile assay herein described is sensitive, specific and accurate and involves a simple pre-analytical sample manipulation; it is therefore suitable for routine analysis and provides data for samples within normal range as well as those with elevated levels. For the first time to our knowledge, cortisone levels are reported in dried blood spots from newborns.     

Fast determination of propranolol in urine and pharmaceutical preparations by stopped-flow and micellar-stabilized room-temperature phosphorescence: validation of the method

The stopped-flow mixing technique has been used to study the kinetic determination of propranolol by means of micellar-stabilized room-temperature phosphorescence. This mixing system diminishes the time required for the deoxygenation of micellar medium by sodium sulfite, allowing a kinetic curve that levels off within only 7s to be obtained. The phosphorescence enhancers thallium (I) nitrate, sodium dodecyl sulfate, and sodium sulfite were optimized to obtain maximum sensitivity and selectivity. A pH value of 6.54 was selected as adequate for phosphorescence development. The kinetic curves of propranolol phosphorescence were scanned at lambda(ex)=290 nm and lambda(em)=524 nm. The calibration graphs were linear for the concentration range from 25 to 400 ng mL(-1). The phosphorescence lifetime of propranolol is approximately 1210 micros. The detection limit calculated as proposed clayton was 13.53 ng mL(-1) and by applying the error propagation theory, the detection limit was 8.37 ng mL(-1). The repeatability was studied using 10 solutions of 200 ng mL(-1) of propranolol; if error propagation theory is assumed, the relative error is 1.94%. The standard deviation for a replicate sample was 4.0 ng mL(-1). This method was successfully applied to the determination of propranolol in commercial formulations and in urine. Suitable recovery values were obtained.     

Development of a highly sensitive chemiluminescent assay for hydrogen peroxide under neutral conditions using acridinium ester and its application to an enzyme immunoassay

We developed a highly sensitive chemiluminescent (CL) assay for hydrogen peroxide using 10‐methyl‐9‐(phenoxycarbonyl) acridinium fluorosulfonate (PMAC) that produced chemiluminescence under neutral conditions and applied it to an enzyme immunoassay (EIA). One picomole of hydrogen peroxide could be detected using the optimized PMAC‐CL method and 6.2 × 10^‐20 mol β‐d ‐galactosidase (β‐gal) could be detected by combining an indoxyl derivative substrate and the proposed PMAC‐CL method. This highly sensitive CL β‐gal assay was applied to an EIA for thyroid‐stimulating hormone (TSH) using β‐gal as a label enzyme; 0.02–100.0 μU/mL TSH in human serum could be assayed directly and with high reproducibility. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of blood sample anticoagulants on lateral flow assays using luminescent photon-upconverting and Eu(III) nanoparticle reporters

Many quantitative and semiquantitative lateral flow (LF) assays have been introduced for clinical analytes such as biomarkers for cancer or acute myocardial infarction (AMI). Various detection technologies involving quantitative analyzing devices have been reported to have sufficient analytical sensitivity and quantification capability for clinical point-of-care tests. Fluorescence-based detection technologies such as quantum dots, Eu(III) nanoparticles, and photon-upconverting nanoparticles (UCNPs) have been introduced as promising solutions for point-of-care devices because of their high detectability by optical sensors. Lateral flow assays can be used for various sample types, e.g., urine, saliva, cerebrospinal fluid, and blood. This study focuses on the properties of serum and plasma because of their relevance in cancer and AMI diagnostics. The limit of detection was compared in LF assays having Eu(III) nanoparticles or UCNPs as reporters and the antibody configurations for two different analytes (prostate-specific antigen and cardiac troponin I (cTnI)). The results indicate a significant effect of anticoagulants in venipuncture tubes. The samples in K₃EDTA tubes resulted in significant interference by decreased reporter particle mobility, and thus the limit of detection was up to eightfold less sensitive compared to serum samples. Despite the matrix interference in the cTnI assay with UCNP reporters, limits of detection of 41 ng/L with serum and 66 ng/L with the Li-heparin sample were obtained.     

A rapid and sensitive method based on magnetic beads for the detection of hepatitis B virus surface antigen in human serum

Current clinically assays, such as enzyme‐linked immunosorbent assay and chemiluminescence immunoassay, for hepatitis B surface antigen (HBsAg) are inferior in terms of either sensitivity and accuracy or rapid and high‐throughput analysis. A novel assay based on magnetic beads and time‐resolved fluoroimmunoassay was developed for the quantitative determination of HBsAg in human serum. HBsAg was captured using two types of anti‐HBsAg monoclonal antibodies (B028, S015) immobilized on to magnetic beads and detected using europium‐labeled anti‐HBsAg polyclonal detection antibody. Finally, the assay yielded a high sensitivity (0.02 IU/mL) and a wide dynamic range (0.02–700 IU/mL) for HBsAg when performed under optimal conditions. Satisfactory accuracy, recovery and specificity were also demonstrated. The intra‐ and interassay coefficients of variation were 4.7–8.7% and 3.8–7.5%, respectively. The performance of this assay was further assessed against a well‐established commercial chemiluminescence immunoassay kit with 399 clinical serum samples. It was revealed that the test results for the two methods were in good correlation (Y = 1.182X – 0.017, R = 0.989). In the current study, we demonstrated that this novel time‐resolved fluoroimmunoassay could be used: as a highly sensitive, automated and high‐throughput immunoassay for the diagnosis of acute or chronic hepatitis B virus infection; for the screening of blood or organ donors; and for the surveillance of persons at risk of acquiring or transmitting hepatitis B virus. Copyright © 2013 John Wiley & Sons, Ltd.     

Continuously increasing sensitivity over three generations of TSH receptor autoantibody assays

Thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (TRAb) are the hallmarks in serological diagnosis of Graves' disease (GD, autoimmune hyperthyroidism). In the 1980s, the first generation liquid-phase TRAb assay with detergent solubilized porcine TSHR was introduced into routine thyroid serology and proved to be highly specific for GD, albeit with moderate sensitivity. In the 1990 s, second generation solid-phase TRAb assays with immobilized porcine or recombinant human TSHR became available, and were clearly more sensitive for Graves' disease without loss of specificity. Recently, third generation TRAb assays have been developed, in which the human thyroid stimulating monoclonal antibody M22 replaces bovine TSH as the competing reagent for TRAb binding to TSHR. Again, an improvement in functional sensitivity was reported for this latest assay generation. To investigate the analytical (aas) and functional assay sensitivity (fas) over 3 generations of TRAb assays, pooled serum samples from patients with GD were measured 10-fold in different assay lots over a few months. The 20% inter-assay coefficients of variation (CV) were calculated and compared taking into account the different calibrations of the assay generations. The fas continuously increased from about 8 U/l of MRC B65/122 in liquid phase TRAb assays, to about 1.0 IU/l (NIBSC 90/672) in TSH based solid phase TRAb assays and to about 0.3 IU/l (NIBSC 90/672) in the M22 based TRAb assay finally. In conclusion, the fas of TRAb measurements has been improved continuously over the last 3 decades.     

Quantitative determination of atractylenolide III in rat plasma by liquid chromatography electrospray ionization mass spectrometry

Atractylenolide III is a major active component in Atractylodes macrocephala. This paper describes a simple, rapid, specific and sensitive method for the quantification of atractylenolide III in rat plasma using a liquid-liquid extraction procedure followed by liquid chromatography mass spectrometric (LC-MS) analysis. A Kromasil 3.5 microm C(18) column (150 mm x 2.00 mm) was used as the analytical column. Linear detection responses were obtained for atractylenolide III concentration ranging from 5 to 500 ng L(-1). The precision and accuracy data, based on intra-day and inter-day variations over 5 days were within 10.29%. The lower limit of quantitation for atractylenolide III was 5 ng mL(-1), using 0.1 mL plasma for extraction and its recoveries were greater than 85% at the low, medium and high concentrations. The method has been successfully applied to a pharmacokinetic study in rats after an oral administration of atractylenolide III with a dose of 20.0 mg kg(-1). With the lower limits of quantification at 5 ng mL(-1) for atractylenolide III, this method was proved to be sensitive enough for the pharmacokinetics study of atractylenolide III.     

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

Background

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.

Methods

As a proof of concept study TSH was measured in routinely collected sera at the University Medical Center Utrecht, Netherlands, using the TSH-CHECK-1 (VEDALAB, Alençon, France), a lateral-flow rapid immunochromatographic assay with a TSH cut-off value of 10 µIU/mL, the standard threshold for initiating treatment. These results were compared with TSH levels measured by a reference standard (UniCel DXi 800 imunoassay system, Beckman Coulter, USA). Sensitivity, specificity, and likelihood ratios were then calculated.

Results

A total of 215 serum samples were evaluated: 107 with TSH values <10 µIU/mL and 108 with values ≥10 µIU/mL. TSH-CHECK-1 test sensitivity was found to be 100.0% (95% CI: 96.6–100.0) and specificity was 76.6% (95% CI: 67.5–84.3). Predictive values (PV) were modelled for different levels of prevalence. For a prevalence of 10% and 50%, the positive PV was 32.2% (95% CI: 25.0–39.7%) and 81.1% (95% CI: 75.0–85.5%), respectively; the negative PV was 100% (95% CI: 98.9–100%) and 100% (95% CI: 91.3–100%) respectively.

Discussion/Conclusions

The TSH-CHECK-1 rapid test was practical and simple to perform but difficult to interpret on weak positive results. All sera with TSH≥10 µIU/mL were correctly identified, but the test lacked sufficient specificity. Given its excellent negative PV in this evaluation, the test shows promise for ruling out hypothyroidism. However, so far it appears that samples testing positive with TSH-CHECK-1 would require confirmation using another method.     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Label-free optical antibody testing kit based on a self-assembled whispering-gallery-mode microsphere

The appearance of antibodies in blood is a critical signal to suggest the infection. A rapid and accurate detection method for the antibody is significant to the disease diagnosis, especially for the epidemic. To this end, a highly sensitive whispering-gallery-mode (WGM) optical testing kit is designed and fabricated for detecting the specific immunoglobulin antibodies. The key component of the kit is a silica self-assembled microsphere decorated with the nucleocapsid proteins (N-proteins) of the SARS-CoV-2 virus. After the N-protein antibody immunoglobulin G (N-IgG) and immunoglobulin M (N-IgM) solutions being injected into the kit, the WGM red-shifts due to the antigen–antibody reaction. The wavelength displacement rates are proportional to the concentrations of these two antibodies from 1 to 100 μg/mL. A good specificity of the kit is demonstrated by the nonspecific human immunoglobulin G (H-IgG) and immunoglobulin M (H-IgM).     

Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia,Unipolar Depression or Bipolar Disorder

The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9–22.3 % for schizophrenia, 13.9–26.0 % for unipolar depression, 10.8–27.6 % for bipolar disorder, 12.2–28.5 % for bipolar depression, and 11.4–24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = ? 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = ? 0.21, p < 0.001), unipolar depression (r = ? 0.23, p < 0.001), bipolar depression (r = ? 0.25, p = 0.002) and bipolar disorder (r = ? 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.     

Persistence of the Nocturnal Thyrotropin Surge and Preservation of the Sleep-Related Variations of TSH in African Trypanosomiasis

The aim of this work was to study the nycthemeral and sleep-related variations of thyrotropin (TSH) in sleeping sickness (Human African trypanosomiasis). Six untreated patients were studied during 24 hours using 10 min blood sampling and polygraphic sleep recordings. These patients were compared to 5 healthy African subjects. The patients were selected during a medical investigation in Congo. Sleeping sickness was diagnosed clinically and confirmed by the detection of Trypanosoma brucei gambiense in the blood, the cerebrospinal fluid, or in a lymph node puncture, and by a serologic immunofluorescence test. Blood was withdrawn continuously via a catheter and sampled into 10 min aliquots in an adjoining room. TSH was measured by a commercial IRMA kit. Sleep was recorded by continuous polysomnography and scored visually. The integrity of the sleep-wake cycle varied greatly among patients, ranging from major disruption with insomnia to almost undisturbed nocturnal sleep. Mean TSH levels were slightly higher in the patients than in the controls, although the difference was not significant. The nocturnal surge was preserved in all but one patient and its amplitude was not different between patients and controls. There were more TSH pulses in the patients, maybe due to fragmented sleep with many awakenings. The relationships between sleep structure and TSH variations were preserved, with decreasing TSH levels during slow-wave sleep and increasing levels after awakenings. We conclude that contrarily to other biological rhythms, the nycthemeral pattern of TSH is preserved in the sleeping sickness patients. The TSH nocturnal surge persisted, unlike in other nonthyroidal illnesses. The relationhsips between TSH variations and sleep structure are also preserved, demonstrating the robustness of this association.     

Persistence of the Nocturnal Thyrotropin Surge and Preservation of the Sleep-Related Variations of TSH in African Trypanosomiasis

The aim of this work was to study the nycthemeral and sleep-related variations of thyrotropin (TSH) in sleeping sickness (Human African trypanosomiasis). Six untreated patients were studied during 24 hours using 10 min blood sampling and polygraphic sleep recordings. These patients were compared to 5 healthy African subjects. The patients were selected during a medical investigation in Congo. Sleeping sickness was diagnosed clinically and confirmed by the detection of Trypanosoma brucei gambiense in the blood, the cerebrospinal fluid, or in a lymph node puncture, and by a serologic immunofluorescence test. Blood was withdrawn continuously via a catheter and sampled into 10 min aliquots in an adjoining room. TSH was measured by a commercial IRMA kit. Sleep was recorded by continuous polysomnography and scored visually. The integrity of the sleep-wake cycle varied greatly among patients, ranging from major disruption with insomnia to almost undisturbed nocturnal sleep. Mean TSH levels were slightly higher in the patients than in the controls, although the difference was not significant. The nocturnal surge was preserved in all but one patient and its amplitude was not different between patients and controls. There were more TSH pulses in the patients, maybe due to fragmented sleep with many awakenings. The relationships between sleep structure and TSH variations were preserved, with decreasing TSH levels during slow-wave sleep and increasing levels after awakenings. We conclude that contrarily to other biological rhythms, the nycthemeral pattern of TSH is preserved in the sleeping sickness patients. The TSH nocturnal surge persisted, unlike in other nonthyroidal illnesses. The relationhsips between TSH variations and sleep structure are also preserved, demonstrating the robustness of this association.