Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Effects of lead exposure on biomarkers of thyroid and renal function tests among panel beaters in Enugu Metropolis, Nigeria.

Background: Occupational lead (Pb) exposure causes multisystem effects at high and sustained low doses. However, there are inconsistencies in the dose-response effects on the thyroid and kidneys. Aim: This study aimed to assess the effects of Pb exposure on the biomarkers of thyroid and renal functions among panel beaters in Enugu Metropolis, Nigeria. Subjects and Methods: This was a cross-sectional analytical study of 428-panel beaters selected using a multistage sampling technique. Blood lead (BPb), thyroid, and kidney biomarkers were analyzed using atomic absorption spectrometer at 238.3 nm wavelength, enzyme-linked immunosorbent assay, and automated chemistry analyzer, respectively. Analyses were performed using median, mean, Chi-square, correlation, and statistical significance. Results: The median BPb levels were 10.0 µg/dl among participants with about half, 211 (49.3%) having BPb within reference levels. Though the mean values of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and creatinine (Cr) were within the reference values, the majority of 275 (64.25%) of the participants had non-euthyroid statuses. Significant differences were found in TSH (P = 0.001), thyroid status (P = 0.0129), and estimated glomerular filtration rate (P = 0.00384) between those with BPb within reference level and those with elevated levels. Conclusion: Though the mean levels of thyroid hormones and Cr were within their respective reference intervals, there was a preponderance of non-euthyroid status among participants in the present study with the majority of the participants falling within CKD grades 2 and 3.

Flexible MoS2-Polyimide Electrode for Electrochemical Biosensors and Their Applications for the Highly Sensitive Quantification of Endocrine Hormones: PTH, T3, and T4.

Flexibile biosensors have a lot of applications in measuring the concentration of target bioanalytes. In combination with its flexibility, electrochemical sensors containing 2D materials have particular advantages such as enlarged area compatibility, transparency, and high scalability. A flexible biosensor was fabricated by direct synthesis of molybdenum disulfide (MoS2) on a polyimide (PI) substrate, which can be used as the working electrode in electrochemistry platforms. The direct formation of 2D-MoS2 on the PI was achieved using plasma-enhanced chemical vapor deposition (PE-CVD). Since the MoS2 provides higher electrical conductivity, the MoS2-Au-PI flexible sensor is able to provide highly sensitive detection of target proteins with a relatively fast response via cyclic voltammetry. To evaluate the high performance of the fabricated sensor, we selected the endocrine-related hormones parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) as analytes because they are one of the most important markers for the determination of endocrinopathy, however, they are very difficult to quantify. The newly developed biosensor achieved highly sensitive detection of the hormones and could determine their location with high accuracy. In addition, we performed electrochemical measurements of hormones obtained from 30 clinical patients' sera with confirmed agreement and compared with the measurements performed with standard immunoassay equipment (E 170, Roche Diagnostics, Germany).

Neonatal Thyroxine, Maternal Thyroid Function, and Cognition in Mid-childhood in a US Cohort.

OBJECTIVE: Examine the associations of maternal thyroid hormones, maternal dietary information, and newborn T4 levels with cognitive outcomes in mid-childhood. METHODS: We studied 921 children born 1999-2003 at gestational age ≥ 34 weeks, who were participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We examined maternal dietary information, maternal thyroid hormone levels, and neonatal levels of T4. Research staff performed cognitive testing in mid-childhood (median age 7.7 years). RESULTS: We included 514 women with measured first trimester thyroid hormone concentrations (mean 10.2 weeks); 15% of women had a thyroid stimulating hormone (TSH) level ≥ 2.5 mU/L, and 71% were college graduates. Newborn T4 was collected from 375 infants (mean 17.6 µg/dl; SD 4.0), on day 2 (mean 1.9 days; SD 0.7) as part of the newborn screening program. Mean (SD) verbal and nonverbal IQ, memory, and motor scores of children were 113.2 (14.3), 107.1 (16.7), 17.1 (4.4), and 92.5 (16.6) points, respectively. In multivariable analysis, first trimester maternal thyroid function (total T3, total T4, free T4, thyroid stimulating hormone (TSH) or total thyroid peroxidase (TPO) antibody levels) or newborn T4 were not associated with any of the cognitive outcomes in mid-childhood after adjustment for sociodemographic and perinatal variables. CONCLUSIONS FOR PRACTICE: Maternal or neonatal thyroid hormone levels were not associated with cognitive outcomes in mid-childhood in this population with generally normal thyroid function. As we studied a highly educated cohort residing in an iodine-sufficient area, findings may not be generalizable.

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p = .051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p = .025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (protein product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in age-related TDP-43 proteinopathy.

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh's indirect method after exclusion of individuals younger than 15 years, subjects with repeated TSH tests and with abnormal free thyroxine (fT4), free triiodothyronine (fT3) or anti-thyroid-peroxidase antibodies. The combined effect of age and gender on TSH values was evaluated. Results RIs estimated in the selected individuals (n = 22602) were, respectively, 0.18-3.54 mIU/L (general), 0.19-3.23 mIU/L (men) and 0.18-3.94 mIU/L (women). Women showed significantly higher median TSH than men (1.46 vs. 1.39 mIU/L; p < 0.0001). Both in men and in women, median TSH decreased along with age; however, although up to 60 years in both men and women showed similar values, afterwards women showed constantly higher TSH than men. Accordingly, statistical analysis showed a significant interaction between gender and age (p = 0.001), suggesting that the effect of age on TSH is different between genders. Conclusions Our findings suggest that the indirect method, with appropriate cleaning of data, could be useful to define TSH RIs.

Thyroid Disease in Pregnancy: A Clinical Survey among Endocrinologists, Gynecologists, and Obstetricians in Israel.

OBJECTIVES: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel. METHODS: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified. RESULTS: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions. CONCLUSIONS: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

Rapid Identification of Unknown Organic Iodine in Small-Volume Complex Biological Samples Based on Nanospray Mass Spectrometry Coupled with in-Tube Solid Phase Microextraction.

A new method for rapid screening of unknown organic iodine (OI) in small-volume complex biological samples was developed using in-tube solid phase microextraction (SPME) nanospray mass spectrometry (MS). The method proposed a new identification scheme for OI based on nanospray high-resolution mass spectrometry (HR-MS). The mass ranges of OI ions were confirmed using the t-MS2 scan mode first; then, the possible precursor ions of OI were selected and identified orderly in full MS/ddMS2 and t-MS2 scan modes. Besides, in-tube SPME was used for the pretreatment of small-volume biological samples, and it was the first time in-tube SPME combined with nanospray MS for OI identification. The whole analysis procedure took only 8 min and consumed 50 µL per sample. Using the new method, six kinds of OI added to urine and an unknown OI C12H23O11I in human milk were successfully identified. Moreover, the proposed identification scheme is also suitable for other ambient mass spectrometry (AMS) to determine unknown compounds with characteristic fragment ions.

Standardization of Free Thyroxine Measurements Allows the Adoption of a More Uniform Reference Interval.

BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests intended to standardize free thyroxine (FT4) immunoassays. We developed a Système International d'Unités traceable conventional reference measurement procedure (RMP) based on equilibrium dialysis and mass spectrometry. We describe here the latest studies intended to recalibrate against the RMP and supply a proof of concept, which should allow continued standardization efforts. METHODS: We used the RMP to target the standardization and reference interval (RI) panels, which were also measured by 13 manufacturers. We validated the suitability of the recalibrated results to meet specifications for bias (3.3%) and total error (8.0%) determined from biological variation. However, because these specifications were stringent, we expanded them to 10% and 13%, respectively. The results for the RI panel were reported as if the assays were recalibrated. We estimated all but 1 RI using parametric statistical procedures and hypothesized that the RI determined by the RMP was suitable for use by the recalibrated assays. RESULTS: Twelve of 13 recalibrated assays had a bias, meeting the 10% specification with 95% confidence; for 7 assays, this applied even for the 3.3% specification. Only 1 assay met the 13% total error specification. Recalibration reduced the CV of the assay means for the standardization panel from 13% to 5%. The proof-of-concept study confirmed our hypothesis regarding the RI but within constraints. CONCLUSIONS: Recalibration to the RMP significantly reduced the FT4 immunoassays' bias, so that the RI determined by the RMP was suitable for common use within a margin of 12.5%.

Incorporating thyroid markers in Down syndrome screening protocols.

OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.

Evidence of the Presence of Thyroid Hormones in Achatina fulica Snails.

The objective of this study was to identify thyroid hormones and to examine their putative site of synthesis in Achatina fulica snails. For this purpose, radioimmunoassays were performed for T3 and T4 before and after long starvation with or without hemolymph deproteinization. Sodium/iodide symporter activity in vivo was analyzed through 125I administration with and without KClO4 pretreatment. Only T4 was detected, and its concentration decreased due to starvation or deproteinization. However, high-performance liquid chromatography analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not detected in the A. fulica hemolymph. The sodium/iodide symporter activity was greater in cerebral ganglia than digestive gland, but KClO4 treatment did not inhibit iodide uptake in any of the tissues analyzed. Altogether, our data confirm for the first time the presence of thyroid hormones in A. fulica snails and suggest their participation in the metabolism control in this species, although the putative site of hormone biosynthesis remains to be elucidated.

A multi-analyte immunoassay for thyroid related analytes.

We describe the development and validation of multianalyte immunoassays (MAIA) for three analytes, viz., thyroxine (T4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) essential for assessment of thyroid function but having widely varying molecular weights. Using polycarbonate (PC) track-etched membranes (TEM) as an immobilization support and 125I as the tracer, both competitive assay for T4 and non-competitive assay for TSH and Tg were performed on the same TEM. MAIA was found to be highly sensitive and precise with clinically useful working range and correlated very well with individual analyte immunoassays. While we have demonstrated this assay format with radiotracer, it can be used with non-isotopic tracers equally well.

[SUBCLINICAL HYPOTHYROIDISM].

Subclinical hypothyroidism is a rather common disorder of the thyroid gland. Despite the fact that subclinical hypothyroidism has no clear-cut clinical picture, this condition is associated with changes in various organs and systems, moreover, it is a risk factor of cardiovascular diseases. The article summarizes the available data on subclinical hypothyroidism, principles of its diagnostics and treatment.

Thyroid function and cardiovascular disease risk factors in euthyroid adults: a cross-sectional and longitudinal study.

OBJECTIVE AND DESIGN: We explored the cross-sectional and longitudinal associations of thyroid function within the normal range with cardiovascular disease (CVD) risk factors and adiposity measures. PATIENTS AND MEASUREMENTS: A total of 3483 (50·4% women) participants for the cross-sectional CVD study and 1630 (41·2% women) participants for the cross-sectional body composition substudy were drawn from the Framingham Third Generation Exam 1; 2912 participants (50·1% women) for the longitudinal CVD study and 713 participants (35·9% women) for the longitudinal body composition substudy were drawn from the Framingham Third Generation Exams 1-2. Thyroid function was assessed by thyrotropin [thyroid-stimulating hormone (TSH)] and free thyroxine (fT4) concentrations within the reference range at Exam 1. The associations between thyroid function and CVD risk factors were modelled via multivariable-adjusted regression models. Multivariable adjustment included age, sex, current smoking, postmenopausal status and BMI. RESULTS: Cross-sectionally, higher TSH concentration was associated with increased odds of hypertriglyceridaemia [odds ratio (OR)=1·10], and higher BMI (ß = 0·19 kg/m2 ), total cholesterol (ß = 0·05 mmol/l), triglycerides (ß = 0·0006 mmol/l) and subcutaneous adipose tissue (SAT) volume (ß = 38·8 cm3 ) (all P < 0·05). Cross-sectionally, fT4 was inversely associated with metabolic and adiposity-related CVD risk factors, including obesity (OR = 1·17), hypertriglyceridaemia (OR = 1·09), BMI (ß = 0·42 kg/m2 ), total cholesterol (ß = 0·05 mmol/l), triglycerides (ß = 0·0002 mmol/l), visceral adipose tissue (VAT) volume (ß = -20·7 cm3 ) and attenuation (0·17 HU) and VAT/SAT ratio (ß = -0·01) (all P < 0·05). However, during 6·1 years of follow-up, baseline TSH and fT4 levels were not longitudinally associated with CVD risk factors and adiposity measures. CONCLUSIONS: Thyroid function within the normal range is cross-sectionally, but not longitudinally, associated with CVD risk factors and adiposity measures.

A low incidence of iodine-induced hyperthyroidism following administration of iodinated contrast in an iodine-deficient region.

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.

Nivolumab-induced thyroid dysfunction.

Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.

Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints.

BACKGROUND: Brominated flame retardants (BFRs) are endocrine disruptors that bioaccumulate in the placenta, but it remains unclear if they disrupt tissue thyroid hormone (TH) metabolism. Our primary goal was to investigate associations between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH sulfotransferase (SULT) activities. METHODS: Placenta samples collected from 95 women who delivered term (>37 weeks) infants in Durham, NC, USA (enrolled 2010-2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6-tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT activities. RESULTS: PBDEs and 2,4,6-TBP were detected in all placenta samples. PBDEs were higher in placental tissues from male infants compared to female infants, with 2,4,6-TBP and BDE-209 levels approximately twice as high. Among male infants, placental BDE-99 and BDE-209 were negatively associated with rT3 placental levels. For female infants, placental BDE-99 and 2,4,6-TBP were positively associated with T3 concentrations. DIO3 activity was also significantly higher in placental tissues from male infants compared to females, while 3,3'-T2 SULT activity was significantly higher in placental tissues from females compared to males. Among males, several PBDE congeners were positively correlated with T3 SULT, while BDE-99 was negatively associated with T3 SULT among females. Associations generally remained after adjustment for potential confounding by maternal age and gestational age at delivery. CONCLUSIONS: These results suggest BFRs accumulate in the placenta and potentially alter TH function in a sex-specific manner, a possible mechanism to explain the sex-dependent impacts of environmental exposure on children's growth and development. More research is needed to elucidate the effects of BFRs on placenta function during pregnancy, as well as the biological consequences of exposure and thyroid disruption.

Pharmaceutical studies of levothyroxine sodium hydrate suppository provided as a hospital preparation.

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital's protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4 °C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.

Aspartate aminotransferase and free thyroid hormones in vaginal washing fluid as markers for preterm pre-labor rupture of membranes.

AIM: To evaluate the diagnostic value of vaginal fluid aspartate aminotransferase (AST), free triiodothyronine (T3) and free thyroxine (T4 ) in women with preterm pre-labor rupture of membranes (PPROM). METHODS: A case-control study was carried out of 100 women: 50 with PPROM (study group) and 50 age-, gestational age- and weight-matched women with intact membranes (control group). All women underwent sterile speculum vaginal examination. The vaginal posterior fornix was irrigated and the retrieved fluid was sent for AST, free T3 and free T4 assays. RESULTS: Median vaginal fluid free T3, free T4 and AST were significantly higher in the PPROM group compared with the control group, with vaginal fluid free T4 having the largest area under the curve on receiver operating characteristic curve analysis (P<0.001). Sensitivity, specificity, positive and negative predictive values for free T3 (cut-off, 1.06 pg/mL) were 88%, 70%, 74.6% and 85.4%, respectively, while those for free T4 (cut-off 0.063 ng/dL) were 86%, 72%, 75.4% and 83.7%, and those for AST (4.5 IU/L) were 56%, 70%, 65.1% and 61.4%, respectively. Vaginal fluid AST had less diagnostic accuracy when compared with either free T3 or free T4. CONCLUSIONS: Vaginal fluid AST, free T3 and free T4 seem to be useful and simple markers in diagnosis of PPROM.

[FT4 immunoassay interference : A case report]. / Interférence sur l'immunodosage de la FT4 : A propos d'une observation.

Measurement of thyrotropin and free thyroxin made using immunoassays are usually needed in clinical endocrinology. Here, we report a case of a patient with type 2 diabetes who presented a weight loss. To eliminate hyperthyroidism, thyroid function tests were performed. Free thyroxin (FT4) was decreased using two automated immunoassays TOSOH AIA 1800 and Roche ELECSYS 2010, with a normal thyrotropin value. Thyroid function tests repeated a month later were normal. The patient's history revealed contact with sheep, which may partly explain the interference. Investigations into the patient's serum were carried out using both the PEG test and dilution test. Interference factors were probably antibodies. Despite progress in immunoassays, we should be aware of interference occurrence since it can lead to false results, unnecessary investigations and incorrect treatment. Thus, simple tests must be carried out as if interference in immunoassays were suspected. Dilutions and PEG tests are generally performed as first line investigations.