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Offie P Soldin

Publications and source records attributed to Offie P Soldin.

13 recordsLinked to original sources

Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals.

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.

Female↗

Pediatric brain natriuretic peptide and N-terminal pro-brain natriuretic peptide reference intervals.

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown to be useful biomarkers for the diagnosis of heart failure. Pediatric reference intervals for these analytes have been reported in part. Previous studies lack large numbers in each group, have not covered all age ranges and have not compared results for BNP with NT-proBNP in simultaneously drawn samples. METHODS: We measured BNP in whole blood using the Biosite Triage point-of-care method and plasma NT-proBNP using the Dade RxL Dimension. We assessed between and within-day precision of both methods and after removing outliers employed the Hoffmann approach to calculate pediatric reference intervals over the age range of 0-21 y. We also compared the 2 methods on simultaneously drawn samples. RESULTS: Reference intervals revealed approximately 20-fold higher 97.5th percentiles for neonates than for children >3 y of age. 97.5th percentiles decreased significantly over the first 3 years of life. As shown by others, the CVs for the automated Dade RxL platform were somewhat lower than those for the POCT method. BNP and NT-proBNP correlated well in simultaneously drawn samples (r=0.947). DISCUSSION: Reference intervals for BNP and NT-proBNP are far higher in neonates and infants than in children older than three years of age. The reasons for this are unknown but resemble the elevated CK-MBs and troponins also found in neonates, although the 97.5th percentiles for these latter 2 cardiac markers decrease more rapidly to values found in older children by 6 months of age.

Adolescent↗

The measurement of free thyroxine by isotope dilution tandem mass spectrometry.

BACKGROUND: Most clinical chemistry laboratories measure free thyroxine (FT4) by an analogue (direct) method. Nevertheless, the validity of analogue FT4 immunoassays has been questioned and patient's results using this approach frequently do not fit in with the clinical presentation. Because of these problems we routinely send out all direct free T4's that are < 2.5th percentile and many that are > 97.5th percentile for measurement by equilibrium dialysis, the gold standard method. In approximately half of these cases, the FT4 by equilibrium dialysis was normal. We developed a rapid, reliable free T4 method employing isotope dilution tandem mass spectrometry and compared our results with both the analogue (direct) free T4 and equilibrium dialysis procedures. METHODS: An API-4000 tandem mass spectrometer (Sciex, Toronto, Canada) equipped with TurboIonSpray and Agilent HPLC system was used employing isotope dilution with deuterium labeled internal standard (IS=l-thyroxine-d2). Serum was filtered through the Centrifree YM-30 ultrafiltration device by centrifugation, IS added to the ultrafiltrate, and 400 microL injected onto a C-18 column. After washing, the switch valve is activated and a methanol gradient allows for elution of both T4 and the IS into the LC/MS/MS system. Quantitation was by MRM analysis in the negative mode. Equilibrium dialysis was performed by the Nichols method and analogue free T4 results were obtained on the Dade Dimension RxL. RESULTS: The within-day and between-day CV's were < 7.1% at all concentrations tested. The results correlated well with equilibrium dialysis (Eq Dial=0.971 MS+0.041, n=68, Syx=1.381, r=0.954). A poor correlation was found with the analogue (direct) free T4 method (IA=0.326 MS+6.27, n=154, Syx=1.96, r=0.459). CONCLUSIONS: Samples can be processed in batches of 30. The free T4 tandem MS method has a rapid turn-around-time vs the equilibrium dialysis procedure, with a chromatographic run time of 8 min per sample.

Chromatography, Liquid↗

Pediatric reference intervals for FSH, LH, estradiol, T3, free T3, cortisol, and growth hormone on the DPC IMMULITE 1000.

BACKGROUND: We studied serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), triiodothyronine (T3), free T3 (FT3), cortisol and growth hormone (GH) concentrations in a population of pediatric patients. The reference intervals were determined separately for females and males stratified by age groups to assess age- and sex-related differences. Our objective was to obtain reference intervals for the 7 serum analytes for our pediatric population using the IMMULITE 1000 system. METHODS: Serum samples of 800 in- and out-patients, newborn to 19 years old were analyzed using the DPC IMMULITE 1000 chemiluminescent immunoassay system. RESULTS AND CONCLUSIONS: We report pediatric reference intervals for FSH, LH, E2, T3, FT3, cortisol, and GH. These reference intervals provide the basis for clinical interpretation of laboratory results using the IMMULITE 1000 system and the assessment of child development.

Adolescent↗

Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry.

OBJECTIVE: To establish normal, trimester-specific reference intervals for serum 17beta-estradiol, progesterone (P), 17alpha-hydroxyprogesterone, cortisol, 11-deoxycortisol, androstenedione, DHEA, and DHEAS, measured simultaneously using isotope dilution tandem mass spectrometry. DESIGN: Sequential cohort study. PATIENT(S): Healthy women undergoing a normal pregnancy (age, 25-38 years; mean, 30 years) attending a prenatal well clinic at gestation weeks 12, 22, and 32 and approximately 1 year postpartum. MAIN OUTCOME MEASURE(S): Trimester-specific reference intervals of endogenous steroid hormones analyzed using an isotope dilution tandem mass spectrometer equipped with an atmospheric pressure photoionization source with deuterium-labeled internal standards. RESULT(S): Serum estradiol, P, 17alpha-hydroxyprogesterone, and 11-deoxycortisol increased throughout pregnancy; cortisol increased up to the second trimester and then remained steady, while androstenedione increased by 80 percent by gestation week 12, then remained constant. Serum DHEA-S decreased by 50% by the third trimester. CONCLUSION(S): Trimester-specific reference intervals are reported for eight serum steroids. The ratios of individual serum hormone concentrations during pregnancy relative to their 1-year postpartum concentrations illustrate the expected normal trends of changes in hormone concentrations during pregnancy.

Adult↗

Do thyroxine and thyroid-stimulating hormone levels reflect urinary iodine concentrations?

The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an "iodine-sufficient population." Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988-1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15-44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status.

Adolescent↗

Serum iron, ferritin, transferrin, total iron binding capacity, hs-CRP, LDL cholesterol and magnesium in children; new reference intervals using the Dade Dimension Clinical Chemistry System.

BACKGROUND: We studied serum/Plasma iron, ferritin, transferrin concentrations, and total iron binding capacity (TIBC) in addition to highly sensitive C-reactive protein (hs-CRP), low-density lipoprotein (LDL) cholesterol and magnesium concentrations in a population of 800 in- and outpatients and defined new 95% reference intervals for pediatrics using the Dade Behring RxL Dimension Clinical Chemistry System. METHODS: Plasma/serum concentrations of the above analytes were determined on patient samples accrued from January to June 2003 and the data were analyzed employing a computer adapted Hoffmann approach. RESULTS AND CONCLUSIONS: New pediatric reference intervals on the Dade RxL Dimension were obtained for serum iron, ferritin, transferrin, TIBC, hs-CRP, LDL-cholesterol and magnesium. This work represents the first hs-CRP data for children <3 years old. The values for all the analytes were established on new data (n=800). These values are new for hs-CRP and LDL cholesterol, while for iron, ferritin and magnesium these intervals are more reliable than those previously published by our group which had used regression equations on samples measured by the old (Vitros/Immuno1) methods for which intervals were available.

Adolescent↗

Isotope dilution tandem mass spectrometric method for T4/T3.

BACKGROUND: The thyroid hormones thyroxine (T4) and 3,5,3'-triidothyronine (T3) are essential for regulating a number of biological processes, including growth, neurodevelopment, carbohydrate metabolism, oxygen consumption and protein synthesis. Immunoassays are the current methods for thyroid hormone measurement and suffer from a lack of specificity. Our objective was to simultaneously measure T4 and T3 using isotope dilution tandem mass spectrometry within a single run. To compare the results obtained by this MS/MS method with those obtained by an immunoassay procedure on the same samples (DPC Immulite for T3, Diagnostics Product, and Dade RxL Dimension for T4, Dade-Behring). METHODS: An API-3000 tandem mass spectrometer (SCIEX, Toronto, Canada) equipped with TurboIonSpray and Shimadzu HPLC system was used employing isotope dilution with deuterium-labeled internal standard (l-thyroxin-d2). The method requires 100 microl of serum and involves addition of internal standard, precipitation of proteins with methanol and injection of the supernatant onto a C-18 column. After washing, the switch valve is activated and T4 and T3 eluted using a methanol gradient. T4 and T3 by immunoassay were performed using the Dade RxL Dimension and the DPC Immulite, respectively. RESULTS AND CONCLUSIONS: An isotope dilution tandem mass spectrometry method for the simultaneous determination of total T4 and T3 in serum is described which is accurate, specific, precise (%CVs 3.5-9.0), simple and fast (<7 min).

Humans↗

Differences between measurements of T4 and T3 in pregnant and nonpregnant women using isotope dilution tandem mass spectrometry and immunoassays: are there clinical implications?

BACKGROUND: It has been established that triiodothyronine (T3) and thyroxine (T4) measurements by tandem mass spectrometry (MS/MS) are more specific and are significantly different from immunoassay (IA) measurements (all p< or =0.05) throughout pregnancy. In this study, we examined the clinical implications of these discrepancies. METHODS: Kappa statistics were used to determine the degree to which IA and MS/MS agreed in their identification of out-of-reference interval observations of circulating T4 and T3 from 52 normal, iodine-sufficient women during each trimester of pregnancy. RESULTS: After taking chance agreement into account, the two methods had poor agreement on classification of T3 values at the first (kappa=0.185) and second (kappa=0.183) trimesters, with extremely poor agreement for the third trimester and 1-year postpartum. Agreement on T4 was poor only for the third trimester (kappa=0.183). The two methods agreed on out-of-range values in only 0-25% of T3 cases and 25-66.7% of T4 cases. CONCLUSIONS: The areas of disagreement suggest that women at risk (i.e., with analyte values outside of the 5-95% range) will not be detected using IA. Based on this cohort, our preliminary estimates are that 25-100% of such women would be missed if IA were used to assay the analyte.

Adult↗

Steroid hormones: relevance and measurement in the clinical laboratory.

Steroid hormones are synthesized in the adrenal cortex, the gonads, and the placenta; are all derived from cholesterol and many are of clinical importance. This article addresses the relevance and methods of measurement of steroid hormones in the clinical laboratory.

Chemistry, Clinical↗

Hypothyroidism during pregnancy.

QUESTION: I have a 27-year-old patient diagnosed with hypothyroidism in the 8th week of pregnancy. She received conflicting opinions regarding risk for her baby and wants to get more information. I also found conflicting information in the literature. How should I advise her? ANSWER: Pregnant patients with untreated hypothyroidism are at increased risk of obstetric complications. Adequate treatment with thyroid hormones greatly reduces the frequency of these complications. Observational studies suggest that children whose mothers had hypothyroxinemia in early pregnancy have lower IQs than matched controls. Another study has shown that even if levothyroxine therapy is started after the first trimester, there is an excellent chance children will have normal neuropsychologic development.

Adult↗

Milk transfer and neonatal safety of tacrolimus.

OBJECTIVE: To report the first case of tacrolimus measurement in human milk following maternal dosing in a woman who breast-fed while taking the medication. CASE REPORT: A 32-year-old white woman who had taken tacrolimus 0.1 mg/kg/d throughout pregnancy contacted the Motherisk Program at 35 weeks' gestation inquiring about the safety of breast-feeding during maternal tacrolimus therapy. After benefit-risk assessment, the mother decided to breast-feed the baby. METHODS: Manually expressed milk samples were collected over 12 hours following the first tacrolimus dose of the day; pre-dosing and 1-hour post-dosing blood concentrations were also determined. The samples were analyzed for tacrolimus by tandem-mass spectrometry. Breast milk and blood samples were collected at steady-state. RESULTS: The highest and mean concentrations of tacrolimus in milk were 0.57 and 0.429 ng/mL, respectively. From these measurements, the exclusively breast-fed infant would ingest, on average, 0.06 micro g/kg/d, which corresponds to 0.06% of the mother's weight-adjusted dose. Given the low oral bioavailability of tacrolimus, the maximum amount the baby would receive is 0.02% of the mother's weight-adjusted dose. The milk-to-blood ratios of tacrolimus at pre-dosing and 1-hour post-dosing concentrations were calculated to be 0.08 and 0.09, respectively. At 2.5 months of age, the infant was developing well both physically and neurologically. COMMENT: This report is the first to measure tacrolimus concentrations in established human milk using tandem-mass spectrometry to detect drug while the infant was exclusively breast-fed by the mother, and in which the infant's growth and development were reported. CONCLUSIONS: Our results suggest that maternal therapy with tacrolimus for liver transplant may be compatible with breast-feeding.

Adult↗