To determine if various medical conditions affect the serum concentrations of 3,3'-diiodothyronine (3,3'-T2).
A total of 100 patients who were recruited from a group of inpatients and outpatients ...with a diverse range of medical conditions, donated a single blood sample that was assayed for thyroid hormone derivatives using liquid-chromatography tandem mass spectrometry (LC-MS/MS). The associations between 3,3'-T2 concentrations and physiologic data and medical conditions were assessed.
Higher quartiles of 3,3'-T2 concentrations (quartile 1: 2.01-7.48, quartile 2: 7.74-12.4, quartile 3: 12.5-17, quartile 4: 17.9-45.8 pg/mL) were associated with decreasing occurrence of critical illness (58%, 11%, 0%, 8%), stroke (29%, 7.7%, 4%, 0%), critical care unit hospitalization (75%, 39%, 8.3 %, 12%), and inpatient status (83%, 42%, 8%, 12%) (all P<.001). The same quartiles were associated with increasing frequency of thyroidectomy (4%, 12%, 17%, 60%). In multivariate analyses, after adjustment for age and sex, inpatient status was associated with decreasing concentrations of 3,3'-T2 (46% decrease for inpatients with 95% confidence interval CI 32-57%, P<.0001). Thyroidectomy was associated with increasing concentrations of 3,3'-T2 (29% increase (CI 0.5-66%, P = .049).
We observed associations between inpatient status and reduced 3,3'-T2 concentrations. This appears to be a global change associated with illness, rather than an association with specific medical conditions. We also observed higher 3,3'-T2 concentrations in athyreotic outpatients receiving thyroid-stimulating hormone (TSH) suppression therapy. This demonstrates that there is production of 3,3'-T2 from levothyroxine (LT4) in extrathyroidal tissues. Conversion of thyroxine (T4) to 3,3'-T2 via both triiodothyronine (T3) and reverse triiodothyronine (rT3) pathways may prevent excessive T3 concentrations in such patients.
We evaluated the clinical validity of serum FT4 measurements by assessing its correlation with log TSH. To provide pediatric reference intervals (representative ranges) for FT4, and TSH on the ...Architect ci8200 integrated system.
This population-based study encompassed 6023 children (3369 females and 2654 males). The percentile and Hoffmann approaches for obtaining reference intervals on these analytes were also compared.
FT4 correlation with log TSH was poor (
r
=
0.010 for males and 0.050 for females). Reference intervals were established. TSH and FT4 did not show a significant sex difference; moreover, the intervals decreased with age for FT4 and TSH.
Whereas in a previous study ultrafiltration tandem mass spectrometry yielded a correlation of
r
=
0.90 for FT4 vs. log TSH this present study reveals a poor FT4 vs. log TSH correlation in the pediatric population studied and indicates the FT4 immunoassay conducted on the Abbott Architect ci8200 is less useful clinically than might have been expected. Reference intervals using the Hoffmann approach for pediatric in- and out-patients compare well with previously published results utilizing the percentile approach.
Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective ...study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms.
Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000.
Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8.
A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.
Maintenance of fluid homeostasis during periods of heightened physical stress can be best evaluated in humans using exercise as a model. Although it is well established that arginine vasopressin ...(AVP), aldosterone and atrial natriuretic peptide (ANP) are the principle hormones regulating fluid balance at rest, the potential contributions of other related endocrine factors, such as oxytocin (OT) and brain natriuretic peptide (BNP), have not been well described during exercise. Seven endurance-trained runners completed three separate running trials: a maximal test to exhaustion (high intensity), a 60-min treadmill run (steady state), and a 56 km ultramarathon (prolonged endurance exercise). Statistically significant pre- to post-run increases were found only following the ultramarathon in AVP(p) (1.9 vs 6.7 pg/ml; P<0.05), OT(p) (1.5 vs 3.5 pg/ml; P<0.05), NT-proBNP(p) (23.6 vs 117.9 pg/ml; P<0.01), interleukin 6(p) (4.0 vs 59.6 pg/ml; P<0.05), cortisol(p) (14.6 vs 32.6 microg/ml; P<0.01), corticosterone(p) (652.8 vs 3491.4 ng/ml; P<0.05) and 11-deoxycortisol(p) (0.1 vs 0.5 microg/ml; P<0.05) while a significant post-run increase in aldosterone(p) was documented after high-intensity (4.9 vs 12.5 ng/ml; P<0.05), steady-state (6.1 vs 16.9 ng/ml; P<0.05) and prolonged endurance running (2.6 vs 19.7 ng/ml; P<0.05). Similarly, changes in fluid balance parameters were significantly different between the ultramarathon versus high-intensity and steady-state running with regard to plasma volume contraction (less % contraction), body weight loss (increased % weight loss), plasma Na(+) Delta (decreased from baseline), and urine osmolality Delta (increase from baseline). Hypothetically driven relationships between OT(p) and AVP(p) (r=0.69; P<0.01) and between NT-proBNP(p) Delta and plasma Na(+) Delta (r=-0.79; P<0.001)--combined with the significant and unexpected pre- to post-race increases after prolonged endurance exercise--allows for possible speculation that OT and BNP may assist their better known companion hormones (AVP and ANP) in the regulation of fluid balance during conditions of extreme physical stress.
This study sought to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex.
A PK study was performed after administration of a tracer dose of carbon-13-labeled ...LT4 (
C-LT4). The study was conducted at an academic medical center. Adults of any age being treated with levothyroxine for hypothyroidism were enrolled in the study. A single dose of
C-LT4 was administered. Eighteen serial plasma samples were collected. One sample was obtained before the
C-LT4 dose, and the majority of the remaining samples were collected over the 120-hour period post dosing.
C-LT4 concentration was quantified using liquid chromatography tandem mass spectrometry. PK analysis was conducted using a linear log trapezoidal non-compartmental analysis using Phoenix 6.4.
Eight males and 33 females with a median age of 50 years (range 22-78 years) and median weight of 65.9 kg (range 50-150 kg) were enrolled in the study. The median
C-LT4 dose administered was 100 μg (range 70-300 μg). The median oral clearance rate (CL/F), apparent volume of distribution (V/F), time to peak concentration (T
), and dose-normalized peak concentration (C
) of
C-LT4 were estimated to be 0.712 L/h, 164.9 L, 4 h, and 7.5 ng/L/μg, respectively. The dose-normalized area under the concentration-time curve from time 0 to 120 hours and half-life of the terminal distribution phase were 0.931 ng.h/mL/μg and 172.2 h, respectively. There was no significant difference in any
C-LT4 PK parameter between patients aged >60 years (n = 10) and patients aged ≤60 years (n = 31), nor was there a relationship between age as a continuous variable and
C-LT4 PK parameters. Sex only affected CL/F, V/F, and dose-normalized C
in univariate analyses. However, after adjusting for weight, sex was no longer a significant covariate. Weight was a significant predictor for CL/F, V/F and dose-normalized C
of
C-LT4 in multivariate analyses.
Prior studies suggest that patient age affects levothyroxine dose requirement. This study did not identify an effect of age and suggests that age-related changes in levothyroxine pharmacokinetics may be mediated by age-related weight differences. Physicians should consider a patient's weight, rather than age, for estimating levothyroxine dosage requirement.
Triptans in pregnancy Soldin, Offie P; Dahlin, Julia; O'Mara, Daniel M
Therapeutic drug monitoring,
02/2008, Volume:
30, Issue:
1
Journal Article
Peer reviewed
Open access
The triptans are a class of tryptamine-based drugs indicated for in the treatment of migraine headaches. The triptans act as serotonin (5-hydroxytriptamine) (5-HT) agonists by binding to various ...serotonin receptors, causing vasoconstriction and neuronal inhibition to alleviate migraines. There are 7 types of triptans currently available on the U.S. market: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. The objective of this study was to examine the use and effects of triptans in pregnancy. Although three of the triptans have pregnancy registries maintained by the manufacturer, triptan use in pregnancy has not been extensively studied. Information on the use of sumatriptan during pregnancy is relatively more abundant, because it has been on the market longer than the other triptans and may also have a higher percentage of the market share. There are no data to suggest teratogenicity for any of the triptans, although preterm birth rates appear to be elevated.
Original Abstract: La modificacion del perfil de acidos grasos (AG) del aceitc de soja constituye una meta estrategica para desarrollar genotipos con valor agregado. El estudio de las correlaciones ...geneticas permite predecir respuestas correlacionadas para disenar la metodologia de seleceion. El objetivo fue determinar las asociaciones geneticas entre variables agronomicas y los AG e identificar genotipos con modificaciones de AG. Se evaluaron 22 lineas F sub(6) de soja, derivadas de cruzamientos dialelicos entre cultivares comereiales y genotipos exoticos, en 2006 en Marcos Juarez (Cordoba) y Villa Mercedes (San Luis), en un discno de bloques completes al azar con 2 repeticiones. Se evaluo: rendimiento (PG), peso de semillas (PS), aceitc (MG), acido oleico, linoleico, linolenico, palmitico, estearico. Las correlaciones geneticas se estimaron con un Analisis de Componentes Principales sobre los residuos que contienen la variation del genotipo mas la interaction genotipo por variable, y se visualizaron en un grafico Biplot. PG presento correlation genetica positiva con MG, oleico, estearico, palmitico y negativa con linoleico. PS manifesto correlacion positiva con oleico y negativa con el resto de los AG. MG tuvo correlacion positiva con estearico, palmitico y linolenico y ncgativa con linoleico. Entre los AG se observaron correlaciones ncgativas dc oleico con palmitico, linoleico y linolenico y positiva con estearico. Se identificaron genotipos que expresaron alto contenido de oleico y mayor PS, genotipos con mayor PG, MG y palmitico y otros con alto contenido de linoleico. La information obtenida aumenta la eficacia de la selection y permite desarrollar genotipos de soja con calidad diferencial mejorada.
Haemolysis of serially collected insulin serum samples frequently causes falsely‐low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if ...bacitracin, an in vitro IDE inhibitor, could prevent haemolysis‐induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose‐finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0‐2.5 g/L) and from non‐experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose‐finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin‐containing samples were significantly higher than from those without bacitracin (P < .01), and not different from non‐haemolysed samples obtained simultaneously from a second intravenous catheter (P = .07). Bacitracin did not significantly alter insulin concentrations in non‐haemolysed samples. Bacitracin attenuates haemolysis‐associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.
Substantial evidence suggests that circulating ovarian steroids modulate behavior differently in women with PMDD than in those without this condition. However, hormonal state-related abnormalities of ...neural functioning in PMDD remain to be better characterized. In addition, while altered neural function in PMDD likely co-exists with alterations in intrinsic cellular function, such a relationship has not been explored. Here, we investigated the effects of ovarian steroids on basal, resting regional cerebral blood flow (rCBF) in PMDD, and, in an exploratory analysis, we tested whether the rCBF findings were linked to the expression of ESC/E(Z) genes, which form an essential ovarian steroid-regulated gene-silencing complex. Resting rCBF was measured with oxygen-15 water PET (189 PET sessions in 43 healthy women and 20 women with PMDD) during three self-as-own-control conditions: GnRH agonist (Lupron)-induced ovarian suppression, estradiol add-back, and progesterone add-back. ESC/E(Z) gene expression data were obtained from RNA-sequencing of lymphoblastoid cell lines performed in a previous study and were examined in relation to hormone-induced changes in rCBF. In the rCBF PET data, there was a significant diagnosis-by-hormone interaction in the subgenual cingulate (P
= 0.05), an important neuroanatomical hub for regulating affective state. Whereas control women showed no hormonally-related changes in resting rCBF, those with PMDD showed decreased resting rCBF during both estradiol (P = 0.02) and progesterone (P = 0.0002) add-back conditions. In addition, in PMDD, ESC/E(Z) gene expression correlated with the change in resting rCBF between Lupron-alone and progesterone conditions (Pearson r = -0.807, P = 0.016). This work offers a formulation of PMDD that integrates behavioral, neural circuit, and cellular mechanisms, and may provide new targets for future therapeutic interventions.
The parallel response of sweat rate and urine production to changes in plasma osmolality and volume support a role for arginine vasopressin (AVP) as the main endocrine regulator of both excretions. A ...maximal test to exhaustion and a steady-state run on a motorised treadmill were both completed by 10 moderately trained runners, 1 week apart. Sweat, urine and serum sodium concentrations (Na+) were evaluated in association with the plasma concentrations of cytokines, neurohypophyseal and natriuretic peptides, and adrenal steroid hormones. When data from both the high-intensity and steady-state runs were combined, significant linear correlations were noted between: sweat Na+ versus postexercise urine Na+ (r=0.80; p<0.001), postexercise serum Na+ versus both postexercise urine Na+ (r=0.56; p<0.05) and sweat Na+ (r=0.64; p<0.01) and postexercise urine Na+ versus postexercise plasma arginine vasopressin concentration (AVP(P)) (r=0.48; p<0.05). A significant positive correlation was noted between postexercise AVP(P) and sweat Na+ during the steady-state condition only (r=0.66; p<0.05). These correlations suggest that changes in serum Na+ during exercise may evoke corresponding changes in sweat and urine Na+, which are likely regulated coordinately by changes in AVP(P) to preserve body fluid homeostasis.
PDF
