A progress report of the IFCC Committee for Standardization of Thyroid Function Tests

BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH). OBJECTIVES: This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range. METHODS: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all-procedure trimmed mean. The manufacturers recalibrated their assays against these targets. RESULTS: All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4. CONCLUSIONS: Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders

Fluxes of dissolved organic carbon in stand throughfall and percolation water in 12 boreal coniferous stands on mineral soils in Finland

Predictors for glucose intolerance postpartum were evaluated in women with gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. 1841 women were tested for GDM in a prospective cohort study. A postpartum 75g oral glucose tolerance test (OGTT) was performed in women with GDM at 14 ± 4.1 weeks. Of all 231 mothers with GDM, 83.1% (192) had a postpartum OGTT of which 18.2% (35) had glucose intolerance. Women with glucose intolerance were more often of Asian origin [15.1% vs. 3.7%, OR 4.64 (1.26–17.12)], had more often a recurrent history of GDM [41.7% vs. 26.7%, OR 3.68 (1.37–9.87)], higher fasting glycaemia (FPG) [5.1 (4.5–5.3) vs. 4.6 (4.3–5.1) mmol/L, OR 1.05 (1.01–1.09)], higher HbA1c [33 (31–36) vs. 32 (30–33) mmol/mol, OR 4.89 (1.61–14.82)], and higher triglycerides [2.2 (1.9–2.8) vs. 2.0 (1.6–2.5) mmol/L, OR 1.00 (1.00–1.01)]. Sensitivity of glucose challenge test (GCT) ≥7.2 mmol/l for glucose intolerance postpartum was 80% (63.1%–91.6%). The area under the curve to predict glucose intolerance was 0.76 (0.65–0.87) for FPG, 0.54 (0.43–0.65) for HbA1c and 0.75 (0.64–0.86) for both combined. In conclusion, nearly one-fifth of women with GDM have glucose intolerance postpartum. A GCT ≥7.2 mmol/L identifies a high risk population for glucose intolerance postpartum

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey.

[en] BACKGROUND: Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. METHOD: Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. RESULTS: Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. CONCLUSIONS: LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit

Normal glucose tolerant women with low glycemia during the oral glucose tolerance test have a higher risk to deliver a low birth weight infant

BackgroundData are limited on pregnancy outcomes of normal glucose tolerant (NGT) women with a low glycemic value measured during the 75g oral glucose tolerance test (OGTT). Our aim was to evaluate maternal characteristics and pregnancy outcomes of NGT women with low glycemia measured at fasting, 1-hour or 2-hour OGTT.MethodsThe Belgian Diabetes in Pregnancy-N study was a multicentric prospective cohort study with 1841 pregnant women receiving an OGTT to screen for gestational diabetes (GDM). We compared the characteristics and pregnancy outcomes in NGT women according to different groups [(<3.9mmol/L), (3.9-4.2mmol/L), (4.25-4.4mmol/L) and (>4.4mmol/L)] of lowest glycemia measured during the OGTT. Pregnancy outcomes were adjusted for confounding factors such as body mass index (BMI) and gestational weight gain.ResultsOf all NGT women, 10.7% (172) had low glycemia (<3.9 mmol/L) during the OGTT. Women in the lowest glycemic group (<3.9mmol/L) during the OGTT had compared to women in highest glycemic group (>4.4mmol/L, 29.9%, n=482), a better metabolic profile with a lower BMI, less insulin resistance and better beta-cell function. However, women in the lowest glycemic group had more often inadequate gestational weight gain [51.1% (67) vs. 29.5% (123); p<0.001]. Compared to the highest glycemia group, women in the lowest group had more often a birth weight <2.5Kg [adjusted OR 3.41, 95% CI (1.17-9.92); p=0.025].ConclusionWomen with a glycemic value <3.9 mmol/L during the OGTT have a higher risk for a neonate with birth weight < 2.5Kg, which remained significant after adjustment for BMI and gestational weight gain

Methylation Defect in Imprinted Genes Detected in Patients with an Albright's Hereditary Osteodystrophy Like Phenotype and Platelet Gs Hypofunction

Pseudohypoparathyroidism (PHP) indicates a group of heterogeneous disorders whose common feature is represented by impaired signaling of hormones that activate Gsalpha, encoded by the imprinted GNAS gene. PHP-Ib patients have isolated Parathormone (PTH) resistance and GNAS epigenetic defects while PHP-Ia cases present with hormone resistance and characteristic features jointly termed as Albright's Hereditary Osteodystrophy (AHO) due to maternally inherited GNAS mutations or similar epigenetic defects as found for PHP-Ib. Pseudopseudohypoparathyroidism (PPHP) patients with an AHO phenotype and no hormone resistance and progressive osseous heteroplasia (POH) cases have inactivating paternally inherited GNAS mutations.We here describe 17 subjects with an AHO-like phenotype that could be compatible with having PPHP but none of them carried Gsalpha mutations. Functional platelet studies however showed an obvious Gs hypofunction in the 13 patients that were available for testing. Methylation for the three differentially methylated GNAS regions was quantified via the Sequenom EpiTYPER. Patients showed significant hypermethylation of the XL amplicon compared to controls (36 ± 3 vs. 29 ± 3%; p<0.001); a pattern that is reversed to XL hypomethylation found in PHPIb. Interestingly, XL hypermethylation was associated with reduced XLalphaS protein levels in the patients' platelets. Methylation for NESP and ExonA/B was significantly different for some but not all patients, though most patients have site-specific CpG methylation abnormalities in these amplicons. Since some AHO features are present in other imprinting disorders, the methylation of IGF2, H19, SNURF and GRB10 was quantified. Surprisingly, significant IGF2 hypermethylation (20 ± 10 vs. 14 ± 7%; p<0.05) and SNURF hypomethylation (23 ± 6 vs. 32 6%; p<0.001) was found in patients vs. controls, while H19 and GRB10 methylation was normal.In conclusion, this is the first report of methylation defects including GNAS in patients with an AHO-like phenotype without endocrinological abnormalities. Additional studies are still needed to correlate the methylation defect with the clinical phenotype

Adrenal insufficiency, be aware of drug interactions!

A 42-year-old man with complaints of muscle soreness and an increased pigmentation of the skin was referred because of a suspicion of adrenal insufficiency. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency (PAI) and treatment with hydrocortisone and fludrocortisone was initiated. An etiological workup, including an assessment for anti-adrenal antibodies, very long-chain fatty acids, 17-OH progesterone levels and catecholamine secretion, showed no abnormalities. (18)Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands and bilateral presence of an adrenal nodule, with (18)fluorodeoxyglucose accumulation. A positive tuberculin test and positive family history of tuberculosis were found, and tuberculostatic drugs were initiated. During the treatment with the tuberculostatic drugs the patient again developed complaints of adrenal insufficiency, due to insufficient dosage of hydrocortisone because of increased metabolism of hydrocortisone

Acute thyrotoxicosis after SCT

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