Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification.

Background: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest.

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients.

Background And Aim: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC.

Methods: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality.

Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells.

Aims: We have tested the hypothesis that selenium (Se)-containing antioxidative enzymes protect thyroid epithelial cells from oxidative damage associated with enzymatic production of hydrogen peroxide required for thyroid hormone biosynthesis. Thyroid epithelial cells therefore express antioxidative enzymes, including catalase, peroxiredoxins, thioredoxin reductases, and glutathione peroxidases (GPxs). The latter two enzyme families contain highly active peroxide-degrading enzymes that carry selenocysteine (Sec) in their active centers.

Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.

Context: Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland.

Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol.

Objective: Because over 90% of serum cortisol is bound to albumin and corticosteroid-binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum-free and salivary cortisol concentrations.

Methods: We assessed basal (T₀) and post-synacthen (T₆₀) serum total cortisol, serum-free and salivary cortisol in 125 consecutive cirrhotics (95 non-septic and 30 septic patients with a Child>8).

Results: Serum total cortisol levels significantly decreased from the Child A-C non-septic group, as did albumin and CBG levels, with a non-significant rise in serum-free cortisol concentrations.

Developmental and cell type-specific expression of thyroid hormone transporters in the mouse brain and in primary brain cells.

Cellular thyroid hormone uptake and efflux are mediated by transmembrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8) is mutated in Allan-Herndon-Dudley syndrome, a severe mental retardation associated with abnormal thyroid hormone constellations. Since mice deficient in Mct8 exhibit a milder neurological phenotype than patients, we hypothesized that alternative thyroid hormone transporters may compensate in murine brain cells for the lack of Mct8.

[New assays of TSH-receptor antibodies: analytical and clinical performances in the diagnosis of Graves' disease].

Graves' disease autoimmunity is attributable to the presence of serum antibodies (Ab) directed against the TSH receptor (TSHR) measured by a second generation (2G) assay using the human TRAK (hTRAK) with a high sensitivity in the diagnosis of Graves' disease. In this study, we have compared both analytical and clinical performances of hTRAK with those of five new methods using a porcine TSHR: two 2G methods and three assays using the monoclonal M22 directed against the TSHR pocket. We showed a bad reproducibility of these new methods with inter assay CVs higher than 10%.

Subclinical hyperthyroidism: considerations in defining the lower limit of the thyrotropin reference interval.

Background: Although numerous reports have discussed the upper limit of the thyrotropin (TSH) reference interval, none have dealt with the lower limit. Recent recommendations regarding subclinical thyroid dysfunction give different advice about its management, depending on whether the TSH concentration is <0.1 mIU/L or 0.

Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis induction and assessment by diffusion tensor magnetic resonance imaging.

The failure of the remyelination processes in multiple sclerosis contributes to the formation of chronic demyelinated plaques that lead to severe neurological deficits. Long-term cuprizone treatment of C57BL/6 mice resulted in pronounced white matter pathology characterized by oligodendrocyte depletion, irreversible demyelination and persistent functional deficits after cuprizone withdrawal. The use of a combination of in vivo diffusion tensor magnetic resonance imaging (DT-MRI) and histological analyses allowed for an accurate longitudinal assessment of demyelination.

Intermethod variability in TSH-receptor antibody measurement: implication for the diagnosis of Graves disease and for the follow-up of Graves ophthalmopathy.

Background: We compared the analytical and clinical performance of 3 porcine thyroid receptor antibody (TRAb) methods (1 second- and 2 new third-generation systems) with the conventional TRAb assay based on the human recombinant TSH receptor (hTRAK).

Patients And Methods: We obtained sera from 86 patients with untreated Graves disease (GD) and 71 healthy controls. We measured TRAb concentrations by radioreceptor assay using the hTRAK (Brahms) or the porcine TSH receptor (pRRA) from Beckman-Coulter, by electrochemiluminescence immunoassay (ECLIA) with the Elecsys/Cobas (Roche), and by ELISA using the Medizym TRAb clone (Medipan).

Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study.

Objective: Increased reverse tritiodothyronine (T(3)) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It can also be found with low or normal T(3) in non-severely ill subjects but its significance remains unclear.

Serum concentration of chromogranin A at admission: an early biomarker of severity in critically ill patients.

Background: Chromogranin A (CGA), a stress marker released with catecholamines by the adrenal medulla, has never been associated with acute inflammation in critically ill patients.

Aim: To determine evidence for a link between serum concentration of CGA, biomarkers of inflammation, and outcome inpatients admitted with or without the systemic inflammatory response syndrome (SIRS).

Methods: At admission, we measured in 53 patients and 14 healthy controls the serum concentrations of CGA,procalcitonin, and C-reactive protein.

Prognostic value of chromogranin A at admission in critically ill patients: a cohort study in a medical intensive care unit.

Background: Risk assessments of patients should be based on objective variables, such as biological markers that can be measured routinely. The acute response to stress causes the release of catecholamines from the adrenal medulla accompanied by chromogranin A (CGA). To date, no study has evaluated the prognostic value of CGA in critically ill intensive care unit patients.

[Interferences in immunoassays: Mechanisms and outcomes in endocrinology].

Immunoassays are used daily by clinical endocrinologists to refute or confirm a diagnosis, or to follow up the course of a treatment. Immunoassays have become increasingly sensitive, specific and reproducible, so that clinicians have great confidence in their results. However, they do not always yield correct results because interferences still occur.

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking.

Objective: The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects.

Design: A prospective multicenter study.

Patients: Three hundred and seventy-five clinically euthyroid subjects.

Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report.

A 25 year old woman consulted for a severe acanthosis nigricans and central distribution of fat. Her masculine type morphology was associated with muscular appearance of the limbs and excess fat deposits in the face and neck. Biological testing confirmed glucose intolerance associated with a severe insulin resistance, hypertriglyceridemia and polycystic ovary syndrome.

Etiological diagnosis of hyperprolactinemia.

There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination.

Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay.

Aim: Glargine, a long-acting insulin analogue, is metabolized in the bloodstream and in subcutaneous tissue. Glargine metabolism and its implications for diabetes therapy remain poorly understood. The aim of our study was to assess in vitro the glargine blood biotransformation and its inter-individual variability.

Use of insulin immunoassays in clinical studies involving rapid-acting insulin analogues: Bi-insulin IRMA preliminary assessment.

Background: In clinical studies involving rapid-acting analogues (RAAs), insulin immunoreactivity is frequently measured, including endogenous, regular insulin (RI) and RAA immunoreactivities. Such a procedure implies equivalent cross-reactivities of all insulins present in serum. Commercially available human insulin immunoassays have been widely used, but their limitations (including hemolysis and anti-insulin antibodies) were not fully investigated.