Sylvie Brailly-Tabard

Reference Values for IGF-I Serum Concentrations: Comparison of Six Immunoassays

Context: Measurement of IGF-I is essential for diagnosis and management of patients with disorders affecting the somatotropic axis. However, even when IGF-I kit manufacturers follow recent consensus guidelines, different kits can give very different results for a given sample. Objectives: We sought to establish normative data for six IGF-I assay kits based on a large random sample of the French general adult population. Subjects and Methods: In a cross-sectional multicenter cohort study, we measured IGF-I in 911 healthy adults (18–90 years) with six immunoassays (iSYS, LIAISON XL, IMMULITE, IGFI RIACT, Mediagnost ELISA, and Mediagnost RIA). Pairwise concordance between assays was assessed with Bland-Altman plots for both IGF-1 raw data and standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorized IGF-I SDS. Results: Normative data included the range of values (2.5–97.5 percentiles) given by the six IGF-I assays according to age group and sex. A formula for SDS calculation is provided. Although the lower limits of the reference intervals of the six assays were similar, the upper limits varied markedly. Pairwise concordances were moderate to good (0.38–0.70). Conclusion: Despite being obtained in the same healthy population, the reference intervals of the six commercial IGF-1 assay kits showed noteworthy differences. Agreement between methods was moderate to good.

Classification of patients with GH disorders may vary according to the IGF-I assay.

ContextnInsulinlike growth factor I (IGF-I) measurement is essential for the diagnosis and management of growth hormone (GH) disorders. However, patient classification may vary substantially according to the assay technique.nnnObjectivenWe compared individual patient data and classifications obtained with six different IGF-I assay kits in a group of patients with various GH disorders.nnnDesignnIn this cross-sectional study, we measured IGF-I with six immunoassays in 102 patients with active or treated acromegaly or GH deficiency. IGF-I normative data previously established for the same six assay kits were used to classify the patients (high, low, or normal IGF-I levels), using both raw data and standard deviation scores (SDSs). Pairwise concordance between assays was assessed with Bland-Altman plots and with the percentage of observed agreement and the weighted κ coefficient for categorized IGF-I SDS.nnnResultsnWe observed marked variability both across each individuals IGF-I raw data and across IGF-I SDS values obtained with each of the six immunoassays. Pairwise concordance between assay values, as assessed with the weighted κ coefficient, ranged from 0.50 (moderate) to 0.81 (excellent).nnnConclusionnEven when using normative data obtained in the same large population of healthy subjects and when using calculated IGF-I SDSs, agreement among IGF-I assay methods is only moderate to good. Differences in assay performance must be taken into account when evaluating and monitoring patients with GH disorders. This argues for the use of the same IGF-I assay for a given patient throughout follow-up.

A Somewhat Bizarre Case of Graves Disease Due to Vitamin Treatment

Context: Accurate measurements of circulating hormones is essential for the practice of endocrinology. Immunometric assays employing the streptavidin-biotin system are widely used to measure hormones. However, these assays are susceptible to interference in patients taking biotin supplementations. This interference could mimic a coherent hormone profile, leading to misdiagnosis and unnecessary treatment. Case description: The patient, a 32-year-old man with X-linked adrenomyeloneuropathy recently diagnosed with Graves disease, was referred to our department to evaluate his response to antithyroid drugs. His thyroid function tests were still consistent with hyperthyroidism while he had been receiving carbimazole 40 mg/d for 6 weeks. We found no signs of thyrotoxicosis on physical examination despite the “frank and severe” biochemical hyperthyroidism. Noticing that all the patient’s assays had been done at the same laboratory, we suspected assay interference. We therefore repeated the thyroid function tests at our hospital laboratory, which uses a different assay platform. Surprisingly, all the results were normal, confirming assay interference. The patient was taking an investigational “vitamin” therapy, which turned out to be biotin, prescribed at a dose of 100 mg tid as part of a trial of high-dose biotin in X-linked adrenomyeloneuropathy. Conclusions: This case should encourage physicians to ask their patients about possible biotin intake, especially when laboratory results are not compatible with clinical findings. If biotin interference is suspected, we propose either using a different assay not based on the streptavidin-biotin system or repeating the analyses after stopping biotin supplementation for one week.

Oestradiol level, oestrogen receptors, and mortality in elderly men: The three‐city cohort study

Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in mens health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied.

0186 Women epidemiology lung cancer (welca) study: reproductive, hormonal, occupational risk factors and biobank

Background Very few studies have examined occupational exposures in jobs that are typically performed by women. WELCA study aims at investigating the aetiology of lung cancer in women, focusing particularly on hormonal and occupational risk factors. Methods WELCA is a population based case-control study in progress (1000 ca/1000 co) ending in 2017. Cases are women with incident lung cancer, living in the Ile de France area and aged up to 75 years. The control group is a random sample of the population living in the same area, frequency-matched for age and additionally stratified on the distribution of socio-professional categories of women residing there. Subjects are interviewed face-to-face using a standardised questionnaire (CAPI) collecting information on reproductive and hormonal factors, tobacco, residential history and a detailed description of occupational lifetime history. Specific questionnaires have been developed concerning jobs and sectors that are frequently considered of particular interest for the study: house cleaning, dry cleaning and laundry, hairdressing, catering and cooking, health, beauty therapist, nail salons. Blood samples and tumours are also collected, to establish a biobank for molecular epidemiology studies. To date 670ca/450co are already included. Discussion The large number of women should allow to uncover occupational exposures more specific of their professional activities. In addition information on many non-occupational risk factors is available, and the study will provide an excellent framework for numerous studies in various fields. Preliminary results on participation rates, biobank, socio-demographic characteristics or number of job periods described will be presented.

Cabergoline Tapering Is Almost Always Successful in Patients With Macroprolactinomas

Context: Cabergoline (CAB) is very effective in the treatment of macroprolactinomas, but there are few data on the CAB dose necessary to achieve and maintain normal prolactin (PRL) levels. Design and Patients: We retrospectively studied 260 patients. CAB was introduced at a mean dose of 0.83 ± 0.52 mg/wk. When the PRL level had normalized, the patients physician chose to either maintain the CAB dose (fixed-dose group) or to taper it (de-escalation group) until the minimal effective dose required to maintain a normal PRL level was established. Results: PRL normalized in 157 patients (60.8%) during CAB treatment. CAB de-escalation was attempted in 84 (53.5%) of these 157 patients and was successful in 77 (91.7%) cases. The mean CAB dose was reduced from 1.52 ± 1.17 mg/wk to 0.56 ± 0.44 mg/wk at the last visit (P < 1 × 10−4). De-escalation was also possible in some “CAB-resistant” patients, namely those requiring ≥2 mg/wk to normalize PRL. CAB de-escalation had no negative long-term effect on tumor size. At the last visit, maximal diameter was 8.8 ± 8.8 mm in the de-escalation group and 13.4 ± 8.5 mm in the fixed-dose group (P < 0.01). Conclusion: In patients with macroprolactinomas, the CAB dosage required to maintain a normal PRL level long term is lower than the initial dosage necessary to normalize the PRL level. After PRL normalization, CAB tapering was almost always successful, even when very high initial doses were necessary. CAB tapering does not undermine tumor control and may attenuate the potential adverse effects of CAB, which appear to be dependent on the cumulative dose.

Women Epidemiology Lung Cancer (WELCA) study: reproductive, hormonal, occupational risk factors and biobank

BackgroundLung cancer aetiology and clinical aspects have been mainly studied in men, although specific risk factors probably exist in women. Here we present the rationale, design and organization of the WELCA study (Women Epidemiology Lung CAncer) that has been launched to investigate lung cancer in women, focusing particularly on hormonal and occupational factors.Methods/DesignWELCA is a population based case-control study and planned to recruit 1000 cases and 1000 controls in three years, based on study power calculation. Eligible cases are female patients newly diagnosed with lung cancer, living in Paris and the Ile de France area and aged up to 75xa0years. Almost all Parisian pneumology and oncology clinical departments are involved. The control group is a random sample of the population living in the same area, frequency-matched on age and additionally stratified on the distribution of socio-professional categories of women residing there. After acquisition of written consent, research nurses administer standardized computer assisted questionnaires to all the subjects in face-to-face interviews and acquire anthropometric measures. Besides usual socio-demographic characteristics, information is gathered about menstrual and reproductive factors, hormonal treatments, lifestyle and leisure characteristics, occupational history, personal and familial medical history. Biological samples are also collected, in order to establish a biobank for molecular epidemiology studies. Molecular characteristics of the tumours will be obtained and patients will be followed up for five years.DiscussionThe WELCA study aims to answer key questions in lung cancer aetiology and clinical characteristics specifically in women. The role of hormonal impregnation is investigated, and the interactions with cigarette smoking or body mass index (BMI) will be analyzed in detail. The occupational history of the subjects is carefully reconstructed, focusing in particular on the service sector. The creation of a biobank for collection of serum, plasma, DNA and tumour tissue will allow the genetic and biochemical characterization of both the subjets and the tumours. The follow-up of the patients will help in disentangling the role of hormonal factors and tumour molecular characteristics in survival.