Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 1: thyroid-stimulating hormone.

Background: Laboratory testing of serum thyroid-stimulating hormone (TSH) is an essential tool for the diagnosis and management of various thyroid disorders whose collective prevalence lies between 4% and 8%. However, between-assay discrepancies in TSH results limit the application of clinical practice guidelines.

Methods: We performed a method comparison study with 40 sera to assess the result comparability and performance attributes of 16 immunoassays.

Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 2: free thyroxine and free triiodothyronine.

Background: Free thyroxine (FT4) and free triiodothyronine (FT3) measurements are useful in the diagnosis and treatment of a variety of thyroid disorders. The IFCC Scientific Division established a Working Group to resolve issues of method performance to meet clinical requirements.

Methods: We compared results for measurement of a panel of single donor sera using clinical laboratory procedures based on equilibrium dialysis-isotope dilution-mass spectrometry (ED-ID-MS) (2 for FT4, 1 for FT3) and immunoassays from 9 manufacturers (15 for FT4, 13 for FT3) to a candidate international conventional reference measurement procedure (cRMP) also based on ED-ID-MS.

Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 3: total thyroxine and total triiodothyronine.

Background: Because total thyroid hormone testing is performed on many automated clinical chemistry instruments, the IFCC Scientific Division commissioned the Working Group for Standardization of Thyroid Function Tests to include total thyroxine (TT4) and total triiodothyronine (TT3) in its standardization efforts.

Methods: Existing SI-traceable reference measurement procedures (RMPs) were used to assign TT4 and TT3 values to 40 single-donor serum samples for subsequent use in a method comparison study with 11 TT4 and 12 TT3 immunoassays. Data from comparison of each immunoassay with the RMPs provided a basis for mathematical assay recalibration.

On the possible role of mammary-derived growth hormone in human breast cancer.

The incidence of breast cancer has risen worldwide, especially in countries where it used to be low, very probably as a result of economic prosperity and changes in life-style. In women, the available data have resulted in the concept of progression from normal breast development to cancer through precursor lesions sensitive to hormones and growth factors that can be produced locally in the mammary gland, acting as paracrine or autocrine stimulating agents. The local endocrine environment in the breast can be different from the situation in the circulation.

Classification and pharmacology of progestins.

Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.

Gene polymorphisms that may influence the biological effects of progestins.

Many of the biological actions of progestins depend on binding to intracellular receptors and through a long chain of events to subsequent stimulation of transcriptional activity and protein synthesis. This process requires at least a few hours in time and many different proteins called coregulators do play a role after binding to the receptor. Evidence for polymorphisms in the gene coding for the PR has been obtained and many studies have already attempted to show associations between particular polymorphisms and human diseases.

Long-term effects of progestins on bone quality and fractures.

The effects of progestins on the quality of bone and their influence on the risk of fractures are reviewed. Data discussed are based on experimental studies in vivo that generally lasted for longer than one year. Information is given on the background of osteoporosis and on several means of inducing changes in bone quality.

Proposal of a candidate international conventional reference measurement procedure for free thyroxine in serum.

In the present paper the IFCC WG-STFT recommends and provides the rationale to establish metrological traceability of serum free thyroxine (FT4) measurements to a candidate international conventional reference measurement procedure. It is proposed that this procedure be based on equilibrium dialysis combined with determination of thyroxine in the dialysate with a trueness-based reference measurement procedure. The measurand is thus operationally defined as "thyroxine in the dialysate from equilibrium dialysis of serum prepared under defined conditions".

Gene polymorphisms involved in the regulation of bone quality.

Osteoporotic fractures in subjects at advanced age constitute a tremendous and growing problem. Established lifestyle risk factors can explain only a modest proportion of the liability to osteoporotic fractures. Bone mineral density (BMD) is considered the best established risk factor for osteoporotic fractures.

Feasibility study of new calibrators for thyroid-stimulating hormone (TSH) immunoprocedures based on remodeling of recombinant TSH to mimic glycoforms circulating in patients with thyroid disorders.

Background: Differences between the glycosylation patterns of a pituitary thyroid-stimulating hormone calibrator (pitTSH) and serum samples have been shown to be responsible for nonidentical epitope expression and for introducing discrepancies in TSH measurements. We studied the feasibility of developing new candidate reference materials by remodeling recombinant TSH (recTSH) to generate potential mimics of serum TSH.

Methods: Terminal sialylation and/or inner fucosylation of recTSH were remodeled by a combination of enzyme treatments followed (or not) by lentil lectin-Sepharose affinity chromatography.

Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?

Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic fluid, 2nd and 3rd trimester maternal serum, and umbilical cord serum at birth. During the critical period of brain differentiation, at the beginning of the second trimester of pregnancy, sex differences in T and A4 were found in amniotic fluid and not in maternal serum.

Local biosynthesis and metabolism of oestrogens in the human breast.

The origin of oestrogens at the level of the breast itself is discussed. In particular in postmenopausal women an accumulation of oestradiol at the site of breast tumours has been documented by a number of independent studies. The mechanism behind the high local oestrogens concentrations is thought to be the in situ production of these steroids by local processes with androstenedione as the main precursor.

CYP17 and CYP19 genetic polymorphisms in endometrial cancer: association with intratumoral aromatase activity.

Excessive estrogenic influence is known to be associated with initiation/promotion of endometrial cancer (EC). Allelic polymorphisms of the genes involved in steroidogenesis/steroid metabolism may contribute to EC susceptibility. It is important to know endocrine mechanisms by which such susceptibility is acquired.

The relationship between aromatase in primary breast tumors and response to treatment with aromatase inhibitors in advanced disease.

Aromatase inhibitors are proving to be more effective than tamoxifen for postmenopausal patients with breast cancer. Estrogen concentrations in the breast are similar in both premenopausal and postmenopausal women, and several fold higher than circulating levels in postmenopausal women. In order to investigate the importance of intratumoral aromatase in stimulating the proliferation of the tumor, we used immunocytochemistry to determine the extent of aromatase expression in relationship to the response of the patient to aromatase inhibitor treatment.

Overview on the effects of progestins on bone.

In view of the fact that fractures are the clinically relevant events, risk factors for fractures are discussed first. Bone mineral density (BMD) appears to be a much less important risk factor for the most severe hip fractures than the risk of falling. No results of experimental studies on hormones and fractures at advanced age are available.

Classification and pharmacology of progestins.

Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.

Endogenous sex hormones in men aged 40-80 years.

Objective: To determine the relationship between aging, life-style factors and health-related factors and endogenous sex hormone levels.

Design: Cross-sectional study of 400 independently living men between 40 and 80 Years of age.

Methods: After exclusion of subjects who were not physically or mentally able to visit the study center, 400 men were randomly selected from a population-based sample.

Endogenous sex hormones and cardiovascular disease in men.

Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. It has, however, become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has for many years remained largely unknown, but during the last decade more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in etiology, prevention, and treatment of male cardiovascular disease.

Sex hormones and male health: effects on components of the frailty syndrome.

Physicians are seeing an increasing number of older male patients with chronic diseases and conditions. However, the potential relevance of low levels of circulating endogenous androgens in connection with these diseases and conditions is generally poorly understood. Research findings have suggested that androgens play a distinct role in bone metabolism, body composition such as muscle and fat mass and fat distribution, cognitive functioning, mood and well being.

Plasma and urinary sex hormones are differently related to lipids in healthy postmenopausal women.

Objective: Endogenous sex hormones can be measured in plasma and urine. We determined the extent to which these two methods provide different information on hormonal status by relating them to lipid profile in postmenopausal women.

Methods: Thirty healthy postmenopausal women collected one 24-h urine sample and a blood sample was taken.