Philippe De Nayer

Serum levels of intact human chorionic gonadotropin (HCG) and its free a and β subunits, in relation to maternal thyroid stimulation during normal pregnancy

The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free α and β-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (≤0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free β-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free β-hCG subunits, compatible with three hypotheses: a) transient overexpression of the β-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production. Increased hCG in women with low TSH was clearly associated with thyroidal stimulation: comparing women with or without low TSH, it was shown that high hCG production was accompanied during the first trimester by a 20% mean increase in free T4 levels and a parallel increase in the TBG saturation levels by T4. Furthermore, thyroidal stimulation during the first trimester was associated with a larger median thyroid volume. During the last trimester and at term, most parameters of thyroid function were similar in both groups. In conclusion, a partial or total serum TSH suppression is a frequent finding during normal pregnancy, usually occurring as a transient feature near the end of the first trimester, in association with high serum hCG levels. The present data indicate for the first time that in these women, circulating hCG is characterized by elevated free β-hCG subunit and intact hCG levels, perhaps resulting from an imbalanced production of hCG. In approximately one percent of pregnancies, excessive thyroidal stimulation may lead to gestational transient thyrotoxicosis during the first trimester. The present studies confirm the role of hCG as an important thyroidal regulator during normal pregnancy.

The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies.

Human chorionic gonadotrophin (hCG) is known to possess thyroid‐stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation.

Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension

Objective To assess whether asymptomatic abnormalities, including thyroid auto‐antibodies, were associated with an abnormal miscarriage rate or a poor obstetric outcome.

Hormone synthesis and storage in the thyroid of human preterm and term newborns: Effect of thyroxine treatment

Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland.

Free to total prostate-specific antigen (PSA) ratio is superior to total-PSA in differentiating benign prostate hypertrophy from prostate cancer

Serum prostate‐specific antigen (PSA) exists in different molecular forms, and their respective concentration has been proposed as a useful tool to improve discrimination between benign prostatic hypertrophy (BPH) and prostate cancer (PC).

Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection.

PURPOSE In order to assess the relation of thyroid function tests to human immunodeficiency virus (HIV) infection, we determined the levels of serum thyroid hormones, serum binding proteins [thyroxine-binding globulin (TBG), cortisol-binding globulin (CBG), and sex hormone-binding globulin (SHBG)], and serum tumor necrosis factor (TNF) in HIV-seropositive subjects at different clinical stages. PATIENTS AND METHODS Thirty-seven HIV-seropositive patients were studied: 7 at stage II, 13 at stage III, and 17 at stage IV (eight ambulatory and nine hospitalized) according to the Centers for Disease Controls criteria. RESULTS As compared with stage II and stage III patients, stage IV patients had significantly higher mean TBG and total thyroxine (TT4) values, similar and normal total triiodothyronine (TT3) levels, and similar and abnormally low reverse triiodothyronine (rT3) concentrations. However, stage IV hospitalized patients had significantly lower TT3 values than stage IV ambulatory patients. In contrast to TBG, mean levels of CBG and SHBG were comparable in the three groups and within normal limits. For the whole population of HIV patients, there was a highly significant correlation between the CD4 lymphocyte count and TBG (r = -0.529, p less than 0.001) but not with CBG and SHBG levels. Finally, TNF values higher than 10 pg/mL were detected in six of the 17 stage IV patients and in only one of the 13 stage III patients (p = 0.059); elevated TNF levels correlated with a lower CD4 count (p less than 0.01) but not with serum TBG levels. CONCLUSION The progression of HIV infection is associated with an elevation of serum TNF and TBG, but not of CBG or SHBG. HIV-infected patients have an unexpectedly normal TT3-low rT3 state.

Free/total PSA ratio does not improve prediction of pathologic stage and biochemical recurrence after radical prostatectomy.

OBJECTIVES Despite several publications, the ability of the free/total (F/T) prostate-specific antigen (PSA) ratio to predict the pathologic extension of prostate cancer is still a matter of controversy. In addition, its ability to predict biochemical recurrence after radical prostatectomy has not yet been reported. METHODS Since January 6, 1996, the F/T PSA ratio was prospectively measured preoperatively in 343 patients undergoing radical prostatectomy as the first treatment for localized prostate cancer. RESULTS The ability to predict organ-confined disease was measured by receiver operating characteristic analysis. The areas under the curve were 0.66 for PSA density, 0.61 for total PSA, 0.60 for Gleason score, and 0.587 for the F/T PSA ratio. In multiple logistic regression analyses, the F/T PSA ratio was not a relevant predictor of organ-confined disease (Wald statistic 0.345 for P = 0.55). Similar results were obtained in the subgroup of patients with a PSA level between 2.5 and 10 ng/mL. The biochemical survival for the 270 patients who did not receive adjuvant therapy was 86% at 61 months. Statistically significant univariate predictors (P <0.05) of PSA recurrence were pT stage (log-rank 18.2) and Gleason grade (log-rank 8.8). The F/T PSA ratio was not a significant predictor of recurrence in the univariate analysis (log-rank 3.6 for P = 0.314) and in multivariate analysis (Wald statistic 0.2 for P = 0.97). CONCLUSIONS These results suggest that the F/T PSA ratio is not helpful for the prediction of organ-confined disease and PSA recurrence after radical prostatectomy.

Iodine and iron status of pregnant women in Lubumbashi, Democratic Republic of Congo.

OBJECTIVE Adequate iodine and Fe intakes are imperative during pregnancy to prevent fetal defects, but such data are not available in the Democratic Republic of Congo. We aimed to assess iodine and Fe status in pregnant women from Lubumbashi. DESIGN Cross-sectional study. We measured urinary iodine concentration (UIC) in random urine samples using a modified Sandell–Kolthoff digestion method; the WHO reference medians were used to classify iodine intake as deficient, adequate, more than adequate or excessive. Serum ferritin concentrations were measured by immunoenzymatic assay and considered insufficient when ,12 ng/ml. SETTING Maternity units from rural, semi-urban and urban areas of Lubumbashi, Democratic Republic of Congo. SUBJECTS Two hundred and twenty-five randomly selected pregnant women attending prenatal consultation, seventy-five postpartum women and seventy-five non-pregnant women as controls. RESULTS Overall median UIC in pregnant women was 138 (interquartile range: 105–172) mg/l, indicating iodine deficiency, whereas postpartum and nonpregnant women had adequate iodine intake: median UIC5144mg/l and 204mg/l,respectively. Median UIC values were lower in late pregnancy than in early pregnancy: in the first, second and third trimester respectively 255mg/l, 70mg/l and 88mg/l in the rural area; 306mg/l, 166mg/l and 68mg/l in the semi-urban area; and 203mg/l, 174mg/l and 99mg/l in the urban area. Fe was insufficient in 39% of pregnant women compared with 21% of non-pregnant and postpartum women. In the third trimester, deficiencies in both iodine and Fe were high: 40%, 12% and 18% in the rural, semi-urban and urban areas, respectively. CONCLUSIONS Our data suggest that pregnant women are at risk of iodine and Fe deficiencies in Lubumbashi. Country policies fighting against iodine and Fe deficiencies during pregnancy should be reinforced.

Performance evaluation of the Precision PCx point-of-care blood glucose analyzer using discriminant ratio methodology.

Abstract Point-of-care glucose testing needs to be integrated into a laboratory information system to provide continuous care. Selecting a particular glucose monitoring system is based on both analytical performance and on users preference. We evaluated accuracy, performance and regulatory compliance of the Precision™ PCx™ glucose analyzer (Abbott), with automatic download into a central station, for remote quality control (QC) management and automatic upgrading. We used the discriminant ratio (DR) methodology, which determines the DR of a test (e.g. the ratio between the underlying SD and the within-subject SD), and compares it to that of another test allegedly measuring the same parameter. Accuracy was evaluated by Clarkes error grid method. Seven hundred and ninety four blood samples were taken from 22 diabetic patients, combined with two capillary blood samples: one for analysis by reference method and the second for PCx™ analysis. Linear regression analysis revealed, over a 2.1 to 26.9 mmol/l glucose concentration range, a correlation coefficient of 0.963, an intercept of 0.7 mmol/l and a slope of 0.851. Mean difference between meter-generated results and the reference method was −7.1±10.8%. Between-run imprecision for PCx™ using Abbotts controls at low and mid-low concentrations was 5.4 and 3.8%, respectively. Clarkes error grid did not show any clinical impact related to difference between methods. DRs were of similar magnitude using both methods. Nursing staff found PCx™ easy for everyday use. Our data show that PCx™ results agree with those obtained with the reference method, as shown by lack of significant difference in DRs, and by excellent correlation.

Interference in thyrotropin (TSH) determination: falsely elevated TSH values in a transplanted patient

We report a falsely elevated TSH value as determined by an immunoradiometric assay. The patient, a thyroidectomized woman on substitutive therapy, underwent a kidney transplantation. She was treated for transplant rejection with OKT 3 (Orthoclone), a mouse monoclonal antibody. The discrepancy between the TSH value (TSH-Riabead II, Abbott) and the thyroid hormones level led us to suspect the presence of antimouse antibodies in the serum of this patient. Indeed, human immunoglobulins directed against mouse IgG2a and IgG2b were detected. We repeated the TSH determination in the presence of normal mouse serum (NMS) and obtained a true TSH value. Upon fractionation of the serum with protein-A chromatography, the falsely elevated TSH immunoreactivity was detected in the IgG fraction.