To treat or not to treat euthyroid autoimmune disorder during pregnancy?

BACKGROUND: Subclinical autoimmune hypothyroidism during pregnancy is associated with an increased risk of miscarriage and has a deleterious effect on fetal development. The aim of this study was to evaluate a screening and treatment strategy of subclinical hypothyroidism, and to establish normal ranges of thyroid-stimulating hormone (TSH) and thyroxine (T(4)) during pregnancy. METHODS: A retrospective study was carried out on 784 consecutive files of pregnant women; the files were systematically searched for thyroid function and antithyroid antibodies in order to determine the effect and the prevalence of anti-thyroid peroxidase antibodies (TPO-Ab) during pregnancy, and to evaluate treatment with levothyroxin (LT(4)) in TPO-Ab carriers. RESULTS: Among the 75 TPO-Ab-positive patients, 42 received LT(4) treatment during pregnancy. Although the range of TSH serum levels was wide, the mean TSH level was significantly higher in TPO-Ab-positive women (3 vs. 1 mIU/l, p < 0.01). No significant difference in the obstetrical complications rate was observed between TPO-Ab-positive and TPO-Ab-negative populations. CONCLUSIONS: Our study provides information on normal ranges of serum TSH and free T(4) for Belgian pregnant women receiving iodide supplementation. Based on our results, we suggest supplementation of TPO-Ab-positive pregnant women with 50 microg/day of LT(4), unless their TSH levels are lower than 1 mIU/l, to avoid the risk of hypothyroidism during pregnancy.

Bone density and markers of bone remodeling in type 1 male diabetic patients.

AIMS: To assess the prevalence and severity of bone disease in type 1 diabetic patients and to determine serum markers of bone remodeling as well as their relationship with bone mineral density (BMD). METHODS: BMD [by dual energy x-ray absorptiometry (DXA)] and serum markers of bone remodeling [osteocalcin, c-terminal telopeptide of type I collagen (CTX)], leptin and osteoprotegerin (OPG) were measured in 42 adult males with type 1 diabetes. Twenty-four non-diabetic subjects served as controls. RESULTS: In 40% of the patients, osteopenia at the lumbar spine (L1-L4) and/or at the left hip was found, and 7% met criteria for osteoporosis. L1-L4 BMD z-score was correlated with age (r=0.365, P=0.018) and a similar trend was observed at left hip. L1-L4 BMD z-score was negatively correlated with CTX and osteocalcin (r=-0.343, P=0.028; r=-0.376, P=0.024, respectively). A significant correlation was evidenced between BMD z-score at both lumbar spine and left hip and leptin values (r=0.343, P=0.03; r=0.395, P=0.012, respectively) but after adjustment for weight this correlation was no longer significant. Osteocalcin, CTX and leptin concentrations were comparable between patients and controls, while OPG concentrations tend to be higher in diabetic subjects (P=0.08). CTX was negatively correlated with age (r=-0.390, P=0.012) and positively correlated with osteocalcin (r=0.696, P<0.001). OPG was positively correlated with age (r=0.507, P=0.001). CONCLUSION: Our results suggest that in diabetic subjects osteopenia is a relatively frequent complication but bone loss is attenuated with age progression. Whether this is also mediated by OPG and/or leptin remains to be confirmed.

Expression of prostate-specific membrane antigen in transitional cell carcinoma of the bladder: prognostic value?

The expression of Prostate-specific membrane antigen (PSMA) mRNA was assessed in the normal bladder urothelium (n = 9), transitional cell carcinoma (TCC) specimens (n = 52), TCC-derived cell lines (n = 3), and preoperative blood samples from TCC patients (n = 27). Specific PSMA mRNA was found in 100% of normal and malignant tissues and two cell lines. PSMA protein was detected in normal (n = 3) and malignant tissues (n = 4). Using a PSMA-specific substrate, PSMA enzymatic activity was found in two bladder cell lines and correlated with immunostaining. Seven of the 27 TCC preoperative blood samples were positive by reverse transcription-PCR. These preliminary results, obtained on a nonrandomized cohort of patients, correlated with tumor invasion (positive RT-PCR: 0% for pT < or = 2 versus 41% for pT > or = 3) and 2-year survival rate (81% in the PSMA-negative group versus 29% in the PSMA-positive group). Although the clinical usefulness of this assay requires confirmation in larger prospective randomized trials, current preliminary results suggest that a blood-borne PSMA mRNA PCR assay may be a useful tool to predict a poor outcome in TCC patients.

Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake.

Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period.

Partial reversibility during late postpartum of thyroid abnormalities associated with pregnancy.

The aim of the present work was to assess during late postpartum the reversibility of thyroidal alterations associated with pregnancy. Thyroid function was reinvestigated 6 months after delivery in 100 randomly selected healthy women and thyroid volume was reevaluated 12 months after delivery in 10 other selected women. The subjects had previously been carefully followed during gestation as they were included in a prospective cohort investigation of the regulation of the thyroid during pregnancy, in an area with a limited dietary iodine intake (less than 100 micrograms/day in 85% of the women). Six months after delivery, an overall normalization of thyroid function was observed. However, an increase in the T3/T4 ratio, which was present in half the cases at delivery, was still evident 6 months postpartum, suggesting the persistence of relative iodine deficiency, probably prolonged in some women through breast-feeding. Furthermore, serum thyroglobulin levels, which were increased in half the women at delivery, remained abnormally high in 40% of them 6 months later. Twelve months after delivery thyroid volume, which had increased in average by 54% during pregnancy, had not reverted to the values found during early gestation. Moreover a goiter was still evident in 2/4 cases in whom it had developed during pregnancy. In conclusion, the present study indicates that pregnancy may constitute a prolonged stimulus for the thyroid and shows for the first time that the alterations associated with gestation are not limited to the period of pregnancy, being only partially reversible during late postpartum. In conditions with a limited iodine intake, pregnancy constitutes a risk for the maternal thyroid: goitrogenesis does occur and may be maintained after delivery. The glandular stress of pregnancy may therefore provide a clue to understanding the high prevalence of thyroid disorders in women. The present study provides additional arguments to suggest that iodine supply be increased during pregnancy but also after parturition, in particular in breast-feeding mothers.

Sex hormone-binding protein in hyperthyroxinemic patients: a discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia.

Sex hormone-binding globulin (SHBG) levels in serum are affected by thyroid status; hyperthyroidism is associated with high SHBG levels, whereas hypothyroid patients have low or normal SHBG levels. This study was undertaken to test the usefulness of SHBG determinations to define the thyroid status in two hyperthyroxinemic states: thyroid hormone resistance (THR) and familial dysalbuminemic hyperthyroxinemia (FDH). Serum SHBG levels were determined in 193 patients and 26 normal subjects using an IRMA-type RIA. In the control group, the mean values in women (58.9 nmol/liter) and men (32.7 nmol/liter) were significantly different (P less than 0.001). In adult subjects with THR, SHBG levels were within the normal range, with mean values of 54.8 nmol/liter (range, 28.7-82.5 nmol/liter) in women and 18 and 20 nmol/liter in two men. In FDH subjects, the mean SHBG levels did not differ from the normal values; they averaged 60.7 nmol/liter in women and 42.3 nmol/liter in men. From these data we conclude that in THR and FDH, free T4 levels elicit an appropriate hepatic response corresponding to the euthyroid status of these subjects. SHBG determination may, therefore, serve as an in vitro test for end-organ sensitivity to thyroid hormones.

Regulation of maternal thyroid during pregnancy.

A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid.

Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.

A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high.

A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.

One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20 micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind protocol into three groups and treated until term with a placebo, 100 micrograms potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day. Parameters of thyroid function, urinary iodine excretion, and thyroid volume were monitored sequentially. Neonatal thyroid parameters, including thyroid volume by echography, were also assessed in the newborns from mothers of the three groups. In women receiving a placebo, the indices of excessive thyroid stimulation worsened as gestation progressed, with low free T4 levels, markedly increased serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal in 20% of the cases at term. Urinary iodine excretion levels were low, around 30 micrograms/L at term. The thyroid volume increased, on the average, by 30%, and 16% of the women developed a goiter, confirming the goitrogenic stimulus associated with pregnancy. Moreover, the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels. In both groups of women receiving an active treatment, the alterations in thyroid function associated with pregnancy were markedly improved. The increase in serum TSH was almost suppressed, serum TG decreased significantly, and changes in thyroid volume were minimized (group receiving KI) or almost suppressed (group receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the two groups receiving an active treatment, serum TG was significantly lower, and thyroid volume at birth was normal. The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone. The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment. However, the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4. Furthermore, the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation. In conclusion, the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Immunoturbidimetric assay of beta 2 microglobulin using latex particles in microplates.

A latex particle immunoturbidimetric assay in microplates has been developed for the quantitation of beta 2 microglobulin. The assay which involves three pipetting steps and one incubation, has a clinically useful range of 0.4-16 mg/l. A comparison of the method with a commercial radioimmunoassay in the analysis of 125 sera revealed a high degree of correlation. Although the assay was performed manually, it showed considerable potential for full automation.

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 Control's 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.

Diagnostic value of free triiodothyronine in serum.

Serum free T3 concentration has been assessed in various thyroid conditions by a T3 analog method and the results compared with those obtained by equilibrium dialysis in the same individuals. The methodology is easy to perform and reproducible. FT3 determination appears to be especially valuable in detecting borderline thyrotoxicosis as in cases previously cured from thyrotoxicosis but suspected of relapse, or in nontoxic goitrous patients overtreated with T4.

Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study.

OBJECTIVE: In Graves' hyperthyroidism treated with antithyroid drugs (ATD), the overall relapse rate reaches 30-50% following ATD discontinuation. Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine (l-T4), and thereafter maintaining l-T4 treatment after ATD withdrawal. Also, clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment. DESIGN: Eighty-two consecutive patients (70 women and 12 men; mean age 36 years) with a first episode of Graves' hyperthyroidism were investigated prospectively; they were treated with ATD for a total of 15 months, combined with l-T4 (for at least 12 months) after they had reached euthyroidism, with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy. Following ATD discontinuation, the patients were randomly assigned (double-blind placebo-controlled trial) to taking 100 microg/day l-T4 (vs placebo) for an additional year. METHODS: The following determinations were carried out at initial diagnosis: serum total T4 and tri-iodothyronine (T3), free T4 and T3, TSH, TSH-receptor antibodies (TSHR-Ab), thyroid scintigraphy and echography. During ATD treatment, serum free T4 and T3 and TSH concentrations were recorded after 1 (optional), 2, 4, 6, 9, 12 and 15 months, and echography at the end of ATD treatment. During the randomized trial, serum free T4 and T3 and TSH concentrations were checked every 3 months (or until a recurrence). TSHR-Ab titers were measured at initial diagnosis, after 6 months with ATD, and at the end of ATD treatment. RESULTS: l-T4 administration, both during and after ATD treatment, did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients (30%). Two parameters were identified that might be useful to help predict recurrence risks after ATD: (i) positive TSHR-Ab (at the end of ATD treatment) was significantly associated with a greatly increased recurrence risk; and (ii) despite the relatively small number of patients who were smokers, regular cigarette smoking was shown, for the first time, to be significantly associated with an increased recurrence risk. Also, the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment. Thus, compared with the overall 30% recurrence risk, non-smoking patients with a negative TSHR-Ab (at the end of ATD) had a lower (18%) recurrence risk; smoking patients with negative TSHR-Ab (at the end of ATD) had a 57% recurrence risk; non-smoking patients with positive TSHR-Ab (at the end of ATD) had a high (86%) recurrence risk; the recurrence risk was 100% in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment. CONCLUSIONS: The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate. Two factors, namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinically useful (albeit not absolute) predictors of the risk of recurrence in patients with Graves' hyperthyroidism treated with ATD. However, due to the relatively small number of smoking patients in the present cohort, this conclusion needs to be confirmed by a larger study.

The role of retinol-binding protein in protein-calorie malnutrition.

Plasma RBP is decreased to 1.62 mg plus or minus 0.71/100 ml, or 31.1 percent of normal, in the acute stage of kwashiorkor. RBP doubles its plasma level after 1 wk and triples after 2 wk of appropriate refeeding. The return to normal of RPB runs in close parallel with prealbumin (PA), implying that both components remain bound by 1:1 molar ratio in the PA-RBP complex. Low values recorded on admission for RBP seem to be the result of reduced liver biosynthesis. On the other hand, a high correlation persists between RBP and retinol plasma level along the successive steps of clinical recovery, suggesting that RBP acts as the limiting factor for retinol transport.

Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA.

OBJECTIVES: Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. METHODS: In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. RESULTS: Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. CONCLUSIONS: These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.

Erectile dysfunction and lower androgenicity in type 1 diabetic patients.

OBJECTIVE: To analyse the clinical characteristics and relevant hormonal profile in type 1 diabetic patients with and without ED. MATERIAL AND METHODS: Fifty one type 1 diabetic patients were studied. ED was assessed by direct interview. Chronic diabetic complications, smoking and alcohol status as well as current use of medications were recorded. Hormonal profile consisted of plasma LH, FSH, prolactin, androstenedione (Delta(4)), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), free testosterone (FT), estradiol (E(2)), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), cortisol, TSH and free thyroxine (FT(4)). RESULTS: ED was present in 24 patients (47%) (group 1), who were older (P<0.001), had a longer diabetes duration (P<0.001) and a higher systolic blood pressure (P=0.017) when compared to the subjects who did not complain (group 2). ED was positively correlated to all diabetes-related complications (P<0.02). Antidepressive drug(s) were more frequent in group 1 (P=0.007), as well as prokinetics (P=0.043) and ACE-inhibitors (P=0.010). HbA(1)c was comparable. Patients with ED had lower levels of Delta(4) (P=0.003), DHEA (P<0.001), DHEA-S (P=0.002), FT (P=0.08) while SHBG (P=0.010) and LH (P=0.022) were higher compared to group 2. Multiple logistic regression analysis showed an independent association of ED with Delta(4) (P=0.016), DHEA-S (P=0.037), SHBG (P=0.001) and insulin dose (P=0.025). There was no significant difference for all other measured hormones. CONCLUSION: ED is impressively prevalent in type 1 diabetes and is associated with age, diabetes duration, chronic complications and decreased androgens.

Albumin, transferrin and the thyroxine-binding prealbumin/retinol-binding protein (TBPA-RBP) complex in assessment of malnutrition.

A comparative study of the level of 4 plasma proteins in malnutrition shows that albumin has low sensitivity, transferrin has intermediate and the TBPA-RBP complex has the highes sensitivity to an alteration in the nutritional status. According to protein and/or iron deficiency, the synthesis of trnasferrin seems to be submitted to contradictory impulses which partially invalidates this test as a reliable index for estimating protein depletion alone. On the contrary, the components of the TBPA-RBP complex respond together and in a parallel direction to protein deficiency. The high degree of sensitivity of TBPA and RBP to an inadequate protein intake is apparently related to their rapid turnover rate and to their unusual richness in tryptophan, which is known to play a key role in the control of protein synthesis. Measurement of TBPA (or RBP) is proposed as a method for the detection of pre-kwashiorkor and early marasmus.

Long-term effects of percutaneous estradiol on bone loss and bone metabolism in postmenopausal hysterectomized women.

OBJECTIVE: To determine whether percutaneous estradiol (pE2) (1.5 mg/day) is able to counteract the postmenopausal bone loss in postmenopausal hysterectomized women, in a double-blind study versus oral estriol (E3) (2 mg/day). METHODS: The bone mineral density of the lumbar spine (LS) and of the proximal femur (PF) was measured every 3 months by dual energy X-ray absorptiometry for 2 years in 43 hysterectomized postmenopausal women (21 in the E2 group and 22 in the E3 control group), and in a subset of patients for a 3rd year. The statistical analyses were performed on Macintosh using Stat View II. RESULTS: A significant bone loss of 1.2 (0.4%)% and of 1.3 (0.3)% per year was observed in the control group, respectively at LS and at PF, versus a significant gain of 1.2 (0.5)% per year in the treated group at the LS. No significant change at PF occurred in the treated group. In the 20 patients followed up for a 3rd year on pE2, an increase of 1.2 (0.9) and 2.5 (1.4)% at LS in the 12 former active group patients and the eight formerly control patients, respectively was seen. The same trend was observed at the proximal femur. CONCLUSION: pE2 (1.5 mg E2) is able to counteract the postmenopausal bone loss in hysterectomized women, whereas E3 (2 mg/day administered orally) is unable to maintain bone mass.

Decreased serum TBG concentration in the face of normal T4-binding capacity in patients on hemodialysis.

Serum TBG concentrations were evaluated in 34 patients on regular hemodialysis. Mean serum TBG level measured by two different radioimmunoassays was markedly decreased (1.24 +/- 0.08 mg/dl - normal limits 1.6-2.4 mg/dl). Twenty-seven (79%) patients had values below 1.6 mg/dl, which contrasted in 21 of them with a lack of reciprocal elevation of T3RU values. By contrast, T4-binding capacity of TBG measured in 14 patients with low TBG concentration was normal, suggesting that the low TBG values were an artefact resulting from an altered immunoreactivity of the protein. In 2 patients with low TBG while on hemodialysis, TBG levels increased significantly after renal transplantation. This suggests that the "low TBG syndrome" (altered immunoreactivity in the face of normal T4-binding capacity) observed in patients on chronic hemodialysis is a consequence of uremia.