High serum prolactin levels in men with rheumatoid arthritis.

OBJECTIVE: High prolactin (PRL) levels have been reported in systemic lupus erythematosus, Reiter's syndrome, and psoriatic arthritis. However, results of PRL investigations in rheumatoid arthritis (RA) are contradictory. We evaluated the PRL status in men with RA and the possible effect on bone mineral density (BMD). METHODS: We studied 91 men with RA and 68 controls. PRL serum levels were analyzed under standardized conditions. Sex hormones (testosterone, androstenedione, and DHEAS) were also studied. BMD was analyzed at L2-L4 and the femoral neck by Hologic QDR1000. Comparative tests, linear correlations, and multiple regression analysis were performed. RESULTS: Serum PRL levels were significantly higher in men with RA (249+/-162 mU/l) than in controls (189+/-85 mU/l) (p=0.0015). High PRL levels were significantly correlated with the duration of RA (r=0.23; p=0.01) and with functional stage according to the Steinbrocker classification (r=0.24; p=0.01). High PRL concentrations were not correlated with the low levels of androgens observed in males with RA. Femoral BMD showed a negative correlation with PRL concentrations (r=0.20; p=0.04). Nevertheless, PRL was not a significant determinant of BMD. CONCLUSION: Men with RA have high serum PRL levels and concentrations increase with longer disease evolution and worse functional stage. Prolactin levels do not have a direct effect on BMD.

Immunological quantitation of nuclear steroid receptors to optimize the biological classification of breast tumors.

We used immunological methods to determine cytosolic and nuclear steroid receptors to evaluate the advantages of nuclear receptor measurement in the selection of breast cancer patients for treatment. Around 75% of tumors showed coincidence between nuclear and cytosolic receptors (+/+ or -/-) for estrogen receptor (ER) and for progesterone receptor (PgR). Only cytosolic receptors were detected in around 20% of tumors. Distributed in the ER/PgR phenotypes according to the nuclear or cytosolic receptors, 64% of tumors remained in the same subgroup, whereas 16% of tumors were classified as hormone dependent according to cytosolic and independent according to nuclear receptors, which could be considered as 'false-positive' results. 6% of tumors would be classified as negative according to cytosolic receptors but positive according to nuclear receptors and would correspond to 'false-negative' results by conventional methods. Cytosolic receptor results may overrate the hormone dependence and cause some 'misclassifications' of patients. This could partially explain the lack of response to therapy in some cases.

Evaluation of circulating type I procollagen propeptides in patients with Paget's disease of bone.

We evaluated circulating aminoterminal and carboxyterminal propeptides of type I procollagen and total alkaline phosphatase levels in eighty consecutive patients affected by Paget's disease of bone. We compared the biochemical data with the extent of bone disease calculated on the basis of the bone scintigraphic indices. Serum aminoterminal propeptide of type I procollagen levels were high in 77% of patients, serum carboxyterminal propeptide of type I procollagen levels in 22% and serum total alkaline phosphatase levels in 76%. We found significant correlations between the three markers studied. The three biochemical markers correlated significantly with the bone scintigraphic activity indices, but the highest correlation coefficient was between the aminoterminal propeptide and total alkaline phosphatase. We conclude that there is a discrepancy between serum levels of the propeptides studied in relation to Paget's disease of bone. The sensitivity of the carboxyterminal propeptide of type I procollagen in this disease is low. In contrast the aminoterminal propeptide may be as sensitive a marker for the evaluation of this disorder as total alkaline phosphatase, and in addition may be more specific.

Changes in serum osteocalcin levels in the follow-up of kidney transplantation.

Serum osteocalcin, total alkaline phosphatase, intact parathyroid hormone (PTH), creatinine, calcium, and phosphate were determined in 23 kidney cadaveric allograft recipients, immediately before and 0.5, 1, 3 and 6 months after surgery. Immunosuppressive treatment was based on low doses of corticosteroids and cyclosporin combined with antilymphoblast globulin. The decrease in serum creatinine was accompanied by falling PTH concentrations. Serum osteocalcin levels were higher than normal before kidney transplantation and diminished at 0.5 and 1 month after surgery. Significant increases in serum osteocalcin concentrations were observed 3 and 6 months after kidney transplantation with a significant correlation with alkaline phosphatase levels. The increase in serum osteocalcin levels observed in our transplanted patients is not related with a parallel increase in serum creatinine levels nor with an increment in PTH levels; it seems to reflect an increase in the osteoblastic activity, which is not altered by steroid therapy.

Evolution of circulating C-terminal propeptide of type I procollagen in patients with chronic renal failure pre and post renal transplantation.

The carboxyterminal propeptide of type I procollagen is a biochemical marker of type I collagen synthesis. We evaluated circulating carboxyterminal propetide of type I procollagen levels in patients with terminal renal failure before and after kidney transplantation. Serum carboxyterminal propeptide of type I procollagen, osteocalcin, total alkaline phosphatase, intact parathyrin, creatinine, calcium and phosphate levels were determined in 20 patients, before and 15, 30, 90 and 180 days after surgery. Serum creatinine and intact parathyrin concentrations showed a significant decrease after kidney transplantation. Immunosuppressive treatment consisted of low dose prednisone, cyclosporin and antilymphoblast globulin. In our group, only 5 patients (25%) showed serum carboxyterminal propeptide of type I procollagen levels higher than normal before kidney transplantation. At 15 and 30 days, carboxyterminal propeptide of type I procollagen concentrations showed a decrease, while at 90 and 180 days there was a significant increase above the normal range (p = 0.006; ANOVA). Serum osteocalcin and total alkaline phosphatase levels increased significantly at the same time. We found a significant correlation between carboxyterminal propetide of type I procollagen and osteocalcin at 15 and 30 days after kidney transplantation. We conclude that the significant increase in carboxyterminal propeptide of type I procollagen levels after kidney transplantation reflect an increase in bone turnover. The low doses of steroids employed do not seem to have a significant inhibitory effect on collagen synthesis.

PDN-21 in premenopausal women with systemic lupus erythematosus treated with glucocorticoids.

OBJECTIVE: To determine if there were changes in PDN-21 and calcitonin levels in women with systemic lupus erythematosus (SLE) treated with glucocorticoids. METHODS: Concentrations of PDN-21 and calcitonin were studied in 52 premenopausal women with SLE treated with glucocorticoids. Bone mineral density analysis was performed by dual energy x-ray absorptiometry. RESULTS: The values of PDN-21 in the SLE group were 354.6 +/- 230.6 pg/ml, significantly higher than healthy women (66.7 +/- 56.8 pg/ml) (p < 0.001). There was no difference in calcitonin values between the SLE and control groups. CONCLUSION: Glucocorticoid therapy in patients with SLE causes increases of PDN-21, probably due in part to the effect on the gastric mucosa of this treatment and subsequent secretion of gastrin.

Sex hormone status and bone mineral density in men with rheumatoid arthritis.

OBJECTIVE: Sex hormone status has been proposed as an important determinant of low bone mineral density (BMD) in both men and women. Our objective was to study the relationship between sex hormones and BMD in patients with rheumatoid arthritis (RA), and how steroid therapy affects both. METHODS: We studied 99 men with RA to assess their BMD and sex hormone status. A comparative group of 68 age paired men was used. We made comparative tests, linear correlations, and multiple regression analysis. RESULTS: We found significant reductions in lumbar BMD (p = 0.0005), femoral BMD (p < 0.0005), salivary testosterone (p = 0.01), androstenedione (p = 0.007), and dehydroepiandrosterone sulfate (DHEAS) (p = 0.03) in patients with RA. In contrast, serum testosterone concentrations were normal. Salivary testosterone showed correlation with femoral BMD (r = 0.36; p < 0.001). By multiple regression analysis, weight, serum testosterone concentrations, and the cumulative dose of corticosteroids were significant predictors of lumbar BMD (r = 0.41; p = 0.001). Weight, age, androstenedione concentrations, and the cumulative dose of corticosteroids were the significant predictors of femoral BMD (r = 0.79; p < 0.0005). CONCLUSION: We confirm there is reduced BMD in men with RA; corticosteroids contribute, but are not the only factor in the pathogenesis of low BMD in patients with RA; we found decreased levels of androstenedione, DHEAS, and salivary testosterone in men with RA; and salivary testosterone, as with free testosterone, is correlated with BMD in patients with RA, with lower levels contributing to low BMD.

[The estrogen receptor/progesterone receptor quotient as an index of the transcriptional activity of estrogen receptors in breast cancer]. / El cociente receptores de estrógenos/receptores de progesterona como índice de la actividad transcripcional de los receptores de estrógenos en el cáncer de mama.

BACKGROUND: The aim of this study was to determine whether the induction of progesterone receptors (PR) for estrogen receptors (ER) in variable in breast cancer, whether it differs among pre and post menopausal women and whether the ER/PR quotient may be an index of tumoral biology. METHODS: The ER and PR content was determined by enzyme immunoassay in 814 breast tumors and the ER/PR quotient was calculated in the ER+PR+ tumors (n = 395). RESULTS: ER/PR values < 1 were more frequent in premenopausal women (66%) than in post menopausal women (38%). No influence was observed with regard to age. CONCLUSIONS: The highest ER/PR values were found in post menopausal women indicating decreased estrogen receptor transcriptional activity in this subgroup contrary to that found in premenopausal women.

Usefulness of an ACTH test in the diagnosis of nonclassical 21-hydroxylase deficiency among children presenting with premature pubarche.

Adrenal steroidogenic function was evaluated in 55 children with typical premature pubarche (PP) to investigate the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) deficiency and to evaluate the usefulness of routine ACTH testing in these patients. Four patients fulfilled criteria for LOCAH due to 21-OH deficiency. Of these, 3 had elevated baseline 17-OHP levels; in the remainder, basal 17-OHP was within normal limits. Mean basal and stimulated 17-OHP responses in children with PP, excluding those with an enzymatic defect, were very similar to those of controls (2.3 +/- 1.8 vs. 1.6 +/- 0.9 and 10.0 +/- 4.0 vs. 9.5 +/- 3.3 nmol/l, respectively). However, 5 patients had basal 17-OHP values exceeding the upper limit of controls and 8 patients, including 2 of those with elevated baseline levels, showed supranormal poststimulated 17-OHP values. Body mass indices, height standard deviation scores (SDS) and bone age SDS showed no correlation with the basal or incremental rises of any hormone. Four (7%) of our population of patients with typical PP had LOCAH due to 21-OH deficiency. Basal 17-OHP levels were helpful in detecting altered steroidogenesis in 3, thus suggesting that in some PP patients, LOCAH due to this enzymatic defect may remain undiagnosed if ACTH stimulation test is not routinely performed.

[Evaluation of salivary 17-hydroxyprogesterone and its clinical usefulness in the study of hirsutism and the partial deficiency of 21-hydroxylase]. / Valoración de la 17-hidroxiprogesterona salival y su aplicación clínica en el estudio del hirsutismo y del déficit parcial de 21-hidroxilasa.

BACKGROUND: The usefulness of the concentration of salivary 17-hydroxyprogesterone (17-OHPRG) in the diagnosis of congenital adrenal hyperplasia by partial deficiency of 21-hydroxylase was studied. As a biologic medium, saliva has important advantages such as facility in sample collection and the avoidance of the stress of venous puncture. METHODS: Salivary 17-OHPRG was measured by a direct solid phase radioimmunoassay. A control group made up of 28 males and 26 females was studied. The group of patients included 30 women, 10 of them with a previous diagnosis of partial deficit of 21-hydroxylase. Basal values were established in the control group and were compared with those found in the patients in whom a stimulation test with adrenocorticotropin (ACTH) was performed collecting blood and saliva samples. RESULTS: The levels of 17-OHPRG observed in the patients with partial deficiency of 21-hydroxylase were significantly higher than those found in the control group and in the group with hirsutism, including both basal levels and those following stimulation. The correlation between the values found in blood and saliva was very significant. CONCLUSIONS: The measure of 17-hydroxyprogesterone in saliva by a method of direct radioimmunoassay is a valid alternative test to serum measure in both basal conditions and following a stimulation test.

Salivary steroid changes and physical performance in highly trained cyclists.

The purpose of this work was to study the seasonal salivary cortisol and testosterone changes, and their relationships with lean body mass variations, in highly trained cyclists. Physical fitness, body composition (6 skinfolds) and basal salivary testosterone were evaluated in 7 male cyclists, on two separate occasions. The first assessment was made at the onset of the competitive season and the second 6 months later. Two kinds of exercise tests were carried out. The first test was an incremental exercise test to determine the maximum O2 consumption (VO2max) and the maximum workload (Wmax). We also measured the VO2 and workload (W) attained at the first and second ventilatory thresholds (VO2VT1, WVT1, VO2VT2, WVT2). During the tests the VO2 was recorded every 30 seconds (Oxycon-5, Mijhardt BV, Odijk). As a second test two days later, we assessed the anaerobic capacity expressed as the maximal accumulated O2 deficit (MAOD). Briefly, each subject underwent five submaximal exercises each lasting 6 min at an intensity of 200, 220, 240, 260 and 280 W. We estimated individually the O2 demand by extrapolating the linear relationship between the power and the O2 demand previously established. Afterwards the subjects performed a supramaximal bout at an intensity producing exhaustion between 2 and 4 minutes. The accumulated O2 demand was calculated by multiplying the O2 demand by the supramaximal test duration. The MAOD was computed as the difference between the accumulated O2 demand and the O2 consumed during the supramaximal rides. We found a significant increase in some physical fitness parameters related to aerobic capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Salivary testosterone as an index of antiandrogen therapy in hirsutism.

The purpose of this study is to examine whether salivary testosterone (ST) in hirsute women treated with antiandrogen therapy can be considered a good parameter for the evaluation of clinical response. Twenty-three hirsute women, four with polycystic ovarian disease and 19 with idiopathic hirsutism were treated with cyproterone acetate and ethynyl-oestradiol with levonorgestrel in a reverse sequential regime for three months. Basal ST from hirsute women was 0.18 +/- 0.11 nmol/L (normal values 0.03-0.17) and a decrease to 0.11 +/- 0.06 was observed in the first month of treatment, to 0.1 +/- 0.059 after two months and to 0.11 +/- 0.06 after three months, all of them significantly different from basal values (p < 0.05). We found a relationship between ST decrease and the clinical response to antiandrogen therapy. On the basis of these results we suggest that ST values could be a good index for the follow-up of antiandrogen therapy in hirsute women.

Salivary testosterone levels in women with systemic lupus erythematosus.

OBJECTIVE: To measure salivary testosterone in women with systemic lupus erythematosus (SLE). METHODS: We investigated concentrations of salivary testosterone in 13 women with active SLE and 47 women with inactive SLE, and in 72 healthy female controls. RESULTS: We found a significant decrease in salivary testosterone concentrations in glucocorticoid-treated SLE patients (mean +/- SD 0.06 +/- 0.04 nmoles/liter) but no differences in concentrations in untreated patients (0.09 +/- 0.03 nmoles/liter), compared with the healthy controls (0.11 +/- 0.04 nmoles/liter). CONCLUSION: Glucocorticoid treatment appears to cause a decrease in the salivary testosterone level. Measurement of salivary testosterone is a simple way of monitoring androgen metabolism in patients with SLE.

[Functional significance of the serum/saliva testosterone ratio in various diseases]. / Significación funcional del cociente testosterona sérica/testosterona salival en distintas patologías.

Serum/salivary testosterone ratio (ST/SlvT) expresses the relationship in absolute values between bound and unbound testosterone. This ST/SlvT ratio in supposedly healthy men (n = 25) and women (n = 72) and in patients with several disorders, prostatic carcinoma (n = 19), varicocele (n = 9) and hirsute women (n = 16), has been studied. Both serum and salivary testosterone were measured by an RIA method. ST/SlvT ratio values found in healthy men (78.4 +/- 30.9) did not differ significantly from values found in the varicocele group (111.1 +/- 49.3), but a significant difference (p less than 0.001) from those found in men with prostatic carcinoma (12.3 +/- 7.2) was observed. When the ST/SlvT ratio values obtained in healthy women (18.1 +/- 7.3) were compared with those obtained in hirsute women (1.56 +/- 5.7) no significant differences were observed. The results obtained may indicate the dissociation among the hormone transport, testosterone metabolic clearance and hormone secretion by the salivary glands.

A fluorometric enzyme immunoassay for follitropin and lutropin.

The analytical performance of the Stratus (Baxter) automatic analyser for human lutropin and follitropin determination was evaluated and compared with that of an immunoradiometric assay. Within-run and between-run imprecision were lower than those of the immunoradiometric assay. No significant differences were obtained in the parallelism study. A good and significant correlation was obtained between both methods. Results obtained for both methods were not interchangeable. The Stratus automatic analyser can replace radioisotopic methods, thus eliminating radioactive hazards.