Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of heart rate variability in Type 2 diabetic patients.

AIM: Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes. METHODS: Thirty-two diabetic patients without (D), 26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C) participated. A 30-min HRV time series was analysed by wavelet transformation and four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). RESULTS: When compared with C, in both D and DAN the normalized power and amplitude of interval II were increased and of interval IV decreased, resulting in a significantly higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of interval I were increased and of interval III decreased when compared with the D and C groups. The diabetic patients were divided in two equal subgroups according to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%, normalized power in interval II was significantly higher and in interval IV significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in DAN patients prescribed ACE inhibitors, the absolute amplitude and power of oscillations were significantly higher than in patients not taking ACE inhibitor therapy. CONCLUSIONS: Patients with diabetes have increased sympathetic and decreased parasympathetic cardiac activity regardless of the presence of autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may favourably influence HRV in diabetic patients without autonomic neuropathy.

GH-binding protein is related to bone mineral density in non-obese androgenized women.

GH and IGF system components are important regulators of bone formation and at the same time pathogenetic factors in functional hyperandrogenism (FH) in lean females. We studied the relationships between bone mineral density (BMD) and serum concentrations of GH, GH-related parameters, androgens and estrogen, in 18 non-obese women of reproductive age with functional hyperandrogenism compared to a group of 10 healthy eumenorrheic age- and weight-matched women. In androgenized women, a significant positive correlation was found between BMD and GH-binding protein (GHBP), whereas BMD did not correlate to GH or other related parameters. It is suggested that higher tissue GH receptor responsiveness in non-obese androgenized women may contribute to their higher BMD.

Etidronate does not suppress periprosthetic bone loss following cemented hip arthroplasty.

Periprosthetic bone loss after arthroplasty may threaten prosthesis survival. The current study investigated the effect of etidronate therapy on periprosthetic, contralateral hip, and spine bone mineral density (BMD) in a one-year, prospective, randomized, double-blind study on 46 patients after cemented hip arthroplasty. BMD was measured with dual-energy X-ray absorptiometry (DXA). There were no significant differences between mean BMD measurements of the etidronate and placebo groups, with the exception of the mean percent change in the spine at six months and 12 months and in Gruen zone 3 at six months; in all three cases, the etidronate group had significantly greater mean values. These findings suggest that cyclic etidronate therapy has no significant effect in suppressing periprosthetic bone loss following cemented hip arthroplasty.

Skin blood flow in the upper and lower extremities of diabetic patients with and without autonomic neuropathy.

BACKGROUND: Microvascular blood flow in the human skin is subject to rhythmic variations reflecting the influence of heartbeat, respiration, intrinsic myogenic activity, neurogenic factors and endothelial activity. The aim of our study was to test the hypothesis that basal skin blood flow (BSBF) and its dynamic components differ (1) among diabetic patients without autonomic neuropathy and with it and healthy control subjects, and (2) among the upper and lower extremities. PATIENTS AND METHODS: BSBF at four recording sites with predominantly nutritive capillary circulation (right and left caput ulnae, right and left medial malleolus) was measured by laser Doppler flowmetry in 25 diabetic patients without cardiovascular autonomic neuropathy (D), 18 neuropathic diabetic patients (DAN) and 36 healthy controls (C). Wavelet transform was applied to the laser Doppler signal. RESULTS: In absolute terms, mean flow, mean amplitude of the total spectrum and mean amplitudes at all frequency intervals were highest in C, followed by DAN and lowest in D. However, these differences were statistically significant only in the left arm. Within all three groups, mean flow and spectral amplitudes were significantly higher in the arms than in the legs, besides there was a significant difference between the two arms in D. CONCLUSION: We have confirmed the differences in BSBF among D, DAN and C, and demonstrated differences among the four recording sites which have not been previously described. The latter indicates an uneven progression of autonomic neuropathy and allows for speculation that the left arm is the latest to be affected.

Methimazole upregulates T-cell-derived cytokines without improving the existing Th1/Th2 imbalance in Graves' disease.

There is probably a systemic shift of cytokine production in patients with Graves' disease (GD) toward the Th2 cytokine response. Methimazole (MMI) is the first choice for patients with GD and presumably has some direct immunomodulatory action. The aim of this study was to evaluate the balance shift in Th1/Th2 cytokines in patients with GD after 1 yr of MMI treatment, when compared to the same balance in patients with newly diagnosed GD before treatment and in healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated from 17 healthy volunteers, from 18 patients with newly diagnosed GD before treatment and from 15 euthyroid patients with GD after 1 yr of MMI treatment. The PBMC were activated with ionomycin and phorbol 12-myristate 13-acetate (PMA). The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. In conclusion, our results show no significant change in the ratio between Th1 and Th2 cytokines produced by PBMC from patients with GD after 1 yr of MMI treatment, when compared to the ratio before treatment. The ongoing prevalence of the Th2 immune response after treatment speaks against the immunomodulatory action of the drug on the systemic level.

Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis.

Osteoprotegerin (OPG) is a recently discovered member of the TNF receptor superfamily that acts as an important paracrine regulator of bone remodeling. OPG knockout mice develop severe osteoporosis, whereas administration of OPG can prevent ovariectomy-induced bone loss. These findings implicate a role for OPG in the development of osteoporosis. In the present study, we screened the OPG gene promoter for sequence variations and examined their association with bone mineral density (BMD) in 103 osteoporotic postmenopausal women. Single-strand conformation polymorphism analysis followed by DNA sequencing revealed a presence of four nucleotide substitutions: 209 G-->A, 245 T-->G, 889 C-->T, and 950 T-->C. The frequencies of genotypes were as follows: GG (89.3%), GA (10.7%) for 209 G-->A polymorphism; TT (89.3%), TG (10.7%) for 245 T-->G polymorphism; and TT (25.2%), TC (53.4%), CC (21.4%) for 950 T-->C polymorphism. Substitution 889 C-->T was found in only two patients. Statistically significant association of genotypes with BMD at the lumbar spine (P = 0.005) was observed for 209 G-->A and 245 T-->G polymorphisms. Haplotype GATG was associated with lower BMD as compared with GGTT haplotype. Our results suggest that 209 G-->A and 245 T-->G polymorphisms in the OPG gene promoter may contribute to the genetic regulation of BMD.

GH-IGF-I axis in non-obese women with functional hyperandrogenism.

The study was conducted to assess the GH-IGF-I axis in non-obese women with functional hyperandrogenism (FH). Eighteen FH women aged 18-35 yr with a body weight within 20% of ideal body weight and 10 weight-matched controls were included in the study. Basal serum GH, GH-binding protein (GHBP), IGF-I, IGF-binding protein-3 (IGFBP-3) levels were determined as well as GH levels during GHRH stimulation. In addition, basal serum androgens [free T (FT), delta4 and DHEAS], insulin and glucose levels were determined. The group of non-obese patients with FH differed from controls in GHBP (1.21+/-0.37 vs 0.93+/-0.25 nmol/l; p<0.05) and androgen levels (FT: 8.0+/-3.2 vs 1.9+/-1.2 pmol/l, p<0.001; delta4: 10.5+/-3.2 vs 5.9+/-2.1 nmol/l, p<0.001; DHEAS: 9.3+/-3.0 vs 5.1+/-1.8 micromol/l, p<0.001). GH (r=0.365; p<0.05) and IGF-I (r=0.508, p<0.01) serum levels were significantly correlated to serum DHEAS levels in a combined group of patients and controls. Our results support the suggestion that the GH-IGF-I axis plays an important role in the evolution of hormonal and metabolic derangement in non-obese FH women.

Comparison of alterations in insulin signalling pathway in adipocytes from Type II diabetic pregnant women and women with gestational diabetes mellitus.

AIMS/HYPOTHESIS: The cellular mechanisms for the insulin resistance in pregnancy and gestational diabetes mellitus are not known. The membrane protein plasma cell glycoprotein PC-1 has been identified as an inhibitor of insulin receptor tyrosine kinase activity and could have a role in insulin resistance. This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptor tyrosine phosphorylation, IRS-1 and PC-1. METHODS: Adipocytes were obtained either during elective cesarean section from three groups of subjects (Type II diabetic pregnant women ( n=6) women with gestational diabetes mellitus ( n=10) and pregnant women with normal glucose tolerance ( n=6) as pregnant control subjects) or during elective gynaecological surgery from non-pregnant ( n=6) control subjects. RESULTS: Insulin stimulated glucose transport was reduced by 50% in women with gestational diabetes mellitus and 70% in pregnant women with Type II diabetes, compared to the non-pregnant control subjects. After maximal insulin stimulation of adipocytes, IRTK phosphorylation was reduced by 29.5% in women with gestational diabetes mellitus and 44.5% in women with Type II diabetes, compared to the non-pregnant control subjects. We also found that IRS-1 phosphorylation was reduced by 32% and 48%, respectively. On the other hand, PC-1 content in adipocytes in women with gestational diabetes mellitus increased by 320% and 668% in Type II diabetic women, compared to the non-pregnant control subjects. CONCLUSIONS/INTERPRETATION: Our results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1. Furthermore, these postreceptor defects in insulin signalling pathway are greater in both groups compared to the women with normal pregnancy. However, results from women with Type II diabetes show that pre-existing insulin resistance lead to an even greater deterioration of the signalling pathway.

New steroid 5alpha-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8.

To date, two genes encoding 5alpha-reductase isoenzymes are known (type I, type II), and one type I pseudogene. The divergent localization of these genes and the still not fully understood function of the encoded enzymes as well as the perplexing results we obtained after sequencing PCR-amplified SRD5A1 gene fragments (out of genomic DNA), made us assume that, in addition to the known SRD5A1 gene, one or more different human 5alpha-reductase type I coding genes may exist. Our research provide the first evidence for the existence of two new SRD5A1 related, previously unidentified sequences in the human genome. These sequences which were localized to chromosomes 6 and 8 are highly homologous (> 99%) to SRD5A1, and also do not contain any deletions or insertions that are otherwise a characteristic of the SRD5API pseudogene. Our results imply that these sequences may be either coding parts of yet unknown, active SRD5A1 genes, and/or of previously unidentified pseudogenes. These findings additionally support data of Chen et al. who confirmed the existence of various SRD5A1 proteins in cultured human skin cells.

Codon 325 sequence polymorphism of the estrogen receptor alpha gene and bone mineral density in postmenopausal women.

Estrogen receptor alpha (ER alpha) encoding gene is one of the candidate genes to be involved in the development of osteoporosis. Until now correlation between three ER gene polymorphisms (identified with PvuII, XbaI and BstUI) and bone mineral density (BMD) have been investigated. The results of these studies are contradictory. Thus the aim of our work was to search for new, yet unknown, and probably more informative polymorphism(s) of the ER alpha gene. For detection of mutations the whole coding region of the ER alpha gene was screened systematically. In a group of 85 late postmenopausal women all of the eight exons were amplified by polymerase chain reaction (PCR) and fragments were further analyzed by single-stranded conformation polymorphism (SSCP) analysis. Mutations were confirmed by direct DNA sequencing. In the whole coding region of the ER alpha gene two silent mutations in codon 87 and 325, respectively, were found. The silent mutation in codon 85 of exon 1 (GCG-->GCC; A87A) was described previously, as BstUI polymorphism. On the other side, the silent mutation in codon 325 (CCC-->CCG; P325P), located in exon 4, has not been analyzed so far in correlation with BMD. According to the distribution of genotypes CC:CG:GG=49.4:41.2:9.4, we can affirm the existence of genetic polymorphism in codon 325 in our population of late postmenopausal women. The mean femoral neck BMD, but not the lumbar spine BMD, was significantly lower (P=0.029) in the homozygous GG-women with CCG/CCG codon 325 as compared to the homozygous CC-women with the normal codon CCC/CCC. Our results suggest that codon 325 sequence polymorphism of the ER alpha gene might be one of the factors associated with low femoral neck BMD.

Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men.

OBJECTIVE: The within subject variability of the insulin tolerance test (ITT) for assessment of growth hormone (GH) status and cortisol reserve has rarely been examined, particularly in patients with hypopituitarism. This becomes important when biochemical criteria are used to determine which adults with hypopituitarism should receive GH and/or cortisol replacement. In the present study we assessed the reproducibility of GH and cortisol responses in repeated ITTs. Baseline insulin-like growth factor 1 (IGF-1) levels were also assessed for reproducibility on each occasion. DESIGN AND PATIENTS: Three consecutive ITTs were performed in seven normal adult men (ages 22-27 years) and two ITTs in 11 men with hypopituitarism and suspected GH deficiency (ages 23-48 years). MEASUREMENTS: Serum GH and IGF-1 were measured by immunoradiometric and cortisol by immunofluorimetric assays. RESULTS: In normal men group peak GH responses did not differ between the three tests. There was no correlation between individual peak values. The within subject peak GH variability was between 4.6 and 59.3%, and the overall variability in 21 tests was 35%. The lowest peak GH concentration was 70 mU/l (27 microg/l). All hypopituitary men had severe GH deficiency (all peak GH concentrations < 4 mU/l (1.5 microg/l) in both tests). There was a highly significant correlation between individual peak GH values (r = 0.95, P < 0.0001). Basal IGF-1-values in normal and hypopituitary men were highly correlated between tests (r = 0.98, P < 0.0001). The overall within subject variability of IGF-1-values was 11.9% in normal and 22.7% in hypopituitary men. In normal men group peak cortisol responses were not different between the three tests. There was a good correlation between individual peak cortisol responses in the three ITTs. The within subject peak cortisol variability (median 8.3%; range 0.7-21.5%) was significantly less than that of GH (P < 0.03) in two of three test comparisons. In hypopituitary men the within subject peak cortisol variability (median 41.6%; range 3.5-92.7%) was significantly greater (P < 0.001) than in normal men. All patients were correctly classified as cortisol deficient or normal in both ITTs. CONCLUSION: The cortisol response to repeated hypoglycaemia is very reproducible in normal men but the GH response is less so. In hypopituitary men the reproducibility of the GH response is good while that of the cortisol response is poor. However, a single ITT did not misclassify hypopituitary patients who are severely GH and/or ACTH deficient and was therefore adequate for clinical decisions regarding GH and/or cortisol replacement. Nevertheless, it remains possible that a single ITT could misclassify some hypopituitary patients with partial GH or ACTH deficiency.

Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in full-time care.

Atraumatic fractures are often seen in children and adolescents with cerebral palsy (CP) and epilepsy in full-time care. Increased bone fragility was postulated to be due to osteopenia resulting from a combination of factors including immobilization and antiepileptic treatment. The aim of this study was to determine the effect of vitamin D and calcium substitution on bone mineral density (BMD) in a group of children with CP in full-time care. Twenty children with the most severe form of CP (spastic quadriplegia) who had been treated with antiepileptic drugs for a relatively long period of time were included in the study. Physical examination and laboratory analyses excluded other possible causes of osteopenia. BMD was measured by dual X-ray absorptiometry. Thirteen patients were treated for 9 months with 1,25-dihydroxy-cholecalciferol vitamin D (0.25 mcg daily) and with calcium (500 mg daily). Seven control children were used for observation only. BMD greatly increased in the treated group, while children with CP in full-time care who did not receive vitamin D and calcium substitution continued to lose their bone mass. It can be concluded that the addition of vitamin D and calcium increases BMD in children with the most severe form of CP, who are receiving antiepileptic drugs.

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.

Chromium status of tannery workers in relation to metabolic disorders.

Chromium (Cr), being an excellent tanning agent, is widely used in the leather industry. In the process of leather production, tannery workers are exposed to either inorganic Cr(III) compounds or Cr bound to proteins (leather dust). The total Cr content in tannery air (1-54 microg m(-3)) is rather high in comparison to ambient air (4-6 ng m(-3)) but the amount of Cr in inhalable particles (<10 microm) is two to three orders of magnitude less (20-60 ng m(-3)). The total daily intake of Cr was estimated by the analysis of diet (24.3 +/- 4.0 microg Cr day(-1)), drinking water (0.3 +/- 0.1 microg Cr dm(-3)) and ambient air. The contribution of the latter was dominant for tannery workers and almost negligible (8%) for the unexposed population. Chromium is an essential nutrient required for sugar and fat metabolism. The normal dietary intake of Cr for the occupationally unexposed population is found to be suboptimal (<30 microg Cr day(-1)) whereas tannery workers receive on average 150-325 microg of supplemental Cr day(-1). Assessment of the Cr status of both populations was made on the basis of the Cr contents of their scalp hair, pre-shift urine and thermally induced sweat. The median Cr contents in these tissues and fluids were significantly higher (P<0.01) in tannery workers (hair: 4 microg Cr g (-1), urine: Cr/creatinine 1.7 microg Cr g(-1), sweat: 25 microg Cr dm(-3)) in comparison with the control group (hair: 0.16 microg Cr g(-1), urine: Cr/creatinine 0.13 microg Cr g (-1), sweat: 0.7 microg Cr dm(-3)). Tannery workers absorbed up to 13 times more Cr in comparison to controls, the amount varying considerably depending on the workplace and duration of exposure. The main route of Cr absorption appears to be through the gastrointestinal tract, where medium to large particles play a dominant role. The absorption of Cr from leather dust may be more efficient in comparison to inorganic Cr(III) compounds. Under normal circumstances sweat Cr losses represent at least 20% of urinary Cr excretion. The incidence of glucose intolerance and disturbed lipid metabolism was compared between the unexposed (control) population (n=150) and a population of tannery workers (n=138) from the same residential area. The percentage of glucose-intolerant subjects was significantly (P<0.01) lower in the older subgroup (age>48 years), who were even more obese, but not in the whole tannery population in comparison to controls. In the group of subjects displaying glucose intolerance, those from the control population showed a significantly higher body mass index (BMI) of 32.3 and a considerably larger proportion of females (86%) in comparison to subjects from the tannery population (28.2 and 60%, respectively). There was no significant difference in total serum cholesterol levels between the groups. Results of other lipid variables, such as high-density lipid (HDL) cholesterol, low-density lipid (LDL) cholesterol and triglycerides, are controversial: namely, the HDL/LDL ratio was higher for the controls, who showed in contrast significantly higher serum triglyceride levels in comparison to the older subgroup of tannery workers. The possible effects of other parameters on serum HDL-cholesterol level are outlined but the influence of Cr on lipid metabolism in tannery workers remains unclear.

VDR genotype and response to etidronate therapy in late postmenopausal women.

Twenty-four late postmenopausal women with osteoporosis were studied. The patients were separated in three subgroups according to the BsmI polymorphism of the vitamin D receptor (VDR) gene: BB (n = 8), Bb (n = 10) and bb (n = 6). They did not differ in age (mean ages were 66.0 years, 65.9 years and 63.9 years, respectively), years after menopause (18.7 years, 18.1 years and 18.4 years) or body weight (64.9 kg, 65.3 kg and 63.8 kg), the variables known to be associated with bone mineral density (BMD). The results show that the response to antiresorptive bisphosphonate therapy in combination with calcium supplementation is modified by VDR genotype. The lumbar spine BMD increased significantly faster in the BB and Bb groups (7.3% and 7.0%, respectively) compared with the bb group (2.5%) during 1 year of cyclic etidronate therapy (400 mg/day) and calcium supplementation (1000 mg/day). The biochemical marker of bone resorption (urinary hydroxyproline excretion) as well as the bone formation marker (serum levels of osteocalcin) decreased during the treatment. With respect to VDR genotype, a significantly higher decrease in osteocalcin level was observed in bb as compared with BB subjects. We conclude that the VDR genotype is involved in an individual's response to cyclic etidronate therapy with calcium supplementation.

CYP17 gene analysis in hyperandrogenised women with and without exaggerated 17-hydroxyprogesterone response to ovarian stimulation.

Nine patients with polycystic ovary syndrome (PCOS) and exaggerated serum level of 17-hydroxyprogesterone (17-OHP) response to gonadotropin (GnRH) agonist stimulation, and seven patients with PCOS, but normal 17-OHP response have been analysed for possible linkage of PCOS with genetic defects on the 17 alpha-hydroxylase/17,20-lyase gene (CYP17). A portion of the regulatory and the entire coding domain for this enzyme have been analysed by PCR-SSCP analysis. Samples have been also screened for the previously reported -34 bp polymorphism, which creates a new SP1-type promoter site, but was excluded as the primary genetic defect. We have varied gel concentrations, reduced running temperatures, added glycerol to polyacrylamide gels and performed electrophoresis on longer gels in order to improve the resolving power of SSCP. Screening of the CYP17 gene revealed no mutations associated with the disease in the examined group of patients. Also, the -34 bp polymorphism proved to be equally distributed among patient and control samples, which in our case were non-related. The results indicate that, when germline mutations in question, CYP17 may be excluded as a candidate gene for these subtypes of PCOS.

Insulin-like growth factor binding protein-3 (IGFBP-3) serum concentrations and ovarian responsiveness in in-vitro fertilization.

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis seems to play an important role in ovarian responsiveness. Recently IGF binding protein-3 (IGFBP-3) serum concentrations have been reported to be a good marker of GH/IGF-I axis activity. In view of this finding, we measured IGFBP-3 serum concentrations in 29 women undergoing in-vitro fertilization. We found a significant correlation among IGFBP-3 serum concentrations and markers of ovarian stimulation including efficacy index, serum oestradiol concentrations and the number of follicles on the day of human chorionic gonadotrophin (HCG) administration. The results of our study add additional evidence to the importance of the GH/IGF-I system in regulating ovarian responsiveness to gonadotrophin stimulation.

Androstanediol glucuronide in patients with pancreatic cancer and in those with chronic pancreatitis.

The differential diagnosis between pancreatic cancer and chronic pancreatitis is extremely difficult. Beside CA19-9 level determinations, many tests have been tried with the aim to facilitate this distinction. Serum androgen levels have been used for this purpose. To further explore the value of androgen markers in differentiating pancreatic cancer from chronic pancreatitis we determined the serum levels of androstanediol glucuronide and of androgens in the two groups of patients and compared them with CA19-9 levels. A total of 25 males were entered into the study. Of these, 13 patients had pancreatic cancer and 12 chronic pancreatitis. They were comparable as to their body weight and age. Patients with pancreatic cancer had significantly lower serum testosterone, dihydrotestosterone and androstanediol glucuronide levels, but not testosterone/dihydrotestosterone ratios when compared to patients with chronic pancreatitis. Only androstanediol glucuronide and dihydrotestosterone serum concentrations had such a small overlap between the two groups that could be used for differentiation, their sensitivity and specificity being comparable to those of CA19-9 levels. The present study has shown for the first time that serum androstanediol glucuronide levels in male patients with pancreatic cancer are significantly lower than in those patients with chronic pancreatitis. Furthermore, the sensitivity and specificity of serum andorstanediol glucuronide levels which can be used to differentiate between pancreatic cancer and chronic pancreatitis are comparable to those of CA19-9.

Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.

Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.