ACTA ENDOCRINOLOGICA (BUC)

Background. Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are associated with disturbed mineral homeostasis and serum bone biomarkers. The interplay between T2DM and CKD on serum bone turnover markers (BTM) is unclear. Our aim was to describe the BTM in patients with T2DM, CKD or both. Methods. In this observational, single-centre, prospective study, we included 320 patients over 40 years, divided into four groups: T2DM and normal kidney function (n=142), T2DM and CKD (n=36), CKD and normal glucose metabolism (n=29) and healthy controls (n=113). We excluded patients treated for osteoporosis and with secondary osteoporosis. Patients were compared by age, levels of glycated hemoglobin, PTH, alkaline phosphatase, osteocalcin (OC), CTx and 25 OH vitamin D. Results. Univariate analysis showed that GFR correlated significantly with PTH (r=0.37), OC (r=0.43) and CTX (r=0.45) in the diabetes group but only with PTH (r=0.34) in the non-T2DM group. Multivariate analysis showed that GFR remained significantly correlated with the same bone markers even after adjustment for age, sex or 25(OH)D levels. Diabetics seem to have lower levels of alkaline phosphatase (68±22.1 U/L) and CTX (0.37±0.24 ng/mL) than those without diabetes (76.7±29.6. U/L and 0.5±0.19 ng/mL, respectively). There was no correlation between BTM and glycated hemoglobin. Conclusions. Bone turnover markers correlate with GFR, particularly in patients with T2DM. However, alkaline phosphatase is lower in T2DM than in non-T2DM.

Aim. To assess the levels of s BGP and BAP and correlate them with the rate of bone remodelling.\r\nPatients and Methods. The study was performed on 74 cases with postmenopausal osteoporosis, divided into two groups, according to the duration of estrogenic deprivation, compared with a control group (n= 20, postmenopausal women without osteoporosis). The serum levels of the discussed markers were measured by ELISA technique. BMD was measured using the DXA technique with the assessment of T score.\r\nResults. In the group I: BGP were 20.12?0.87ng/mL (p<0.03), those of BAP 13.76?0.6&#956;g/mL (p<0.001) and sT spine were -3.63?0.65DS (p<0.001). In the group II: BGP were 15.12?1.55ng/mL (p<0.05), those of BAP 11.88?0.38&#956;g/mL (p<0.001) and sT spine were -3.78?0.36DS (p<0.001). The control group presented: BGP of 16.22?1.62ng/mL, those of BAP of 8.68?0.44&#956;g/mL and sT spine of -1.78?0.11DS. The serum levels of BGP in postmenopausal osteoporosis cases were increased in group I (suggesting an osteoblastic activation) and decreased in group II (probably secondary to the stimulation of osteoblastic apoptosis). The serum levels of BAP are significantly increased\r\nin postmenopausal osteoporosis versus control group, attesting osteoblastic activation.\r\nConclusion. Bone resorption begins gradually to outrun a new bone formation rhythm associated with low BMD.

Background. sRANKL (soluble receptor activator of nuclear factor-kB ligand) and OPG (osteoprotegerin) represent a novel cytokine system with pleiotropic effects on bone remodeling.\r\nAim. The aim of this study was to assess the implications of serum levels of sRANKL, OPG and E2 (estradiol) in the process of bone remodeling of postmenopausal women with osteoporosis.\r\nMethods. The study was performed on 74 patients with postmenopausal osteoporosis, divided into two groups of patients according to the duration of estrogenic deprivation, compared with a control group (n= 20 postmenopausal women without osteoporosis). The serum levels of the enunciated markers were measured by ELISA technique.\r\nResults. In the group I (n= 48, bellow 15 yrs of estrogenic deprivation) the serum levels of sRANKL were 67.63?3.55 pg/mL (p<0.002), those of OPG were 42.15?0.55 pg/mL (p<0.002) and the levels of E2 were 28.32?1.78 pg/mL (p<0.004). In the group II (n= 26, over 15 yrs of estrogenic deprivation) the serum levels of sRANKL were 49.26?2.85 pg/mL (p<0.003), those of OPG 27.78?1.04 pg/mL (p<0.003) and the serum levels of E2 were 19.66?1.23 pg/mL (p<0.002). In the control group (n=20), the serum levels of sRANKL were 32.48?3.03 pg/mL, those of OPG 38.05?4.89 pg/mL and the serum levels of E2 were 43.07?4.04 pg/mL.\r\nConclusions. The serum levels of sRANKL are significantly higher in postmenopausal women with osteoporosis versus postmenopausal women without osteoporosis, attesting osteoclasts activation. The serum levels of OPG in postmenopausal women with osteoporosis were increased in group I, suggesting the osteoblastic activation and decreased in group II, probably secondary to the stimulation of osteoblastic apoptosis.

Central precocius puberty (CPP) is characterized by abnormalities in the setting up of the gonadotropin ?pubertal? release, which occurs earlier. The gonadotropin releasing hormone (GnRH) was used initially to test the pituitary regarding FSH and LH release in both precocious and delayed puberty. Various GnRH superagonists were used for the same purpose, including triptorelin. A triptorelin test was applied to 14 girls with premature thelarche by using the subcutaneous administration of 0.1 mg/sqm and blood sampling at 2, 3 and 4 hours for serum LH and FSH and at 24 hours for serum estradiol. Serum mean levels of LH were >7.8 mIU/ml at all intervals, suggesting a ?pubertal? type of LH release. As concerns the individual levels of LH, only 5 out of 14 girls showed a value greater than 8 mIU/ml, which is the cutoff limit for the diagnosis of precocious puberty. These girls also met the other clinical and radiological criteria necessary for the diagnosis of precocious puberty. It was concluded that soluble triptorelin may be useful in detecting ?pubertal? type of LH release in girls exhibiting premature thelarche. Regarding the FSH and estradiol levels, they were considered irrelevant for the diagnosis.

Introduction. Vitamin D deficiency has been proven to have a deleterious effect on bone remodeling and bone mineral density, by inducing secondary hyperparathyroidism. The lack of a present consensus on optimal serum 25(OH)D levels required for the preservation of physiologic bone metabolism renders its follow-up difficult.\r\nMaterials and Methods. The cross-sectional study was performed on a sample of 69 healthy men aged 50-70. Serum 25(OH)D, total testosterone, sex hormone binding globulin, s-CTX (Crosslaps), and osteocalcin were assessed. BMD was measured by DXA at lumbar spine and hip levels. Statistical relationships between these parameters were calculated.\r\nResults. We found a significantly negative correlation between 25(OH)D and s-CTX (r = -0.30. p<0.05), but not between 25(OH)D and osteocalcin, although s-CTX correlated positively with osteocalcin (r = 0.49, p<0.001). Serum CTX was negatively correlated with lumbar BMD (r = -0.35, p<0.001), while osteocalcin was negatively correlated with total hip BMD (r = -0.26, p<0.01). Comparing mean s-CTX levels in insufficient and sufficient subjects at different cut-off points for 25(OH)D, significant differences appeared the strongest at 60 ng/ml. The percentage of 25(OH)D deficient or insufficient subjects was 50.7% at a 30 ng/ml cut-off point.\r\nConclusions. The results of the present study confirm the benefit in maintaining a normal bone turnover offered by serum 25(OH)D in the upper normal range. The large percentage of patients with vitamin D insufficiency reinforce the necessity of a specific follow-up and of epidemiologic studies dedicated to our geographic area.

Endemic goiter occurred in different degrees throughout 2/3 of Romania, mainly in the Carpathian area. The prophylaxis of iodine deficiency disorders (IDD) using salt iodization was introduced in 1956 with potassium iodate, KIO3, 15-25 mg/1kg salt, but only in 23 districts. In 2002 a new legislation introduced the mandatory use of the iodized salt in a higher concentration in households of all 41 districts and also in the baking industry. The study aims to evaluate the effects of iodine legislation changes upon the urinary iodine excretion (UIC) in schoolchildren (study group A) and pregnant women (study group B). Urine samples were collected from 3737 schoolchildren aged 6-14 years of 14 districts and from 1283 pregnant women of 11 districts in the years 2004-2005. In two areas - Bistrita Nasaud and Bucharest - the number of schoolchildren was larger, i.e. 465 and 1617 respectively. UIC was determined in spot urine samples by Sandell Kolthoff?s method. The results show in schoolchildren an increase of the median UIC in 9 out of 14 districts up to 90 ? 61.1 ?g/L (range 12.5-300 ?g/L). Six of these districts are in the Carpathian area. However, in pregnant women in 2004, UIC still showed low levels of 55 ? 48.78 ?g/L (range 12.5-280 ?g/L) in all 11 studied districts and in Bucharest, close to the UIC obtained in the year 2001. In conclusion, this study revealed an increase of median values of UIC in schoolchildren after universal salt iodization program. The persistence of iodine deficiency in pregnant women in the studied districts is an emergency problem that has to be solved as soon as possible. This fact involves the necessity of a large monitoring program in the next years, in all districts in urban and rural areas and in all known pockets of endemia.

INTRODUCTION: The aim of our study was to evaluate the cure rate of macroprolactinomas treated for a long term (> 4 years) or a short term (<4 years) with dopamine agonists (DA) alone or combined with radiotherapy (RT). Sometimes pituitary\r\nsurgery was performed.\r\nMATERIAL AND METHODS: We performed a retrospective study in 111 patients with macroprolactinomas, hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005. There were two groups, according to the length of DA therapy: group\r\nA =41 patients, treated more than 4 years and group B =70 patients, treated less than 4 years. Overall, 25 patients underwent additional radiotherapy, 13 in group A and 12 in group B. 28 patients were submitted to pituitary surgery, 9 in group A and 19 in group B.\r\nRESULTS: The cure rate (i.e. normalization of prolactin=PRL level and absence or minimal residual tumor mass, stable minimum 2 years after DA withdrawal) was 5/41 (12.1%) in group A and none in group B. 48 out of 111 patients achieved significant improvement (serum prolactin level less than 20 ng/ml and tumor shrinkage more than 50%) during DA therapy, but not after DA withdrawal: 17/41patients (41.5%) in group A and in 31/70 patients (44.3%) in group B, p=NS. Radiotherapy produced an additional improvement: in serum PRL levels only in group A, in 4/13 patients- 2/8 patients responsive to DA therapy and 2/5 patients resistant to DA therapy. In group B, the 3 patients resistant to DA submitted to radiotherapy were evaluated before the interval necessary for maximal effect of radiotherapy, but in 4/9 patients responsive to DA, we noticed further reduction in tumor volume, 2/4 progressing from mild to significant tumor shrinkage and ? progressing from no shrinkage to mild shrinkage. After radiotherapy, the medium prolactin level was 5.1 ng/ml in 10 patients from both groups on low bromocriptine (BRC) dose (7.5 mg/day), significantly less than in patients without radiotherapy, i.e. than in 19 patients from group A (serum PRL 49.5 ng/ml, p=0.02) and in 29 patients from group B (serum PRL 30.3 ng/ml, p=0.01). So, the daily BRC dose could safely decrease from 30 mg/day to 7.5 mg/day in those patients previously submitted to radiotherapy. Among 23 patients resistant to initial DA treatment, only 8 patients were submitted to radiotherapy, 2 became responsive to DA thereafter and 2 others obtained a significant decrease of prolactin levels.\r\nCONCLUSIONS: The overall cure rate is quite low in prolactinomas and it was noticed only after long-term treatment with dopamine agonists; it was improved up to 12.1% by the additional high voltage radiotherapy, useful even in DA resistant cases. The addition of radiotherapy is indicated for the cure of most prolactinomas.

Cardiovascular disorders represented by congenital malformations, hypertension, aortic dilatation which can emerge in dissection or rupture and ischemic heart disease are common in Turner syndrome (TS) and life-threatening. Echocardiography and magnetic resonance imaging represent complementary diagnostic methods used to assess cardiovascular status. Unfortunately, normal reference ranges for cardiac and aortic measurements are established only in unselected TS patients, preventing a delineation between patients with and without cardiovascular pathology. We performed echocardiography in 15 patients with TS, aged 12-33 years (mean 21.8 years, standard deviation 6.37 years) without cardiovascular and renal malformations, hypertension or aortic dilatation and 30 normal controls; karyotype was 45,XO in 11 patients and 45,XO/46,XX in four patients. To minimize the influence of body size, ratios of aortic and cardiac chambers dimensions were calculated. As expected, we found smaller dimensions in TS versus controls but only the ascending aorta, left atrium and diastolic left ventricular diameters and the ratio diastolic / systolic left ventricular diameters reached statistical significance. Only aortic dimensions were entirely independent of age, height, weight and BMI with a 95% confidence interval of 14.28 &#8211; 25.32 (mean 19.8) mm for the aorta at the annulus and 95% CI 21.42 &#8211; 29.36 (mean 25.54) mm for the ascending aorta. The ratios ascending aorta/ systolic left ventricular diameter (95% confidence interval 0.54 &#8211; 1.34; mean 0.94), aorta at the annulus/systolic left ventricular diameter (95% CI 0.44 &#8211; 0.92; mean 0.68) and aorta at the annulus/ diastolic left ventricular diameter (95% CI 0.36 &#8211; 0.61; mean 0.49) are independent of age, height, weight and can also be reliable for detection of aortic dilatation.

Aims. The aims of our study were to assess the prevalence of prostate tumors in patients with metabolic syndrome.\r\nMaterial and methods. Subjects were patients recruited from three medical centers in Bucharest, Romania. For this study we selected men over 45 years of age with metabolic syndrome. The anthropometric measurements included height, weight, waist circumference and hip circumference. We calculated the body mass index (BMI) and measured the\r\nblood pressure. Biochemical tests included fasting plasma glucose (FPG), HbA1c, total cholesterol (TC), TG, HDL-C, fasting plasma insulin (FPI), prostate-specific antigen (PSA)and free-PSA. The prostate gland volume was measured by transrectal ultrasound. The diagnosis of prostatic cancer was based on a positive finding of the histological\r\nexamination obtained from 14-core biopsy.\r\nResults. There was a high prevalence of prostate tumors (benign and malignant) - 82.85% (n=343). Prostate cancer was\r\ndiagnosed in 7.9% of patients (n=33) using DRE, PSA, free PSA/PSA ratio and TRUS. The prevalence of BHP was 74.9% (n=310). The results of the present study indicate that\r\nPSA detects a significant number of prostate tumors missed in DRE. The use of DRE, PSA and TRUS, in combination, provided the highest rate of detection of prostatic tumors in patients with metabolic syndrome without infectious diseases of the prostate.\r\nConclusions. The prevalence of prostatic tumors, prostate cancer and benign prostatic hyperplasia in metabolic syndrome patients is high. Due to its increased prevalence, the BPH can be considered as a feature of metabolic syndrome.

Aim. The efficacy of various treatment regimens in severe premenstrual syndrome, (PMS), and premenstrual dysphoric disorder, (PMDD).\r\nStudy design. The study group of 92 patients, aged 20-36 years, was assessed for 2 months before and at the end of one of the following 4 months treatment regimens, randomly assigned: A - combined oral contraceptives with drospirenone; B - oral contraceptives without drospirenone; C - selective serotonin reuptake inhibitors; D - EPO and vitamin B6. A not blinded control group of 92 age-matched patients with severe PMS, without medication, was used.\r\nMethods. All 184 patients completed the Prospective Record of the Impact and Severity of Mastodynia (PRISM) calendar published in 1985 (11) for every of the 6 months of the study. We did not manage or analyze PMDD separately from severe PMS. Simple t test of the initial PRISM results was used, as well as Student t test, or the chi2 test / Fisher test for qualitative data for subgroup analysis.\r\nResults. Oral contraceptives with drospirenone (treatment A) significantly improved the breast tenderness (average severity score was 14.5 ? 0.6 before and 8.9 ? 0.7, p< 0.05, after treatment) and the lack of self-control (average severity score was 14.3 ? 0.7 before and 9.1 ? 0.5, p< 0.05 after treatment). However, oral contraceptives without drospirenone (treatment B) also significantly improved the same parameters of PMS: breast tenderness (average severity score was 15.3 ? 0.4 before and 9.2 ? 0.5, p< 0.05 after treatment) and the lack of self-control (average severity score was 15.5 ? 0.5 before and 9.8 ? 0.7, p< 0.05 after treatment). The subgroup on drospirenone oral contraceptives did not show any premenstrual weight gain, unlike the other subgroups. SSRIs (treatment C) significantly improved the lack of self-control (p< 0.01), but without significant effect on breast tenderness and without any effect on the weight gain. EPO and vitamin B6 (treatment D) showed no significant effects.\r\nConclusion. Concerning the number of patients, drospirenone containing oral contraceptives showed effective improvement of PMS in 67.9% (remission) versus 35.9% (remission in the control group without any medication). However, the authors suggest that SSRIs (and not oral contraceptives with or without drospirenone) might be the treatment of choice in cases where mood / behavioral symptoms prevail over physical symptoms.