ACTA ENDOCRINOLOGICA (BUC)

Background. People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. Objective. Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. Materials and methods. Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. Results. Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 μg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 μg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 μg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. Conclusion. Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.

Context. GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective. To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design. A descriptive observational study. Subjects and Methods. Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results. The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH – PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions. There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed.

Background. Arecoline, a plant alkaloid of betel nut, is consumed by millions of people, for increased capacity of work. It causes immunosuppression, hepatotoxicity, and disturbance in antioxidant production, but it stimulates HPA axis and induces thyroid dysfunction.\r\nAim. To investigate the role of arecoline on adrenal activity, glycemia and glycogen profile in mice.\r\nMaterials and methods. Arecoline was injected intraperitoneally at a dose of 10 mg/kg body wt for 20-60 min for acute administration. In chronic administration the same dose was used daily for 15 days. Corticosterone, epinephrine, norepinephrine, blood glucose and liver glycogen profiles were measured after 20, 40 and 60 min, in acute administration and after 15 days in chronic administration.\r\nResults. Arecoline in acute administration increased corticosterone, norepinephrine and epinephrine levels and induced hyperglycemia with depletions of liver glycogen. But\r\nchronic arecoline administration with the same dose for 15 days caused ultrastructural degenerations of adrenal cortex and medulla with the elevation of corticosterone, and\r\ndepletions of norepinephrine and epinephrine levels. Arecoline also caused hypoglycemia and elevated liver glycogen. Atropine (arecoline receptor antagonist) prevented arecoline action on adrenal activity or blood glucose ? liver glycogen interaction.\r\nConclusion. The findings indicate that arecoline initially stimulates adrenal activity, but subsequently inhibits it with alterations of glycemic and glycogen profiles. Arecoline action is mediated by arecoline receptor in mice. Arecoline may have immunological action via adrenal hormonal suppression in mice.

Background. Hirsutism is part of current criteria of polycystic ovary syndrome (PCOS), as a clinical expression\r\nof hyperandrogenism.\r\nObjective. To evaluate the significant factors for hirsutism severity in PCOS.\r\nPatients. A total of 235 PCOS patients, consecutively coming for medical advice, aged 18-35 yrs, all of Romanian origin, were diagnosed according to Rotterdam criteria.\r\nMethods. Hirsutism, quantified using the modified Ferriman-Gallwey (mFG) procedure, was defined by values equal or\r\nmore than 6. Other parameters evaluated were: body mass index (BMI), fasting insulinemia, insulin resistance quantified by QUICKI, total testosterone (TT), free androgen index (FAI), dehydroepiandrosterone sulfate (DHEAs), 17OH progesterone, fasting glycemia. In a subset of 106 patients, androgen receptor (AR) was explored by CAG repeat\r\ngenotyping and X-chromosome inactivation analysis.\r\nResults. The total PCOS population (235) was divided in group A (n=139, 59.14%) with hirsutism and group B (n=96, 40.85%) without hirsutism. In univariate correlations, serum\r\ninsulin levels (p<0.05) and insulin resistance quantified by QUICKI (p<0.05), but not FAI, TT, DHEAs, 17OH progesterone or BMI were associated significantly with mFG score, in group A of hirsute PCOS patients and also in group B\r\nof nonhirsute PCOS. In a stepwise regression mFG model,\r\nincluding TT, insulin and BMI, only insulin remained independently associated with mFG score (p<0.05) in the group A of hirsute PCOS patients, whereas in group B\r\nof the nonhirsute PCOS, there were not significant associations. Androgen receptor parameters explored in 106 cases, i.e. by the biallelic means and X-weighted biallelic means of CAGn, did not show significant associations with mFG score in univariate correlations. Only insulin was significantly associated (p<0.05) in another stepwise\r\nregression model of mFG including as parameters insulin, TT, biallelic means of CAGn and BMI.\r\nConclusions. Our results support that insulin is significantly associated with the\r\nseverity of mFG score in PCOS patients, independent of serum androgens or androgen receptor sensitivity expressed by\r\nCAGn polymorphism. This suggests a possible pathogenic role of high insulin level for the development and progression\r\nof hirsutism, at least in PCOS.

Context. Retinal microvascular dysfunction differs in macular edema lesions in the two eyes of the same patient with diabetic retinopathy. Objective. To evaluate the relationship between central macular thickness (CMT) and metabolic/systemic factors including anthropometric and laboratory findings, in patients with regressed diabetic retinopathy and a history of pars plana vitrectomy (PPV) combined with internal limiting membrane peeling in one eye. Subjects and Methods. Forty-two eyes with PPV and the same patients’ fellow 42 eyes (without PPV) included this study. Fasting blood samples of these 42 diabetics were collected to study adiponectin levels and other routine parameters. Results. The average hemoglobinA1c value was 7.3±1.3%. CMT of the vitrectomized eyes were significantly correlated with atherogenic index of plasma, total cholesterol, low density lipoprotein cholesterol and uric acid (UA). On the other hand, CMT of the nonvitrectomized fellow eyes significantly correlated with glucose levels and diabetes duration. Adiponectin, adiponectin/body mass index, adiponectin/fibrinogen were found significantly higher in the subgroup with CMT≥300µm in the vitrectomized eyes (P<0.05). UA levels were higher in the subgroup with CMT≥300µm in the fellow (nonvitrectomized) eyes (P<0.05). Conclusions. Although there was no relationship between CMT and hemoglobinA1c values, CMT seemed to be affected by atherogenicity, prooxidant chemical alterations in the course of inflammation, so determination of adiponectin and UA levels may be suggested before surgery to predict the atherosclerotic damage and the postoperative CMT value. Vitrectomy performed at the proper time may be helpful in metabolic remodeling process of the retinal tissue along with life style changes, well control of diabetes, and intraocular treatments.

Introduction. Bone formation takes place through a continuous remodeling process, which involves the resorption of old bone by osteoclasts and the formation of new bone tissue by osteoblasts, melatonin contributing to the hormonal modulation of the action of osteoblasts and osteoclasts. Aim. The aim of this study is to evidence the influence of melatonin administered in combination with estrogen on bone turnover markers in female Wistar rats with bilateral surgical ovariectomy. Material and method. The study was performed on 40 female Wistar rats with a weight of 160-200 g, which underwent bilateral surgical ovariectomy. At 14 days postovariectomy, hormone replacement therapy (estradiol benzoate – E2b – 10 μg/day) and combined estrogen (estradiol benzoate – E2b – 10 μg/day) and melatonin (added to the drinking water in a concentration of 25 μg/mL or 50 μg/mL – ethanol concentration 0.01%) – treatment were initiated over a period of 12 consecutive weeks. Subsequently, venous blood was collected for the determination of serum osteocalcin and C-terminal telopeptide of collagen type I levels. Results. Melatonin administered in combination with estrogen to ovariectomized female rats induces an increase in serum osteoalcin levels (statistically significant differences between all four groups p=0.001) and a decrease in serum C-terminal telopeptide of collagen type I levels (statistically significant differences between group I and the other three groups p=0.005; p=0.001; p=0.001 and between group II and group IV p=0.007). The influence on bone formation and resorption markers depends on the administered melatonin dose and on the post-ovariectomy estradiol level. Conclusions. Melatonin potentiates the effects of estradiol on bone in ovariectomized rats.

Context. Polycystic ovary syndrome (PCOS) is associated with increased prevalence of preeclampsia (PE); microRNAs (miRs) could play an important role in the pathogenesis of PE and PCOS. Objective. To investigate the expression levels of miRs 155-5p and 518b in blood leukocytes of patients with PE and PCOS. Design. Using real-time quantitative PCR method, miR-155-5p and miR-518b were examined from PE, PCOS, PE+PCOS, and controls. Subjects and Methods. The relative expression of the target miRs in patient samples was compared to control samples. The results were calculated as relative quantification values. Results. Confounding variables were controlled using analyses for covariance. Significant differences were observed in miR-155-5p (p=0.008) and miRNA-518 (p=0.016) expression levels among the groups. miR-155- 5p (p=0.014) and miR-518b (p=0.036) were upregulated in PCOS patients and miR-518b (p=0.028) were increased in cases with PCOS+PE. Near significant difference was found (p=0.06) in miR-518b expression levels in cases with PE, compared to controls. miR-518b was observed to be positively correlated with alanine transaminase in cases with PE (r=0.80; P=0.017) and PE+PCOS (r=0.80, p=0.017). Conclusions. Our preliminary findings suggested that expression profiling of miR-155-5p and miR-518b in blood leukocytes were upregulated in pregnant women with PCOS. Moreover, miR-518b was found to be related to PE in cases with PCOS

Objective. To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. Methods. The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. Results. While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). Conclusion. The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

Background. If not diagnosed at birth, congenital hypothyroidism (CH) can cause deleterious, irreversible neurodevelopmental sequels. The importance of thyroid newborn screening (NBS) is therefore well established. Objective. To evaluate the efficacy of NBS for CH in North-East Romania. Methods. Retrospective, descriptive study involving 271662 newborns screened between 2010 and 2019 for CH and phenylketonuria in maternities from six Romanian NorthEastern counties by measuring neonatal TSH (neoTSH) in the whole blood extracted from the heel between days 3 and 5 after birth. Values found higher than a cut-off level of 10 mIU/L were followed by serum evaluation of TSH and fT4 for the confirmation of CH. Thyroid ultrasound was further performed at children found with CH. Results. NeoTSH was found elevated in 417 newborns, but CH was subsequently confirmed in only 57 cases (1/4766 newborns). Mean age at the time when diagnosis was communicated was of 37.2 ± 15 days (between 9 and 157 days). Mean age when therapy was started was of 44.2 ± 17.9 days (between 13 and 160 days) with a mean delay of one week from diagnosis (between 0 and 62 days). Thyroid ultrasound revealed athyreosis in only 3 cases, atrophic thyroid gland in other 10 cases, whereas the thyroid was described as present in the remnant 44 cases. The number of first year follow-up visits greatly varied from 0 to 5, with an average of 2. Conclusions. NBS allowed rapid diagnosis of CH in North East Romania. The communication of diagnosis to families and therapy onset were however often delayed. Diagnosis and therapy onset before the age of two weeks, as well as a tighter follow-up should be assured by the healthcare system. Etiological diagnosis should be more accurate, for a better prognosis of disease severity, as well as the possibility of genetic advice in selected cases.

Aim. Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. Materials and Methods. In this study, 238 adult LT patients were evaluated in terms of PTDM development. Results. Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/ m2 : 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p<0.001 p= 0.028). PTDM and t-HG patients mean age was higher than non-PTDM patients (51.5± 9.68, 48.2± 11.1 and 41.5± 14 years, respectively, p= 0.002 p= 0.023). In the univariate analysis, the only independent risk factor for PTDM was age (OR 1.93, 95% CI 1.31-2.97). Conclusion. Age is the most important risk factor for PTDM development after LT. PTDM was found more common in the patient group with greater body weight. Patients with older age and greater body weight should be examined more carefully for PTDM before LT.