ACTA ENDOCRINOLOGICA (BUC)

Introduction. Induction of heme oxygenase (HO) gene expression can protect lungs from Hypoxic Pulmonary\r\nVasoconstriction (HPV). Furthermore, there is evidence that Rho-kinase (ROCK) may be involved in HPV. Studies are going on to detect the real mechanisms involved in the phenomenon. Ghrelin, a 28-amino-acid peptide, has been shown that it may protect lungs from HPV side effects. The aim of this study was to evaluate the effect of exogenous ghrelin on HO and ROCK isoforms gene expression during chronic hypoxia (CH).\r\nMaterial and Method.Twenty four adult male Wistar rats were divided randomly in three groups. Hypoxic rats with saline or ghrelin treatment were placed in a normobaric hypoxic chamber (O2 11%), for two weeks. Controls remained in room air. HO and ROCK isoforms gene expression was measured by Real-Time RT-PCR. Lung tissues were histologically processed and stained with hematoxylin-eosin for morphometric analysis.\r\nResults. Morphometric analysis showed that ghrelin reversed the hypoxia induced pulmonary artery wall thickness (P < 0.001). In hypoxic animals, the amount of HO-1 expression increased but there was suppression in HO-2 gene expression (P < 0.05). Both ROCK-1 and ROCK-2 gene expressions were diminished after two-week hypoxia. Ghrelin treatment reduced the overexpression of HO-1 (P < 0.05), but had noeffect on ROCK gene expression.\r\nConclusion. Ghrelin by decreasing the expression of HO-1 and HO-2 in hypoxic animals may be involved in an adaptation\r\nmechanism during CH. However, ghrelin did not change ROCK isoforms gene expression, thus it could not affect HPV in this way. Nevertheless, more studies are needed to justify the protective roles of ghrelin for HPV.

Context: rising incidence of Gestational diabetes mellitus (GDM) has been reported in the recent years and it has become an important public health problem, mainly among women aged 35-39 years. Objectives: Frequency of GDM in the females who are living in the northwest of Iran was evaluated. Subjects and Methods: two hundred and fifty pregnant women at 24-28th weeks of gestation were screened using 50 g oral glucose challenge test (OGCT), and the subjects with blood sugar levels equal or greater than 130 mg/dl were referred to diagnostic 100 g oral glucose tolerance test (OGTT). GDM was diagnosed according to Carpenter and Coustan criteria. Results: eighty six women (34.4%) with positive result of screening test were selected for subsequent OGTT with 100 g oral glucose. GDM was diagnosed in twenty four women (9.6 %) with at least 2 abnormal values. Frequency of GDM in the older subjects or the subjects with high pre-pregnancy or 24-28th weeks’ body mass index(BMI) were significantly higher than younger pregnant females or the subjects with low BMI. Conclusion: Prevalence of GDM in the current study was 11.9%, which is higher than earlier reports and implicates that the prevalence of gestational diabetes mellitus has markedly been increasing in Iran and associated with maternal age and body mass index.

Objectives. The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.- 280G>T) polymorphisms and endometriosis in Romanian women. Material and methods. We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results. There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.- 280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions. FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Granulomatous hypophysitis is a very rare inflammatory lesion of the pituitary gland. Its typical clinical presentation is as an expanding sellar mass mimicking an adenoma, making it difficult to confirm the disease without a histopathological examination. Furthermore, determining the underlying etiology is a significant diagnostic challenge for clinicians. Case Report. We report the case of a 42-year-old female who presented with a history of severe headache and a sellar mass on imaging; she was initially diagnosed with an invasive pituitary adenoma but received a final diagnosis of granulomatous hypophysitis. The differential diagnosis was focused on idiopathic granulomatous hypophysitis versus tuberculous hypophysitis. On the one hand, the patient did not present signs of active tuberculosis nor of a systemic disease, and the PCR for mycobacteria on the pituitary tissue was negative; therefore, a diagnosis of idiopathic granulomatous hypophysitis would be appropriate. However, because the patient was proceeding from an endemic zone of tuberculosis and her Mantoux and QuantiFERON tests were positive, tuberculous hypophysitis could not be totally excluded. Conclusions. This case highlights the difficulties of correctly diagnosing granulomatous hypophysitis, even postoperatively, and the need to be aware of this rare entity when evaluating a pituitary enlargement in order to provide the most appropriate treatment.

Background. The aim of this study was to observe the differences in serum 25-hydroxyvitamin D(3) levels in nondiabetic healthy control subject and type 2 diabetic patients, and to investigate the differences in serum 25-hydroxyvitamin D(3) levels in type 2 diabetic patients with normo-, micro- and macroalbuminuria. P atients and Methods. Total 140 nondiabetic healthy controls and 384 type 2 diabetic patients (156 normoalbuminuric, 152 microalbuminuric and 76 macroalbuminuric) were included in the study. 25-hydroxyvitamin D(3) levels were measured in sera with the method of electrochemiluminescence using modular immunoassay analyzer. Results. Vitamin D deficiency was detected in 70.85% and 22.9% of type 2 diabetic patients and nondiabetic healthy controls, respectively. Serum 25-hydroxyvitamin D(3) levels were significantly lower in type 2 diabetic patients compared to nondiabetic healthy controls (16.4 ± 9.5 ng/mL vs. 28.2 ± 11.6 ng/mL, p=0.0001). Serum 25-hydroxyvitamin D(3) levels were lower in albuminuric and nonalbuminuric diabetic patients (14.3 ± 7.9 ng/mL vs. 19.6±10.9 ng/mL, respectively, p=0.013). Serum 25-hydroxyvitamin D(3) levels were 19.6 ± 10.9 ng/mL in normoalbuminuric, 14.9 ± 8.8 ng/mL in microalbuminuric and 12.9 ± 5.8 ng/mL in macroalbuminuric diabetic patients. While lower serum 25-hydroxyvitamin D(3) levels were detected both in microalbuminuric (p=0.028) and macroalbuminuric diabetic patients (p=0.014) compared to normoalbuminuric diabetic patients, 25-hydroxyvitamin D(3) levels did not change significantly between microalbuminuric and macroalbuminuric diabetic patients (p=0.67). Serum 25-hydroxyvitamin D(3) levels correlated negatively with urinary albumin excretion (r=-0.24, p=0.016) in patients with diabetes mellitus. Conclusion. Findings of the present study demonstrated reduced serum 25-hydroxyvitamin D(3) levels which were significantly related with albuminuria in type 2 diabetic patients.

Objectives. The objective of this study was to assess the impact of endometriosis on the quality of life. Patients and methods. Study group of 205 women, aged between 18-45 years old, hospitalized in the “Cuza-Voda” Hospital of Iasi, between 2013-2015. We used the Fertility Problem Inventory, the Endometriosis Health Profile and the Beck Depression Inventory. Results. We first realized a descriptive analyses of patients’ health related quality of life - 60% of women reported higher infertility distress associated with relationship issues caused by difficulties to conceive. The descriptive analysis over the quality of life in patients with endometriosis suggests that the high level of stress related factors, are: the loss over the control of the symptoms, dyspareunia and altered emotional status. Regarding the sexual aspect of life, almost a quarter of the women complained about an altered sexual status, due to both fear of failing in conceiving and dyspareunia caused by the endometriosis. The descriptive analysis over the infertility related stress suggests that the factors associated with a high level of stress are: sadness, pessimism, feeling of failure, irritability, lack of confidence, self-hatred and fatigue. Conclusions. Patients with endometriosis are dealing daily with a large spectrum of symptoms, including pain, dyspareunia, emotional instability and high levels of stress, which have a negative impact upon the quality of life, by lowering it on different levels. Also, within the present study we showed a significant presence of high infertility stress in patients of all ages that lead to depression and social anxiety.

Context. Therapeutic plasma exchange (TPE) provides time for thyroidectomy in thyrotoxic patients. Objective. TPE is indicated in cases where antithyroid medications cannot be used due to the side effects or attain no adequate hormonal suppression response at the highest dosage and in cases of rapid onset of clinical symptoms. This study presents the treatment results of patients who underwent TPE and were subsequently operated for thyrotoxicosis. Design. The patients who underwent thyroidectomy and TPE between January 1999 and February 2019 were retrospectively analyzed. Subjects and Methods. The files of 27 patients with thyrotoxicosis who performed TPE prior to surgery were analyzed in relation to the demographic and clinical features. Results. We included 15 (55.6%) females, 12 (44.4%) males with a mean age of 44 (23-82) years. The pre-TPE mean free thyroxine (fT4) level was 12 (5-46) pmol/L while free tri-iodothyronine (fT3) level was 34 (17- 141) pmol/L. The post-TPE fT4 level was 6 (3-10) pmol/L while the fT3 level was 21 (12-41). There was one case of an allergic reaction during the procedure. In the postoperative follow-up, there was transient hypocalcemia in 8 (29%) patients, permanent hypocalcemia in 1 (3.7%) patient, and surgical site infection in 1 (3.7%) patient. Conclusion. Preoperative TPE is an alternative treatment option for thyrotoxic patients. This is an especially effective treatment for patients with inadequate response or adverse reaction to antithyroid drugs or patients who need urgent surgery for thyroid storm.

Context. Diabetes is one of the causes of cardiovascular damage because it increases production of free radicals. Antioxidants, such as vitamin E (vit E), have been tested for efficacy in defending against free radical mediated tissue injuries. Objective. We aimed to investigate the effect of vit E on oxidative stress status and homocysteine (Hcy) in cardiac tissue of diabetic rats. Subjects and Methods. Sixteen Wistar male rats were treated with streptozotocin (STZ) (60 mg/kg) to induce diabetes. Diabetic rats were divided into two groups: non-treated diabetic (NTD) and vit E-treated diabetic (VETD) rats. The VETD group received 300 mg/kg vit E with daily feeding. Eight normal rats of the same age were used as the control group. After 6 weeks, the rats were anesthetized, their cardiac tissue was removed, and homogenated supernatant was separated. Samples were assayed for total antioxidant capacity (TAC), lipid peroxidation (LPO), nitrite (NO2-), nitrate (NO3-) and homocysteine (Hcy). Results. The contents of LPO, NO3- and Hcy in NTD compared to control group indicate a significant increase, but the levels of these parameters decreased in VETD (P<0.05). There was a significant decrease in the amount of TAC in the NTD group but in VETD group, that significantly increased (P<0.05). The amount of NO2- in NTD and VETD groups, compared to the control group, did not show any significant changes (P>0.05). Conclusions. Significant decrease in the cardiac tissue oxidative stress and Hcy resulted from vit E supplementation strongly indicated that this radical scavenger may promote a protective effect on diabetic cardiomyopathy through the attenuation of oxidative stress and increase antioxidant defense mechanism.

Context. Severe hypertriglyceridemia (SH), which calls for a triglyceride (TG) level above 1000 mg/dL, remains an important health issue. While some data exist to offer combination of heparin, insulin and fenofibrate as a reasonable treatment option, safety and benefits of this therapy have not been accurately weighted, largely due to the limited sample size of the relevant studies. Aim. Assess the efficacy and safety of the heparin, insulin and fenofibrate combination in the treatment of patients with SH. Patients - Methods. Patients aged ≥18 years with TG level above 1000 mg/dL and adequate organ function were included. Triglyceride levels were measured immediately before the treatment and on the 3rd and 6th days of the treatment. Treatment dosage, duration, response and side effects were assessed. Patients with hypertriglyceridemia presenting with acute pancreatitis were treated additionally with lipid apheresis. Results. A total of 42 patients were included. Of these, 85.8% came to medical attention with some kind of secondary hypertriglyceridemia causes. The baseline median TG value of the cases was 2141.0 mg/ dL (1026-12250). There were 6 patients (14.3%) with acute pancreatitis at presentation. In patients without pancreatitis, with administration of insulin infusion, unfractionated heparin infusion and fenofibrate capsule, median TG values decreased to 921 mg/ dL (190-6400) on the 3rd day and to 437 mg/ dL (112-1950) on the 6th day of the treatment (p<0.0001, Friedman test). Potential toxicities related to insulin, heparin and fenofibrate combination treatment including hypoglycemia, hemorrhage, rise in creatine kinase levels, hepato - and nephrotoxicity were not observed. Conclusion. In this trial involving patients with SH, our data suggest that insulin, heparin and fenofibrate combination therapy was safe and effective.

Objective. Unilateral adrenalectomy (UA) is an alternative for treatment in bilateral adrenal incidentaloma (AI) to avoid possible long-term risks of bilateral adrenalectomy. In this study, we aimed to evaluate the effectiveness of UA in bilateral AI patients with subclinical hypercortisolemia (SH). Method. A total of 35 patients were included in this study. The patients were divided into two groups; those who underwent UA (n=27) and patients without adrenalectomy (PWA) (n=8). Hormone tests related to cortisol mechanism were reviewed to analyze results at the time of diagnosis compared to the latest available results to figure out any changes in cortisol mechanism and determine whether SH has recovered or not. Results. Median age of PWA group were higher compared to UA group (p=0.03). Median duration of followup in groups were similar (p=0.3). In the PWA group, none of the patients recovered from hypercortisolemia during their follow-up. In UA group 92.6% of the patients went into remission, whereas during follow-up 3.3% had recurred and another 3.3% were found to have post-adrenalectomy persistent SH. Patients in UA group had lower final cortisol level following dexamethasone suppression (p=0.003) and higher final adrenocorticotrophic hormone (ACTH) levels (p=0.001) than patients in PWA group. In UA group, final basal cortisol level (p=0.009) and final cortisol level after 1 mg dexamethasone suppression test (DST) (p=0.004) were lower than corresponding levels at the time of diagnosis. Discussion. Our study demonstrates unilateral adrenalectomy targeting the side with the larger lesion is an effective approach to reduce excess cortisol levels in bilateral AI patients with SH.