ACTA ENDOCRINOLOGICA (BUC)

Introduction. Antigonadotropic effect of melatonin in seasonally breeding rodents is due to the influence of this indol on the reproductive axis hypothalamicpituitary-gonads, although it is known that melatonin has a negative effect on the hormonal function of the reproductive axis, and is unknown whether it can affect the fertility of male Wistar rats.\r\nAim. The objective of this study was to investigate the effects of melatonin application on the fertility of the male Wistar rat.\r\nMaterials and Methods. Sixteen male Wistar rats were used. Rats were divided into two groups, Control and the group of animals treated with melatonin 1mg/kg (M) injected i.p. daily for two months. The evaluation of fertility was\r\ndetermined by the number of pregnant female rats. In addition, it was quantified the number of spermatozoa and Leydig cells in the seminiferous tubules. After removing\r\nthe treatment for two months, the experiments were repeated, to determine the possible recovery.\r\nResults. The results showed that rats treated with melatonin were able to impregnate only 25% of the mated female rats\r\n(p<0.05). In this group, the number of sperm decreased with a significance of p< 0.001 while the number of Leydig cells increased with respect to the control group with a significance of p< 0.001. After removing the treatment for two months, both the sperm and the Leydig cells were recovered at similar levels as the control group, while the fertility was not totally recovered in the group treated\r\nwith melatonin. These results suggest that the exogenous melatonin application (1mg/kg i.p) induces infertility.

Introduction. Acromegaly is a chronic disease associated with high mortality rate if untreated. The aim of the study is to evaluate mortality ratio in Romanian patients with acromegaly in latest years, with new therapeutic options. Patients and Methods. This retrospective study analyzed 336 (111M/225F, mean age 48.13±12.40 years) consecutive patients with acromegaly between 1st January 2001 and 31 December 2014, median follow-up 7.36 years (0.48-13.99 years). PAMCOMP computation program assessed standardized mortality ratio (SMR). Kaplan Meier curve was used for comparison between of different cut-off levels of the last GH level on survival. Serum GH levels were measured by IRMA (sensitivity 0.1 ng/mL). Results. During follow-up 2596.34 person-years, 41 patients died, with a SMR of 1.34 (CI 0.96-1.82). Mean age at death was 63.19±11.66 years. Females with acromegaly died 83% more frequently than women in general population: SMR-1.83 (CI 1.21-2.67). Females were older at diagnosis (p=0.006), and were less probable to receive substitution of gonadotrophic failure than males (p<0.001). Independent factors correlated with mortality were age at baseline (p<0.001, HR=1.07), last GH level (p=0.003, HR=1.01) and systolic blood pressure (p=0.029, HR=1.02). Patients with last GH level ≤ 1 ng/mL had a better survival than patients with GH>1 ng/mL (p Log Rank=0.002). SMR of patients with last GH >1 ng/mL was 1.59 (CI 1.08-2.26) for the entire group, 2.2 (CI 1.32-3.44) for females and 1.3 (CI 0.67-2.29) for males. Conclusion. Patients with acromegaly have a high mortality ratio compared to general population, especially in women and those with post-therapeutic serum GH levels over 1 ng/mL. Longer follow-up is needed for the evaluation of the effect of new therapies on mortality.

Pituitary radiotherapy (RT) has undergone important progress in the last decades due to the development of new stereotactic techniques which provide more precise tumour targeting with less overall radiation received by the adjacent brain structures. Pituitary surgery is usually firstline therapy in most patients with nonfunctioning (NFPA) and functioning adenomas (except for prolactinomas and large growth hormone (GH) secreting adenomas), while RT is used as second or third-line therapy. The benefits of RT (tumour volume control and, in functional tumours, decreased hormonal secretion) are hampered by the long latency of the effect and the potential side effects. This review presents the updates in the efficacy and safety of the new stereotactic radiation techniques in patients with NFPA, GH-, ACTH- or PRL-secreting pituitary adenomas. Methods. A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in pituitary adenomas from 2000 to 2017 were included. Results. Stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) provide high rates of tumour control i.e. stable or decrease in tumour size, in all types of pituitary adenomas (median 92 - 98%) at 5 years. Endocrinological remission is however significantly lower: 44-52% in acromegaly, 54-64% in Cushing’s disease and around 30% in prolactinomas at 5 years. The rate of new hypopituitarism varies from 10% to 50% at 5 years in all tumour types and as expected increases with the duration of follow-up (FU). The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and extremely low for secondary brain tumours), however longer FU is needed to determine rates of secondary tumours. Notably, in acromegaly, there may be a higher risk for stroke with FSRT. Conclusion. Stereotactic radiotherapy can be an effective treatment option for patients with persistent or recurrent pituitary adenomas after unsuccessful surgery (especially if residual tumour is enlarging) and/or resistance or unavailability of medical therapy. Comparison with conventional radiation therapy (CRT) is rather difficult, due to the substantial heterogeneity of the studies. In order to evaluate the potential brain-sparing effect of the new stereotactic techniques, suggested by the current data, longterm studies evaluating secondary morbidity and mortality are needed.

Context. Laparoscopic sleeve gastrectomy (SG) has gained popularity as a metabolic procedure, but its longterm effectiveness for Romanian patients remains unclear. Objectives. To assess the long-term efficacy of SG for Romanian patients and to evaluate the differences between 5 years and 1 year follow-up. Design. A longitudinal, prospective analysis of collected data from 68 patients undergoing SG between 2009 and 2014 was performed. Long-term outcomes at 5 years were analyzed in terms of total weight loss (%TWL), excess weight loss (%EWL), body composition and glucose homeostasis. Subjects and Methods. All patients meeting the standard criteria for SG before inclusion were prospectively enrolled in the study. Of the 68 patients, eight were lost to follow-up, therefore, 60 patients (41.7±12.5 years, baseline body mass index [BMI] 44.6±9.9Kg/m2) were analyzed. Results. The BMI decreased at 12 months with 30.7% from the preoperative BMI (p<0.001) and subsequently stabilized at 5 years. TWL and EWL were 30.6% and 83.1%, respectively at 1 year, with a slightly increase at 5 years. Therapeutic success rate (%EWL≥50) and diabetes remission rate (Buchwald criteria) were 93.3% and respectively 63.6% at 5 years. Insulin sensitivity index and metabolic clearance rate of glucose increased with 92.5% and 60.1% respectively, in the third month from baseline (p<0.001), while estimated second phase of insulin secretion decreased with 7.9% in the first month postoperatively (p=0.04), remaining stable afterwards. Conclusions. SG was effective in terms of %EWL, body composition and glucose homeostasis improvement for Romanian patients, the outcomes stabilizing after 1 year follow-up.

Background. Ganglioneuroma (GN) is a rare, benign, neuroblastic tumor. It may arise from the sympathetic plexus or adrenal medulla. Its most common location is the posterior mediastinum (41.5%), while in approximately 21% of patients the tumor is located in the adrenal gland. Median age of adults at diagnosis is approximately 40 to 50 years of age. Since GN is most commonly asymptomatic, the diagnosis is usually accidental, i.e. when radiological examinations are performed due to other indications. This slow-growing tumor can reach a large size. In a small percentage of patients the tumor secretes catecholamines. We present five ganglioneuroma patients, who were hospitalized in our Department from 1993 through 2012. Their mean age was 31 years. In four cases the tumor was located in the adrenal gland and in one - extra-adrenally, which was revealed during surgery. In three out of five presented cases pathological hormone secretion by the tumor was confirmed in laboratory results.

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Introduction. Bartter’s Syndrome is a renal tubular defect characterized with low or normal blood pressure, hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism due to renal sodium loss. Herein we reported a case who presented with growth retardation, growth hormone deficiency previously treated with growth hormone for a period of 6 months in mind and with hypopituitarism similar findings such as primary amenorrhea, fatigue, weakness and just diagnosed as Bartter’s syndrome. Case report. A 18 year-old female patient was referred to our hospital for amenorrhea, growth retardation and fatigue. Her history revealed that she was diagnosed with growth hormone deficiency two years ago and given growth hormone treatment for 6 months. Physical examination showed growth retardation. Laboratory tests revealed that serum potassium was 2,3 mmol/L. Further investigations demonstrated metabolic alkalosis, increased urinary potassium excretion and hyperreninemic hyperaldosteronism. The patient was considered as Bartter syndrome and spironolactone, indomethacin and potassium chloride were initiated. While she had growth retardation and primary amenorrhea, we searched basal hormone levels and performed stimulation tests for evaluating pituitary reserve. Insulin tolerance test showed that serum growth hormone and cortisol levels were 10 mcg/dL and 19 mcg/dL respectively during hypoglycemic period. It demonstrated that both of the axes were intact. Luteinizing hormone releasing hormone test showed that hypothalamo pituitary gonadal axis was also intact. Conclusions. Bartter syndrome can lead to growth retardation that mimicking hypopituitarism in case of delay in diagnosis.

Introduction. The Antley-Bixler syndrome (ABS) is an extremely rare syndrome characterized by congenital\r\ncraniosynostosis and radiohumeral synostosis. Many patients demonstrate defects in steroidogenesis and disturbances\r\nof sexual development.\r\nAim: To present the first documented case of a Romanian patient with ABS.\r\nMaterial and Methods. Alexandru, a 3 year old child, was referred to our department for elucidating a complex\r\nmalformative syndrome that consisted of ambiguous genitalia and skeletal anomalies. We performed a complete assessment that ranged from obtaining a detailed medical history to gene sequencing. The hospital?s Ethical Committy gave\r\nthe authors its approval for using the medical data concerning the case, after the parents signed an informed consent.\r\nResults. Medical history. We note 4 previous admissions to our hospital during which efforts were made to diagnose the\r\nchild?s disorder of sexual development. At 3 months Edwards syndrome was suspected, which was later infirmed. During the third and fourth admission (8 months, 10 months respectively) the suspicion of congenital adrenal hyperplasia (CAH) was raised and then confirmed (impaired steroidogenesis, 46 XX karyotype). The patient was lost to\r\nfollow-up since then, probably due to the parents? inability to cope with the implications of their child?s condition.

The COVID-19 pandemic affected 62 million people and caused more than 1.4 million deaths globally till the end of November 2020. Our study aimed to explore the association between obesity and the negative outcomes of COVID-19 worldwide. The prevalence of obesity and overweight per country was extracted from the World Health Organization information system and, for measuring the COVID-19 negative outcomes, we calculated the cumulated notification rate and the mortality for the interval since starting of pandemic till the 29th of November 2020. We explored the linear relationship between COVID-19 and obesity by a bivariate Spearman rank correlation, interpreted using the rule of thumb for 95% level of confidence. We found globally a positive, moderate, and statistically significant correlation between prevalence of obesity and overweight and the negative outcomes of COVID-19. Some of the results found at global level were confirmed in the disaggregated analysis per WHO regions. Due to the linear association of obesity with the COVID-19 negative outcomes, effective actions are needed for keeping the health systems resilience during the COVID-19. Preventing the obese and overweight people to be infected, prioritizing access to vaccination and to adequate care and treatment could be effective.