ACTA ENDOCRINOLOGICA (BUC)

Objective. To assess the outcome of clinical and endocrinological dysfunctions after transsphenoidal decompression in parasellar meningioma. Methods. Retrospective pre- and postoperative evaluation of 40 patients (30 women, 10 men; mean age, 55.9±11.9) who underwent decompressive transsphenoidal microsurgeries. The preoperative investigation took place one month prior surgery, the first follow-up within one week, the second follow-up within three months postoperatively. Results. The most common symptom in our study was diplopia (47.5%, n=19) which showed improvement in 21.1% (n=4) of cases. Preoperative hyperprolactinemia, presented in 52.5% of patients (n=21) with hyperprolactinemia remaining in just 20% of patients (n=8) in the first follow-up. Other endocrine axes were affected less frequently, but also majorly showed improvements. The corticotropic axis was affected in 8.8% (n=3) and remained unchanged. Female gonadotropic axis irritation decreased from 34.5% (n=10) to 31.0% (n=9), male axis deterioration improved in two cases from 50% (n=5) to 30% (n=3). The somatotropic and thyrotropic axes were never negatively affected. Adjuvant radiotherapy was carried out in 60% (n=24) of patients and not yet commenced in an additional nine (22.5%). Conclusion. Experience shows that transsphenoidal decompression is a useful and low complication associated procedure in the initial management of cavernous sinus meningioma.

Context. Overproduction of proinflammatory cytokines plays a significant role in the pathogenesis of Hashimoto’s thyroiditis (HT). Recent studies revealed a prominent role of newly discovered Th17 subset in the induction of autoimmune disorders and that the signaling induced by IL-23 on Th17 cells is crucial to obtain a pathogenic and sustained phenotype. The objective of this study was to provide the involvement of interleukin IL-23/ IL-17 axis in pathologic processes. Design. Serum levels of IL-23 and IL-17 in controls and HT patients were studied in different stages of disease activity. Subjects and methods. We investigated 93 patients with HT: 33 patients with newly diagnosed euthyroid HT (Group I), 11 patients with newly diagnosed hypothyroid HT (Group II), and 49 subjects treated with Levothyroxine (Group III). Thirty healthy subjects were included as controls. Concentrations of IL-23 and IL-17 in the serum samples of patients and controls were evaluated by enzymelinked immunosorbent assay. Results. Serum level of IL-23 was significantly higher in all HT patients (p<0.0001) as well as in subgroups of patients in comparison with controls (p<0.01). Serum concentrations of IL-17 were statistically increased in the group of HT patients (p=0.014); the differences in IL-17 levels between groups I and III in comparison to healthy controls were also significant, but not for group II. Conclusions. Our results highlight the involvement of the IL-23/IL-17 axis in the development of HT and its severity. Moreover, upregulated secretion of IL-23 could be a biomarker for progression and monitoring of HT.

Context. Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, steatohepatitis (NASH) which can evolve with progressive fibrosis, cirrhosis and hepatocellular carcinoma. As liver biopsy cannot be used as a screening method, noninvasive markers are needed. Objective. The aim of this study was to test if there is a significant association between vitamin D deficit and the severity of NAFLD. Design. The patients were divided into two groups (vitamin D insufficiency/deficiency) and statistical analyses were performed on the correlation of clinical and biochemical characteristics with histopathological hepatic changes. Subjects and methods. We prospectively studied 64 obese patients referred for bariatric surgery between 2014 and 2016 to our Surgical Unit. Anthropometric, clinical measurements, general and specific biological balance were noted. NAFLD diagnosis and activity score (NAS) were evaluated on liver biopsies. Results. Increased serum fibrinogen was correlated with NASH (p=0.005) and higher NAS grade. T2DM was positively correlated with liver fibrosis (p=0.002). 84.37% of the patients had vitamin D deficit and 15.62% were vitamin D insufficient. Lobular inflammation correlated with vitamin D deficit (p=0.040). Fibrosis (p=0.050) and steatohepatitis (p=0.032) were independent predictors of low vitamin D concentration. Conclusions. Vitamin D status in conjunction with other parameters - such as T2DM - or serum biomarkers – namely fibrinogen level and PCR level - may point out the aggressive forms of NAFLD and the need for liver biopsy for appropriate management.

Polycystic ovary syndrome (PCOS), the main cause of androgen excess in women of reproductive age, is a multifaceted, dynamic and clinically heterogenic disorder. Rotterdam 2003 ESHRE/ASRM definition criteria were recently reinforced at the NIH Consensus Meeting 2012. Concomitant identification of the clinical phenotypes of the syndrome is mandatory in medical care and clinical studies, as these are strongly related to reproductive, cardiovascular and metabolic outcomes. Documentation of polycystic ovarian morphology (PCOM) is challenging, with the AE/PCOS Task Force 2014 suggesting a threshold of ≥25 follicles/ovary in 18- 35 years old women when using high-frequency transducers. Elevated levels of total testosterone and/or free testosterone and/or low sex hormone-binding globulin (SHBG) stand for androgen excess in women, as stated by the ESE Position Statement 2014. Despite evidence of increased metabolic and cardiovascular risk, increased prevalence of cardiovascular events linked to PCOS status per se is still insufficient documented, mainly because of the clinical heterogeneity of studies populations and lack of prospective data. First-line therapy in the medical management of PCOS is metformin, at least 1.5 g/d, in all patients with documented insulin resistance and hyperinsulinemia. According to Endocrine Society Guidelines 2013, other insulin-sensitizers (e.g. thiazolidinediones) raise safety concerns on the long-term, whereas statins need further evaluation to demonstrate their benefits in the treatment of PCOS, however, are indicated in dyslipidemic patients. Anti-androgens and combined oral contraceptives (COC) are targeting androgen excess, particularly in non-insulin resistant patients, with an overall benefit to risk ratio in PCOS favoring benefits.

We report a case of an infant with syndromic 46,XY disorder of sexual development. The subject was born at term, to unrelated parents with no relevant medical history. At birth the infant was assigned female. Physical examination showed dysmorphic features and ambiguous external genitalia. Cytogenetic analysis of cultured peripheral blood lymphocytes revealed a male karyotype. The result of the chromosomal investigation showing male genetic sex, together with the ambivalent aspect of the external genitalia (Prader IV) and gonads that are exclusively testes led to the diagnosis of 46,XY disorder of sexual development. The clinical management will help the child and the family deal effectively with this condition A multidisciplinary approach to this problem involving pediatricians, specialists in the field of endocrinology, genetics, surgery and psychiatry is necessary in order to reach a prompt and correct diagnosis and treatment.

At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia in China and it spread quickly to other countries. Although Covid-19 causes severe pneumonia, it is known that it can be associated with different diseases and prognosis of disease can be due to many of disorders such as hyponatremia. A 65-year-old female patient with sarcoidosis, cronic obstructive lung disease, hypertension and congestive heart failure presented to the emergency department with shortness of breath and fever. Oropharyngeal swab for Covid-19 PCR test was positive. After the initiation of treatment, the patient developed hyponatremia. This case is remarkable because there is no reported case of Covid-19 and inappropriate ADH syndrome coexistence and it demonstrates that there may be a correlation between Covid-19 infection prognosis and hyponatremia.

Context. Phosphoinositide-3-kinase (PI3K) pathway inhibitors are increasingly used as targeted therapy in malignancies. We discuss here three cases of PI3K inhibitor induced hyperglycemia and discuss the mechanism of action of these medications and treatment of this class side effect. Objectives. Alpelisib (Piqray) is the newest PI3K inhibitor used in conjunction with Fulvestrant to treat specific types of breast cancer. Since PI3K is a critical mediator of insulin signaling, hyperglycemia is an on-target, unfortunate side effect of this treatment. We present a case series of severe hyperglycemia induced by the alpelisib in three women without a history of diabetes. Design. All three women in this study had hormone receptor (HR) positive, human epidermal growth factor receptor 2 (Her2) negative, PI3K mutated breast cancer. They were referred to our clinic by Oncology for alpelisibinduced hyperglycemia. Subjects and Methods. Review of laboratory values and glucometer values were conducted during each visit allowing treatment decisions. Two of these women are actively managed by us for their diabetes. One woman recently died due to progression of malignancy. Results. All three women presented with new onset of severe hyperglycemia after the initiation of PI3K inhibitor, alpelisib. At least one case noted maximal glucose elevation in the hours following drug ingestion. In another, cessation of Alpelisib reversed the hyperglycemia within the span of one week. Conclusion. Hyperglycemia induced by PI3K inhibitors can be recalcitrant and might necessitate interruption of chemotherapy. Optimal glucose-lowering therapy remains unclear as exogenous insulin has the theoretical potential to overcome PI3K inhibition.

Pituitary stalk interruption syndrome (PSIS) is characterized by the coexistence of an absent or thin pituitary stalk, an ectopic posterior pituitary (EPP) lobe, and an absent or hypoplastic anterior pituitary lobe. A 1-year-old boy presented with micropenis, and undescended testis associated with growth hormone, thyroid stimulating hormone, and gonadotropin deficiencies. Pituitary hypoplasia, EPP, and a missing pituitary stalk were seen on magnetic resonance imaging (MRI). Whole-exome sequencing (WES) revealed compound heterozygous variants in the KATNIP gene (NM_0.15202.5: c1461G>A / c.4035delC) in the recruited individual, and subsequent familial segregation showed that family established the trans position for c.1461G>A and c.4035delC variants.

Objectives. Turner Syndrome (TS) is associated with a high risk of cardiac anomalies and cardiovascular disease. We aimed to evaluate patients with TS (n=33) for cardiac and aortic pathology using thorax magnetic resonance angiography (MRA). Subjects and methods. Clinical findings, karyotypes, echocardiogram (ECHO) findings and thorax MRA results were evaluated. Aortic dimensions were measured and standard Z scores of aortic diameters along with aortic size index (ASI) were calculated. Results. Mean age of the patients was 13.7±3.4 years. MRA revealed cardiovascular pathology in 10 patients (30%). CoA (n=4), aberrant right subclavian artery (n=3), dilatation of the ascending aorta (n=1), tortuosity of the descending aorta (n=1) and fusiform dilatation of the left subclavian artery (n=1) were found. Two of the four patients with CoA found on MRA were detected with ECHO. Mean diameter of the sinotubular junction was found to be elevated [mean±SD: 2.4±1.5]. Z scores for the diameters of the isthmus, ascending aorta and descending aorta were in normal ranges. 45,X patients were found to have significantly higher ASI values than non 45,X patients (p=0.036). Conclusion. Our findings indicate that patients with TS should be evaluated with MR imaging studies in addition to ECHO to reveal additional subtle cardiac and vascular anomalies. CoA which is very distally located or which has mild nature may not be seen by ECHO. The increase in ASI observed in 45,X patients may herald the development of life-threatening complications. Therefore, frequent followup is warranted in these patients.

Objectives. The aim of this study was to evaluate serum levels of interleukin (IL)-8 in pre- and postmenopausal women and in patients with surgically-induced menopause, and the relationship between IL-8 and vasomotor symptoms. Material and Method. 175 women were enrolled and were divided into 5 groups (I – Fertile women; II – Pre- and perimenopausal women; III – Postmenopausal women; IV – Surgically-induced menopause; V – Chronic inflammation). Multiplex cytokine kits were used to evaluate serum levels of interleukin-8. We determined the serum levels of the follicle stimulating hormone, of the luteinizing hormone, 17β-estradiol, progesterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate using sandwich ELISA. The severity of the vasomotor symptoms was evaluated according to FDA guidelines. Results. Serum concentration of IL-8 in women with natural menopause (233.0±226.5 pg/ml; p<0.001) and in women with surgically-induced menopause (148.0±162.0 pg/ml; p=0.045) is significantly higher than in women of reproductive age (84.88±82.32 pg/ml). Serum levels of IL-8 in premenopausal women, postmenopausal women, and in women with surgically-induced menopause, respectively, with severe and moderate hot flashes, on one hand (174.8±90.94 pg/ml, 369.3±194.2 pg/ml, respectively 274.1±146.3 pg/ml), is significantly higher than in women without vasomotor symptoms or with mild hot flashes, on the other hand (19.97±22.15 pg/ml, 28.66±35.72 pg/ml, respectively 28.94±37.68 pg/ml; p<0.001). Serum levels of IL-8 are significantly higher in women of reproductive age with chronic inflammatory pathology (152.3±121.0 pg/ml) than in women without such pathology (84.88±82.32 pg/ml; p=0.02). Conclusions. IL-8 is significantly higher in postmenopausal women with vasomotor symptoms than in women without vasomotor symptoms. In the postmenopausal group, the serum levels of IL-8 are similar to those in women with chronic inflammatory pathology. IL-8 could be a key factor in occurrence of hot flashes in menopause and could be associated with peripheral vasodilatation in these women.