ACTA ENDOCRINOLOGICA (BUC)

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.

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.

Context. Prognostic considerations include assessing the risk of liver fibrosis in people with nonalcoholic fatty liver disease (NAFLD). Objectives. This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods. Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results. Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib- 4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion. HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether nonobese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis.

Context. Different vitamin D analogs might have advantages over calcitriol. Objective. To evaluate the effects of paricalcitol vs. calcitriol based vitamin D receptor activators on calcium-phosphate metabolism and pulse wave velocity in hemodialysis patients. Design. Observational, cross-sectional and 1 year follow-up study. Subjects and Methods. 181 hemodialysis patients were enrolled in this study as divided in to 5 groups based on vitamin D therapy. Baseline and 12th month data on blood biochemistry, pulse wave velocity and cumulative dose of treatments were compared in each study group as well as in overall paricalcitol vs. calcitriol-based treatment groups. Results. From baseline to 12th month, significant improvement in pulse wave velocity and parathyroid hormone was shown in paricalcitol-based treatment group without a significant change in calcium, phosphate, alkaline phosphatase. A significant increase in pulse wave velocity, serum phosphate levels, calcium x phosphate product and serum alkaline phosphatase levels were noted in calcitriolbased treatment group with no significant change in serum calcium and parathyroid hormone levels. Conclusion. Our findings revealed superiority of paricalcitol than calcitriol based vitamin D receptor activator therapy in terms of serum phosphate levels, CaxP product, dose requirement for vitamin D and the control of pulse wave velocity.

Context. The aim of this study was to explore the prognostic significance correlation between the endocrinopathy and the size of the pituitary adenoma with the sellar floor bone mineral density values using microfocus computerized tomography (μCT) analysis. Subjects and Methods. 16 consecutive patients with pituitary adenomas had full endocrinological and radiological work up prior to endoscopic transnasal transsphenoidal surgery. Multiple bony samples were collected from the sellar floor during surgery, and labeled and analyzed in a double blind fashion. Each bone sample was analyzed for bone mineral density (BMD) and Hounsfield units (HU) with microfocus CT. Results. There was no correlation between adenoma size and BMD values of sella floor but grade IV macroadenomas were found to have lower BMD levels. Statistical analysis showed that the level of correlation between grouped BMD (<1.0 and >1.0) data with ACTH (<46 and >46), IGF (<303 and >303), and PRL (<29.93 and >29.93) levels were insignificant (P=.569, P=.315, and P=1.00, respectively) Conclusion. We have found no clinical relationship between sellar floor BMD values and endocrinopathy and the size of the adenoma. However, it was found out that preoperative conventional CT evaluation seemed insufficient in predicting the sellar floor bone integrity and may mislead the surgeon.

Background. Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. C ase presentation. We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. Conclusions. Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.

Tuberculosis continues to be a universal health problem and recent studies showed an increased incidence of all forms of this disease. We report the case of a 81 year old female patient with a large left cervical tumour and cutaneous lesions that proved to be an unusual form of tuberculosis. The patient had a 2 years history of slowly increasing left cervical mass with no significant clinical manifestation. Medical assistance was requested mostly by the family, concerned about the large mass visible on the left side of the patient?s neck. Clinical and laboratory investigation revealed: a large left laterocervical tumour and the presence of erythematous, non pruriginous skin lesions. No significant changes were shown by routine blood tests. Thyroid function was in the normal range. Neck ultrasound revealed the presence of a 5/6 cm, well defined hypoechoic mass and the thyroid scan showed no accumulation of the radiotracer in the cervical tumour. Routine tuberculosis test was negative and the patient had no sign of pulmonary involvement. Histopathological examination after ablation of this tumour showed the presence of granulomatous lesions suggesting tuberculosis or sarcoidosis. The same aspect was seen after histopathological examination of the specimens from cutaneous biopsy. The diagnosis was certified by the PCR amplification of the DNA extracted from the skin lesions, which led to the identification of Mycobacterium tuberculosis. The cutaneous lesions were clearly improved after tuberculostatic treatment, supporting the hypothesis of a rare form of cutaneous tuberculosis.

Context. Impaired flow mediated dilatation (FMD) and increased carotid intima media thickness (CIMT) are the antecedent forms of atherosclerosis. Objective. The aim of this study was to evaluate vascular structural and functional changes in patients with asymptomatic primary hyperparathyroidism (APHPT), and whether biochemical alterations, related with PHPT and oxidative stress marker serum advanced oxidation protein products (AOPPs), may have influence on vascular alterations. Design. This is a cross sectional clinical study. Subject and Methods: Thirty-four patients with APHPT and 29 sex- and age and cardiovascular risk factors matched control cases were included in this study. Endothelial function was evaluated by FMD of the brachial artery; CIMT was measured by ultrasonography; in addition serum AOPPs and biochemical parameters were determined. Results. Serum Ca levels were higher in the patient group [10.93±0.60mg/dL vs. 9.45±0.31; p<0.001]. FMD measurement was significantly lower in patients group [0.07 (0.01-0.26) % vs. 0.14 (0.04-0.22) %; p=0.01]. CIMT measurements were comparable between the groups [52 (35- 69) mm vs. 56 (38-70) mm; p=0.821]. AOPPs levels were significantly higher in the patients [136.43 (55.14-1352) mmol/L vs. 84 (53.18-595.48) mmol/L; p=0.026]. There were significant negative correlations between FMD and serum Ca (r=–0.339, p<0.001); and serum AOPPs levels (r=–0.275, p<0.005). Serum Ca (p=0.007, β=–0.353) and AOPPs (p=0.024, β=–0.243) levels and hyperlipidemia (p=0.024, β=–0.288) were the predictors of FMD. Conclusions. Vascular endothelial function is impaired in patients with APHPT. Hypercalcemia, increased oxidative stress and hyperlipidemia may have role in the pathogenesis of endothelial dysfunction in patients with APHPT.

Context. Patients with Cushing’s syndrome (CS) of any etiology experience a number of physical and psychological symptoms which impact negatively on healthrelated quality of life (HRQoL). Subjects and methods. HRQoL was measured using CushingQoL questionnaire. Results. The first part of our study was a crosssectional analysis of 141 patients with CS over a 10-year period. CushingQoL score was lower in pituitary CS compared to adrenal CS. Remission and older age were associated with better outcome on item 7 (physical appearance anxiety). In a multivariate regression analysis after adjustment for etiology, remission status, age, UFC, duration of hypercortisolism and presence of hypercortisolism-associated comorbidities the female gender was the only negative predictor associated with poorer outcome on each of the three scores. The presence of hypercortisolism-associated comorbidities independently predicted poorer outcome on the psychological and the global subscales. The second part of our research was a prospective study of 27 patients with adrenal adenoma. Achievement of remission independently predicted improvement of the total score of any patient. Conclusion. Studying in details and understanding the mechanisms of the impaired HRQoL in patients with CS is the only way to become aware of the problem and create methods that could help these patients.