ACTA ENDOCRINOLOGICA (BUC)

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy.

Context. Melanoma is the most aggressive skin cancer, with significant morbidity and mortality, and one factor that may influence the course of disease is stress. Objective. Our aim was to evaluate the effect of corticosterone, norepinephrine, epinephrine on murine B16F10 melanoma cells in vitro proliferation. Methods. B16F10 melanoma cells were treated with different concentrations of tested hormones. The proliferative capacity of melanoma cells was quantified by MTS assay and the cell viability was quantified as membrane integrity evaluation measured by lactate dehydrogenase (LDH) release. Results. B16F10 cells treated with corticosterone showed no significant changes. In contrast, norepinephrine exposure stimulated the cell proliferation (P = 0.0003). Treatment with 1 μM norepinephrine induced the highest increase in cell proliferation (OD 492 = 0.27 ± 0.02) statistically significant to both control (OD 492 = 0.17 ± 0.01; p = 0.0003), 10 nM norepinephrine (OD 492 = 0.16 ± 0.00; p = 0.0004) and 100 nM norepinephrine (OD 492 = 0.19 ± 0.01; p = 0.002). Likewise, treatment with epinephrine increased cell proliferation (p = 0.0004). Exposure to 5 μm epinephrine induced a stimulation of cell proliferation (OD 492 = 0.28 ± 0.02) significantly higher compared to controls (OD 492 = 0.17 ± 0.01; p = 0.0004), 50 nM epinephrine (OD 492 = 0.17 ± 0.00; p = 0.001) and 500 nM epinephrine (OD 492 = 0.173 ± 0.00; p = 0.001). Conclusions. Our results may open new perspectives concerning the link between stress hormones and melanoma, emphasizing a direct stimulating in vitro effect induced by catecholamines on melanoma B16F10 cells proliferation.

The conventional treatment of hypoparathyroidism consists of vitamin D analogues in combination with oral calcium\r\nsupplementation. This treatment modalities induce chronic hypercalciuria which leads to nephrocalcinosis, nephrolithiasis and renal insufficiency. Here we report the case of a 32-year-old woman who developed hypocalcemia and hypercalciuria under treatment with high doses of vitamin D\r\nanalogs and oral calcium. She had cerebral calcification, nephrocalcinosis under this treatment. Stable calcium levels were achieved with synthetic human parathyroid hormone treatment that was given in alternate days. PTH appears to be an alternative and effective treatment in hypoparathyroidism.

Background. Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity. Objective. To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus adults in a large mixed cohort. Material and methods. We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016. Results. A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults). Conclusions. Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children

Mixed gonadal dysgenesis and ovotesticular disorders of sex development, are rare conditions that occur sporadically,\r\nwith unknown prevalence. Clinical manifestation of this diseases is sexual ambiguity. The authors present a pediatric\r\ncase with sexual ambiguity and karyotype 45, X/46, XY, the child of a HIV-positive mother receiving multiple antiretroviral treatments for a period of 16 years.

Background. Heart failure (HF) is a disease with a high prevalence in the elderly population. Problems posed by HF diagnosis and management within this special category validate the interest in studying ways to improve the quality and duration of life in these patients. Aim. To determine the prognostic accuracy of certain clinical and laboratory parameters and to predict mortality rates in elderly patients with HF. Study design. It is a cohort, analytical, prospective, observational, crosssectional study conducted between 2006- 2008. Data regarding patient survival over a period of six months were recorded from the moment of enrollment. Subjects and methods. The study group consisted of 177 patients of over 65 years of age admitted to geriatrics, internal medicine and cardiology units, diagnosed with HF. A series of clinical and laboratory data from these patients has been examined, including NT-proBNP and CRP. Results. CRP levels higher than 3.57 mg/dL determined a hazard ratio (HR) of 3.9 (CI95% 1 - 15.2, p=0.04), urea levels higher than 79 mg/dL determined a HR of 8.8 (CI95% 1.1 - 37.4, p=0.003) and NT-proBNP levels higher than 9370 pg/mL determined a HR of 18.6 (CI95% 5.2 - 66.2, p<0.001). After multiple comparison adjustments (Bonferroni correction), only urea and NT-proBNP remained independent variables predicting 6-month mortality in elderly patients with HF. Conclusion. High NT-proBNP and urea levels were independent predictors for mortality in elderly patients with heart failure.

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Background. The modern management of phenylketonuria (PKU) consists of generalized newborn screening (NBS) for hyperphenylalaninemia (HPA), confirmation of HPA in children detected in the NBS, introduction of dietary treatment in the first weeks of life, followed by monitoring the treatment of PKU for decades to maintain phenylalaninemia within the limits that will not affect the brain. The present study aimed to evaluate the usefulness of two chromatographic methodologies for determination of plasma Phe level in the routine management of PKU: the two dimensional thin layer chromatography (2D - TLC) and the high performance liquid chromatography (HPLC) procedures, respectively. Material and Methods. Samples of blood from 23 children with HPA detected by neonatal screening or with confirmed PKU who received treatment by low-Phe diet were analyzed to estimate the plasma Phe level by the two chromatographic procedures. Results. In case of three subjects the very low concentrations of plasma Phe could not be detected by the 2D - TLC methodology, since the spot was not visible on the chromatogram. In four patients the differences between the values of plasma Phe determined by the two methodologies are not statistically significant, while in fifteen subjects the differences are highly statistically significant. This is due to the greater errors that appear in the case of 2D - TLC methodology. In the range of concentrations of plasma Phe higher than 360 μmol/L (which is the cut-off value for HPA), although in four cases there were statistically significant differences in the level of plasma Phe determined by the two methodologies, the value obtained by the 2D - TLC methodology was high enough to influence the decision of changing the diet so that HPA is kept under control. In addition, the intense spot of Phe on the 2D - TLC chromatogram may be detected even by un unexperienced laboratory specialist. Conclusion. The HPLC procedure for measurement of plasma Phe level is very suitable to be used in the routine management of PKU. The 2D - TLC procedure may be accompanied by relatively high errors; however, it detects patients with severe PKU.

The anaesthetic management of pheochromocytoma is complicated and challenging. However, preoperative pharmacologic preparation, modern anaesthetic techniques and drugs associated with advanced monitoring in conjunction with the evolution of surgical techniques (open laparotomy to laparoscopic surgery and robotic approaches in the present day) improved significantly perioperative outcome, and intraoperative and postoperative hemodynamic stability. Although there are not randomised clinical trials to suggest one approach over another and there is a high international variability amongst intraoperative anaesthetic techniques, most management principles are still universal.

The role of osteocalcin in atherogenesis is unclear. We investigated the association between osteocalcin and carotid atherosclerosis in Chinese middle-aged and elderly male adults and further determined whether osteocalcin is independently associated with the carotid intima-media thickness (CIMT) in hyperglycemia subgroups. Subjects and methods. A total of 84 male participants (mean age, 59.13 years) were enrolled in groups of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) according to the oral glucose tolerance test. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima–media thicknesses (CIMT) were measured using ultrasonography. The circulating osteocalcin was measured using quantitative enzyme immunoassay. Results. Both IGT and newly diagnosed T2DM groups had significantly lower osteocalcin levels compared with the NGT group (5.01 ± 0.68 μg/L, and 6.173 ± 0.68 ng/mL vs. 11.55 ± 0.57 μg/L, respectively). Multivariate linear stepwise regression analysis demonstrated that waisthip ratio(WHR) (standardized β = -0.408, P = 0.000), 2 hour plasma glucose after glucose load, (PPG) (standardized β = -0.235, P = 0.025), homeostasis model of assessment for insulin resistance index(HOMA-IR) (standardized β = -0.287, P = 0.004), and Glycosylated haemoglobin (HbA1c) (standardized β = -0.250, P = 0.015) were independently and inversely associated with serum osteocalcin in hyperglycemia subgroups; PPG(standardized β = -0.476, P = 0.015), osteocalcin(standardized β = -0.486, P = 0.001) were negatively associated with CIMT, while TG (standardized β = 0.647, P = 0.000) was positively associated with CIMT in T2DM. Conclusion. These results showed that osteocalcin is independently associated with carotid atherosclerosis in men with T2DM. It is tempting to suggest that osteocalcin may be implicated atherosclerosis.