ACTA ENDOCRINOLOGICA (BUC)

Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by congenital deficiency of enzymes involved in cortisol biosynthesis from cholesterol in the adrenal cortex. In this article, we aimed to present a 29-year-old female patient with I2 splice point mutation detected in one allele and P453S mutation on the other allele of CYP21A2 gene associated with 21-hydroxylase deficiency. Her further investigation revealed that her mother had P453S mutation and her father had I2 splice mutation. Case report. A 29-year-old woman with CAH was admitted to our clinic with the request of pregnancy. Her physical examination revealed a height of 151 cm, weight 59 kg, body mass index 25.8 kg/m2. According to Tanner staging, she had Stage 3 breast development and pubic hair. Her laboratory test results were as follows: Glucose: 79 mg/dL (70-100 mg/dL), Creatinine: 0.6 (0.5-0.95 mg/ dL), Sodium: 138 mEq/L (135-145 mEq/L), Potassium: 4.4 mEq/L (3.5-5.1 mEq/L), Cortisol: 0.05 μg/dL, ACTH: <5.00 pg/mL (5-46 pg/mL), 17-OH progesterone: 7.67 ng/mL (0-3 ng/mL). Chromosome analysis revealed a 46, XX karyotype. CYP21A2 gene mutation analysis was performed for the patient whose clinical history and laboratory results were compatible with congenital adrenal hyperplasia. During the reverse dot blot analysis, I2 splice mutation in one allele and P453S mutation in the other allele were detected. Conclusion. Although the I2 splice mutation detected in our case was mostly associated with a saltwasting form of CAH, it was thought that the other P453S mutation detected may explain the relatively good clinical course in our case.

Context. Pituitary adenomas are benign tumors, usually found in men in their 3rd and 5th decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment. Objective. This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions. Design. This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach. Subjects and Methods. We performed an advanced search on Web of Science and PubMed databases on October 10th, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria’s, 19 studies were fully read and analyzed. Results. Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential. Conclusions. For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they’re cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined “above and below” simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage.

Background. There are few data to demonstrate the usefulness of N-terminal pro B-type natriuretic peptide (NT-proBNP) for the left ventricular diastolic dysfunction (LVDD) diagnosis in metabolic syndrome (MSy) patients as the relationship between NT-proBNP and MSy components is still under study. Objectives. The present study aims to determine the influence of MSy components on NT-proBNP concentrations. In this respect, we tried to identify the relationship between NT-proBNP concentrations and LVDD in patients with MSy and preserved LV systolic function. Methods. 68 hospitalized obese patients with MSy (IDF2006 definition) were taken under study. All patients underwent Doppler echocardiography. NT-proBNP was determined using the ELISA method (Biomedica). The data obtained in the study group were compared to those of 70 obese subjects, age and sex matched, without MSy. Results. The median of plasmatic NT-proBNP level in MSy patients was 155 pmol/L significantly (p=0.002) higher than in the control group (120 pmol/L). Median NTproBNP was significantly higher (p=0.0266) in MSy patients presenting LVDD (160 pmol/L) as compared to those with normal left ventricular function (125 pmol/L).In the LVDD subgroup NT-proBNP level was positively and significantly correlated with age (r=0.326, p=0.025), SBP (r=0.508, p=0.0003) and DBP (r=0.396, p=0.005) and negatively correlated with waist circumference (r=-0.380, p=0.008). Dyslipidemia, impaired fasting glucose and body mass index (BMI) did not significantly influence NT-proBNP levels. Conclusions. MSy patients had higher NT-proBNP concentrations as compared to obese subjects without MSy, due to the presence of LVDD and the positive and statistically significant correlation with age, SBP and DBP.

Purpose. About 30% of patients with liver cirrhosis have diabetes. Postprandial hyperglycemia is more problematic than fasting hyperglycemia when managing diabetic patients with cirrhosis. Nateglinide decreases in the mealtime plasma glucose levels. The present study aims to determine\r\nwhether nateglinide is suitable for the management of diabetic patients with liver cirrhosis.\r\nMethods. This was a retrospective analysis of the cirrhotic patients who were treated at CNUH between Jan 2003 and Dec\r\n2009. A total of 81 Child-Pugh Class A or B patients who had been treated with insulin (I, n=27) or nateglinide (N, n=27) for at least 12 months were included in the study, while 27 cirrhotic patients without diabetes (C, n=27) were included as a control group. We compared the efficacy of treatment and the safety between the groups.\r\nResults. The basal mean HbA1c level was higher in the insulin treatment group than that in the nateglinide treatment group. The mean HbA1c was lowered in thepatients treated with insulin (9.36 ? 1.71% &#8594; 7.69?1.52%, p=0.026), but this was not changed in the patients treated with\r\nnateglinide (8.01?2.37 % &#8594; 7.78?2.11%, p=0.692) after 12 months treatment. There was no change in the Child-Pugh score in all the groups.\r\nConclusion. In case of mild hyperglycemia, nateglinide may be used for glycemic control in diabetic patients with\r\ncirrhosis as an insulin substitute without worsening the state of liver cirrhosis.

Denosumab,a monoclonal IgG2 antibody directed against RANK-L,is used as a neoadjuvant therapy for inoperable or metastatic giant cell tumor of bone. Many side effects like as hypocalcemia during treatment and rarely severe hypercalcemia especially in children after discontinuation of denosumab occurred. The unpredictable onset and recurrent episodes of severe hypercalcemia increase the duration of hospitalization and the risk of complications. Persistent hypercalcemia and difficulties in management have prompted the search for different more effective therapeutic options. Objectives. To share our experience with the use of oral bisphosphonate in acute and long-term therapy of severe hypercalcemia following high-dose denosumab therapy and to review the literature on this subject Case. We report the management of a case of severe hypercalcemia that developed 4 months after the completion of 18-month denosumab treatment in a 9-year-old girl who was followed up with a giant cell bone tumor for 6 years. Based on an evaluation aiming to determine etiology, hypercalcemia was considered as "rebound-linked" upon denosumab discontinuation. Severe hypercalcemia attacks recurring with an interval of 2 weeks were treated with IV bisphosphonate, but when mild hypercalcemia developed again, treatment with 70 mg per week of oral bisphosphonate was planned. After the second dose of alendronate, the calcium level always remained below 10.5 mg/dl. In the 14-month follow-up, no hypercalcemia attack was observed again. Results. Rebound hypercalcemia can occur as an unpredictable recurrent episode at any time after denosumab cessation. Thus, the patient should be closely monitored especially in childhood due to rapid bone cycle. In longterm follow-up, oral biphosphonates can be used effectively to reduce hospitalization time and the management of especially life-threatening recurrent attacks.

Hypoglycemia from a non-insulin-secreting extrapancreatic tumor is a paraneoplastic syndrome characterized by the tumor production of a substance with an insulin-like effect (insulin-like growth factor 1 or 2 - IGF 1 or 2). Diagnosis is confirmed by the determination of IGF-1 and IGF-2 and finding an elevated IGF - 2/IGF- 1 ratio. The availability of these tests is limited in many laboratories, so prompt recognition and therapies are late. We present the case of a 70-year-old patient diagnosed with right lower lobe bronchopulmonary neoplasm who presented to the emergency department with an altered general condition and hypoglycemic coma. The evaluation revealed low levels of insulin and C-peptide along with an elevated IGF-2/IGF-1 ratio of more than 10, suggesting a diagnosis of lung sarcoma with production of IGF-2. Because the tumor could not be resected in this case, chemotherapy and radiotherapy were performed, along with glucocorticoid therapy to prevent recurrent hypoglycemia. In the case of a patient with lung sarcoma and recurrent hypoglycemia (especially severe hypoglycemia or coma), extrapancreatic non-hyperinsulinemic hypoglycemia should be determinate tumor IGF-2 secretion.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-β plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-β activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations

The topic of fertility preservation has been gaining increasing importance since the beginning of this century. The reasons for this development are the advances in oncological therapy over the past few decades, with cure rates of approximately over 90%, and the fact that starting families is increasingly postponed in later periods of life in industrialized countries. Since March 2020 the whole medical and non-medical world experiences a pandemic due to Covid-19 (coronavirus disease 2019) which has never been seen before. This created a plenty of challenges for both, the patients and healthcare providers. This review article presents the fertility-protective methods currently available for women and men suffering from cancer with their clinical approach, value, advantages and disadvantages. Besides, it focuses on the changes and special considerations which have to be taken into account during pandemic times including preventive measures as well as the patient`s access to the fertility preserving options. In conclusion every premenopausal woman and every man with incomplete family planning suffering from cancer should be counselled about the existing fertility preserving techniques before commencing cancer therapy.