ACTA ENDOCRINOLOGICA (BUC)

Objective. Graves' orbitopathy (GO) is an autoimmune inflammatory disorder characterized by proptosis, diplopia, and extraocular motility restriction. Intravenous glucocorticoids (IVGC) are the mainstay of treatment in active moderate-to-severe GO; however, some patients require additional therapy. This study compared the clinical outcomes of IVGC alone and in combination with orbital radiotherapy (RT) or mycophenolate mofetil (MMF). Methods. Forty patients with active moderate-tosevere GO (Clinical Activity Score ≥3) treated between 2015 and 2023 were included. Patients were grouped as IVGC monotherapy (n=24), IVGC+RT (n=8), and IVGC+MMF (n=8). Outcomes included CAS, proptosis (Hertel exophthalmometry), diplopia, and motility restriction at baseline and 6 months. Results. CAS significantly decreased in all groups (p<0.001). A ≥2-point reduction in CAS was observed in 91.7% of the IVGC group and in all combination therapy groups (p=1.000). Proptosis reduction ≥2 mm occurred in 57.1%, 100%, and 71.4% of patients in the IVGC, IVGC+RT, and IVGC+MMF groups, respectively (p=0.534). No statistically significant differences were detected in diplopia or motility outcomes between treatment groups. However, these findings should be interpreted cautiously given the limited sample size and unequal group distribution. Conclusion. IVGC effectively reduces disease activity in active moderate-to-severe GO. Although combination therapies showed numerically favorable trends in some outcomes, the retrospective design, unequal treatment allocation, and limited sample size preclude definitive conclusions regarding comparative efficacy between treatment strategies. Larger prospective studies are warranted to better delineate the role of combination approaches in active moderate-to-severe GO.

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.

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.

Sotos syndrome is characterized by overgrowth, macrocephaly, distinctive facial features, and learning disabilities and is associated with alterations in the nuclear receptor binding SET domain protein 1 (NSD1) gene. Due to the advanced bone age, the eventual adult height is usually at the upper limit of normal. In this case report, a 6-year and 10-month old boy who presented with Sotos syndrome was described. He also had increased testicular volumes with advanced bone age. The stimulated levels of gonadotropins revealed central precocious puberty and brain magnetic resonance imaging (MRI) showed a pineal cyst. A heterozygous duplication variant [NM_022455.4:c.4560dup; p.(His1521Thrfs*9)] in the NSD1 was identified. Triptorelin acetate treatment was started. The aim was to report the novel duplication variant in the NSD-1 in a patient with Sotos syndrome accompanied by a pineal cyst and central precocious puberty, and also to discuss the rationale for treating precocious puberty.

Introduction. Sudden cardiac death (SCD) is a widespread and devastating event. As much as a quarter or half of all cardiovascular (CV) deaths are due to SCD. A lot of work is done to decrease the number of SCD. Recently several publications pointed out (very) high CV risk in Cushing’s syndrome (CS) and CV risk is generally associated with SCD. Therefore, the aim of the study is to analyze the available publications regarding CS and SCD. Materials and methods. We initiated the search in SCOPUS using the terms “Cushing” and “sudden death”. The additional documents were retrieved from Medline, Springer, SAGE, Science Direct, Cambridge, Wiley, PubMed, and Oxford Journals. There are no trials or registries published and therefore the narrative review is an appropriate approach to describe the problem, appraise the available evidence, and propose a solution. Results. There are four papers available from SCOPUS and four additional papers from other sources. The oldest paper on the topic is almost a century old (from 1927), the last one 33 years old, suggesting that this problem (SCD in CS) was not considered important for three decades. Therefore, a paucity of papers analyzed SCD risk in CS. We managed to identify several RFs of SCD that are prevalent in CS. Conclusion. Clustering of SCD risk factors suggest increased risk of SCD in Cushing disease (CD) and CS. The risk stratification tools for CV events should be studied, particularly so for SCD. Preventive measures should be tailored to the level of CV risk in individual CS patients. In addition, it carries a promise of prevention in individual patients, since SCD is preventable in part.

Context. Thyroidectomy is becoming an ambulatory surgical procedure. By predicting hypocalcemia,duration of hospital stay might decline. We tried to determine whether measuring parathormone two hours after total thyroidectomy predicts hypocalcemia. Objective. We aimed to design a protocol for early prediction of hypocalcemia by defining PTH measurement time and cut-off value of our center. Design. One hundred and six patients undergoing total thyroidectomy between November 2017 and October 2018 were prospectively studied. Methods. Pregnant women, patients with renal failure, parathyroid disease, previous neck operation and thyroid malignancy requiring neck dissection were excluded from the study. Parathormone (PTH) and calcium measurement was done preoperatively and in the postoperative second hour. Results. Group 1 consisted of 75 normocalcemic patients while group 2 had 31 hypocalcemic patients. Mean age was 45±13.1 (age range: 18-76). Female/male ratio was 82/24. While with a 8.36 pg/mL postoperative second hour PTH, hypocalcemia can be predicted with a 51.5% sensitivity and 90.7% specificity while with a PTH decline of 40.8% hypocalcemia can be diagnosed with a 83.9% sensitivity and 52% specificity. Conclusion. Postoperative second hour PTH and PTH percentage decline can predict postoperative hypocalcemia in total thyroidectomies. Preoperative Dualenergy X-ray absorptiometry (DXA) was not found useful in hypocalcemia prediction.

Objective. Hyperkalemia is one of the most common acute life-threatening metabolic emergencies. Alterations in serum potassium (K+) levels can have dramatic effects on\r\ncardiac cell conduction and may lead to electrocardiographic (ECG) changes. But in some\r\npatients ECG changes do not accompany serum K+ abnormalities. Severe hyperkalemia secondary to Addison Disease (AD) is rare.\r\nCase. A 40-year-old woman with AD was admitted to emergency service with generalized pain. The patient?s serum K+ level was found to be at the highest level that can be detected in our laboratory (>10.0 mmol/L, normal 3.5-4.5 mmol/L) and repeated serum K+ confirmed the previous result. Results of repeated ECGs have revealed a normal sinus rhythm. Our case is particularly interesting because it demonstrates an Addison patient that has an extremely high level of K+ (>10 mmol/L) without any accompanying ECG changes.\r\nConclusion. Our case confirms that diagnostic ECG changes do not always accompany severe hyperkalemia. Therefore, clinicians should be careful that ECG may look\r\nnormal in the presence of severe hyperkalemia.

Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

Background: Hereditary Haemorrhagic Telangiectasia (the Rendu-Osler-Weber syndrome) is a relatively common, underrecognized autosomal dominant disorder that results from multisystem vascular dysplasia. It makes vascular walls vulnerable to trauma and rupture, causing telangiectases and\r\narteriovenous malformations of skin, mucosa and viscera. It is clinically characterized by recurrent epistaxis, telangiectasia lesions on the face, hands and oral cavity, visceral arteriovenous malformations and positive family history. Epistaxis is often the first manifestation associated with haematologic, neurologic, pulmonary, dermatologic and gastrointestinal complications.\r\nCase report: a patient came to our observation presenting recurrent epistaxis with a severe iron deficiency anaemia and hypoparathyroidism. Genetic, laboratory and imaging findings were compatible with the presence of Rendu-Osler-Weber syndrome associated to a form of idiopathic hypoparathyroidism that could find its physiopathological origin in a consequence of an autoimmune process affecting\r\nparathyroids.

Context. Chronic unpredictable mild stress (CUMS) has been widely shown to impact neurological disorders. Recently, growing evidence suggests that CUMS may also contribute to the development of metabolic conditions such as diabetes mellitus. Objective. This study aimed to investigate blood glucose levels and histopathological and immunohistochemical changes in the endocrine pancreas in an experimental rat model of CUMS, as well as the potential protective effects of vortioxetine (VOR) treatment. Subjects and methods. A total of 28 rats were divided into four groups. The CUMS group was exposed to random stressors once daily for six weeks. Rats in the VOR and CUMS+VOR groups received VOR treatment. The VOR and control groups were housed separately, without exposure to CUMS. At the end of the experiment, blood and pancreatic tissue samples were collected from all rats. Results. Blood glucose levels were elevated in the CUMS group compared to the other groups. Histopathological analysis revealed a reduction in insulin, amylin, and insulin receptor expression, along with a slight increase in glucagon expression and a small number of necrotic cells in the CUMS group. VOR treatment improved all these parameters. Conclusions. Our findings suggested that CUMS may contribute to endocrine pancreatic damage resembling diabetes mellitus, while VOR treatment may mitigate this effect.