ACTA ENDOCRINOLOGICA (BUC)

Aim. There is no data for platelet distribution width (PDW) levels as a marker of platelet activation in patients with\r\nmetabolic syndrome (MetS). The present study tested the hypothesis that PDW levels may be elevated in MetS patients. Based on this hypothesis, PDW levels in patients with MetS were compared with those of patients without MetS. The relation between PDW levels and cardiometabolic risk factors was also evaluated.\r\nMaterials and Methods. Two hundred and nineteen non-diabetic MetS patients (MetS group; 155 females, 64 males) and 155 non-diabetic patients without MetS (Control group; 123 females, 32 males) were included consecutively. The primary endpoint of the study was to compare the PDW levels between the groups, while the secondary endpoint was to evaluate the relationship between PDW and cardiometabolic risk factors.\r\nResults. PDW levels were 16.75?1.73%, and 16.89?1.92% in MetS patients and control subjects, respectively (p>0.05). In correlation analysis, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (r:0.193, p:0.004, and r:0.215, p:0.001, respectively) were associated with the PDW.\r\nConclusion. Although there is a weak positive correlation between PDW and insulin and HOMA-IR, these findings do\r\nnot support our hypothesis that PDW levels may be elevated in MetS patients.

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.

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.

Anaplastic thyroid cancer (ATC) is a highly uncommon (less than 2% of thyroid malignancies) and aggressive type of cancer, with aggressive behavior and, therefore, exhibiting poor prognosis. ATC tumors are automatically labeled as stage IV disease regardless of standard criteria such as tumor burden or metastasis. ATC tumors require a diversified treatment approach that includes surgical resection, followed by a complete an aggressive combination of radiation and chemotherapy and/or palliative care. Despite best efforts, 1-year overall survival of patients is 20% to 40% with nearly universal mortality rate. Consequently, novel approaches (targeted therapy, immunotherapy) have been studied, alone or in combination, to improve the dire prognosis of these patients. BRAF V600E mutation is the most common genetic mutation found in ATC. We report the case of a 57-year-old man diagnosed with stage IVc (undifferentiated) ATC with hepatic and osseous metastases. The molecular analysis of the tumor revealed a V600E BRAF-mutation. The patient was treated with Dabrafenib and Trametinib, and achieved remission 5 weeks after starting the treatment. Subsequently, he had a thyroidectomy, and pembrolizumab was added to the two tyrosine kinase inhibitors. 9 months later he is still in remission. This case illustrates the importance of obtaining molecular information in anaplastic thyroid cancer and the urgent need of studies investigating the combination of tyrosine kinase inhibitors and check-point inhibitors in patients with V600E BRAF- mutations.

Background. Coronary artery disease (CAD), often asymptomatic, is the most common cause of morbidity, mortality and costs in diabetes. Early detection of CAD in patients with diabetes may be of paramount importance and substantially improve the outcome in diabetic patients. Objective. The aims of the current study were to determine if there are significant differences concerning the prevalence of occult CAD in asymptomatic type 2 diabetic patients compared to asymptomatic nondiabetic patients. Design, subjects and methods. The authors retrospectively reviewed a group of 120 non-diabetic (77 men, 43 women, mean age 61±10.2 years) and 120 diabetic (81 men, 39 women, mean age 58±11.4 years) asymptomatic patients that underwent coronary computed tomography angiography (CCTA) for various reasons between January 2013 and January 2014. Results. Coronary plaques were identified in 105 diabetic patients (87.5%) and in 75 non-diabetic patients (62.5%) the prevalence being significantly different (p=0.023). Regarding plaque composition and degree of stenosis, we found a higher prevalence of calcified (p=0.016) and significantly stenotic (≥50% luminal narrowing) plaques (p=0.008) in the diabetic group. Agatston calcium score, relevant for atherosclerotic plaque load, was higher (p=0.005) in type 2 diabetic patients (350.3) compared to non-diabetic patients (158.7). Conclusion. CCTA could represent a screening method able to detect silent atherosclerotic plaques thus contributing to the prevention of acute coronary syndrome (ACS) by an early and adequate treatment of CAD. Obstructive atherosclerotic plaques can be accurately identified using CCTA, limiting the use of invasive imaging methods and selecting patients that could benefit of coronary revascularization.

Objective. Antithyroid drugs, surgical excision, and radiation therapy with 131I are the common treatment modalities thyrotoxicosis. The medical treatment of\r\nthyrotoxicosis has approximately 0.35% serious complications which consist of agranulocytosis, liver necrosis and failure. Therapeutic plasma exchange is an effective\r\npreoperative preparation method in thyrotoxicosis patients who are candidates for surgery and unable to manage an euthyroid state with medical treatment.\r\nPatients and Methods. This study was constructed between 2002-2009 in 9 patients who were resistant or had complications with medical treatment of thyrotoxicosis. The\r\ntherapeutic plasma exchange procedures were performed with discontinuous flow cell separator devices.\r\nResults. Seven patients were females and 2 patients were males. The mean age was 51.22 years (32-78 years). The mean duration of the disease was 35.4 months (3-120 months). The patients underwent 3.3 (2-6 sessions) session of therapeutic plasma exchange before surgery. The mean volume of\r\nplasma exchange was 10549 mL (7150-18372 mL). The plasma is exchanged with %10 albumin and/or fresh frozen plasma. The\r\ncomplication rate was 22% during therapeutic plasma exchange. Four patients underwent near total thyroidectomy and five patients underwent total thyroidectomy. The mortality rate was zero. Neck hematoma causing acute\r\nrespiratory compromise and requiring urgent evacuation developed in one patient.\r\nConclusions. Total plasma exchange is an effective and safe procedure in preoperative preparation of the patients with thyrotoxicosis who were resistant or complicated with\r\nantithyroid drug in which a high level of concern and steady supervision is mandatory to prevent life threatening preoperative and postoperative complications.

Introduction. Gitelman Syndrome (GS) is a genetic tubulopathy frequently linked with insulin resistance. The possibility of developing Diabetes Mellitus (DM) in GS increases with the causes of insulin resistance. Hypokalemia is one of the most common electrolyte disorders in GS, and most diabetic drugs can cause hypokalemia. Considering this dilemma, we presented a DM treatment experience in a GS case. Case presentation. A 47-year-old male GS patient with a potassium-rich diet complained of weight loss and dry mouth for 2-3 months. The laboratory tests revealed a higher HbA1c level, as high as 11.8%. The remaining abnormal laboratory test results (hypokalemia, hypomagnesemia, metabolic alkalosis) indicated a patient with GS. The patient was placed on a metformin+gliclazide-based treatment. Oral potassium and magnesium supplementation were started for the patient whose hypokalemia increased in the first control, and the potassium dose was doubled in the third control. In the first-month follow-up visit, it was observed that the blood potassium level was improved, and hyperglycemia was optimized. Conclusion. In brief, any treatment for DM can be selected in GS patients with DM by performing frequent electrolyte monitoring. Like our case, oral potassium supplementation was adequate for the metformin + gliclazide combination-coincidence hypokalemia.

Ectopic lingual thyroid is a rare developmental abnormality caused by aberrant embryogenesis during thyroid migration. Even though, most patients are asymptomatic, uncommonly the mass can be enlarged and cause dysphagia, dyspnea, upper airway obstruction, dysphonia, hypothyroidism. We report a very rare case of ectopic lingual thyroid presenting with massive hematemesis.

Only a few subacute thyroiditis (SAT) cases secondary to hypocortisolemia developed after successfully treating Cushing's disease (CD) have been reported. In this report, we present an SAT case, which developed immediately after discontinuation of steroid treatment for hypocortisolemia after the successful treatment of CD. A 54-year-old female patient who had recently been diagnosed with type 2 diabetes mellitus was admitted to our center with complaints of proximal myopathy and obesity. Serum cortisol did not suppress adequately after the 1 mg dexamethasone suppression test. Pituitary MRI of the patient with increased basal plasma ACTH level revealed a 6 x 5 mm right-sided adenoma. After successful surgical treatment, the patient was given ten months of steroid therapy due to a suppressed corticotroph axis. Shortly after the steroid treatment was discontinued, the patient was admitted with neck pain, fever, and thyrotoxicosis. The patient was diagnosed with SAT, and methylprednisolone treatment was started again. The underlying pathophysiological mechanisms in SAT cases that develop after the treatment of CD can only be speculated. One possible mechanism could be that the glucocorticoid deficiency develops after effective treatment of hypercortisolism alters the immunological responses or generates self-reactive cells and prepares an appropriate environment for the thyrolytic process.

Context. Postmenopausal women are at risk of developing primary hyperparathyroidism (PHPT) and the underlying\r\ndisturbance in calcium homeostasis is suspected to have been established for some time prior to diagnosis.\r\nObjectives. Pre-menopausal women with disturbance in calcium homeostasis suggesting PHPT have been evaluated during\r\nmenopausal transition regarding associated morbidity.\r\nDesign and subjects. Premenopausal women, 40 to 50 years of age, were screened with parameters of calcium homeostasis in\r\nconjunction with routine mammography during 2002-2003. Those who fulfilled preset criteria of mild PHPT (cases) (n=173) were matched to controls (n=193). The pre/perimenopausal\r\nwomen were investigated for the prevalence of PHPT in association with skeletal changes, morbidity and impact on\r\nquality of life (base-line data already published). They have now been re-evaluated regarding different health aspects after three years follow-up.\r\nResults. The cases still had lower bone mineral density (BMD) in total hip, femoral neck and distal third of radius than controls (p<0.05) after three years followup. Time of follow-up, menopausal status, and weight affected BMD independently.\r\nConclusion. Middle-aged women with mild disturbances of calcium homeostasis suggesting early PHPT, had lower BMD in the hip and radius, but the decline in BMD was not accelerated during menopausal transition.