ACTA ENDOCRINOLOGICA (BUC)

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.

Aim. To investigate the cause of infertility in an azoospermic man and to describe the phenotype of a new 46,XX male case. Case report. We present the case of an infertile man, 33 years old, with a history of several years of infertility, diagnosed with the 46,XX male syndrome, SRY positive. The patient was diagnosed by clinical, hormonal, ultrasound and genetic criteria. Our patient was born at 39 weeks of pregnancy, from unrelated parents. The mother’s age was 22 years old and father’s age was 23 years old at the time of the conception. Both of his parents were exposed to chemical noxae before his conception. The case we report is a SRY positive 46,XX male with complete masculinization, confirmed by FISH and molecular analyses, caused by an X/Y chromosome inter-change during paternal meiosis. Conclusions. In our case, the SRY translocation, could probably be related to the paternal exposure to external factors like chemical noxae, but more data are necessary. Cytogenetic and molecular analyses are necessary for an accurate diagnosis, as well as endocrine testing and pelvis ultrasound.

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Aim. The purpose of this study was to examine various hormonal, biochemical and environmental factors (i.e., smoking and alcohol intake) and to investigate their possible correlation to the development of polycystic ovary syndrome (PCOS). The main objective was to evaluate the associations between hormonal profile and the antimüllerian hormone (AMH) levels in PCOS patients and their relation to environmental factors. Patients and Methods. In two gynecological clinics, 38 women with PCOS (defined according to the Rotterdam criteria) were enrolled and observed in relation to AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), Δ4-androstendione (Δ4- A), dehydroepiandrosterone sulfate (DHEA-S) and glucose plasma concentrations. Obesity, smoking and alcohol exposure were also studied. Results. AMH, T, Δ4-Α, DHEA-S, LH and FSH were increased in 76.3%, 50%, 31.8%, 23.7%, 21% and 18.4% of the patients, respectively. The LH/FSH ratio and glucose concentrations increased abnormally in 18.4% and 15.8% of the patients, respectively. AMH and T levels were both increased in 47.4% of the patients whereas both AMH and LH levels increased in 21% of the patients. Smoking, alcohol intake, obesity and glucose concentrations were not associated with AMH concentrations. On the contrary, high levels of T and LH were linked to higher levels of AMH. FSH concentrations were not increased in these patients. Conclusion. AMH is an important hormonal parameter for the diagnosis of PCOS. Larger clinical controlled studies are necessary in an effort to further investigate the inclusion of AMH measurement in the diagnostic criteria of PCOS.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.

Context. Osteonecrosis (ON) is bone death caused by inadequate blood supply and its optimal management remains uncertain. Objective. We describe the outcomes of BP (pamidronate) treatment in our patients. Design. Data regarding clinical, laboratory, magnetic resonance imaging (MRI) studies, and bone mineral density measurements (BMD) were recorded before and one year after treatment (reevaluation). The severity of the clinical picture was assessed using the criteria of the common terminology criteria for adverse events (CTCAE). Subjects and Methods. There were four female patients (patient 1, acute lymphoblastic leukemia; patient 2, immune thrombocytopenic purpura; patients 3 and 4, systemic lupus erythematosus) .All of them had been treated with high-dose prednisolone. Clinical picture of all patients were consistent with grade 3 according to CTCAE(: severe symptoms, limiting self-care ). Results. ON lesions were multifocal in the lower limbs in all of them and none of them had any fractures. All of them had been treated with high-dose glucocorticoid. Patients were treated with pamidronate (1 mg/kg/day, with maximum dose of 60 mg/day, for two days, quarterly). At the time of re-evaluation(one year after treatment), the lesions were stable on MRI, and their clinical condition was consistent with grade 1 according to CTCAE(asymptomatic). No side effects related to the use of bisphosphonates were observed except for increased BMD (SD score of 2.9) in one of the patients. Conclusions. Pamidronate may be an effective treatment for the improvement of functional impairment and pain among patients with severe osteonecrosis (ON) lesions.

Objective. To examine the prevalence of laryngopharyngeal reflux disease (LPRD) in patients with hypothyroidism.\r\nMaterials and Methods. A total of 85 patients with hypothyroidism vs 31 matched controls were recruited. Demographic data was collected and an RSI questionnaire\r\nfilled. A score > 10 was considered diagnostic of LPRD. The average score of every question was computed for all patients and compared to the corresponding average score in controls.\r\nResults. Mean age of hypothyroidism patients was 44.92 ? 13.77 years (83% females). One third of subjects were smokers and 10% had allergy. In 78.8% of the cases Hashimoto?s disease was the etiological factor and 22.4% patients had history of thyroidectomy. At the time of examination, only 30% had a TSH > 4.2 mU/L. There was\r\na borderline significance where more patients than controls had a RSI > 10 (24.7% patients vs. 9.1% controls), but with non-significant difference (p = 0.077). Similarly, closer\r\nexamination of those with TSH > 4.2mU/L compared to those with controls revealed a higher prevalence in the former group, but statistically non-significant (p = 0.275). A\r\ncomparison between those with TSH > 4.2 mU/L and cases diagnosed with hypothyroidism and normal TSH revealed no\r\nsignificant difference in the prevalence of LPRD. All laryngopharyngeal questions had a score higher in the hypothyroid group than controls.\r\nConclusion. LPRD is more prevalent in hypothyroidism patients compared to normal individuals, but with nonstatistically significant difference. The prevalence of symptoms should alert physicians to the possibility of LPRD and prompt further diagnostic tests and therapeutic intervention.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDLcholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.