ACTA ENDOCRINOLOGICA (BUC)

Objective. We aimed to determine the risk of hypercalcemia in a geriatric population with very high dose levels of 25-hydroxy-vitamin D (25(OH)D). Patients and Method. This study was designed as a retrospective, cross-sectional two-center study for examining the elderly patients with very high 25(OH)D levels (>88ng/mL) between January 2014 and December 2019. After recruitment, subgroup analyses of the patients were performed based on their calcium and vitamin D levels. Results. A total of 81.101 elderly patients, who had been evaluated for their vitamin D levels, were screened. Of the 458 (0.6%) elderly patients with 25(OH)D>88 ng/ mL according to our criteria, 217 patients with complete data were accepted into our study. The median 25(OH)D level was 103.7ng/mL (min-max:88.2-275.9). Most of the elderly patients (86.6%) with very high 25(OH)D levels were normocalcemic. When patients with hypercalcemia were compared with normocalcemic group, no difference was observed in the levels of 25(OH)D, intact parathormone (iPTH), phosphorus, alkaline phosphatase (ALP), and their age. However, the PTH suppression rate was significantly higher in hypercalcemic group (p=0.005). Conclusion. The elderly patients with very high 25(OH)D levels would appear to be mostly normocalcemic whereas life-threatening hypercalcemia would also occur. Treatment and follow-up planning should be done according to the clinical guideline recommendations.

Objective. To evaluate circulating FFAs in relation to glucose and insulin metabolism and to different fat compartments in men with and without diabetes. Patients and Methods. Thirtythree men with uncomplicated type 2 diabetes mellitus (T2DM) and 28 controls underwent an oral fat load and were studied at baseline and for 5 hours postprandially for serum FFAs, glucose and insulin. Abdominal fat distribution and gluteal fat accumulation were evaluated by anthropometrics and axial MRI images. Insulin resistance and sensitivity were estimated by HOMA and Matsuda index respectively. Results. Fasting and postprandial FFAs were higher in diabetics (p=0.007) despite similar fat accumulation and distribution between groups. Postprandial FFAs correlated positively with postprandial glucose, and fasting and postprandial insulin levels (p< 0.05) in controls, and with fasting and postprandial insulin levels (p< 0.05 and p < 0.01 respectively) in diabetics. Postprandial FFAs were positively correlated to HOMA (p<0.01) and negatively to Matsuda index (p<0.05), and positively to total visceral and retroperitoneal fat,the strongest association observed at L2- L3 (p<0.05 and p<0.001 respectively) in diabetics. Conclusions. Diabetics have higher serum FFAs, despite similar levels of adiposity and fat distribution. Interestingly, postprandial FFAs correlate strongly and positively with total visceral fat, underlying the importance of visceral fat in metabolic abnormalities in diabetes.

Objective. To compare two chromatographic methodologies for determination of plasma phenylalanine (Phe) and their usefulness for diagnosing hyperphenylalaninemia (HPA) and phenylketonuria (PKU). Methods. The plasma amino acids were isolated and concentrated from blood collected from infants with HPA detected by newborn screening. The plasma Phe was determined in parallel by HPLC and by image-densitometry of 2D-TLC plates. Results. Typical examples of 2D-TLC plates and HPLC chromatograms from infants with HPA and PKU are presented and evaluated. The Phe spot was visible on 2D - TLC plates at Phe concentrations higher than 300 μmol/L. The standard calibration curve traced after imagedensitometry of the Phe spot presented high dispersion of values at each concentration of Phe, high SD values, the equation of the curve having a low R-squared value (0.862). In contrast, the standard calibration curve obtained by HPLC shows linearity on the range of concentrations from 100 - 16,000 μmol/L, extremely small SD values, the equation of the curve has a very high R-squared value (0.999). Conclusions. The HPLC methodology is appropriate to confirm HPA detected by newborn or selective screening of PKU. The 2D - TLC methodology is adequate to detect patients with severe PKU.

Background. Gestational diabetes mellitus (GDM) is associated with high frequency of obstetric complications, such as gestosis, polyhydramnios, urogenital infection, premature birth. An increase in the number of cases of detection of GDM in pregnant women living in Kazakhstan is noted recently. Objective. This research was carried out in order to see the influence of GDM on the course of the third trimester of pregnancy, outcomes and fetal status in women of Kazakh ethnic group. Research design. Cohort observational study. Subjects and Methods. The main group of research consisted of 61 pregnant women with GDM (Meanage= 32.8±6.314), the control group included 39 pregnant women with normal glucose tolerance (Meanage=30±5.432 years). The pregnant women in both groups were examined by calculation of body mass index (BMI), determination of fasting plasma glucose and the system of hemostasis. Also, the fetal ultrasound was implemented and the uterineplacental, fetal-placental blood flow were evaluated using the Doppler mode. Results. In the main group initial BMI was equal to Mean=31.1±7.433 kg/m2; we revealed manifestation of gestational hypertension in 36.1%, 95%CI (2.52, 48.6); preeclampsia was diagnosed in 14.8% (95%CI (8; 25.7); the disorders of uteroplacental and fetoplacental blood flow recorded significantly more frequently in main group RR=6.393, 95%CI (1.581-25.840), like the diabetic fetopathy RR=5.115, 95%CI (1.240-21.033). The premature delivery, the prevalence of induction of delivery and intranatal trauma were significantly more frequent in women with GDM. Conclusions. GDM significantly worsens course of gestation.

The coexistence of Cushing’s syndrome (CS) and pregnancy is uncommon due to the suppression of gonadotropin secretion in CS. Adrenocorticotropic hormone (ACTH) dependent CS in pregnancy is less frequent than adrenal causes. The diagnosis of CS during pregnancy is difficult since physiological changes in the hypothalamopituitary- adrenal axis may cause dynamic tests to be misinterpreted. Radiological imaging is limited. We report the case of a 27-year old woman with Cushing’s disease (CD) diagnosed in the 5th-week of pregnancy. The mild symptoms of hypercortisolism did not lead to serious complications for the mother or the fetus, so insulin was the only treatment used. The pregnancy was completed without any complications, and at 38 weeks of gestation a healthy female infant was delivered vaginally. Complications, such as hypocortisolemia and hypoglycemia, were not observed in the infant. Postpartum tests were consistent with CD. Contrast-enhanced pituitary magnetic resonance imaging revealed a microadenoma which was removed with transsphenoidal surgery. Histopathology revealed a pituitary adenoma with positive immunohistochemical staining for ACTH. Biochemical remission required prednisolone treatment, but the insulin requirement decreased significantly over time. As a conclusion, CD with mild features can be well tolerated during pregnancy, but the mother and the fetus must be monitored closely.

Background Supplementation of Lcarnitine is associated with improvement in some abnormalities present in hemodialysis (HD) patients. Objective. The study aim was to analyze the effect of oral L-carnitine supplementation on endothelial dysfunction (ED), oxidative stress (OS), inflammation and anemia in HD patients. Design. A prospective, longitudinal and observational study was performed in a single dialysis unit. Subjects and methods.We studied 31 HD patients: 21 patients formed the Lcarnitine supplementation group (group 1) and 10 entered the control group (group 2). At baseline and after 3 months of L-carnitine supplementation (500mg/day) we determined endothelial-dependent flow-mediated vasodilatation (FMD) and nitroglycerin induced endothelium independent vasodilatation, involving ultrasonographic brachial artery measurements, serum visfatin, malondialdehyde, body mass index, systolic blood pressure, diastolic blood pressure, interdialytic body weight gain, C-reactive protein, albumin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ferritin, transferrin saturation, hemoglobin, erythropoietin dose, calcium (Ca), phosphorus (P), parathormone and Kt/V . Results. In group 1, FMD (8.9 (4.5-12.5) to 10.6 (6.7-18), p=0.04) and Ca (8.4±0.6 to 8.8±0.5 mg/dL, p<0.001) significantly increased after L-carnitine supplementation, while visfatin (1.0 (0.2-1.3) to 0.4 (0-0.9) pg/mL, p=0.03), malondialdehyde (2.8 (2.4- 3.2) to 1.3 (1.2-1.5) nmol/mL, p<0.001) and P (5.6±1.3 to 5.0±1.2 mg/dL, p=0.005) significantly decreased. Albumin increased significantly in both groups (3.9±0.3 to 4.2±0.3 mg/dL, p<0.001 in group 1 and 3.7±0.3 to 4.0±0.3 mg/dL, p=0.02 in group 2). There were no other significant variations of the studied parameters. Conclusions. L-carnitine supplementation reduces ED, visfatin levels and markers of OS, but has no effect on inflammation, nutrition and anemia in HD patients.

Background. Sweet's syndrome (SS) or acute febrile neutrophilic dermatosis is a dermatological illness that can be described by tender erythematous plaques or nodules and acute onset fever. The etiology is multifactorial and is not fully understood. SS is separated in three subclasses: classical, malignancy-associated, and drug-induced. It was shown that this syndrome can reveal an underlying hematological or solid malignancy. Case presentation. We report the case of a 55-yearold female patient referred to the Urology department for management of pheochromocytoma in the right adrenal gland, revealed by abdominal imaging in another medical unit during the evaluation and diagnosis of multiple mucocutaneous lesions, characterized by erythematousviolaceous plaques and nodules, and painful aphthous ulcers of the tongue. The eruption of each lesion was preceded by low-grade fever and chills. The hormonal profile highlighted the presence of elevated normetanephrines. We performed 3D laparoscopic transperitoneal right adrenalectomy after preoperative treatment with alpha blocker therapy. The clinical outcome was favourable, given that the cutaneous lesions started to heal after the surgery. Conclusions. Sweet’s syndrome in association with pheochromocytoma is a very rare condition, only few cases were described in literature to our knowledge. The multidisciplinary collaboration is extremely important in the management of such cases.

Introduction. Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. Case report. The authors report the case of a young male patient with a history of multiple idiopathic nonvertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient’s mother, who was also tested positive for both gene polymorphisms. Conclusion. This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. Aim. To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. Design. The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). Subjects and Methods. Exclusion criteria: age <40/ or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological subregion where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. Results. A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study. The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6- 6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/ obesity and smoking were associated with high CVR categories. Conclusion. Romania is one of the countries with high CVR, requiring CVD prevention measures.

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.