ACTA ENDOCRINOLOGICA (BUC)

kidney disease (CKD), a growing public health issue, than in general population. The key issue in management of fragility fracture in CKD patients is determining whether fractures have occurred as a result of qualitative abnormalities (consequences of renal osteodystrophy or CKD-mineral and bone disorder), a reduced bone mineral density (osteoporosis) or a combination of both. In CKD patients bone histomorphometry is the gold standard for evaluating bone quality and strength, but the routine use of this method is not practical. Fracture risk can be assessed in this population by DEXA (Dual-Energy X-Ray Absorptiometry), but biochemical markers, like intact PTH and bone-specific alkaline phosphatase may be helpful. The new and emerging high resolution imaging tools need more studies for a correct evaluation of their utility in predicting fracture risk. Pharmacological therapies for fragility fracture based on current understanding of the metabolic disturbances in CKD will be reviewed. Antiresorptive and anabolic agents used in the treatment of osteoporosis are discussed with special focus on CKD population.

Context. The metabolic syndrome is a profound, systemic impairment of the metabolism of lipids, carbohydrates and branched amino-acids, affecting specially obese people. Recently, many studies outlined the presence of the metabolic syndrome, also in non obese persons. Objective and design. To assess the relationship between insulin resistance and the cardiovascular component of the metabolic syndrome in a group of young, non obese subjects using a cross sectional study. Subjects and methods. We enrolled 103 subjects with body mass index < 30 Kg/m2, without metabolic syndrome to whom fasting glucose, triglycerides, high density lipoprotein cholesterol, insulinemia, waist circumference and arterial pressure were recorded in a crosssectional approach. Insulin resistance was evaluated using the homeostasis model assessment for insulin (HOMA-IR) index. Statistic data processing included Pearson relation and multiple regression (backward method), using the SPSS version 21 software. Results. A significant relationship between waist circumference, diastolic blood pressure and HOMA-IR is found. High value of HOMA-IR (>2.6) was more frequently in men (p=0.011). The incidence of the 2 metabolic components mentioned above was higher in the high value HOMA-IR group: 33% vs. 7% in women and 50% vs. 4% in men. Multiple regression showed a strong correlation between HOMA-IR and waist circumference (p<0.001) and diastolic blood pressure (p=0.008) that was maintained inside the women group (p=0.016 and p=0.032, respectively). In men, HOMA-IR correlated with waist circumference (p=0.031). Conclusion. We found a significant interdependence between waist circumference, diastolic blood pressure and HOMA-IR. Based on our results, we consider that lifestyle intervention should start as soon as abnormal waist circumference is recorded.

Background and aims. Increased fat accumulation associated to increased cardiometabolic risk factors is a prominent feature of type 2 diabetes. In type 1 diabetes, increased fat accumulation is not prevalent and its metabolic impact has not been fully evaluated. We aimed to evaluate differences in body composition, clinical and metabolic\r\nprofile in type 1 and type 2 diabetes patients with varying degrees of adiposity.\r\nMaterials and methods. Clinical, biochemical and body composition data (using a bioelectric impedance analyzer) from 96 type 1 and 253 type 2 adult diabetes patients have\r\nbeen collected.\r\nResults. In type 1 patients estimated visceral fat area (eVFA) increased significantly (84.3?27.9 vs. 103.0?27.9 vs. 128.1?29.1 cm2, p=0.006, 0.003, and <0.001) while BMI, body fat mass (BFM) did not differ across age tertiles. Between normal weight (BMI<25 kg/m2) and overweight (BMI>25 kg/m2) type 1 patients there were no significant differences either in triglycerides (128.7?135.6 vs. 92.8?50.6 mg/dl, p=0.1), HDL-cholesterol (53.6?15.9 vs.\r\n52.3?13.7 mg/dl, p=0.6) and uric acid levels (3.4?2.0 vs. 2.9?1.2 mg/dl, p=0.2), or in hypertension (39.5% vs. 40.0%, p=0.7) and nonalcoholic hepatosteatosis (NASH) (10.0% vs.\r\n10.5%, p=0.6) prevalences. In type 2 patients, BMI (32.3?5.9 vs. 29.5?5.1 vs. 27.9?5.0 kg/m2, p=0.001, p=0.04, p<0.001) and BFM (34.5?12.7 vs. 29.6?10.2 vs. 27.1?10.8 kg, p=0.007, p=0.11, p <0.001) decreased, while eVFA did not differ across age tertiles, suggesting that older age increases central fat distribution. Compared to normal weight, overweight type 2 diabetes patients had greater triglycerides (218.8?303.4 vs. 110.9?44.9 mg/dl, p=0.01), uric acid (4.5?2.4 vs. 3.3?1.4 mg/dl, p=0.01), and lower HDL-cholesterol (43.9?12.9 vs. 54.1?15.4 mg/dl, p<0.001) serum levels, and higher prevalences of hypertension (71.8% vs. 39.4%, p=0.005) and NASH (59.1% vs. 25.0%, p=0.005).\r\nConclusion. Visceral fat accumulation is associated with older age in both types of diabetes, but only in type 2 diabetes is associated with cardiometabolic anomalies.

We report a case of anaplastic thyroid carcinoma mimicking acute thyroiditis with skin necrosis. A 82 years woman, with no significant previous medical disorders, was admitted with a few weeks history of a painful rapidly enlarging neck mass associated with hoarseness, dysphagia to solids, dyspnea and a general state deterioration. Physical exam was significant for a left-anterior lateral neck tumor of about 7 cm. The mass was tender, firm, nonpulsatile and nonfluctuant; it was fixed to the underlying cervical tissues. Antero-cervical skin tissues were swollen, hyperemic, presenting necrosis with penetrating tendency, severe neck pain and tenderness, associated with fever, suggesting an acute thyroiditis. The thyroid function was normal (TSH = 0.81 mUI/L, TT3 = 62 ng/dL, TT4= 8.77 ug/dL) as well as antithyroid peroxidase antibody (0.5 UI/mL), while thyreoglobulin was high (384 ng/mL). Thyroid scintigram revealed a cold nodule. Thyroid ultrasound revealed a giant left thyroid mass with necrosis, lymph nodes involvement and displacement of trachea. Fine needle aspiration confirmed the clinical suspicion features of anaplastic thyroid cancer: mitoses, anisocytosis and marked anisokaryosis with enlarged nuclei. Computed tomography confirmed a voluminous mass involving the thyroid, with calcifications, necrosis with multiple latero-cervical lymph nodes, compressing right carotid artery and internal jugular vein; it was detected also a pulmonary metastasis (right medium pulmonary lobe). The patient was diagnosed on having a thyroid carcinoma of the anaplastic type, TNM stage IVc. Surgery was performed through cervical approach without sternotomy, by total thyroidectomy and resection of proximal cervical structures involved by the tumor mass. After surgery, the patient was started on levothyroxine 100 &#956;g/ day and scheduled for cervical radiotherapy, but the tumor relapsed in several weeks. Local disease can be controlled with radiotherapy either alone or in combination with chemotherapy.

Context. Primary hyperparathyroidism related hypercalcemic crisis (PHHC) is a condition that may result in fetal course. So, the early diagnosis and treatment of these patients are important Objective. This study aimed to investigate the clinical features for hypercalcemic crisis (HC) by comparing the groups with and without primary hyperparathyroidism related calcemic crisis. Design. All patients operated with primary hyperparathyroidism (PH) diagnosis in a single clinic between March 2015 and March 2020 were included in this retrospective study. Subjects and Methods. 119 patients included the study.Patients with serum calcium (Ca) level > 14 mg/dl were regarded as HC and the patients were divided into two groups as HC and non-HC. These two groups were compared for demographic data, preoperative biochemical parameters, preoperative localization studies, histopathological assessment and postoperative results. Results. Serum Parathormone (PTH), Ca, Alkaline phosphatase (ALP) and creatinine values among preoperative biochemical parameters were higher in the HC group than the non-HC (p<0.005). The hyper-functional parathyroid size of the patients in the HC group was also bigger compared to non-HC (p<0.05). No difference was observed in the demographic and histopathological data, preoperative localization studies and postoperative results of the two groups (p>0.05). Conclusions. PH is usually an elective operation and PHCC treatment should be relatively more urgent as it can be mortal. Higher HC occurrence possibility should be considered in PH patients with high serum PTH, ALP and creatinine values and large tumor diameters and those patients should be prioritized for treatment.

Context. Diabetes mellitus is the most frequent chronic complication in pregnancy and continues to contribute to increased perinatal morbidity and mortality in newborns. Macrosomia, respiratory distress syndrome, metabolic and electrolytic disturbances, and increased rates of congenital structural defects are well-known neonatal complications associated with maternal diabetes, even if well-controlled. Case report. A macrosomic infant born from an insulin-dependent mother, with uncontrolled diabetes and lack of adequate prenatal care, prenatally diagnosed with hydrocephaly showed a complicated postnatal course. Initial respiratory distress syndrome and transient hypoglycemia, rapidly corrected under treatment, were followed by persistent hypocalcemia and hyperphosphatemia due to hypoparathyroidism and evolving hydrocephaly. Ventriculoperitoneal shunting was followed by resolution of hypocalcemia, but seizures associated with schizencephaly and recurrent respiratory tract infections, aggravated by spondylocostal dysplasia, concurred to infant’s demise at the age of 5 months. Conclusions. The reported case is rare due to multiple aspects: persistent hypoparathyroidism, uncommon association of schizencephaly, and even rarely association with spondylocostal dysplasia, all these conditions requiring a multidisciplinary therapeutic approach. Also, the reported case is evocative for challenges associated with infants born from diabetic mothers.

Context. Accumulating data supports the key role of disrupted amino acids (AAs) metabolism in diabetes. Conflicting data regarding the relevance of serum AAs in diabetes and hypertension suggest that their relationship needs further investigation. Objective. To investigate serum AAs as biomarkers of increased BP variability evaluated during 24-hour ambulatory BP monitoring in the presence of type 2 diabetes. Design. Cross-sectional. Subjects and Methods. We analyzed serum AAs using targeted metabolomics (ultrahigh-performance liquid chromatography/mass spectrometry) in patients with type 2 diabetes (n=80). BP variability was assessed using 24-hour ambulatory BP monitoring. Participants were divided into two groups based on the 24-hour diastolic BP variability median value. Results. Aspartic acid, isoleucine, leucine, and phenylalanine were significantly lower, while glutamine was significantly higher in the group with higher diastolic BP variability (p-value <0.05 and variable importance in the projection >1). Corresponding pathways identified as disrupted in patients with diabetes and a higher 24-hour diastolic BP variability were phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and alanine, aspartate, and glutamate metabolism (pathway impact value >0). Conclusions. We identified specific changes in serum AAs and target AAs pathways in relation to increased 24-hour diastolic BP variability in patients with type 2 diabetes.

Background. Idiopathic hypoparathyroidism is a rarely seen disease which progresses with the hypocalcaemia, hyperphosphatemia and low level of parathyroid hormones. The main symptoms such as leg cramps and generalized muscle weakness result from neuromuscular irritability due to hypocalcaemia, and skeletal abnormalities as well as ectopic calcifications are among the well known features. Case Report. A 32 year-old male patient was referred to our clinic with four years of progressive inflammatory low back and hip pain, prolonged morning stiffness. Upon physical examination limited movements and posture resembling that seen in patients with ankylosing spondylitis (AS) were observed. In laboratory investigation revealed hypocalcaemia (4.6 mg/dL), hyperphosphatemia (7.0 mg/dL) and hypoparathyroidism (7.2 pg/mL). Serum C reactive protein and erythrocyte sedimentation rate were normal. The direct graphic and sacroiliac magnetic resonance image were identified sacroiliitis. A rise in bone density in dual-energy x-ray absorptiometry was recorded. According to the Modified New York criteria, AS includes the whole diagnostic criterias completely. Conclusion. Idiopathic hypoparathyroidism, when undiagnosed for a long period, may result in extreme calcification of soft and bony tissues. The vertebral calcification may be so intense that it may result in an AS like clinical picture. Therefore, idiopathic hypoparathyroidism should also be considered in the differential diagnosis of AS .

The stress driven cortisol dynamics of the Hippocampal-Hypothalamic-(Anterior) Pituitary-Adrenal (HHPA) axis with its negative feedback loops from the adrenals to pituitary and hypothalamus, in particular relation with hippocampus, have been the focus of the last few years boom of papers\r\nusing various distinctive mathematical models, simulations, stability analyses and optimal control of these models. These many quantitative approaches led to discovering unknown connections between cortisol feedback loop dysfunctions and stress disorders (post-traumatic stress\r\ndisorder (PTSD), depression, chronic fatigue syndrome (CFS)), adrenal suppression and atrophy, Alzheimer (AD)\r\nand hypocampal cognitive dysfunctions (memory loss) leading to new drug treatment strategies. We assemble here together and unify these results, including our own early work, in order to create an integrative mathematical system theory framework for HHPA & HPA and stress driven cortisol dynamics in which various clinical disorders appear as various quantifiable negative feedback loop dysfunctions and drug therapies correcting these disorders appear as feedback model based treatments: a neuroendocrine system theory for cortisol ?feedback pathology? and its existing and future possible ?feedback therapies?.