ACTA ENDOCRINOLOGICA (BUC)

Objective. To compare results of treatment of primary hyperparathyroidism (PHPT) in two teaching hospitals (eastern and western Europe) and to establish conclusions regarding quality of surgery for PHPT in Romania. Methods. We reviewed two prospectively collected databases of patients submitted to open minimally invasive parathyroidectomy (OMIP) for symptomatic PHPT in two centers from Romania and the United Kingdom (UK). We included patients with biochemically proven PHPT and positive pre-operative localization studies. We excluded patients with negative localization studies, suspected multiglandular disease, concomitant thyroid disorders and chronic renal failure. Results. 60 patients were included, 27 in group A (Romanian cohort) and 33 in group B (UK cohort). We noted significant differences between groups in pre-operative serum calcium and phosphorus levels (p<0.5). There were no differences between groups regarding the presence of symptoms; in group A we had significantly more patients with renal calculi history (p=0.02), digestive symptoms (p=0.006) and osteitis fibrosa cystica (p=0.01). Two patients from the UK group had lithium associated hyperparathyroidism and 2 patients had genetic disease. Intraoperative parathyroid hormone measurement (ioPTH) was available only for group B and frozen sections were selectively used in both groups. Both the adenoma size and weights were significantly higher in group A. The median operative time was significantly longer in Romanian group (p=0.001); in this group we noted the single conversion to traditional cervicotomy (3.7%) from all studied patients. In group A we noted two patients (7.4%) with failed parathyroidectomy and persistent PHPT; the cure rate was 92.5% for Romanian group and 97% for the UK group. Conclusions. OMIP can be performed safe with a high cure rate in “small” volume endocrine centres with results comparable to western experienced endocrine centres. Romanian patients presented with more severe PHPT with more frequent end-organ damage, due probably to late diagnosis.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Context. Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The increasing evidence supports links between inflammation and AF. There is evidence showing that obesity is a major cause of adipose tissue (AT) inflammation. Ghrelin (GHRL), through its growth hormone secretagogue receptor (GHS-R) present on adipose tissue macrophages (ATMs), could modulate AT inflammation. Objective. Our study aimed to evaluate the role of adipose tissue macrophages (ATMs) and their GHS-R in adipose tissue samples of right atrial appendages (RAA) biopsies. Subjects and Method. We obtained RAA biopsies from 10 obese patients, undergoing cardiac surgery for coronary artery bypass graft (CABG) and developing postoperative atrial fibrillation (POAF). The epicardial tissue samples were examined using immunohistochemistry to visualize and quantify CD68 and GSH-R expression of the ATMs. Results. Histologically, the mean adipocyte diameter (MAD) of epicardial adipose tissue (EAT) was larger in EAT samples with inflammation as compared to EAT without inflammation (84.2 μm vs. 79.6 μm). The expression of CD68 was lower in EAT without inflammation as compared to EAT with inflammation in adipose tissue samples. Similarly, the expression of GSH-R was lower in EAT samples without inflammation as compared to EAT samples with inflammation in adipose tissue. Conclusions. Increased epicardial fat area, macrophage infiltration, and GHS-R expression in epicardial ATMs appeared to be associated with postoperative atrial fibrillation in obese patients.

Renal osteodystrophy (RO) encompasses the full range of disorders of mineral metabolism that affects the skeleton in patients with chronic renal failure (CRF). The present study tries to analyze some clinical and biochemical features of RO in a group of cases presenting CRF in hemodialysis program. The study group included 45 cases with different nephropathies. The patients were in a longstanding hemodialysis program (mean period 7.46 ? 8.9 yrs). The cases were divided into three subgroups in relation with the length of dialysis time. The performed determinations comprised: a profile of phospho-calcium metabolism, calciotropic hormones (25-hydroxyvitamin D ? 25 (OH) D3; 1, 25 dihydroxyvitamin D ? 1, 25 (OH)2 D3; serum intact PTH) and serum osseous alkaline phosphatase. Paraclinical investigations were represented by X ray examination of bone and joints (certain sites) and bone mineral density measurements by double energy X-ray absorptiometry (DXA) method. The clinical symptoms and signs of RO were represented by: bone pains, height loss, fractures and acute arthritis. Biochemical assessment showed marked alteration of phosphocalcium metabolism and of the levels of calciotropic hormones, related to the stage of CRF and length of hemodialysis.\r\nThe radiographic aspects displayed different patterns, while DXA revealed in most of studied cases different degrees of bone loss, related to end-stage renal disease and associated factors.

Aim. To compare the red blood cell (RBC) diffusional water permeability (Pd) in elderly human subjects and mature\r\nsubjects.\r\nPatients and methods. 58 apparently healthy subjects, aged 65-80 years, were divided into two groups: 44 mature (35-64.9 years) and 14 elderly subjects (65-80 years). The morphological characteristics of RBCs were determined from light microscopic measurements and their Pd was measured\r\nby a NMR method. The inhibition of Pd induced by p-chloromercuribenzoate (PCMB) and the activation energy (Ea,d) of water diffusion across the RBC membrane\r\nwere also determined.\r\nResults. No significant differences between the RBCs of the two groups were found in regard with morphological parameters. Pd (10-3 cm/s) was in case of mature subjects ~ 3.1 at 15?C, 3.6 at 20?C, 4.2 at 25?C, 5.0? at 30?C, 6.1 at 37?C and 7.3 at 42?C, while for elderly subjects Pd was ~ 3.4 at 15?C, 3.9 at 20?C, 4.5 at 25?C, 5.3 at 30?C, 6.6 at 37?C and 7.9 at 42?C. Although rather small these differences were statistically significant: p<0.004 to p <0.04 at various temperatures. This means that RBCs from\r\nelderly people have a higher Pd. In agreement with this suggestion, the values of inhibition of water permeability induced by PCMB were higher for the RBCs from elderly individuals; however, the differences were not statistically significant. Ea,d was the same (~23 kJ/mol) for the RBCs from both groups. After incubation with PCMB Ea,d was ~ 37 kJ/mol for the mature individuals and ~ 31 kJ/mol for\r\nelderly individuals; however, the differences were not statistically significant.\r\nConclusion. A small, but statistically significant, increase in Pd of RBCs from elderly individuals was observed. This can be correlated with peculiarities of a less physically active organism.

Female sex steroids play considerable roles in body weight and insulin physiology.\r\nEnhanced or reduced female sex steroids affect insulin sensitivity.\r\nThe aim of the present study was to examine the effects of female sex steroids on body\r\nweight and insulin sensitivity through ovariectomy and progesterone or estradiol\r\nadministration in rats.\r\nMaterials and Methods. 7 week old female albino (Wistar) rats were used in our study.\r\nAnimals were randomly divided into control, uni-ovariectomised, bi-ovariectomised, sham,\r\nvehicle receiving sham and vehicle or hormone receiving female groups. Progesterone (20\r\nmg/kg/day) or estradiol valerate (200 &#956;g/kg/day) were injected subcutaneously, starting on the\r\nthird day after surgery and continued at daily intervals. After 4 weeks, animals were measured\r\nfor body weight and killed. Following serum collection, fasting serum insulin and glucose were\r\nmeasured and fasting glucose to insulin ratio was considered as index of insulin sensitivity\r\nwhich were compared statistically between the groups.\r\nThe results showed increased insulin sensitivity (glucose to insulin ratio) (IS) and body\r\nweight (BW) in both bi-ovariectomised (bi-ovx) (IS=14.76, BW=237.40 g) and uniovariectomised\r\n(IS=11.33, BW=225.53) rats compared with the control group (IS=9.36,\r\nBW=205.32) (p<0.01). Progesterone or estradiol replacement in bi-ovx rats was followed by\r\nincreased or decreased body weight (264.50 or 205.10) and increased or decreased insulin\r\nsensitivity (20.38 or 8.50) compared with bi-ovx rats, respectively (p<0.05). In nonovariectomised\r\nrats, administration of progesterone resulted in increased and of estradiol in\r\ndecreased body weight (220.6 g and 185.35 g) and insulin sensitivity (18.36 and 5.35)\r\ncompared with control animals (p<0.01).\r\nConclusively, our findings indicate that progesterone is enhancer and estradiol is reducer\r\nof insulin sensitivity in rats. In addition, weight gain after ovariectomy or progesterone\r\ntreatment and weight loss following estradiol treatment did not probably contribute in acting on\r\ninsulin sensitivity.

Background. Prevalence of congenital hypothyroidism is about one per 414 live births in Kurdistan Province, a western province in Iran. Recently, a surveillance system (diagnosis, report and treatment) was developed to control the disease in Iran. Aim. This study aimed to compare the IQ of children with congenital hypothyroidism with normal children in this province, where the disease is highly prevalent. Subjects and Methods. This retrospective cohort study was conducted on 100 children with congenital hypothyroidism under continuous treatment with thyroxine and a group of 100 healthy infants. Two tests of Goodenough draw-a-man test and Proteus Mazes were used to measure IQ. Statistical analysis was done by SPSS 16 and multiple regression. Results. The average IQ of the patient group treated for 42 months with thyroxine and healthy group were 103.4 (±16.9) and 103.4 (±15.4), respectively (p=0.989). There was no statistically significant difference between the IQ of children with transient and permanent hypothyroidism. In multivariate analysis, the only effective factor on IQ was mothers’ education. Conclusion. There was no statistically significant difference between the IQ of children with congenital hypothyroidism who have been treated with thyroxine and the IQ of healthy children. So, there is appropriate quality of care for patients who are living in this province where the disease is highly prevalent.

Background. Skull metastasis has not been reported from mixed medullary follicular thyroid carcinoma (MMFTC). Objective. To present a patient with expansile lytic skull metastasis. Case report. A 61 year lady is presented with goiter for 7 years and 8 cm diameter painful swelling over frontal bone for 18 months, aspiration from which revealed sheets and clusters of polygonal cells, similar to aspiration from hypoechoic nodule in right thyroid lobe. Serum calcitonin (569pg/mL) and carcinoembryonic antigen (11.2ng/mL) were elevated. Histopathology of 3.8×3.1cm nodule in thyroidectomy specimen revealed irregular islands of small polygonal tumor cells with extracellular amyloid deposits (suggesting medullary thyroid carcinoma (MTC)), intermingled with thyroid follicular cells showing capsular and vascular invasion (follicular thyroid carcinoma (FTC)). Immunohistochemistry of the thyroid tumor was negative for calcitonin and for thyroglobulin. Post-operative serum calcitonin and stimulated thyroglobulin were respectively 97 pg/mL and 11.5 ng/mL. I131 whole body scan revealed intense uptake in region of the skull metastasis with small uptake in thyroid bed. She received 150 mCi of I131with resolution of pain, heaviness, throbbing, reduction in swelling size, and lack of disease progression. Conclusions. Skull metastasis was the presenting feature of MMFTC which improved with I131 therapy. Patients with lytic skull metastasis should be evaluated for occult thyroid malignancy.

Objective. Ectopic posterior pituitary gland (EPP) is usually characterized by an abnormal pituitary stalk and hypoplasia of the anterior hypophysis. The genetic mechanisms involved in the development of EPP remain uncertain. The aim of this study is to determine whether mutations in the three genes, PROP-1, LHX2, and POU1F1, are associated with the risk for and the characteristics of EPP. Methods. In the Endocrinology Outpatient Clinic of “Dr. Behcet Uz” Children’s Hospital, 27 patients with EPP were submitted to sequencing analyses of the PROP-1, LHX2, and POU1F1 genes. Results. Growth hormone, thyrotropin, corticotropin, gonadotropin, and vasopressin deficiency were observed in 22 (81.5%), 23 (85.2%), 17 (63%), 14 (51.9%), and two (7.4%) patients. Thirteen patients (48.1%) presented with hyperprolactinemia. Fourteen patients (51%) had a history of birth dystocia, and 12 cases (42.1%) had a history of breech presentation. Central nervous system abnormalities included five cases with corpus callosum agenesis, one case with schizencephaly, and one case with Chiari type 1 malformation. We identified a homozygous p.S109* mutation in exon 2 in one male patient with EPP and two different PROP1 gene polymorphisms (A142T or c.109+3 G>A polymorphism) in thirteen patients. Conclusions. Our results suggest that PROP1 gene abnormalities might explain the genetic mechanisms involved in the development of EPP.

Aim. Is to evaluate the influence of glucovance therapy on biomechanical properties of bone in streptozotocin - induced diabetes mellitus (DM) in rats. Materials and Methods. A total of 28 male Wistar- Albino rats (12-week-old; 210-300 g) were divided into 4 groups including control (C; no treatment; n=7), sham [Sh; distilled water (gavage, for 8 weeks); n=7], diabetes [DM; streptozotocin (45 mg/kg, single i.p injection); n=7] and diabetes+ Glucovance treatment [DM+G; streptozotocin (45 mg/kg, single i.p injection) + Glucovance (Glucovance, 500/5 mg/kg/day/rat, gavage, for 8 weeks); n=7] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated. BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). Results. A significant difference was not detected between groups with regard to cross-sectional area of diaphyseal femur (p>0.05). Maximum load, energy absorption capacity, ultimate stress, ultimate strain, toughness and displacement were shown to decrease and stiffness was shown to increase in DM rats (p<0.05). Ultimate stress and maximum load were significantly increased in DM+G groups compared to DM groups (p<0.05). Conclusion. Glucovance treatment seems to be effective in restoration of biomechanical deterioration of bone specific to STZ-induced DM.