ACTA ENDOCRINOLOGICA (BUC)

Previous studies have correlated the expression of PAR proteins with breast cancer invasiveness. The scope of this study was to evaluate the expression of PAR-1 in human breast cancer specimens and investigate possible correlations with tumor size, grade and lymph node status, as well as covariations with estrogen and progesterone receptors, c-erbB-2 protein and lysosomal protease Cathepsin D. Formalin-fixed paraffin-embedded sections of 75 mastectomy specimens deriving from patients with primary breast carcinomas were implemented. Expression of PAR-1 was detected employing immunohistochemical assays utilizing a goat polyclonal PAR-1 antibody. The granular pattern of cytoplasmic immunoreaction was considered indicative for the protein?s expression. Statistical assessment was performed using SPSS 13.0 statistical package, Pearson?s correlation, &#967;2 and Fisher?s exact test. Expression of PAR-1 protein had a statistically significant correlation (p<0.001) with tumor grade, while in invasive tumors a similar relationship (p<0.001) was documented between PAR-1 expression and presence of positive axillary lymph nodes. However, PAR-1 expression did not exhibit a significant correlation with tumor size or with the expression of ER, PR, c-erbB-2, or Cathepsin D molecules. PAR-1 possesses a role in tumor invasion and contributes to the metastatic potential of certain types of breast carcinomas. The disassociation between expression of PAR-1 and that of the ER, PR, c-erbB-2, or Cathepsin D might imply participation in alternative pathways of malignant transformation and tumor progression.

Obesity is an important risk factor for obstructive sleep apnea syndrome (OSAS). One would expect that effective treatment by continuous positive airway pressure (CPAP) would lead to weight loss due to decreased daytime sleepiness and improved physical activity. However, many papers suggest that shortage of sleep is a risk factor for obesity.\r\nAim. To assess the weight change after 1 year of effective CPAP treatment for OSAS.\r\nMethods. In this retrospective study OSAS was diagnosed in 109 subjects (50 women, 59 men; age 58?13 years). Eighty subjects used CPAP > 5 h per night in > 70% of nights and were considered treatment subjects. Twenty-nine subjects used CPAP < 5 hours per night or < 70% of nights and were considered control subjects. Patients were diagnosed using complete full-night or split-night polysomnography (70 and 39 patients respectively). Mean effective titrated CPAP pressure was 9.8 cm H2O. CPAP compliance was assessed through downloadable data from CPAP machine (19 patients) or clinical exam (90 patients). Body mass\r\nindex (BMI) was determined at the time of diagnosis and 1 year later (range 10-15 months).\r\nResults. Treatment and control subjects were similar regarding age, sex, BMI and apnea hypopnea index (AHI) at baseline. Weight increased in CPAP users (n=80) by 1.3 kg (CI 95% 0.4, 2.25; p<0.01) but not in control subjects (n=29) (mean difference in controls 0.37 kg, CI 95% -1.8, 2.5; p>0.05). BMI significantly increased in men (p<0.005), in subjects with severe OSAS (AHI>30 events/hour) (p<0.009) and in those younger than 65 years (p<0.01). Sleep architecture was investigated by full-night polysomnography in 50 regular CPAP users and 20 controls. In the subgroup of 18 treatment patients with lack of slow wave sleep (SWS) the increase in body weight was 2.6 kg (CI 95% 0.4, 4.9, p=0.02), more than double as compared with patients with SWS at baseline (n=32).\r\nConclusion. Effective CPAP treatment leads to a modest, but significant weight gain after 1 year in OSAS patients, especially in men with severe sleep apnea. This seems to be in relation to lack of SWS at baseline. An independent medical intervention for weight loss should be associated with CPAP treatment in sleep apnea syndrome.

As the medical utility of injectable therapeutic peptides is expanding, so is the challenge of developing technologies that allow the administration of such molecules via alternative routes, considering that chronic patients requiring treatment with parenteral formulations are less adherent and compliant to the therapeutic regimens. Hence, substantial efforts have been made to develop technologies that allow the oral formulation of peptides. Due to their importance in the field of pharmaceutical technology, we describe the latest advancements made in the development of oral salmon calcitonin and oral semaglutide, in co-formulation with absorption enhancers such as 8-[(5-chloro-2-hydroxybenzoyl) amino] octanoic acid (or 5-CNAC) and N-[8-(2-hydroxybenzoyl) amino] caprylate (or SNAC). Oral semaglutide is considered to be a landmark for oral peptide delivery technology, as it is one of the very few successful examples of peptides that can be administered orally. Unlike semaglutide, oral calcitonin is still not approved by the regulatory authorities because it failed to demonstrate the anticipated effects in phase III clinical trials conducted so far. However, the efforts for obtaining an oral form of calcitonin have significantly contributed to the development of technologies that facilitate the absorption of peptide-structure macromolecules.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Purpose. Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. Methods. The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. Results. Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). Conclusions. The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

Context. Diabetes insipidus (DI) is rare in the neonatal period but of great importance due to increased renal risk and mental retardation despite treatment. Objective. This report describes the case of a patient with congenital nephrogenic diabetes insipidus (NDI). Detection of this pathology during the neonatal period, especially in premature newborns, is difficult because of the electrolyte variations that occur as a result of the immature kidney function. Subjects and methods. The subject was a preterm infant with very low birth weight (VLBW) and persistent hypernatremic hyperosmolarity that developed polyuria and polydipsia in the first weeks of life. Results. Taking into account blood and urine laboratory tests, vasopressin levels, as well as family history, the infant was diagnosed with congenital NDI. Early treatment allowed a good development, proving that the prevention of long-term complications is possible through multidisciplinary care and frequent monitoring. The particularity of this case was the presence of persistently elevated presepsin levels. This association prompted the investigation into underlying renal hypernatremia. Conclusions. NDI is a rare condition and the onset in the neonatal period is a sign of severity and hereditary causality. Early diagnosis, symptomatic treatment and multidisciplinary monitoring may decrease the risk of longterm complications.

Morris Syndrome is a pathological condition which needs a special approach regarding both diagnosis and treatment\r\nbecause of its rarity. While the diagnosis is based on karyotype test, the treatment should follow the idea of harmless and cosmetic benefits as well as complete gonads removal. This paper is presenting the usefulness and advantages of minimally invasive surgery as a feasible treatment for such a disease. A retrospective study was performed for two patients with Morris Syndrome, admitted to\r\nthe ?CI Parhon? National Institute of Endocrinology, Bucharest, Romania, followed-up for 4 - 16 years, and operated to the Department of Surgery, Emergency\r\nHospital, Bucharest, Romania. Patients with primary amenorrhea have been clinically observed and three patients\r\nwith 46, XY karyotype have been identified as Morris Syndrome cases needing surgical removal of the intraperitoneal gonads because of the risk of malignant transformation. A minimally invasive surgical technique has\r\nbeen chosen for proper treatment: the anterior transperitoneal laparoscopic approach. The surgery was adapted to every case, in according with preoperative imagistic diagnosis of the intraperitoneal testes\r\n(localization, dimensions, adjacent organs involvement, surgical access). No postoperative complications were noticed and specimens' pathology confirmed the final\r\ndiagnosis. Cosmetic benefits were achieved for every young patient as well as rapid postoperative recovery (discharge after 48 hours). The authors concluded that Morris Syndrome patients could benefit from the laparoscopic surgery which is a feasible, safe and proper treatment for such cases.

experience regarding the first 24 patients diagnosed with refractory secondary and/ or tertiary hyperparathyroidism (HPT) who underwent subtotal parathyroidectomy (sPTx) in our clinic between 2010 and 2012. Methods. Data were retrospectively retrieved from a prospectively maintained database. We included patients diagnosed with refractory secondary and/or tertiary HPT who underwent sPTx; we excluded patients who underwent total parathyroidectomy (tPTx) and patients followed-up for less than six months. Results. We analyzed 24 patients,16 women (66.7%) and 8 men (33.3%) who were evaluated in a prospective manner in a short (1-6 months)/ medium (6-18 months) term follow up. Preoperative intact parathyroid hormone level (iPTH) was characterized by a median of 2131 pg/ mL (range: 1141-10000); in the first month after surgery the median iPTH level was 28 pg/mL (range: 3-1263). We found a statistically significant difference (p<0.01: Student test) in calcium level between preoperative values and values in the first month after surgery. Postoperative serum phosphorus (nv: 2.7-4.5 mg/dL) normalized in 19 patients (79.16%) and serum alkaline phosphatase values decreased significantly in the interval 2-6 months postoperative versus preoperative levels (p-0.002). We tried to establish a correlation between preoperative alkaline phosphatase (Alk Phos) and postoperative calcium level in the first month postoperatively. The overall clinical response to sPtx was good and we did not encounter postoperative mortality in our series. Conclusion. We believe that subtotal parathyroidectomy is feasible, safe and effective for patients with refractory secondary and tertiary hyperparathyroidism.

Introduction. Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation. A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions. The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.