ACTA ENDOCRINOLOGICA (BUC)

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.

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.

Background. Multiple endocrine neoplasia type 2B (MEN 2B) is a rare hereditary syndrome caused mainly by Met918Thr germline RET mutation and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and typical phenotypic features. MEN 2B cases previously reported in the literature have variable clinical course. Objectives. We aimed to discuss the characteristics of four MEN 2B cases with unusual presentations,clinical course and review the recent clinical data on MEN2B Results. All patients had de novo M918T mutation and no family history. The mean age of patients was 38.2 years (27-56). Two patients had typical phenotypic features of MEN 2B; the other two patients had no striking phenotypic features. First detected MEN 2B component was MTC in two, intestinal ganglioneuromatosis in one, and PHEO in one of the cases. Bilateral PHEO was detected in all four cases. Conclusions. MEN 2B is a complex syndrome characterized by wide phenotypic variability and different clinical outcomes. To diagnose sporadic MEN 2B cases, genetic testing should be performed in all cases with suspicious clinical features. Although early diagnosis is the main factor that increases life expectancy, some MEN 2B patients with late diagnosis may exhibit a mild clinical course and better prognosis than expected, with effective treatment.

Introduction. Vitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function. Aim. To examine the relationship between Cdx- 2 polymorphism (rs17883968), the methylation status of VDR’s promoter and serum levels of 25-hydroxyvitamin D in male infertility. Patients and Methods. A total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm. Results. Vitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values. Conclusion. The results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.

Introduction. The pituitary gland serves as the center of the endocrine system. Stem cells are typically found in a specialized microenvironment of the tissue, called the niche, which regulates their maintenance, self-renewal, fate determination, and reaction to external influences. The aim of this study is to elucidate the role of stem cells in the initiation, invasion, and progression of pituitary adenomas. Materials and methods. All specimens were collected between January 2007 and April 2015. Radiological classification (invasiveness) for all cases was performed according to the Wilson-Hardy classification system. Immunohistochemical staining was performed to all specimens for CD133, Oct4, Sox2 and nestin. Results. The study included 48 patients. Of 48 patients, 17 (35.4%) were male and 31 (64.6%) were female. Mean age is 47.10±14.14 (17–86 yrs.). According to the Wilson-Hardy classification system, 27 (56.3%) were noninvasive adenomas. There was no statistical significance between the expression of pituitary stem cell markers (CD133, OCT4, SOX2, nestin) and invasiveness. Conclusion. All stem cell markers are stained extensively in pituitary adenomas, except for SOX2 which was stained weakly. However, there is no effect of stem cells on invasiveness of pituitary adenomas because we cannot find a difference of the staining level between invasive and non-invasive adenomas. Nestin was stained extensively in functional adenomas, especially for GH, PRL, and gonadotropin secreting adenomas. SOX2 was stained extensively for ACTH-secreting adenomas.

Context. The current therapeutical management of secondary hyperparathyroidism (S-HPTH) is difficult to obtain due to the lack of kidney donors. Surgical intervention on the pathologic parathyroid tissue has been suggested as a method to alleviate symptoms in patients with chronic kidney disease (CKD). Objective. The aim of our study was to evaluate the outcomes of parathyroid surgery in patients with S-HPTH and the advantages of intraoperative quick PTH (iqPTH) to improve surgical results. Material and methods. In a real-life study, we compared one group of S-HPTH with iqPTH performed after removing all suspected glands and before wound suture (Group 1) and one group in that iqPTH was not assessed (Group 2). When iqPTH dropped less than 50%, additional exploration followed. Results. Eight out of the 34 patients from Group 1, who underwent subtotal parathyroidectomy, showed elevated levels of serum PTH and calcium, which remained elevated during follow-up, thus, suggesting disease persistence. From the 21 patients in Group 2, none showed early postoperative disease persistence. Serum calcium, but not PTH was increased in one patient from the iqPTH group but normalized after one month. Overall, iqPTH allowed detection of a supplementary parathyroid gland in one case, thereby increasing early post-surgery remission to 100% in Group 2 compared to 76.47% in Group 1. Late postoperative remission of hyperparathyroidism with no further increase in the rate of hypoparathyroidism was obtained in Group 2. Conclusions. Assessment of intra-operative PTH levels proved to be a useful tool in augmenting the outcome of S-HPTH surgery. In patients which are eligible for renal transplantation who undergo a subtotal resection, iqPTH can enhance the post-operative quality of life by lowering disease recurrence rates until the kidney transplant procedure.

Introduction. The most frequent abdominal tumors in newborn girls are ovarian cysts, with an incidence of more than 30%. Smaller cysts (<4-5 cm) can regress spontaneously within the first 1-6 months after birth and usually require periodic follow-up, while larger cysts have a greater risk of torsion (50-70% of cases), rupture, hemorrhage or can determine compression on nearby organs. There still is no general consensus regarding the optimal management of ovarian cysts in newborns and infants Patients. Methods. Seven newborn female patients were referred to our hospital from maternity wards with a prenatal diagnosis of abdominal mass, over a period of 4 years (2011-2015). In all cases the postnatal ultrasound confirmed the presence of a cystic mass pertaining to the right or left ovary. We divided the patients into 2 groups taking into account the size of the cystic masses and their radiological characteristics: if the cyst was smaller than 4 cm, we followed the patient with periodic ultrasounds and in cases where the cyst was greater than 4 cm, surgical management was considered if the patient presented with complications. Of the 7 cases, 4 underwent surgery, while in 3 cases the decision was made to perform periodic followups. Conclusion. Ovarian cysts are frequently encountered in the neonatal period. No precise guide to the management of this pathology has been established. Close follow-up should be performed and surgical intervention should be done in order to avoid complications.

Background. Repeated implantation failure (RIF) is the most important problem in assisted reproductive technologies (ART). In the process of embryo implantation, accurate function of progesterone through progesterone receptors (PR) is crucial for establishment of a receptive endometrium. FKBP51 and FKBP52 are two co-chaperones acting as negative and positive regulators of PR function, respectively. Studies have shown that any deficiencies in expression of PR or its co-chaperones causes reproductive disorders. Materials and Methods. In this study we evaluated the PR protein expression by immunohistochemistry and expression of PR, FKBP51, FKBP52 genes by quantitative real-time PCR in endometrial tissue of normal and RIF women during the window of implantation. Results. Immunohistochemical studies showed that the PR protein expression in stromal cells is significantly higher in the endometrium of normal women than RIF women (P< 0.001). In addition, a significantly lower PR and FKBP52 gene expression was observed in endometrial tissue of RIF women compared to normal women (P< 0.001 and P< 0.001, respectively), whereas there was no significant difference in PR protein in epithelial cells (P= 0.3) and FKBP51 gene expression between the two groups (P= 0.6). Conclusion. The results indicate that altered expression of PR protein in stromal compartment and gene expression of PR and FKBP52 gene in endometrial tissue can be related to endometrial receptivity defects and occurrence of RIF.

Introduction. Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods. The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as “positive s-Tg”. Results. DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of “positive s-Tg” for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of “positive s-Tg” for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion. Method of TSH stimulation did not influence the reliability of DxWBS. The “positive s-Tg level” had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

Background. The aim of the present study was to measure the effects of raloxifene on bone metabolism and strength in orchiectomized male rats. Materials/Methods. Forty-three 4-month-old Wistar albino male rats were used and divided into 3 groups as orchiectomy (ORCX; n=23), sham (n=15), and control (n=5). Raloxifene (10 mg/kg/day) and methylcellulose (0.5 mL/day, as a vehicle treatment) treatments were initiated 2 months after ORCX for 2 months, then the rats were sacrificed. The left femur and fourth lumbar vertebrae (LV4) were measured to assess the effects of the orchiectomy and the raloxifene treatment and maintenance regimens. Bone strength was assessed using a compression test for the vertebrae and a three-point bending test for the femurs (N/mm). Results. Raloxifene increased femoral and vertebral bone strength in osteoporotic rats, but this increase was not statistically significant. Bone strength was found to be 267.44±18.03 in the femurs of the ORCXraloxifene group and 246.32±49.37 in the femurs of the ORCX-C group (p>0.05). Vertebral bone strength was 147.78±09.51 in the ORCX-raloxifene group and 114.61±05.93 in ORCX-C group (p=0.488). Raloxifene also increased the femoral and vertebral bone density compared with the control group, but the change was not significant. While raloxifene significantly decreased the serum osteocalcin levels (p=0.007), it did not decrease the carboxyterminal cross-linking telopeptide of bone collagen (CTX) levels significantly (p=0.066). Conclusions. Raloxifene caused a statistically significant decrease in serum osteocalcin levels and a non-significant reduction in NTX levels in orchiectomized rats.