ACTA ENDOCRINOLOGICA (BUC)

Sotos syndrome is characterized by overgrowth, macrocephaly, distinctive facial features, and learning disabilities and is associated with alterations in the nuclear receptor binding SET domain protein 1 (NSD1) gene. Due to the advanced bone age, the eventual adult height is usually at the upper limit of normal. In this case report, a 6-year and 10-month old boy who presented with Sotos syndrome was described. He also had increased testicular volumes with advanced bone age. The stimulated levels of gonadotropins revealed central precocious puberty and brain magnetic resonance imaging (MRI) showed a pineal cyst. A heterozygous duplication variant [NM_022455.4:c.4560dup; p.(His1521Thrfs*9)] in the NSD1 was identified. Triptorelin acetate treatment was started. The aim was to report the novel duplication variant in the NSD-1 in a patient with Sotos syndrome accompanied by a pineal cyst and central precocious puberty, and also to discuss the rationale for treating precocious puberty.

Objectives. This work aimed to study the influences of carbonated beverages (CBs) on the testis growth and the expression levels of androgen receptor (AR) of mice. Methods. Two experimental groups of 30 mice each PEP-1 and PEP-2 drank 50% and 100% Pepsi-Cola, respectively for 15 days. Other 2 experimental groups of 30 mice each COC-1 and COC-2 drank 50% and 100% Coca- Cola, respectively for 15 days. The control group (CG) of 30 mice drank water. Bilateral testes were harvested aseptically on days 0, 5, 7, 10, 13 and 15. Real-time PCR and Western blot were implemented to detect levels of androgen receptor (AR) mRNA and protein in testis tissues. Results. Testes masses of PEP-2, COC-1 and COC-2 were greater than those of PEP-1 and CG (P < 0.05). On day 15, testis longitudinal diameter (TLD) of CBs-treated mice was increased as compared to CG. TLD, testes transverse diameters (TTD) and AR proteins levels of PEP-2 and COC-2 were increased in comparison with CG (P<0.05). Serum testosterone concentrations of PEP-2 were higher than that of COC-1 and CG (P < 0.05). Levels of AR mRNAs of four CBs-treated mice were increased by 60.18%, 67.26%, 65.93% and 78.76%. Conclusions. A high concentration of Coca-Cola and Pepsi-Cola could raise TLD and TDD, enhance testosterone secretion, and increase serum EGF concentrations.

Context. The detrimental effects of hyperinsulinemia on human ovaries during follicular development process have been shown in various studies, particularly in women with polycystic ovary syndrome. To our knowledge there is no study regarding the effect of insulin resistance (IR) on the intrauterine insemination (IUI) success in women with unexplained infertility (UEI). Objective. To evaluate the effects of IR on the occurrence of pregnancy among infertile women undergoing ovulation induction (OI) with IUI for UEI. Design. Prospective cohort study. Subjects and Methods. 173 patients who met the criteria for UEI and under the age of 35 were included in this study. All women underwent OI with IUI and, subsequently, they were divided into two groups based on the presence of pregnancy. Data reviewed for analysis were demographic, clinical, and laboratory features. Results. There were 37 (21.4%) cycles with pregnancy and 136 (78.6%) cycles without pregnancy. Median infertility duration was significantly lower in the pregnant group when compared with non-pregnants (p=0.018). The mean number of previous cycles per patient was also lower in this group (p=0.028). No significant differences were found between the groups in terms of other variables. Levels of insulin, fasting glucose and HOMA-IR were also similar between the two groups. Conclusions. IR calculated by using HOMA-IR index has no positive or negative effect on the occurrence of pregnancy in women undergoing OI therapy with IUI for UEI.

Objective. Thyroid fine-needle aspiration (FNA) and cytology is a reliable diagnostic method used in the assessment of malignancy when evaluating thyroid nodules, in conjunction with clinical and ultrasonographic findings. The aim of this study is to compare clinical, ultrasonographic, cytological and histopathological findings in children who underwent thyroid FNA. Methods. Subjects comprised 80 patients (52 female) aged 13.7±2.8 years at the time of FNA who where evaluated for thyroid nodules. Clinical, ultrasonographic and cytological findings of patients were evaluated retrospectively. Results. Autoimmune thyroiditis was present in 30% and history of radiotherapy to the head or neck in 10%. The cytological diagnosis of patients included: inadequate or hemorrhagic sample in 10%; benign in 42.5%; atypia or follicular lesion of undetermined significance (AUS/FLUS) in 15%; suspicion of follicular neoplasia (SFN) in 7.5%; suspicion of malignancy (SM) in 8.8%; and malignant in 16.3%. Thirty-seven patients underwent thyroidectomy. Malignancy rates for histopathologic follow-up were 75%, 85.7% and 100% for SFN, SM and malignant categories, respectively. Only one benign and two AUS/FLUS FNAs were found to be malignant on histopathological examination. Among patients who had received radioiodinetherapy, 87.5% had malignancy. In this study, the sensitivity of FNA was 96%, specificity 50%, positive predictive value 90.9%, negative predictive value 75%, and diagnostic value of FNA was 89.2%. Conclusion. Thyroid FNA results were highly compatible with histopathological examination. Sensitivity, positive predictive value and diagnostic value of FNA were high.

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.

Background. To evaluate iodine status and the prevalence of thyroid disorders in different populations of Zhoushan Island, China.\r\nMethods. A total of 3284 inhabitants of Zhoushan Island were surveyed, including 1389 urban residents, 737 salt workers, 502 peasants, 362 fishermen, and 294 monks from Mount Putuo. All subjects, except for salt workers, consumed iodized salt. A thyroid ultrasound was performed and serum levels of\r\nthyroid hormones and thyroid peroxidase antibody were measured.\r\nResults. The median urinary iodine concentration was significantly higher in subjects who consumed iodized salt than in those who consumed non-iodized salt. No significant differences were noted in the prevalence of thyroid ultrasound abnormalities and functional thyroid disorders between subjects who consumed non-iodized and iodized salt except between salt workers and monks from Mount Putuo. The prevalence of thyroid ultrasound abnormalities differed\r\nsignificantly between males and females and was positively correlated with advanced age (r=0.212, P<0.001).\r\nConclusions. Iodine intake is considered adequate, more than adequate, or excessive amongst the study populations. The\r\nprevalence of both thyroid ultrasound abnormalities and functional thyroid disorders is extremely high in Zhoushan Island. Advanced age and female gender are significant predictors of thyroid ultrasound abnormalities.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

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).

Context. Red cell distribution width (RDW) has been associated with type 2 diabetes (T2DM), however data in relation to diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar non-ketotic acidosis (HONK) remains unclear. Objective. The aim of this study was to evaluate the association between RDW, MCV, and RDW/MVC values and acute complications in T2DM. Patients and Methods. RDW was measured in 90 T2DM patients (30 DKA, 30 HONK and 30 T2DM without acute complications). Clinical variables were analyzed by One –Way ANOVA, Kruskal-Wallis and Pearson analysis with SPSS software. Diagnostic screening tests and ROC curve analysis determined the cut-off point of MCV,RDW and RDW/MCV values. Results. DKA patients had higher levels of plasma glucose (524.20±201.43mg/dL, p<0.001), HbA1c (10.73±2.29%, p<0.001), osmotic pressure (310.32 mosm/L, p<0.001), RDW (14.61±1.75g/L, p<0.01), and the RDW/MCV ratio (0.17±0.04%, p<0.01), compared to HONK patients. RDW/MCV cut-off value was 0.15 with 90% sensitivity 50% specifity these values for only MCV were 76.67%-70%, for only RDW were 76.67%- 63.33% respectively. The area under curve values for the ability to reflect DKA for RDW and the RDW/MCV ratio were 0.708 and 0.766, respectively (p<0.001). Conclusions. RDW and RDW/MCV ratio were found associated with DKA and valuable in predicting DKA. However these parameters were not valuable in predicting HONK.

Context. Minimally invasive parathyroidectomy (MIP) procedure has become a widely accepted alternative to the standard four-gland exploration nowadays. Objective. The aim of this study was to evaluate patients with primary hyperparathyroidism (PHPT), who had been treated with thyroidectomy and bilateral neck exploration (BNE), rather than MIP alone, due to coexisting thyroid nodules and to determine the benefits of simultaneous thyroidectomy and the possible negative outcomes of not performing this additional procedure. Design. There were 185 patients who were operated for PHPT at our clinic from January 2014 to November 2016. Subjects and Methods. 50 patients meet inclusion criteria: have thyroidectomy at the same time of parathyroid surgery, have concordant findings of parathyroid adenoma localization at preoperative MIBI-SPECT and the cervical US and have not had malignancy on fine needle aspiration biopsy (FNAB). Results. The mean age of the patients was 55.3±10.4, and female to male ratio was 7:1. All patients had parathyroidectomy with BNE and thyroidectomy: 11 (22%) patients had micropapillary thyroid cancer (mPTC), 2 (4%) had papillary thyroid cancer (PTC). Conclusion. The results were inconclusive in clearly demonstrating which patients presenting with coexisted thyroid nodules should undergo thyroidectomy, rather than MIP, and which should be monitored for thyroid nodules after MIP. However, we consider that in cases who are not clearly indicated for thyroidectomy, MIP followed by monitoring of thyroid nodules can be the treatment approach.