ACTA ENDOCRINOLOGICA (BUC)

Obesity epidemic, developed in recent decades with global dissemination, brings scientific interest in causes and consequences for mankind. It is of interest whether obesity existed under different, non-obesogenic environments in ancient time. There is evidence for particular obesity existence in artefacts and pictures from caves, originated in ancient times. Human female figurines from Stone Age that represent obesity were discovered in different countries indicating that some form of obesity existed 30.000 years ago. It is supposed that most of these figures represent in some way “Mother of Goddess “ connected with fertility. Records from Ancient Egyptian and Biblical eras through Greco-Roman to Medieval times indicate that obesity was present throughout peoples of previous centuries in history, although peoples of previous centuries would probably have experienced overweight and obesity as exceptional rather than normal.

Background. 21-hydroxylase deficiency (21 OHD) is the most common form of congenital adrenal hyperplasia (CAH) and it has been widely described in the literature. Adrenocortical incidentalomas are unfrequently the presenting manifestations of CAH, especially in nonclassical form of 21 OHD (NC 21 OHD). Myelolipoma has previously been reported more frequently than other adrenal adenomas associated with CAH. Case. We report a 40-year old male case of NC 21 OHD with hypoadrenocorticism after unilateral adrenalectomy of the right side because of a large solid incidentaloma (5×4×4cm3) at the age of 31. This patient began to suffer from obvious symptoms of adrenal insufficiency after 9 years from the surgery. He was reviewed and a very low-density adrenal mass (4.1×3.9cm) was found on computed tomography of the abdomen. After he was admitted to our hospital, this patient was confirmed with NC 21 OHD and presented low level cortisol, striking elevated ACTH, aldosterone insufficiency, increased 17-hydroxyprogesterone, progesterone, decreasing androgens and azoospermatism. Conclusion. Patients with 21 OHD could be on risk not only for adrenal hyperplasia, but also to develop adrenal adenomas, particularly if the disease was poorly controlled.

Context. Osteonecrosis (ON) is bone death caused by inadequate blood supply and its optimal management remains uncertain. Objective. We describe the outcomes of BP (pamidronate) treatment in our patients. Design. Data regarding clinical, laboratory, magnetic resonance imaging (MRI) studies, and bone mineral density measurements (BMD) were recorded before and one year after treatment (reevaluation). The severity of the clinical picture was assessed using the criteria of the common terminology criteria for adverse events (CTCAE). Subjects and Methods. There were four female patients (patient 1, acute lymphoblastic leukemia; patient 2, immune thrombocytopenic purpura; patients 3 and 4, systemic lupus erythematosus) .All of them had been treated with high-dose prednisolone. Clinical picture of all patients were consistent with grade 3 according to CTCAE(: severe symptoms, limiting self-care ). Results. ON lesions were multifocal in the lower limbs in all of them and none of them had any fractures. All of them had been treated with high-dose glucocorticoid. Patients were treated with pamidronate (1 mg/kg/day, with maximum dose of 60 mg/day, for two days, quarterly). At the time of re-evaluation(one year after treatment), the lesions were stable on MRI, and their clinical condition was consistent with grade 1 according to CTCAE(asymptomatic). No side effects related to the use of bisphosphonates were observed except for increased BMD (SD score of 2.9) in one of the patients. Conclusions. Pamidronate may be an effective treatment for the improvement of functional impairment and pain among patients with severe osteonecrosis (ON) lesions.

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.