Vanishing testes syndrome is often referred to as testicular regression syndrome (TRS) in the recent medical literature. The most characteristic histological findings are presence of a fibrovascular nodule with associated hemosiderin-laden macrophages and dystrophic calcification. Residual testicular tubules are found in less than 10% of cases, with prevalence being unrelated to age at surgery. Presence of seminiferous tubules and viable germ cells in testicular remnant tissue has been reported in some series. TRS theoretically carries a potential for malignant degeneration in the long term and therefore removal of any remnant is a common practice to eliminate this risk. However, no case series has reported germinal dysplasia or intratubular germ cell neoplasia in any of the specimens taken from these patients.

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH.
Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH.
Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency.
Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.

Objective: Insulin pumps have been well established for insulin delivery. However, questions about long-term efficacy of insulin pump therapy still remain. We evaluated the long-term efficacy of continuous insulin infusion pump therapy (CSII) in pediatric patients with type 1 diabetes mellitus (T1DM).
Methods: This was a retrospective observational study which included 131 patients with T1DM who transitioned to an insulin pump from multiple daily insulin (MDI) injections between 1999 and 2009 and were followed by one endocrinologist. Data were collected from 6 months prior to switching to CSII to 30 months after initiation of CSII and included glycated hemoglobin (HbA1c) and insulin requirement. Of the 131 patients, 45 had complete data consisting of a visit and HbA1c every 6 months for 30 months after transition to CSII and were included for analysis.
Results: Mean HbA1c prior to starting the CSII was 8.0 +0.9 %, 7.7 +1.0 % at 6 months and 7.8+1.2 % at 1 yr post initiation of CSII. However, at 30 months, HbA1c increased to 8.0+1.3%. A trend in transient improvement in HbA1c was limited only to those patients >11 yr of age and those requiring >0.75 u/kg/day of insulin at transition and was not seen in those <11 yr of age or those requiring <0.75 u/kg/day and did not persist beyond 1 year.
Conclusions: There was no long-term significant difference in glycemic control in patients with CSII as compared to MDI.

Objective: Intrauterine growth references are primarily useful indicators in the assessment of the general health status of newborn infants. Although Lubchenco’s references are still used in many neonatal care units, we believe that there is a need for up-to-date intrauterine growth references specific for different populations. To develop gestational age-and gender-specific national references for birth weight, birth length and head circumference.
Met­hods: Data were collected from neonatal records of perinatology services of eleven hospitals from January to December 2009. The anthropometry of a total of 4750 singleton live births born between 28 and 41 weeks of gestation were recorded. Means and standard deviations were calculated, and percentiles for each gender and gestational week were produced using the LMS program. The results were compared with US infants and also with local data.
Re­sults: Gestational age- and gender-specific 3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th and 97th percentile values were produced. Comparison of the 10th, 50th and 90th percentile values showed that the boys were heavier and longer than the girls. Head circumference values were also higher in the boys. Proportions of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants in the sample were 10.1%, 79.1% and 10.8%, respectively.
Conc­lu­si­on: These gender- and gestational age-specific references will be of use in clinical practice and also for research purposes until more comprehensive, reliable and accessible national data pertaining to the intrauterine growth of Turkish infants are produced.

Objective: Premature thelarche (PT) refers to isolated onset of thelarche in girls younger than 8 years of age. Most cases have an onset under 2 years of age. We aimed to establish whether the onset of thelarche under 2 years of age certifies a transient clinical course, as suggested by several authors.
Methods: Sixty-seven girls with an onset of PT under 2 years of age were classified as having early puberty (EP) or classical PT after one year of follow-up. Progression of pubertal findings or absolute growth velocity (GV) standard deviation score (SDS) above 1 SDS constituted the criteria for a diagnosis of EP.
Results: Twenty (29.1%) girls were classified as having EP and 47 (70.1%) girls as having classical PT. Basal serum luteinizing hormone (LH; ICMA) values at a cut-off level of 0.3 IU/L were found to be a significant risk factor for having an atypical course [OR=7.8; CI (95%): 2.04– 30.4, p=0.003].
Conclusions: Onset of thelarche under 2 years of age does not assure a transient course in a remarkable proportion of girls with PT. An absolute GV value of >1 SDS or a basal LH level ?0.3 IU/L are suggested as indicators for close follow-up.

Objective: We determined the profile of coagulation/fibrinolytic and vascular endothelial cell function parameters including plasminogen activator inhibitor (PAI) and thrombin-activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), and tissue plasminogen activator (tPA) levels in children with hypothyroidism.
Methods: Forty children with hypothyroidism aged 0-16 months who presented for the first time to our hospital and 29 age-and sex-matched healthy controls were enrolled in the study. All coagulation tests were performed with ELISA method. One year after Na-L-thyroxine treatment, the study parameters were re-evaluated in 25 euthyroid children out of the 40 patients diagnosed with hypothyroidism.
Results: Although no significant effect was detected regarding PAI antigen (Ag) and tPA Ag, the levels of TAFI, TM, and TFPI were consistent with subclinical hypercoagulability and hypofibrinolysis. There was a significant increase in TAFI Ag levels and a significant decrease in TFPI Ag and TM Ag levels in hypothyroid patients compared to healthy controls. As a result of correlation tests, the largest impact of hypothyroidism on coagulation system was on TFPI. In accordance with these findings, TAFI Ag levels decreased and TFPI Ag and TM Ag levels increased with hormonal replacement therapy.
Conclusions: Increased TAFI and decreased TFPI and TM in patients with hypothyroidism may indicate a potential hypercoagulable and hypofibrinolytic state as well as possible endothelial dysfunction, which may increase the risk of atherosclerotic and atherothrombotic complications. Thyroid hormone levels should also be checked in patients with a predisposition to coagulation, and thyroid replacement therapy should be initiated.

Congenital adrenal hyperplasia (CAH) is a group of disorders affecting the adrenal steroid synthesis. The most common form, 21-hydroxylase deficiency (21-OHD), leads to decreased production of cortisol and aldosterone with increased androgen secretion. In classic CAH, glucocorticoid treatment can be life-saving and serves to bring the symptoms under control. However, the treatment challenge is to effectively control the excess androgen effect by using the lowest possible glucocorticoid dose. Previous studies suggested a relationship between ovarian cyst formation and adrenal androgen excess, but neonatal large ovarian cysts have been very rarely reported in newborns with CAH. Here, we present the unique case of a neonate with classical 21-OHD who underwent surgery for a giant (10x8x7 cm) unilateral solitary ovarian follicular cyst on the 2nd postnatal day. Hormonal evaluation of the patient revealed high-dose hook effect for serum testosterone levels for the first time by a two-site immunoradiometric assay. Possible mechanisms by which androgen excess may cause ovarian cyst formation are discussed.

Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by a temporary isolated elevation of serum alkaline phosphatase activity (ALP), predominantly its bone or liver isoform, in either sick or healthy children under 5 years of age. Return to normal ALP levels usually occurs within four months. Spontaneous rise of ALP might concern the physician, especially when treating seriously ill children. However, THI is considered a benign biochemical disorder with no clinical consequences. Some existing reports support the hypothesis that THI is a result of increased bone turnover. We present evidence of normal bone turnover in two children with THI. In a one-year-old girl and a boy of the same age, high ALP levels (31 and 109 µkat/L, respectively) were accidentally detected. The children had no signs of metabolic bone disease or of liver disease. The high ALP levels returned to normal in two months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were neither elevated, nor did these markers follow the ALP dynamics, thus reflecting normal bone turnover in THI. Children with THI should be spared from extensive investigations and unnecessary vitamin D treatment.

Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.Key words: Cushing’s syndrome, eye drops, dexamethasone, epistaxis

Fibrous dysplasia (FD) is categorized as either monostotic or polyostotic and may occur as a component of McCune-Albright syndrome (MAS). Imaging findings can mimic neoplastic diseases. We present a case of MAS initially suspected to have neoplastic disease. A 9-year-old girl was admitted to pediatric emergency with ataxia. Upon hospitalization, an extradural mass was seen on cranial magnetic resonance imaging (MRI) and the bone survey showed lytic lesions in the long bones. The patient was referred to the pediatric oncology department with a presumptive diagnosis of Langerhans cell histiocytosis or metastatic tumor. Further investigations demonstrated that the patient had MAS and coexisting postinfectious cerebellitis. The findings in this patient demonstrate that the radiographic findings and the clinical presentation of FD and MAS may be similar to those of malignant diseases.

Bilateral macronodular adrenocortical disease as a part of McCune Albright Syndrome (MAS) is the most common cause of endogenous Cushing’s syndrome (CS) in infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We report the case of a girl with CS who presented at age 4 months with obesity and growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone levels were 49.3 µg/dL and <1 pg/mL, respectively with non-suppressed serum cortisol (41 µg/dL) on high-dose dexamethasone suppression test. Abdominal computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal mass with distinct borders. Laparotomy following pre-operative stabilization with ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with intact capsule and weighing 115 grams. Histopathology showed small round adrenal tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The cells were separated by fibrous septae without any evidence of vascular or capsular invasion– findings consistent with adrenal adenoma. On the 8[sup]th[/sup] post-operative day, after withholding hydrocortisone supplementation, the 8 am cortisol level was <1 µg/dL, suggestive of biochemical remission of CS. The patient improved clinically with a 7.5 kg weight loss over the next 3.5 months. This is perhaps the youngest ever reported infant with CS due to adrenal adenoma. Lack of clinical and biochemical evidence of hyperandrogenism as well as the benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are some of the unique features of our patient.