Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics.

AIMS/HYPOTHESIS: Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing. METHODS: We conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity). RESULTS: Thirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p < 0.0001). All conventional criteria for identifying monogenic diabetes (parental diabetes, not requiring insulin treatment, HbA1c ≤ 58 mmol/mol [≤7.5%] and a composite clinical probability of MODY >10%) assisted the identification of the dominant (all p ≤ 0.0003) but not recessive cases (all p ≥ 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases. CONCLUSIONS/INTERPRETATION: Recessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.

An endoscopic endonasal approach to craniopharyngioma via the infrachiasmatic corridor: a single center experience of 84 patients.

OBJECT: The infrachiasmatic corridor is the most important surgical access route for craniopharyngiomas and was identified and used in clinical series. The aims of this study were to describe the characteristics that assist dissection and resection rates in endoscopic surgery of solid, cystic, and recurrent cases and their importance in the infrachiasmatic corridor in endoscopic surgery. METHODS: One hundred operations on 84 patients with pathologically identified craniopharyngioma were included in the study. The MRI findings were evaluated, and the location of the lesions was classified as (1) infrasellar; (2) sellar; or (3) suprasellar. In the sagittal plane, we measured the longest diameter of cystic and solid components and the height of chiasm-sella. Images were assessed for the extent of resection and were classified as gross total resection. This was deemed as the absence of residual tumor and subtotal resection, which had residual tumor. RESULTS: The infrasellar location was reported in 7/84 (8.3%) patients, the sellar location in 8/84 (9.5%), and the suprasellar location in 69/84 (82.1%) patients. The narrow and high chiasm-sella were observed in 28/69 (40.5%) and 41/69 patients (59.4%), respectively. The mean distance of the chiasm-sella was 9.46± 3.76. Gross total tumor resection was achieved in 60/84 (71.4%) and subtotal tumor resection was performed in 24/84 (28.6%) patients. The results revealed that suprasellar location (OR: 0.068; p = 0.017) and recurrent cases (OR: 0.011; p<0.001) were negative predictive factors on GTR. Increasing the experience (OR: 42,504; p = 0.001) was a positive predictor factor for GTR. CONCLUSION: An EETS approach that uses the infrachiasmatic corridor is required for skull base lesions extending into the suprasellar area. The infrachiasmatic corridor can determine the limitations of endoscopic craniopharyngioma surgery. This corridor is a surgical safety zone for inferior approaches.

Measured parental height in Turner syndrome-a valuable but underused diagnostic tool.

Early diagnosis of Turner syndrome (TS) is necessary to facilitate appropriate management, including growth promotion. Not all girls with TS have overt short stature, and comparison with parental height (Ht) is needed for appropriate evaluation. We examined both the prevalence and diagnostic sensitivity of measured parental Ht in a dedicated TS clinic between 1989 and 2013. Lower end of parental target range (LTR) was calculated as mid-parental Ht (correction factor 12.5 cm minus 8.5 cm) and converted to standard deviation scores (SDS) using UK 1990 data, then compared with patient Ht SDS at first accurate measurement aged > 1 year. Information was available in 172 girls of whom 142 (82.6%) were short at first measurement. However, both parents had been measured in only 94 girls (54.6%). In 92 of these girls age at measurement was 6.93 ± 3.9 years, Ht SDS vs LTR SDS - 2.63 ± 0.94 vs - 1.77 ± 0.81 (p < 0.001), Ht SDS < LTR in 78/92 (85%). Eleven of the remaining 14 girls were < 5 years, while karyotype was 45,X/46,XX in 2 and 45,X/47,XXX in 3. CONCLUSION: This study confirms the sensitivity of evaluating height status against parental height but shows that the latter is not being consistently measured. What is Known: • Girls with Turner syndrome are short in relation to parental heights, with untreated final height approximately 20 cm below female population mean. • Measured parental height is more accurate than reported height. What is New: • In a dedicated Turner clinic, there was 85% sensitivity when comparing patient height standard deviation score at first accurate measurement beyond 1 year of age with the lower end of the parental target range standard deviation. • However, measured height in both parents had been recorded in only 54.6% of the Turner girls attending the clinic. This indicates the need to improve the quality of growth assessment in tertiary care.

Ovotesticular disorder of sexual development and a rare 46,XX/47,XXY karyotype.

Ovotesticular disorder of sexual development (DSD) is characterized by the presence of both ovarian and testicular tissues in the same individual. The most common karyotype is 46,XX. Here, we report the case of a boy with a 46,XX/47,XXY karyotype diagnosed as ovotesticular DSD by gonadal biopsy. A 5-month-old boy presented with hypospadias, unilateral cryptorchidism, and a micropenis. Pelvic magnetic resonance imaging revealed a suspicious gonad tissue that is solid in structure in the right scrotum and a suspicious gonad that is cystic in structure in the left inguinal canal. He underwent a diagnostic laparoscopy. Cytogenetic analysis of peripheral blood revealed a 46,XX/47,XXY karyotype. Histopathologic examination of the left gonad showed ovarian tissue containing primordial follicles with ipsilateral undifferentiated tuba uterina. The right gonad showed immature testis tissue. He underwent left gonadectomy and hypospadias repair, and was raised as a male. Through this rare case, we highlight the importance of histological and cytogenetic investigation in DSD.

A case of adrenal insufficiency during multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a disease related to coronavirus disease 2019 (COVID-19). Although the effects of COVID-19 on many systems are known, there is limited data regarding its effects on the endocrine system. This study aimed to discuss the effect of COVID-19 on cortisol dynamics in a patient who developed adrenal insufficiency after COVID-19 infection. An 11-yr-old boy with polymerase chain reaction-proven COVID-19 one month previously was referred with a five-day history of fever, vomiting, and rash. On admission, he had hypotension, tachycardia, and severe hyponatremia. After the evaluation, he was diagnosed with MIS-C and glucocorticoid therapy was initiated. During follow-up, the patient experienced adrenal insufficiency, and hydrocortisone treatment was initiated at a crisis dose. Four months later, the adrenal axis function had not recovered. The adrenocortical response in COVID-19 patients may be significantly impaired, resulting in increased mortality or morbidity.

Nutritional status of students in Kocaeli, Turkey: a population-based study.

BACKGROUND: The aim of this study was to determine the nutritional status of students in Kocaeli, Turkey. METHODS: This cross-sectional study was carried out among the students of secondary schools in Kocaeli. Of the students, 2491 subjects were selected using multi-stage stratified sampling. RESULTS: Of the students, 51.1% were male and 48.9% were female. Mean age was 14.35±1.87 (range 10.1-19.8) in overall subjects, 14.38±1.87 in boys and 14.31±1.85 in girls. The prevalence of obesity and of overweight was estimated as 7.3% and 11.8%, respectively. Also, 3.1% of the subjects were underweight and 2.9% were thin. The rate of obesity was 1.5 times higher in girls and that of overweight was 1.2 times higher in girls. Similarly, students aged 15 years old and younger were 1.2 times more obese and 1.7 times more overweight than older students. Students living in urban areas had a higher prevalence of obesity and of overweight. CONCLUSION: Nutritional problems in students should be dealt with by some regulations in schools; for example, providing healthy food in schools or food aid, particularly in poor regions.

Spondyloenchondrodysplasia: a rare cause of short stature.

Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement.

Hypogonadism in the Prader-Willi syndrome from birth to adulthood: a 28-year experience in a single centre.

BACKGROUND: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. OBJECTIVE: To evaluate gonadal status and outcome in patients attending a Scottish PWS clinic from 1991-2019. METHODS: In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. RESULTS: Females: Of 22 patients aged >11, 9 had reached B4-5, while 5 were still at B2-3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8-21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum estradiol 129 (70 - 520) pmol/L. Only 5 patients received oestrogen replacement. Males: Fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged >11, 14 (9 with failed/untreated bilateral cryptorchidism) failed to progress beyond G1, 15 arrested at G2-3 (testes 3-10 ml), and 8 reached G4-5. Gonadotrophins were unremarkable except in boys at G2-5 in whom FSH was elevated: 12.3/27.3 vs 3.25/6.26 U/L in controls (p<0.001). In males aged >13, testosterone was 3.1 (0.5-8.4) nmol/L. Androgen therapy, given from 13.5-29.2 years, was stopped in 4/24 patients owing to behavioural problems. CONCLUSION: Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Objective: Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes. Methods: Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. Cases with positive initial screening underwent second tier testing by steroid profiling in DBS using liquid chromatographyt-andem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.7 (increased from ≥0.5 in the earlier pilot study) were referred to pediatric endocrinology clinics for diagnostic assessment. Results: In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 with salt-wasting and four with simple virilising CAH), and four cases were identified with 11ß-OHD CAH. No case of salt-wasting CAH was missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11ß-OHD in the screened population was 1:15,067 and 1:60,270, respectively. Conclusion: Turkish neonatal CAH screening effectively led to earlier diagnosis of 21-OHD and 11ß-OHD, using steroid profiling as a second-tier test. This will result in improved care of these patients in the future.

Prevalence of metabolic syndrome in schoolchildren and adolescents in Turkey: a population-based study.

AIM: To determine prevalence of the metabolic syndrome (MS) in the pediatric population. METHODS: We studied 2,491 schoolchildren randomly selected aged 10-19 years using a multistage, stratified sampling design. Obese and overweight participants were called for further investigation (n = 456). Of these, 310 participants underwent OGTT. MS was defined according to IDF, NCEP and modified WHO guidelines. RESULTS: The prevalence of obesity and overweight were 6.8% and 11.5%, respectively. While MS was found in 2.3% of the total population according to IDF guidelines, its prevalence was increased among overweight and obese individuals. MS prevalence was similar by both IDF and NCEP definitions but higher according to WHO definition. Individuals with MS were consistent by both IDF and NCEP definitions (sensitivity = 100%, specificity = 99%, positive predictive value = 95.2%). IDF and WHO defined different individuals as having MS (sensitivity = 67.5%, specificity = 90%, positive predictive value = 67.5%). CONCLUSIONS: Although not as high as in developed countries, MS prevalence determined in schoolchildren and adolescents in Turkey warrants preventive measures. MS diagnosis in one of every three obese children shows that MS is an important public health problem in Turkey as well.

Evaluation of nutritional status in children with amblyopia.

PURPOSE: We aimed to compare the body mass index and vitamin and mineral status of children with and without amblyopia. METHODS: Amblyopic children aged between 5 and 18 years (n=46) and age-matched control children (n=32) were evaluated in terms of anthropometric parameters, including height, weight, body mass index and demographic features. Serum vitamin B12 and folate were measured using an Advia Centaur XP (Siemens, Ireland) biochemistry analyzer. We evaluated the inorganic mineral elements from hair samples with inductively coupled plasma-mass spectrometry using a Thermo XSeries 2 analyzer (Thermo Fisher Scientific, Bremen, Germany). RESULTS: No significant difference was found between the two groups in terms of height, weight, and body mass index or serum B12 and folate concentrations (p>0.05). Children with severe amblyopia had lower vitamin B12 and folate and higher body mass index. The levels of phosphorus (p=0.012), selenium (p=0.002), molybdenum (p<0.001), iodine (p=0.002), chromium (p=0.022), boron (p<0.001), and beryllium (p=0.005) were all significantly lower in the amblyopia group compared to the control group. All of these minerals, except phosphorus, were also significantly lower in those with severe amblyopia compared to those with milder amblyopia and controls (p<0.05). CONCLUSION: Amblyopic children are significantly deficient in some inorganic elements. Inorganic elements, vitamin B12, and folate may play an important role in the visual development of amblyopic children.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

Objective: Congenital adrenal hyperplasia (CAH) is the most common form of primary adrenal insufficiency in children. Neonatal screening for CAH is effective in detecting the salt-wasting (SW) form and in reducing mortality. In this study, our aim was to estimate the incidence of CAH in Turkey and to assess the characteristics and efficacy of the adopted newborn CAH screening strategy. Methods: A pilot newborn CAH screening study was carried out under the authority of the Turkish Directorate of Public Health. Newborn babies of ≥32 gestational weeks and ≥1500 gr birth weight from four cities, born between March 27-September 15, 2017 were included in the study. Screening protocol included one sample two-tier testing. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. The cases with positive initial screening were tested by steroid profiling in DBS using a liquid chromatography-tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione as a second-tier test. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.5 were referred to pediatric endocrinology clinics for diagnostic assessment. Results: 38,935 infants were tested, 2265 (5.82%) required second-tier testing and 212 (0.54%) were referred for clinical assessment, six of whom were diagnosed with CAH (four males, two females). Four cases were identified as SW 21-hydroxylase deficiency (21-OHD) (two males, two females). One male baby had simple virilizing 21-OHD and one male baby had 11-OHD CAH. The incidence of classical 21-OHD in the screened population was 1:7,787. Conclusion: The incidence of CAH due to classical 21-OHD is higher in Turkey compared to previous reports. We, therefore, suggest that CAH be added to the newborn screening panel in Turkey. The use of steroid profiling as a second-tier test was found to improve the efficacy of the screening and reduce the number of false-positives.

Evaluation of diagnosis and treatment results in children with Graves' disease with emphasis on the pubertal status of patients.

This retrospective study evaluated the clinical and laboratory characteristics at presentation and treatment results of patients with Graves' disease (GD) with respect to pubertal status. Records of 143 patients (108 F, 35 M) were reviewed in a multicenter study. At diagnosis, 38% of patients were prepubertal. Anti-thyroid drugs (ATD) were used as initial therapy. There was no significant difference in clinical and laboratory characteristics at diagnosis, during treatment and adverse reaction to ATD with respect to pubertal status. Twenty patients (7 prepubertal, 13 pubertal) reached remission on ATD. Surgery was performed in seven and radioiodine (RAI) in four patients. Duration of treatment needed to achieve remission was longer in prepubertal (4.2 +/- 1.0 yr) than in pubertal patients (3.1 +/- 1.3 yr) (p = 0.02). The rate of remission was not different between prepubertal (25.9%) and pubertal patients (33.3%) (p = 0.59). ATD were associated with low remission rate in pediatric GD and required longer duration of therapy in prepubertal patients. For definitive treatment in older children, RAI could be evaluated as the initial therapy.

Metabolic syndrome in obese Turkish children and adolescents: comparison of two diagnostic models.

There is no consensus on whether or not the diagnostic criteria of metabolic syndrome (MS) defined for adults [National Cholesterol Education Panel (NCEP) and World Health Organization (WHO)] can be used in childhood as well. We aimed to compare prevalence of metabolic syndrome among obese children and adolescents using WHO and NCEP guidelines. A total of 112 obese children and adolescents were assessed. MS was diagnosed according to both modified WHO and NCEP criteria using cut-off values for children. Abnormal glucose homeostasis was identified in 46.6% of the subjects. Fasting glucose levels for all subjects were less than 110 mg/dl and no subjects had type 2 diabetes. Overall, dyslipidemia was present in 42.9% and hypertension in 42.9% of the subjects. While 24% of the subjects were diagnosed as MS according to NCEP, a rate of 38.8% were diagnosed according to WHO-defined MS. There was a moderate agreement between NCEP and WHO guidelines. More children were diagnosed as MS based on the WHO guidelines. This may lead to better monitoring for these children and prevention of their chronic diseases in the future. Therefore, we recommend using WHO guidelines in the diagnosis of MS with a specific emphasis on definition of abnormal glucose homeostasis.

Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus.

BACKGROUND/AIMS: Maturity onset diabetes of the young (MODY) is a rare condition often misdiagnosed as type 1 diabetes (T1D). The purposes of this study were: to identify any patients followed in a large Turkish cohort as T1D, with an atypical natural history, who may in fact have MODY, and to define the criteria which would indicate patients with likely MODY as early as possible after presentation to allow prompt genetic testing. METHODS: Urinary C-peptide/creatinine ratio (UCPCR) was studied in 152 patients having a diagnosis of T1D for at least 3 years. Those with a UCPCR ≥0.2 nmol/mmol were selected for genetic analysis of the Glucokinase (GCK), Hepatocyte nuclear factor 1a (HNF1A), Hepatocyte nuclear factor 4a (HNF4A), and Hepatocyte nuclear factor 1b (HNF1B) genes. This UCPCR cut-off was used because of the reported high sensitivity and specificity. Cases were also evaluated using a MODY probability calculator. RESULTS: Twenty-three patients from 152 participants (15.1%) had a UCPCR indicating persistent insulin reserve. The mean age ± SD of the patients was 13.6 ± 3.6 years (range 8.30-21.6). Of these 23, two (8.7%) were found to have a mutation, one with HNF4A and one with HNF1B mutation. No mutations were detected in the GCK or HNF1A genes. CONCLUSION: In Turkish children with a diagnosis of T1D but who have persistent insulin reserve 3 years after diagnosis, up to 9% may have a genetic mutation indicating a diagnosis of MODY.

Neonatal Features of the Prader-Willi Syndrome; The Case for Making the Diagnosis During the First Week of Life

Objective: Early diagnosis is of proven benefit in Prader-Willi syndrome (PWS). We therefore examined key perinatal features to aid early recognition. Methods: Data were collected from case records of subjects attending a multi-disciplinary clinic and from a retrospective birth questionnaire. Results: Ninety patients (54 male-36 female) were seen between 1991-2015, most with paternal deletion (n=56) or maternal isodisomy (n=26). Features included cryptorchidism in 94% males, preterm birth (26%), birthweight <2500 g (24%), polyhydramnios (23%), breech presentation (23%) and need for nasogastric feeding (83%). Reduced fetal movements (FM) were reported in 82.5% patients compared with 4% healthy siblings. Of 35 children born since 1999, 23 were diagnosed clinically within 28 days while diagnosis in 12 was >28 days: 1-12 months in seven; and 3.75-10.5 years in five. Typical PWS features in these 12 infants included hypotonia (100%), feeding difficulties (75%), cryptorchidism (83% males) and reduced FM (66%). Causes other than PWS including neuromuscular disease were considered in nine patients. Conclusion: Neonatal hypotonia, reduced FM, feeding difficulties and cryptorchidism should immediately suggest PWS, yet late diagnosis continues in some cases. Awareness of the typical features of PWS in newborn units is required to allow prompt detection even in the presence of confounding factors such as prematurity.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Evaluation and Treatment Results of Ovarian Cysts in Childhood and Adolescence: A Multicenter, Retrospective Study of 100 Patients.

STUDY OBJECTIVE: To investigate the characteristics of children with ovarian cysts and evaluate treatment strategies. DESIGN: Retrospective study. SETTING: Eight pediatric endocrinology clinics, Turkey. PARTICIPANTS: A total of 100 children and adolescents with ovarian cysts. INTERVENTIONS: Patient data collected via retrospective chart review. Patients were stratified according to age into 4 groups (newborns, 1-12 months, 1-8 years, and 8-18 years). MAIN OUTCOME MEASURES: Special emphasis was given to torsion and tumor cases, concomitant diseases, treatment modalities, and problems during follow-up. RESULTS: Most newborns and infants were asymptomatic with the cysts being discovered incidentally; in girls ages 1-8, symptoms were common, including breast budding (47.1%, 16 of 34) and vaginal bleeding (29.4%, 10 of 34). Girls older than 8 years mostly presented with abdominal pain (31.6%, 12 of 38) and menstrual irregularity (21.1%, 8 of 38). Most of our patients were diagnosed with a simple ovarian cyst, but 9 patients were found to have ovarian tumors. Ovarian torsion was detected in 7 patients; 5 with large and 2 with small cysts (<20 mm). Two patients had central precocious puberty (CPP) at presentation and 5 patients developed CPP during follow-up. The surgical intervention rate was high (38%, 38 of 100), but was associated with earlier treatment year, and this association remained significant after adjusting for confounders (P = .035). CONCLUSION: Most girls have simple cysts, which have a favorable prognosis without intervention; however, there might be coexisting pathologies or complications such as tumors, torsion, and CPP; hence these patients should be evaluated accordingly and treated with a multidisciplinary approach.

Use of alendronate in the treatment of vitamin D intoxication in infants.

Vitamin D intoxication remains a challenging problem due to lack of an efficient treatment. Bisphosphonates, inhibitors of osteoclast-mediated bone resorption, however, have been proposed as a safe and effective alternative in the treatment of vitamin D intoxication. We present here two infants with vitamin D intoxication who were successfully treated with alendronate. We propose that oral alendronate is an alternative to intravenous bisphosphonates in the treatment of vitamin D intoxication in infancy.

Cerebral complications in diabetic ketoacidosis.

Although much is known about diabetic ketoacidosis (DKA) and its treatment, the pathology of cerebral complications in patients who develop ketoacidosis is not yet well understood. In this article, we discuss the cerebral complications due to DKA by presenting two cases who were admitted with severe DKA and who both developed early and severe neurological complications.