Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Clinical Characteristics of Children with Combined Pituitary Hormone Deficiency and the Effects of Growth Hormone Treatment.

AIM: We aimed to describe the clinical characteristics of patients with congenital combined pituitary hormone deficiency (CPHD) and evaluate the first-year growth responses of individuals with CPHD and isolated growth hormone deficiency (IGHD) in order to establish the influence of other hormone deficiencies on growth response. PATIENTS AND METHODS: This retrospective study was conducted in four tertiary care centers in Turkey. The records of patients diagnosed with CPHD (n=39) and severe IGHD (n=50) were collected. Cases with acquired lesions or chronic diseases were not included in the study. Data are presented as median (interquartile range). RESULTS: Among 39 patients (13 females; 33%) with a diagnosis of CPHD, the majority of patients (64%) presented initially with combined deficits at baseline examination, whereas isolated deficiencies (36%) were less prevalent. Among all patients with GH deficiency, TSH, ACTH, FSH/LH, and ADH deficiencies were present in 94%, 74%, 44%, and 9% of patients, respectively. Patients with CPHD were diagnosed at a younger age (4.9 (8.4) vs. 11.6 (4.1), p<0.001, respectively) and had lower peak GH concentrations (0.4 (1.8) vs. 3.7 (2.9), p<0.001, respectively) than patients with IGHD. Patients with IGHD and CPHD had similar first-year growth responses (Δheight SD score of 0.55 (0.63) vs. 0.76 (0.71), respectively, p=0.45). CONCLUSIONS: We established the nature and timing of numerous hormonal deficits emerging over time. We also identified that the existence of CPHD did not hinder growth response.

POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in POU6F2 in 15 patients. POU6F2 encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing GNRH1 expression. In addition, the impact of the two most prevalent POU6F2 variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.

Resting Electroencephalography Differences Between Eyes-Closed and Eyes-Open Conditions in Children with Subclinical Hypothyroidism.

OBJECTIVE: Electroencephalography changes that occur during the transition from eyes-closed to the eyes-open state in resting condition are related to the early phase of sensory processing and are defined as activation. The present study aimed to reveal the potential deteriorations that may occur in the initial period of sensory processing in resting electroencephalography between children with subclinical hypothyroidism and a control group. MATERIALS AND METHODS: Electroencephalographies of 15 children with subclinical hypothyroidism and 15 healthy children aged 10 to 17 years were recorded for 2 minutes for EC and 2 minutes for eyes-open conditions in resting state. Absolute electroencephalography band powers (µV2 ) within the delta, theta, alpha, and beta frequency bands were calculated in Fz, Cz, Pz, and Oz electrodes, respectively, for eyes-closed and eyes-open conditions. RESULTS: The results show that, although there was no noteworthy difference between the powers of the electroencephalography frequency bands of children with subclinical hypothyroidism and healthy children during the eyes-open condition, the alpha powers of the control group were significantly higher in all electrodes during the eyes-closed condition. Furthermore, the powers of all frequency bands were observed to decrease in the eyes-open condition in the control group. However, the same net decrease was not observed in the frequency powers of children with subclinical hypothyroidism. CONCLUSION: According to the results of this study, children with subclinical hypothyroidism may experience information processing impairments starting in the early stages of sensory processing.

Atypical STAT5B deficiency, severe short stature and mild immunodeficiency associated with a novel homozygous STAT5B Variant.

STAT5B deficiency, a rare autosomal recessive disorder characterized by severe growth hormone insensitivity (GHI) and immunodeficiency, can manifest as fatal pulmonary complications. We describe atypical STAT5B deficiency associated with a novel homozygous frame-shift STAT5B variant [c.1453delG, p.(Asp485Thrfs*29)] identified in a young 17.6 yr old female subject who had severe postnatal growth impairment, biochemistries typical of GHI, an immune profile notable for hypergammaglobulinaemia and elevated B lymphocytes, and lack of pulmonary disease. Marked elevation of serum prolactin and pathologically diagnosed eczema were evident. In reconstitution studies, the STAT5B p.(Asp485Thrfs*29) was expressed although expression was reduced compared to wild-type STAT5B and a previously identified STAT5B p.(Gln368Profs*9) variant. Both truncated STAT5B peptides could not be activated by GH, nor mobilize to the nucleus. We conclude that an intact, functional, STAT5B is essential for normal GH-mediated growth, while expressed loss-of-function STAT5B variants may alleviate severe immune and pulmonary issues normally associated with STAT5B deficiency.

Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.

Are Thyroid Functions Affected in Multisystem Inflammatory Syndrome in Children?

Objective: Multisystem inflammatory syndrome in children (MIS-C), associated with Coronavirus disease-2019, is defined as the presence of documented fever, inflammation, and at least two signs of multisystem involvement and lack of an alternative microbial diagnosis in children who have recent or current Severe acute respiratory syndrome-Coronavirus-2 infection or exposure. In this study, we evaluated thyroid function tests in pediatric cases with MIS-C in order to understand how the hypothalamus-pituitary-thyroid axis was affected and to examine the relationship between disease severity and thyroid function. Methods: This case-control study was conducted between January 2021 and September 2021. The patient group consisted of 36 MIS-C cases, the control group included 72 healthy children. Demographic features, clinical findings, inflammatory markers, thyroid function tests, and thyroid antibody levels in cases of MIS-C were recorded. Thyroid function tests were recorded in the healthy control group. Results: When MIS-C and healthy control groups were compared, free triiodothyronine (fT3) level was lower in MIS-C cases, while free thyroxine (fT4) level was found to be lower in the healthy group (p<0.001, p=0.001, respectively). Although the fT4 level was significantly lower in controls, no significant difference was found compared with the age-appropriate reference intervals (p=0.318). When MIS-C cases were stratified by intensive care requirement, fT3 levels were also lower in those admitted to intensive care and also in those who received steroid treatment (p=0.043, p<0.001, respectively). Conclusion: Since the endocrine system critically coordinates and regulates important metabolic and biochemical pathways, investigation of endocrine function in MIS-C may be beneficial. These results show an association between low fT3 levels and both diagnosis of MIS-C and requirement for intensive care. Further studies are needed to predict the prognosis and develop a long-term follow-up management plan.

The effect of breast milk nesfatin-1 and ghrelin levels on growth in infants with SGA.

BACKGROUND: Current studies claim that peptides such as leptin, adiponectin, ghrelin, and nesfatin-1 found in breast milk may be responsible for the growth of infants. Therefore, we aimed to determine the association between breast milk total ghrelin and nesfatin-1 levels and anthropometric measurements of infants who were small for gestational age (SGA). METHODS: 20 SGA and 20 appropriate for gestational age (AGA) infants were enrolled in the study. Anthropometric measurements of infants were carried out at birth, 1st, and 4th months. In addition, total ghrelin and nesfatin-1 levels in the breast milk were concomitantly measured. RESULTS: Total ghrelin at the 4th month in breast milk waslower-level in the SGA group (p=0.015). In both groups, nesfatin-1 levels at the 4th month were lower than the values at the 1st month. Additionally, nesfatin-1 levels of SGA infants at the 4th month were higher (p=0.035). CONCLUSIONS: Breast milk total ghrelin and nesfatin-1 levels differed in both groups, and it is probably referred to the growth discrepancy of these infants during the first months of life. Furthermore, we consider that higher breast milk nesfatin-1 levels at the 4th month may be a preventive against obesity in SGA infants who have potential risk for obesity in childhood and adulthood.

Elevated neurotensin levels among obese adolescents may be related to emotion dysregulation and impulsivity: a cross-sectional, case-control study.

BACKGROUND: In this study, we aimed to evaluate the serum neurotensin (NT) levels and their relationships with self-reported anxiety, emotion regulation skills and impulsivity in healthy and obese adolescents. METHODS: Adolescents who gained weight between 12- 17 years of age and who were above the 95th percentile (p) for body mass index (BMI) > 95p were compared with age- and gender-matched healthy adolescents with a BMI of 3-85 p. Anthropometric measurements were performed, and serum NT levels were analyzed with ELISA method in all participants. Barrat Impulsivity Scale-11 (BIS-11), Screen for Child Anxiety Related Disorders (SCARED) and Difficulties in Emotion Regulation Scale (DERS) were used for evaluating self-reported impulsivity, anxiety and emotion regulation. MANOVA with follow-up univariate ANOVAs (Bonferroni corrected) were used for group comparisons. P was set at 0.05 (two-tailed). RESULTS: Sixty-five obese and 65 healthy adolescents were included in the study. In the obese group, NT levels were significantly elevated compared to the control group. Self-reported emotion-regulation difficulties, anxiety and impulsivity were significantly elevated among obese adolescents. Serum NT levels among the obese group were positively correlated with emotion dysregulation and impulsivity scores. CONCLUSIONS: In this study, we found emotional dysregulation, anxiety, impulsivity, and serum NT levels were significantly elevated among obese adolescents compared to controls. NT levels in the obese group correlated with impulsivity and emotion dysregulation. Further studies should evaluate the potential role of NT in the etiology of psychopathology among adolescents who are obese.

A rare endocrinological complication of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) may lead to increase in serum levels of peptide hormones as a result of changes in peripheral metabolism. The pathogenesis of uremic hyperprolactinemia in CKD is not fully understood. Plasma prolactin levels are elevated in women, pubertal girls, and also in men with chronic kidney disease. But this is not comon in prepubertal boys. Also in prepubertal children and postmenopausal women, hyperprolactinemia rarely results in galactorrhea. We aimed to discuss hyperprolactinemia and galactorrhea in a 12-year-old male with CKD. CASE: A twelve-year-old boy with chronic kidney disease (CKD) suffered from bilateral galactorrhea. He was on follow-up at Pediatric Nephrology Department from the age of two due to bilateral dysplastic kidney. On physical examination, his weight was - 0.59 SDS, height was -2.82 SDS, Blood pressure was 115 / 72 (75p), stretched penis length was 6 cm, testicular volume was 3mL / 3mL, pubic hair was Tanner Stage 1, breast examination did not reveal plaque on bilateral breast. He was receiving recombinant erythropoietin, sodium bicarbonate, polystyrene sulfonate, calcium acetate, and calcitriol treatments. Glomerular filtration rate was 23ml/min/1.73 m2 (CKD stage IV). Serum prolactin (PRL) was > 200 µg/L (N, 2.64-13.13). The pituitary adenoma was excluded with pituitary and cranial magnetic resonance imaging (gadolinium). Cabergoline (0.5 mg/ twice weekly) was initiated to decrease PRL levels and reduce galactorrhea. In the second week of treatment, serum PRL level was suppressed (0.4 µg/L) and galactorrhea was completely resolved. CONCLUSIONS: Although uremic hyperprolactinemia is very rarely seen in childhood, it is important to evaluate, and initiate an appropriate treatment since it is associated with delayed puberty and infertility in adulthood in many cases.

Childhood-onset mild diabetes caused by a homozygous novel variant in the glucokinase gene.

PURPOSE: Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause MODY 2, which is characterized by asymptomatic fasting hyperglycemia and does not require insulin treatment. Conversely, homozygous loss-of-function mutations in the same gene give rise to permanent neonatal diabetes mellitus (DM) that appears in the first 6-9 months of life and necessitates lifelong insulin treatment. We aimed to present the genotypic and phenotypic features of a 13-year-old patient diagnosed with DM at the age of 3 years due to a homozygous variant in the GCK gene. METHODS: The patient's clinical and laboratory findings at follow-up were not consistent with the initial diagnosis of type 1 DM; thus, next-generation sequencing of MODY genes (GCK, HNF1A, HNF1B, and HNF4A genes) was performed to identify monogenic causes of DM. RESULTS: A novel homozygous variant c.1222 G > T in the GCK gene was revealed. In silico analysis identified it as a pathogenic variant. His mother, father, and brother had the same heterozygous variant in the GCK gene and were diagnosed with MODY 2 (mild fasting hyperglycemia and elevated HbA1c) after genetic counseling. CONCLUSION: In this case report, a patient with a homozygous variant in the GCK gene, who was diagnosed with DM after the infantile period, was presented, highlighting the fact that cases with homozygous variants in the GCK gene can, though rarely, present at a later age with a milder phenotype.

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.

Diagnostic Value of Bilateral Petrosal Sinus Sampling in Children with Cushing Disease: A Multi-center Study

Objective: Although the sensitivity and specificity of bilateral inferior petrosal sinus sampling (BIPSS) were shown to be quite high in adult patients, pediatric studies are limited in number and have conflicting results, since BIPSS is much less commonly performed in children. The aim of this study was to assess the role of BIPSS in the detection and accuracy of lateralization of pituitary adenomas in pediatric patients with Cushing disease (CD) and its possible advantage over other diagnostic methods. Methods: This was a multicenter, nationwide, web-based study. The diagnostic value of BIPSS in 16 patients, aged between four and 16.5 years with a confirmed diagnosis of CD, was evaluated retrospectively. The sensitivity and specificity of BIPSS and magnetic resonance imaging (MRI) were calculated, and compared statistically. Results: Standard tests, except for morning cortisol level, were effective in proving the presence of Cushing syndrome. While MRI findings were consistent with microadenoma in eight cases (50%), CD presence and lateralization was successfully predicted in 14 of 16 patients using BIPSS. BIPSS compared with MRI examination was significantly more accurate, both in pre-stimulation and post-stimulation results (p=0.047 and p=0.041, respectively). BIPSS showed a significantly higher sensitivity (92.8%) than MRI in detecting the pituitary source of adrenocorticotropic hormone secretion. Conclusion: These results suggest that BIPSS is superior to MRI for diagnostic work-up to confirm the diagnosis of CD. Moreover, in line with previous studies, BIPSS was shown to provide better information about adenoma location, which is vital for possible surgical intervention.

High serum neurotensin level in obese adolescents is not associated with metabolic parameters, hyperphagia or food preference.

OBJECTIVES: Obesity is often the result of a high-calorie and unbalanced diet for a long time and can sometimes be associated with hyperphagia and eating disorders. Neurotensin (NT) is an anorexigenic peptide, which is secreted from the central nervous system and intestines, and increases intestinal fat absorption. In the literature, conflicting results regarding serum NT level in obesity and the relation of NT with metabolic parameters were reported. Besides, there is no data regarding the relation of NT with eating disorders or food preference in obese individuals. We aimed to evaluate the relation of serum NT level with metabolic parameters, hyperphagia, binge eating disorder (BED) and food preference in obese adolescents. METHODS: The study included 65 obese adolescents and 65 healthy controls. Anthropometric measurements, biochemical analyzes and body fat analyzes were performed in all cases. Hyperphagia score, presence of BED and three-day food intake records were also evaluated. RESULTS: NT level was significantly higher in obese adolescents than in controls and it was not associated with metabolic parameters, hyperphagia or food preference. In the obese group, NT level was not significantly different according to the presence of BED. CONCLUSIONS: Serum NT level is high in obese adolescents; however, it is not associated with metabolic parameters, hyperphagia, BED or food preference.

Oxytocin receptor gene polymorphism and low serum oxytocin level are associated with hyperphagia and obesity in adolescents.

BACKGROUND/OBJECTIVES: In recent years, oxytocin (OXT) and polymorphisms in the oxytocin receptor (OXTR) gene have been reported to play roles in obesity pathogenesis. However, there was no study evaluating OXTR gene variants in childhood obesity. The aim of the study was to investigate the relation of OXTR gene polymorphisms and serum OXT levels with metabolic and anthropometric parameters in obese and healthy adolescents. SUBJECTS/METHODS: The study was a multi-centered case-control study, which was conducted on obese and healthy adolescents aged between 12 and 17 years. Serum OXT and leptin levels were measured, and OXTR gene variants were studied by qPCR (rs53576) and RFLP (rs2254298) methods. RESULTS: A total of 250 obese and 250 healthy adolescents were included in this study. In the obese group, serum OXT level was lower and leptin level was higher than the control group. In the obese group, frequencies of homozygous mutant (G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were higher than the control group. Homozygous mutant(G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were found to increase the risk of obesity compared to the wild type (A/A) genotype [OR = 6.05 and OR = 3.06; p < 0.001, respectively]. In patients with homozygous mutant (G/G) and heterozygous (A/G) genotype for rs53576 polymorphism, serum OXT levels were lower than the wild type (A/A) genotype. In the obese group, hyperphagia score was higher than the control group and correlated negatively with serum OXT level. CONCLUSIONS: This study revealed that low serum OXT level, which is associated with hyperphagia may be an underlying cause for obesity in adolescents. For rs53576 polymorphism of the OXTR gene, obesity risk is higher in patients with homozygous mutant(G/G) and heterozygous(A/G)genotypes.

Clinical and Hormonal Profiles Correlate With Molecular Characteristics in Patients With 11ß-Hydroxylase Deficiency.

BACKGROUND: Given the rarity of 11ß-hydroxylase deficiency (11ßOHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11ßOHD) and nonclassic 11ßOHD (NC-11ßOHD). OBJECTIVE: To characterize a multicenter pediatric cohort with 11ßOHD. METHOD: The clinical and biochemical characteristics were retrospectively retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. RESULTS: 102 patients (C-11ßOHD, n = 92; NC-11ßOHD, n = 10) from 76 families (46,XX; n = 53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female adult height was 152 cm [-1.85 SD score (SDS)] and male 160.4 cm (-2.56 SDS).None of the NC-11ßOHD girls had ambiguous genitalia (C-11ßOHD 100%), and none of the NC-11ßOHD patients were hypertensive (C-11ßOHD 50%). Compared to NC-11ßOHD, C-11ßOHD patients were diagnosed earlier (1.33 vs 6.9 years; P < 0.0001), had higher bone age-to-chronological age (P = 0.04) and lower adult height (-2.46 vs -1.32 SDS; P = 0.05). The concentrations of 11-oxygenated androgens and 21-deoxycortisol were low in all patients. The baseline ACTH and stimulated cortisol were normal in NC-11ßOHD. Baseline cortisol; cortisone; 11-deoxycortisol; 11-deoxycorticosterone and corticosterone concentrations; and 11-deoxycortisol/cortisol, 11-deoxycorticosterone/cortisol, and androstenedione/cortisol ratios were higher in C-11ßOHD than NC-11ßOHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11ßOHD, NC-11ßOHD, and control groups. CONCLUSION: NC-11ßOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11ßOHD.

Early and late diagnoses of 17ß-Hydroxysteroid dehydrogenase type-3 deficiency in two unrelated patients.

17ß-hydroxysteroid dehydrogenase type 3 deficiency is a rare cause of 46 XY disorders of sexual development. Mutations in the HSD17B3 gene result in reduced activity of the 17ß-HSD3 enzyme, decreasing the conversion of androstenedione to testosterone. In this report, two cases, admitted with different clinical findings in the neonatal and adolescent periods and were decided to be raised in different genders are presented. The first case who had complete female external genitalia presented on the third postnatal day with the complaint of swelling in the groin. He was decided to be raised as a male and was treated successfully with parenteral testosterone in order to increase phallus size before surgical correction of the external genitalia. The second case was an adolescent girl who presented due to pubertal virilisation and primary amenorrhoea and chose female gender. Molecular genetic analyses of the HSD17B3 gene revealed two different previously reported homozygous variants. We emphasise that patients with 17ß-hydroxysteroid dehydrogenase type 3 deficiency can present with heterogeneous clinical findings in different age groups. Early diagnosis is important to prevent future gender confusion and related problems.

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aim: We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH). Materials and methods: Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) "uncontrolled" [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) "controlled" [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system. Results: There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status. Conclusion: In this study, the CIMT values of CAH cases were similar to those of healthy subjects.

Does fludrocortisone treatment cause hypomagnesemia in children with primary adrenal insufficiency?

Background/aim: Aldosterone is a mineralocorticoid that secreted from adrenal glands and a known factor to increase magnesium excretion by direct and indirect effects on renal tubular cells. Although the frequency of hypomagnesemia was found to be approximately 5% in adult studies, there is no study in the literature investigating the frequency of hypomagnesemia in children by using fludrocortisone, which has a mineralocorticoid activity. Materials and methods: A multi-center retrospective study was conducted, including children who were under fludrocortisone treatment for primary adrenal insufficiency and applied to participant pediatric endocrinology outpatient clinics. Results: Forty-three patients (58.1% male, 41.9% prepubertal) included in the study, whose median age was 9.18 (0.61-19) years, and the most common diagnosis among the patients was a salt-wasting form of congenital adrenal hyperplasia (67.4%). Mean serum magnesium level was 2.05 (±0.13) mg/dL, and hypomagnesemia was not observed in any of the patients treated with fludrocortisone. None of the patients had increased urinary excretion of magnesium. Conclusion: Unlike the studies performed in adults, we could not find any evidence of magnesium wasting effect of fludrocortisone treatment with normal or even high doses in children and adolescents.

Comparison of the effectiveness of simple carbohydrates on hypoglycemic episodes in children and adolescents with type 1 diabetes mellitus: A randomized study in a diabetes camp.

BACKGROUND: Hypoglycemia is the most common and severe complication of insulin treatment during the management of type 1 diabetes mellitus (T1DM). Despite its importance, there is a lack of data about the efficacy and superiority of the carbohydrate sources used in hypoglycemia management in children and adolescents. OBJECTIVE: We aimed to compare the effectiveness of honey, fruit juice, and sugar cubes as simple carbohydrates used in the primary treatment of hypoglycemia in children and adolescents with T1DM, who attended a diabetes summer camp. METHODS: A prospective randomized study was performed in a 5-days-long diabetes summer camp. Three different types of simple carbohydrates; sugar cubes, honey, or fruit juice were randomly given for the treatment of hypoglycemia and the recovery results in the three groups were compared. RESULTS: About 32 patients (53.1% male, mean age 12.9 ± 1.9 years) were included and 158 mild hypoglycemic episodes were observed. Sugar cubes, honey, and fruit juice were given in 46 (29.1%), 60 (37.9%), and 52 (33%) events, respectively. We found that honey and fruit juice had similar efficiency in recovering hypoglycemia in 15 minutes with a rate of 95% and 98%, respectively. However, sugar cubes had a significantly lower impact on treatment of hypoglycemia than the others, with a recovery rate of 84.7% at 15 minutes. CONCLUSIONS: This study showed, for the first time, that honey and fruit juice were more effective in treating hypoglycemia than sugar cubes, and can be preferred in treating hypoglycemic events in children and adolescents with T1DM.