Very High Dehydroepiandrosterone Sulfate (DHEAS) in Serum of an Overweight Female Adolescent Without a Tumor.

Introduction: An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are typical for adrenal tumors. Approximately 74% of DHEAS is hydrolyzed to DHEA by the steroid sulfatase (STS). The reverse reaction is DHEA sulfation. Besides these two enzyme reactions, the DHEAS transported through the cell membrane is important for its distribution and excretion. Case Presentation: We present a female adolescent with overweight and a very high DHEAS. The presence of a DHEAS-producing tumor was rejected using ultrasonography, Magnetic Resonance Tomography (MRT), and dexamethasone suppression. STS deficiency was suspected. Sequence analysis revealed a heterozygous nonsense mutation which predicts a truncation of the carboxyl region of the STS that is implicated in substrate binding. No partial gene deletion outside exon 5 was detected by multiplex ligation-dependent probe amplification. The bioassay revealed normal enzyme activity in the patient's leukocytes. A defect of transporter proteins was suggested. Both efflux [multidrug-resistance protein (MRP)2 and breast cancer-resistance protein (BCRP)] and uptake [organic anion-transporting polypeptide (OATP) and organic anion transporter (OAT) carriers] transporters were studied. Sequence analysis of exons revealed a heterozygous Q141K variant for BCRP. Conclusions: A novel heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene were found. The heterozygous nonsense mutation in the STS gene is not supposed to be responsible for STS deficiency. The BCRP variant is associated with reduced efflux transport activity only in its homozygous state. The combination of the two heterozygous mutations could possibly explain the observed high levels of DHEAS and other sulfated steroids.

Accuracy of Endocrine Tests for Detecting Hypogonadotropic Hypogonadism in Girls.

OBJECTIVE: To assess the accuracy of inhibin B and the gonadotropin releasing hormone agonist test for the diagnosis of hypogonadotropic hypogonadism (HH). STUDY DESIGN: We performed a retrospective analysis of data collected 2009-2014 using a strict clinical protocol. All prepubertal nonunderweight girls, aged 13-17.5 years with Tanner breast stage B1/B2 and low estradiol levels, were tested and re-examined at 6-month intervals (n = 21). Constitutional delay of growth and puberty was defined by spontaneous menarche; HH was identified by association with specific causes of HH or no spontaneous progress of puberty during follow-up. Inhibin B was measured using enzyme-linked immunosorbent assay, and follicle-stimulating hormone and luteinizing hormone (basal and stimulated by triptorelin) were measured using a chemiluminescence immunoassay. RESULTS: The cohort comprised 12 girls with constitutional delay of growth and puberty and 9 girls with HH. The causes of HH included hypopituitarism (n = 3), Prader-Willi syndrome, chromosomal aberration, intellectual disability syndrome with ataxia, and idiopathic causes (n = 2). Each measurement, basal inhibin B <20 pg/mL or stimulated follicle-stimulating hormone (4 hours) <11 IU/L, demonstrated a sensitivity and a specificity of 100% for the detection of HH. Stimulated luteinizing hormone (4 hours) <9 IU/L showed 100% sensitivity but only 83% specificity. CONCLUSIONS: Inhibin B seems to be the ideal measurement for detecting HH in girls. The gonadotropin releasing hormone agonist test is an alternative diagnostic modality, although this approach is more invasive and laborious.

Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys.

OBJECTIVE: The distinction between constitutional delay of growth and puberty (CDGP) and isolated hypogonadotropic hypogonadism (IHH) in males with delayed puberty is difficult but important for timely treatment. We assessed the accuracy of the GnRH agonist test (triptorelin 0·1 mg) in comparison with inhibin B alone or in combination with basal LH for the diagnosis of IHH. PATIENTS AND MEASUREMENTS: Ninety-seven prepubertal males aged 13·7-17·5 year, with testicular volumes ≤4 ml, were examined every 6 months. CDGP was defined by a testicular volume ≥8 ml after 18 months, and IHH was defined by a testicular volume <5 ml after 24 months follow-up. Inhibin B concentrations were measured by ELISA, and LH concentrations were measured by CLIA. RESULTS: At follow-up, the cohort comprised 52 boys with CDGP and nine with IHH. The other patients were lost for follow-up (n = 10), had not reached follow-up yet (n = 20) or did not reach a definite testicular volume (n = 6). Basal LH <0·3 IU/l, stimulated LH (4 h) <5·3 IU/l or inhibin B <111 pg/ml had 100% sensitivity for IHH. Only LH (4 h) <5·3 IU/l had a specificity of 100%, and the specificities of basal LH <0·3 IU/l (88%) or inhibin B <110 pg/ml (92%) were lower. The combination of LH <0·3 IU/l with inhibin B <111 pg/ml increased the specificity to 98·1%. CONCLUSIONS: The LH response 4 h after GnRH agonist stimulation has an excellent accuracy for the diagnosis of IHH in prepubertal boys with delayed puberty. However, the measurement of inhibin B and basal LH in combination is a valid, reliable and less-invasive alternative test.

Higher glucose concentrations following protein- and fat-rich meals - the Tuebingen Grill Study: a pilot study in adolescents with type 1 diabetes.

OBJECTIVE: Traditionally insulin dosage is focused on the carbohydrate amount of meals. We investigated the influence of a fat- and protein-rich meal in the evening on glucose concentration over night in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen patients, mean age 16.8 [standard deviation (SD) 2.9] yr participated in the study. Mean glycated hemoglobin (HbA1c) was 6.9 (range: 6.0-8.9) %. On two consecutive days the patients received a standard meal (SM) and a fat-protein-rich evening meal (FPRM). The carbohydrate amount remained identical and insulin was adjusted to this carbohydrate amount with the individual carbohydrate bolus. Glucose was measured continuously over night with the Enlite sensor and the Guardian system (Medtronic) during the following 12 h after the meal. RESULTS: Glucose area under the curve (AUC) for SM was 1400 (SD 580) mg/dL/12 h and for FPRM 1968 (SD 394) mg/dL/12 h (p < 0.05). There was a significant difference in the AUC between 4 and 12 h after the meal. Maximal AUC difference was 6 h after the meal. Glucose concentration in the morning (12 h after the meal) differed: 91 (SD 34) mg/dL after SM and 153 (SD 60) mg/dL after FPRM (p < 0.05). For SM 31% of glucose level were <80 mg/dL and 24% >150 mg/dL, for FPRM it was 3 and 48%. CONCLUSIONS: Twelve hours after a FPRM glucose concentration is significantly higher. Dietary counseling should include the effect of protein and fat on glucose levels in adolescents with type 1 diabetes. The data indicate clearly a need for additional insulin for fat-protein-rich meals.

Effects of light and circadian clock on growth and chlorophyll accumulation of Nannochloropsis gaditana.

Circadian clocks synchronize various physiological, metabolic and developmental processes of organisms with specific phases of recurring changes in their environment (e.g. day and night or seasons). Here, we investigated whether the circadian clock plays a role in regulation of growth and chlorophyll (Chl) accumulation in Nannochloropsis gaditana, an oleaginous marine microalga which is considered as a potential feedstock for biofuels and for which a draft genome sequence has been published. Optical density (OD) of N. gaditana culture was monitored at 680 and 735 nm under 12:12 h or 18:6 h light-dark (LD) cycles and after switching to continuous illumination in photobioreactors. In parallel, Chl fluorescence was measured to assess the quantum yield of photosystem II. Furthermore, to test if red- or blue-light photoreceptors are involved in clock entrainment in N. gaditana, some of the experiments were conducted by using only red or blue light. Growth and Chl accumulation were confined to light periods in the LD cycles, increasing more strongly in the first half than in the second half of the light periods. After switching to continuous light, rhythmic oscillations continued (especially for OD680 ) at least in the first 24 h, with a 50% decrease in the capacity to grow and accumulate Chl during the first subjective night. Pronounced free-running oscillations were induced by blue light, but not by red light. In contrast, the photosystem II quantum yield was determined by light conditions. The results indicate interactions between circadian and light regulation of growth and Chl accumulation in N. gaditana.

Eating disorder pathology in adolescents participating in a lifestyle intervention for obesity: associations with weight change, general psychopathology and health-related quality of life.

OBJECTIVE: The aim of this study was to identify the prevalence of eating disorder symptoms in obese adolescents participating in a lifestyle intervention for weight loss and to investigate possible relationships with weight change, general psychopathology, and health-related quality of life (HRQOL). METHOD: At the beginning and after completion of a 6-month lifestyle intervention, 41 participants (20 females; age: 13.7 ± 1.4 years) reported on core symptoms of eating disorders (SCOFF), self-esteem (Rosenberg Self-Esteem Scale, RSES), and HRQOL (Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents, KINDL), while parents filled in a questionnaire assessing their children's internalizing and externalizing behavioral problems (Child Behavior Checklist, CBCL). RESULTS: Compared to age-matched normative samples, patients showed increased behavior problems and an impaired HRQOL. 43% of the patients were screened positive for an eating disorder pathology, and this subgroup showed an increased psychopathological burden compared to patients that were screened negative. The lifestyle intervention resulted in a significant weight loss which was unaffected by the presence of an eating disorder pathology. The screening rate for eating disorders remained stable after the intervention. CONCLUSION: The large overlap, mutual interaction, and high burden of eating and weight problems in children and adolescents underpin the need for an integrated view in both prevention and treatment approaches in pediatric obesity.

Three children with triple A syndrome due to a mutation (R478X) in the AAAS gene.

OBJECTIVE: To investigate the phenotype and genotype of 3 unrelated children with triple A syndrome from southern Turkey. METHODS: The coding sequence of the AAAS gene was sequenced including exon-intron boundaries. Haplotype analysis using markers from AAAS region was performed in order to assess potential founder effects. RESULTS: In all 3 patients, the identical nonsense mutation (R478X) in exon 16 of the AAAS gene was identified. The patients who may be distantly related appeared phenotypically similar with the classical triad of the triple A syndrome (adrenal insufficiency, alacrima and achalasia) with dermatological manifestations while lacking neurological features except for mild mental retardation. CONCLUSION: The R478X mutation tends to result in a rather severe phenotype although genotype-phenotype relationships cannot be drawn due to the small number of patients.