A Randomized Trial of the Effect of a GnRH Analogue Injection on Ghrelin Levels in Girls.

INTRODUCTION: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels. METHODS: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH® (100 µg/m2) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels. RESULTS: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 ± 257.1 vs. 247.6 ± 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5-115.7] vs. 143.5 [71.4-285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = -0.73, p = 0.005, and r = -0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = -0.57, p = 0.041). CONCLUSION: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels.

Delayed puberty in boys in central Sweden: an observational study on diagnosing and management in clinical practice.

OBJECTIVES: To compare the usefulness of the classical definition of delayed puberty (DP) in boys with puberty nomograms and to describe the management of DP in boys in a hospital-based setting. STUDY DESIGN: Observational retrospective multicentre study with a short-term follow-up. SETTING AND PARTICIPANTS: Boys diagnosed with DP during 2013-2015 at paediatric departments in four counties in central Sweden. The medical records of 165 boys were reviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: Number of boys with DP after re-evaluation of the diagnosis according to the classical definition in comparison with puberty nomograms. Description of investigations performed and treatment provided to boys with DP. RESULTS: In total, 45 and 58 boys were found to have DP according to the classical definition and the nomograms, respectively. Biochemical and/or radiological testing was performed in 91% of the 58 boys, but an underlying disease was only found in 9% of them. Approximately 79% of the boys received testosterone treatment, either as injections of testosterone enanthate or as testosterone undecanoate. CONCLUSIONS: Puberty nomograms may be helpful instruments when diagnosing pubertal disorders in boys as they are not limited to an age close to 14 years and also identify boys with pubertal arrest. The majority of boys with DP undergo biochemical or radiological examinations, but underlying diseases are unusual emphasising the need for structural clinical practice guidelines for this patient group.

The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden.

BACKGROUND: We found an increase in the incidence rate (IR) of childhood thyrotoxicosis (CT) during the 1990s in central Sweden. The optimal treatment method for CT is a subject that is still debated upon. OBJECTIVES: To investigate whether the increase in IR of CT in Sweden persists and to study the treatment outcome. METHOD: Children <16 years of age diagnosed with CT during 2000-2009 and living in 1 of 5 counties in central Sweden were identified retrospectively using hospital registers. Data on clinical and biochemical characteristics and outcomes of treatment were collected from medical records. The corresponding data from 1990 to 1999 were pooled with the new data. RESULTS: In total, 113 children were diagnosed with CT during 1990-2009 in the study area. The overall IR was 2.2/100,000 person-years (95% CI 1.2-2.5/100,000 person-years). The IR was significantly higher during 2000-2009 than during 1990-1999 (2.8/100,000 [2.2-3.6] vs. 1.6/100,000 person-years [1.2-2.2], p = 0.006). The increase was significant for both sexes. Seventy percent of the patients who completed the planned initial treatment with antithyroid drugs (ATDs) and were not lost to follow-up relapsed within 3 years. Boys tended to relapse earlier than girls (6.0 months after drug withdrawal [95% CI 1.9-10.0] vs. 12.0 months [95% CI 6.8-17.3], p = 0.074). CONCLUSIONS: The IR of CT is increasing in both girls and boys. Relapse rate after withdrawal of ATD treatment is 70%. Boys tend to relapse earlier than girls, and this needs to be further investigated.

Serum kisspeptin concentrations are negatively correlated with body mass index in adolescents with anorexia nervosa and amenorrhea.

OBJECTIVE: To measure, for the first time, serum kisspeptin concentrations in adolescent females with anorexia nervosa (AN) and associated amenorrhea, and investigate potential correlations of kisspeptin with anthropometric, bone and hormonal data. DESIGN: Setting: University Adolescent Medicine Center. PARTICIPANTS: Females aged 12-20 years with typical or atypical AN (based on DSM-5 diagnostic criteria) and controls. INTERVENTIONS: Measurement of body mass index (BMI), whole body/lumbar spine bone mineral density and serum concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine, estradiol (E2), 17-hydroxyprogesterone. MAIN OUTCOME MEASURES: Kisspeptin serum concentrations and correlations between kisspeptin and AN-related anthropometric, bone and hormonal changes. RESULTS: Participants included 37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the control group. All typical AN patients had secondary amenorrhea. Wide inter-subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no significant differences among study groups; there was a trend toward higher concentrations in the atypical AN group. Adolescents with typical AN had significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2 (P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse correlation between BMI and serum kisspeptin was noted in the typical AN group (r=-0.60, P=0.012). CONCLUSIONS: Serum kisspeptin concentrations overlapped between patients and controls; in typical anorexic adolescents kisspeptin concentrations were negatively correlated with BMI. Future studies are needed to explore kisspeptin physiology in AN.