Association of urinary sex hormones with mood and behavior changes in a community adolescent cohort.

OBJECTIVE: To examine the contribution of variation in sex hormone excretion to mood and behavioral changes in adolescent females and males. DESIGN: Prospective, longitudinal observational cohort study. METHODS: Participants were 342 volunteers aged 10-12 years living in rural Australia. Urinary estradiol and testosterone levels measured by liquid chromatography-mass spectrometry were obtained at three-month intervals for three years. Integrated measures (area-under-curve) of urinary steroid excretion summarised as absolute and variability during each 12-month period of the study. Psychosocial data were gathered annually with the primary outcome of depressive symptomatology. Secondary outcomes were the other subscales of the Youth Self-Report, impulsive-aggression, sleep habits, and self-harm. RESULTS: 277 (158 male) participants contributed data over the full duration of the study and could be included in the analyses. In females, analyses of absolute urine hormone levels found no relationship between estradiol and any outcome, but higher testosterone was significantly associated with depression and poorer sleep. Greater variability of both urine estradiol and testosterone was associated with lower total psychopathology, anxious/depressed and social problems scores. Greater variability in urine estradiol was associated with lower attention problems and impulsive aggression in females. In males, higher testosterone and estradiol levels were associated with rule-breaking, and poorer sleep, and no associations were found for gonadal hormone variability for males. CONCLUSIONS: Longitudinal measurement of both iso-sexual and contra-sexual gonadal hormones contributes to a more nuanced view of the impact of sex steroids on mood and behavior in adolescents. These findings may enlighten the understanding of the impact of sex steroids during normal male and female puberty with implications for hormone replacement therapies as well as management of common mood and behavioral problems.

Conjunctival Melanoma in Childhood and Adolescence: A Systematic Review.

BACKGROUND: Conjunctival melanoma is rare in adults and rarer in children. We systematically reviewed the presentation, diagnostic and management strategies as well as outcomes for conjunctival melanoma in children and adolescents. METHODS: The following databases were searched: Medline, Embase, Web of Science and Scopus for cases of conjunctival melanoma occurring in children and adolescents < 18 years of age. RESULTS: Seventeen studies with 32 patients (18 males) were identified. The median age at presentation was 11 years (range 4-18 years). Most patients were white. Most patients presented with a conjunctival mass or naevus with a recent history of growth or change. Excision biopsy provided diagnosis and management for all cases. Adjuvant chemotherapy and radiotherapy were also used. One patient had metastatic disease at diagnosis and 3 developed metastatic disease (range 1-10 months). Two patients died from disease and one was alive with metastatic disease. Two patients had disease recurrence. Outcomes were observed to be better where diagnosis was made earlier and "no-touch" excision biopsy was performed in an appropriate specialist setting. CONCLUSIONS: Conjunctival melanoma occurs rarely in children and adolescents. Surgery is the mainstay of management. The prognosis is guarded in metastatic disease due to the small sample size and limited follow-up.

Foot Length Growth as a Novel Marker of Early Puberty.

Foot growth is part of overall pubertal growth but its relation to other anthropometric and hormonal changes is unclear. Our objective was to determine how foot length changes relate to changes in other growth parameters (height and weight), Tanner stage, and serum hormones. Adolescents (n = 342) were recruited to a 3-year longitudinal cohort study, underwent annual anthropometric assessments (height, weight, and foot length), and provided self-rated Tanner staging. They also provided blood samples that were analyzed using liquid chromatography-tandem mass spectrometry for serum testosterone and estradiol and classified as pre-pubertal or pubertal based on circulating hormone levels. Average annual percent increase in foot length was greater for pre-pubertal adolescents compared with pubertal. Increased foot length was associated with increases in height, weight, Tanner stage, and serum hormones in males and pre-menarcheal females but not post-menarcheal females. Foot length offers a novel, noninvasive, cost-effective, and easily demonstrable marker of early pubertal changes.

Self-rated Tanner stage and subjective measures of puberty are associated with longitudinal gonadal hormone changes.

Introduction In large community-based studies of puberty, Tanner staging by a clinician is often not possible. We compared self-rated Tanner staging and other subjective ratings of pubertal development with serum hormone levels measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reassess the utility of self-rated pubertal stage using highly sensitive and specific hormone analysis. Methods Adolescents and their parents enrolled in the Adolescent Rural Cohort study of Hormones and health, Education, environments and Relationships (ARCHER) answered annual survey questions on pubertal development. Annually, adolescents provided blood samples for serum testosterone and estradiol measured by LC-MS/MS. Results Longitudinally, self-rated Tanner stage was positively associated with serum testosterone and estradiol levels in both sexes. Confirmation by adolescent and parent that puberty had commenced was associated with higher gonadal hormone levels in both sexes. Parent and adolescent responses demonstrated 'fair' to 'moderate' agreement. Conclusions Over a 3-year follow-up, self-rated Tanner staging and simple questions regarding pubertal onset and development are positively associated with adolescent gonadal hormone concentrations in serum measured by mass spectrometry. Thus, self-report of puberty stage still has a role in large community-based studies where physical examination is not feasible.

Alectinib is effective, safe and tolerable in an adolescent with stage IVB ALK-rearranged adenocarcinoma of the lung.

Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC). There are no data for alectinib's safety or efficacy in younger patients, though it is superior to crizotinib in adult trials. We present a 14-year old girl diagnosed with stage IV-B ALK-positive adenocarcinoma of the lung after presenting with cough and fever. She was commenced on alectinib at adult dose and has had sustained complete metabolic remission for 9 months. She is the youngest patient with lung adenocarcinoma to be treated with alectinib.

Adenocarcinoma of the Lung in Childhood and Adolescence: A Systematic Review.

Primary lung cancer is extremely rare in children. It often presents with metastatic disease and carries a poor prognosis. Adenocarcinoma is the most common type of bronchogenic carcinoma in children and adults. Our aim was to systematically review the presenting features, approach to diagnosis and management, as well as the outcomes of primary pediatric adenocarcinoma of the lung. This systematic review was prospectively registered with PROSPERO. The following databases were searched: Medline, Embase, Web of Science, and Scopus for English language cases of primary pediatric adenocarcinoma of the lung. Forty-eight studies were included, comprising 62 patients with adenocarcinoma and 21 cases of adenocarcinoma in situ. Presenting features were nonspecific, with cough and dyspnea the main symptoms at diagnosis. The majority of patients with adenocarcinoma had metastatic disease at diagnosis. Surgery was the most common form of management. More than half the patients with adenocarcinoma had died at final follow-up, whereas 5 of 21 with adenocarcinoma in situ died. Medical management did not improve outcomes, except for two ALK receptor tyrosine kinase (ALK)-rearranged adenocarcinomas that responded to ALK inhibitor therapy alone. Primary pediatric adenocarcinoma of the lung is a rare entity which often presents with metastatic disease and portends a poor prognosis. Surgery is associated with disease-free status, although new agents such as ALK-inhibitors are able to prolong life without surgical management.

Visual Acuity Improves in Children and Adolescents With Idiopathic Infantile Nystagmus.

PURPOSE: Idiopathic infantile nystagmus is associated with reduced visual acuity. Recent work has linked extraocular muscle surgery to improvements in visual acuity through childhood but no work has reported long-term secular trends in visual acuity in infantile nystagmus. Our aim is to describe visual acuity changes for children and adolescents with idiopathic infantile nystagmus to allow comparison for future interventional studies. DESIGN: Retrospective chart review. METHODS: Review of patients attending our center up to the age of 18 with a diagnosis of idiopathic infantile nystagmus and visual acuity measured using Snellen visual acuity. Patients provided informed consent. RESULTS: We observed improvements in best corrected visual acuity in 43 children and adolescents with idiopathic infantile nystagmus. Binocular best corrected visual acuity improved at a rate of -0.16 logarithm of the minimum angle of resolution (logMAR)/log year of age (P < 0.001), an improvement of 0.05 logMAR (half a Snellen line) as the age doubles. Intraclass correlation was 0.95 and interindividual correlation between visual acuity and age was significant (r = -0.24, P < 0.001). CONCLUSIONS: We describe a natural history of gradual improvement in binocular visual acuity in infantile nystagmus and provide a baseline against which future interventional work can be compared.

Urinary Sex Steroids and Anthropometric Markers of Puberty - A Novel Approach to Characterising Within-Person Changes of Puberty Hormones.

BACKGROUND/AIMS: The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development. METHODS: A community sample of 104 adolescents (57 female) was studied over 12 months with annual anthropometric assessment, blood sampling and self-rated Tanner staging and urine collected every 3 months. Serum and urine sex steroids (T, E2) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LH by immunoassay. RESULTS: A high proportion (92%) of scheduled samples were obtained with low attrition rate of 6.7% over the 12 months. Urine hormone measurements correlated cross-sectionally and longitudinally with age, anthropometry and Tanner stage. CONCLUSION: We have developed a feasible and valid sampling methodology and measurements for puberty hormones in urine, which allows a sampling frequency by which individual pubertal progression in adolescents can be described in depth.

Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

OBJECTIVES: Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. DESIGN AND METHODS: The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. RESULTS: Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. CONCLUSIONS: Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable.

The effects of estradiol on mood and behavior in human female adolescents: a systematic review.

UNLABELLED: Mood disorders and health risk behaviors increase in adolescence. Puberty is considered to contribute to these events. However, the precise impact of pubertal hormone changes to the emergence of mood disorders and risk behaviors is relatively unclear. It is important that inappropriate attribution is not made. Our aim was to determine what is known about the effect of endogenous estradiol on human adolescent girls' mood and behavior. The databases searched were MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre-MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion, contemporaneous hormone and mood or behavioral assessment was required. Data were extracted following a template created by the authors. Fourteen studies met our inclusion criteria. There was some consistency in findings for mood and estradiol levels, with associations between estradiol and depression and emotional tone and risk taking. Results were less consistent for studies assessing other mood and behavioral outcomes. Most studies were cross-sectional in design; assay methodologies used in older studies may lack the precision to detect early pubertal hormone levels. CONCLUSION: Three longitudinal and several cross-sectional studies indicate potential associations between estradiol and certain mood or affective states, especially depression and mood variability though there are insufficient data to confirm that the rise in estradiol during puberty is causative. We believe that it is important for health professionals to take care when attributing adolescent psychopathology to puberty hormones, as the current data supporting these assertions are limited.

Testosterone and its effects on human male adolescent mood and behavior: a systematic review.

PURPOSE: During human puberty, there is an approximate 30-fold increase in testosterone production in boys. This increase is often linked to changes in mood and behavior in adolescence such as aggression, an increase in risk taking, and depression. The aim of this systematic review was to determine what evidence exists on the effects of endogenous testosterone on behavior and mood in males during adolescence. METHODS: The following databases were searched: MEDLINE, Pre-MEDLINE, Education Resources Information Centre, PsycINFO, EMBASE, Scopus, and Web of Science. Only human studies were included. The study is community based, and the participants were healthy male adolescents within the age range of 9-18 years. Studies were required to have a validated mood and/or behavior assessment contemporaneous with a timed testosterone measurement. RESULTS: A total of 27 studies met the inclusion criteria of which only one was a longitudinal study. The remaining 26 studies were cross sectional in their analysis. As a variety of measurement tools were used, no meta-analysis was possible. Most studies focused on aggression. The one longitudinal study looking at testosterone and aggression showed little relationship with concurrent changes in aggression. Most of the cross-sectional studies of adolescent males observed relationships between aggression and testosterone levels. With respect to other behaviors and moods and/or affect, no consistent relationships with testosterone were observed in cross-sectional studies. CONCLUSIONS: This systematic review concludes that there are insufficient longitudinal data of high methodological quality to currently confirm that changing testosterone levels during puberty are significantly associated with mood and behavior in adolescent males. To discount these findings is to risk apportioning blame inappropriately and missing other important diagnoses in adolescent males.

Text messaging is a useful reminder tool.

INTRODUCTION: Longitudinal studies of adolescents must be 'adolescent-friendly', to collect data and to encourage maintenance in the study cohort. Text messaging may offer a feasible means to do both. METHODS: Adolescents in the Adolescent Rural Cohort, Hormones and Health, Education, Environments and Relationships (ARCHER) study (n=342) are sent automated text messages every 3 months, prompting biological specimen collection. RESULTS: A total of 99.2% of participants (or their parents) owned a mobile phone, of which 89.1% of participants responded to text messages and 97.3% of intended urine samples were collected. The average time to provide a urine sample after prompting correlated with time to reply to Short Message Service (SMS). CONCLUSIONS: This study shows SMS can be used effectively in longitudinal research involving adolescents and is feasible and useful as a reminder tool for regular biological specimen collection.

Low glycaemic index dietary interventions in youth with cystic fibrosis: a systematic review and discussion of the clinical implications.

A systematic review was conducted to assess what is known about the effect of low glycaemic index (GI) diets on glycaemic control, weight and quality of life in youth with cystic fibrosis (CF). Eligibility criteria were systematic reviews, randomised and non-randomised trials of low GI dietary interventions in CF. Outcomes examined were glycaemic control, quality of life, anthropometry and respiratory function. Reference lists were manually searched and experts in the field were consulted. Four studies met the eligibility criteria; two were excluded because they did not include data on any of the outcomes. The remaining two were studies that examined GI secondary to any other intervention: one used GI as a factor in enteral feeds and the other incorporated low GI dietary education into its treatment methodology. There is insufficient evidence to recommend use of low GI diets in CF. Since there is evidence to support use of low GI diets in type 1, type 2 and gestational diabetes, low GI diets should be tested as an intervention for CF. The potential risks and benefits of a low GI diet in CF are discussed.