Orhan Derman

The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents

As IGF-1 is the major factor that affects bone growth, and both osteocalcin and bone-specific alkaline phosphatase are important markers of bone formation during puberty, there must be a relationship between these markers that does not change according to sex. The aim of this study was to investigate the relationships between pubertal development, the IGF-1 axis, and bone formation in healthy adolescents. Two hundred and five healthy children and adolescents were included in this cross-sectional study. Tanner’s classification was used to determine the pubertal developmental stage. Serum IGF-1 levels and IGF-1/IGFBP-3 ratios increased with advancing pubertal stages, and maximum mean values were found at stages III–IV in girls and at stage IV in boys. Serum IGF-1 and IGFBP-3 levels were significantly correlated with osteocalcin and bone-specific alkaline phosphatase levels in boys, but not in girls. This difference between the sexes, and the relation of the IGF-1 axis to increased bone formation during puberty in both sexes, can be explained by the rate of increase of the IGF-1/IGFBP-3 ratio. We conclude that the timing of the increased bone formation rate during puberty; that is, the timing of the pubertal growth spurt, is determined by the maximum increase rate of the IGF-1/IGFBP-3 ratio. But this new hypothesis needs to be supported by longitudinal studies.

Tamoxifen treatment for pubertal gynecomastia.

We evaluated the efficacy of the tamoxifen treatment in 37 patients with pubertal gynecomastia. All had distinct, easily palpable breast swellings with a diameter of over three cm. Pain, tenderness, and swelling associated with gynecomastia were reported by six patients. Eight of the patients were obese. One patient also suffered from varicocele. Pain and size reduction was seen in all patients with tamoxifen treatment. No long-term side effects of tamoxifen were observed. The dose of tamoxifen was increased in three patients due to poor response. Two of the treatment group had recurrence problem at follow-up. We did not need to refer any patient to surgery. Tamoxifen treatment is relatively non-toxic, may be beneficial and we think it should be considered for pubertal gynecomastia.

Prevalence of obesity in adolescents and the impact of sexual maturation stage on body mass index in obese adolescents.

OBJECTIVE Puberty is a high-risk period for the development of obesity. The aim of this study was to determine the prevalence of obesity in adolescents admitted to an outpatient adolescent clinic and investigate the relationships between the increase of body mass index and sexual maturation stages in obese adolescents. MATERIAL AND METHODS We recruited 6,462 adolescents, aged 9-16 years, admitted to the outpatient clinic of our Adolescent Unit, between May 1999 and September 2000. BMI was calculated as weight per height with weight in kilograms and height in meters. Adolescents with a BMI > or = 95th percentile for age and sex were defined as obese, with BMIs > or = 90th percentile but < 95th percentile were defined as overweight and considered at risk for obesity. Obese adolescents, with endocrine problems identified to cause obesity, were excluded from this study. Pearson correlation coefficients were used to assess the relationships between BMI and age. The differences between the sexual maturation stages were evaluated with Mann-whitney U Test. RESULTS Out of 6,462 cases screened, 151 obese adolescents were found. Prevalence of obesity for the total sample surveyed was estimated at 2.3%. BMI values were significantly correlated with age in both sexes. In girls, only the increase of BMI values from stage I to stage II was found to be statistically significant. In boys, BMI values did not differ significantly between the sexual maturation stages but the number of obese cases were high in stages I and II. DISCUSSION AND CONCLUSION The pubertal growth spurt (timing determined by sexual maturation stage) effects the amount of fat accumulation and the distribution of fat in different ways in boys and girls. So, not only the age and sex but also the sexual maturation stage has to be taken into account while evaluating the BMI values for investigating the risk of obesity in puberty.

The Novel Genetic Disorder Microhydranencephaly Maps to Chromosome 16p13.3-12.1

We studied a large consanguineous Anatolian family with children who exhibited hydranencephaly associated with microcephaly. The children were severely affected. This novel genetic disorder is autosomal recessive. We used autozygosity mapping to identify a locus at chromosome 16p13.3-12.1; it has a LOD score of 4.11. The gene locus is within a maximal 11-cM interval between markers D16S497 and D16S672 and within a minimal critical region of 8 cM between markers D16S748 and D16S490.

Establishment of interdisciplinary child protection teams in Turkey 2002–2006: Identifying the strongest link can make a difference!

OBJECTIVES The University of Iowa Child Protection Program collaborated with Turkish professionals to develop a training program on child abuse and neglect during 2002-2006 with the goals of increasing professional awareness and number of multidisciplinary teams (MDT), regional collaborations, and assessed cases. This paper summarizes the 5-year outcome. METHODS A team of instructors evaluated needs and held training activities in Turkey annually, and provided consultation when needed. Descriptive analysis was done via Excel and SPSS software. RESULTS Eighteen training activities were held with 3,570 attendees. Over the study period, the number of MDTs increased from 4 to 14. The MDTs got involved in organizing training activities in their institutions and communities. The number of medical curriculum lectures taught by MDTs to medical students/residents, conferences organized by the MDTs, and lectures to non-medical professional audiences increased significantly (R(2)=91.4%, 83.8%, and 69.2%, respectively). The number of abuse cases assessed by the MDTs increased by five times compared to pre-training period. CONCLUSIONS A culturally competent training program had a positive impact on professional attitudes and behaviors toward recognition and management of child abuse and neglect in Turkey. The need to partner with policy makers to revise current law in favor of a greater human services orientation became clear. PRACTICE IMPLICATIONS Pioneers in developing countries may benefit from collaborating with culturally competent instructors from countries with more developed child protection systems to develop training programs so that professional development can improve recognition and management of child abuse and neglect.

The relationships between dental age, chronological age and bone age in Turkish adolescents with constitutional delay of growth.

The aim of this study was to investigate the relationships between dental age and bone age in Turkish adolescents with constitutional delay of growth and compare them with a group of normal, healthy adolescents. Left hand and wrist radiographs and dental panaromic radiographs of 33 adolescents (25 boys and 8 girls) aged between 10 and 16 years with constitutionally delayed growth were assessed. The control group comprised 41 healthy adolescents (24 boys, 17 girls) aged between 10 and 16 years. Bone age was determined according to Greulich and Pyle; dental age was assessed using the Demirjian method. In the control group, no statistical difference was found between chronological, bone and dental ages. In the group of adolescents with constitutional growth delay, there was no significant difference between chronological age and dental age, but the differences between dental age and bone age and between chronological age and bone age were found to be statistically significant. It was found that Demirjians dental age assessment is a valid method for scoring dental age in Turkish adolescents. Adolescents with constitutional delay of growth had dental maturation appropriate for chronological age, but not for bone age.

Osteocalcin. A biochemical marker of bone turnover during puberty

During bone remodelling, osteocalcin is produced by osteoblasts and its level increases during the events characterized by rapid bone turnover. Osteocalcin is a bone matrix protein, which is specific for bone metabolism and it is not influenced by metabolic bone disorders. Osteocalcin is an important marker of bone turnover in physiological and pathological conditions. Physiologically, serum osteocalcin was increased in children, particularly during the first year of life and during puberty, when evolution of the concentration was related to rapidity of physical growth. Evidence of a correlation with growth rates comes from the observation that serum osteocalcin levels parallel the height velocity curve, with higher values in childhood and during adolescence, that later fall to adult values. There are previous studies reporting that there is age- and sex-dependent change in serum osteocalcin levels in children and adolescents with a pattern resembling height velocity curves for children and serum osteocalcin elevation coincides with the pubertal growth spurt. These findings demonstrate that pubertal development and sex should be taken into account rather than chronological age when serum levels of osteocalcin are evaluated. In most of the studies relationships among osteocalcin and chronological age and bone age, but not pubertal developmental stage (sexual maturation stage) were investigated. The aim of our study was to determine whether osteocalcin is a useful marker for the pubertal growth spurt period. In this study, osteocalcin levels in male adolescents were examined in relation to their sexual maturation stage and age. According to our findings, the follow up of osteocalcin levels in relation to sexual maturation stages could be a new method to determine the phase of the pubertal growth spurt. An increase or decrease in osteocalcin levels on consecutive measurements may indicate the childs entering accelerated or decelerated stages of the growth spurt, respectively. We emphasize that the follow up of adolescent growth is made by determination of the sexual maturation stage, and not by age. Osteocalcin is a highly specific, reliable and useful marker for evaluation of the growth spurt and is not influenced by nonosseous disorders.

Long-term follow-up of tamoxifen treatment in adolescents with gynecomastia.

Ten pubertal boys treated with tamoxifen for gynecomastia for more than 3 months were evaluated after 2.5-7 years (mean 4.6 years) to determine the side effects of this therapy. We assessed the safety of long duration in adolescents with pubertal gynecomastia treated with tamoxifen. We did not find any serious side effects of tamoxifen in these patients.

Coagulation disorders as the cause of menorrhagia in adolescents.

This study was undertaken to assess the frequency of coagulation disorders as a cause of menorrhagia in adolescents. A retrospective chart review was conducted of all adolescents with menorrhagia admitted to the Adolescent Unit of Ihsan Doğramaci Childrens Hospital of Hacettepe University Faculty of Medicine in Ankara, Turkey from May 1999 to April 2002. 47 admissions for menorrhagia were identified, 44 were dysfunctional uterine bleeding due to anovulation, while a primary coagulation disorder was found in three patients. Two had Von Willebrand disease and one factor 11 deficiency. We suggest that pediatricians, gynecologists and other adolescent health care providers should be aware of the primary coagulopathy as a cause of menorrhagia in adolescence.

Occupational asthma in apprentice adolescent car painters

Occupational asthma (OA) is one of the leading causes of pulmonary diseases and has been extensively studied in adults. Childhood employment, a significant problem in many developing countries, should be studied to determine and evaluate its effects on psychosocial and lung health. In order to investigate the presence of work‐related asthma‐like symptoms and OA in apprentice adolescent car painters, 72 adolescents between the ages of 15–20 yr studying in Vocational Training Centres of Ankara were investigated using questionnaire, pulmonary function test (PFT), serial peak expiratory flow (PEF) measurements and methacholine inhalation tests. As a control group, 72 adolescents studying in Industrial and Commercial Training Centres located in the same environment were investigated with questionnaire and PFT. Almost 50% of the study group had work‐related asthma‐like symptoms for which occupational dermatitis history was predictive [odds ratio: 2.9 (1.026–8.13) (95% confidence interval)]. Seventeen of 22 with serial PEF measurements showed a variability of ≥20% and three (4.2%) of 12 tested with methacholine inhalation test had a PC20≤8 mg/ml, which led to the diagnosis of OA. There was no statistically significant difference between study and control groups in terms of PFT. In conclusion, the high prevalence of work‐related asthma‐like symptoms among adolescent car painters clearly indicates the need for routine follow‐up of adolescent workers for lung health.