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   2014| November  | Volume 18 | Issue 7  
    Online since November 20, 2014

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Nutrition and pubertal development
Ashraf Soliman, Vincenzo De Sanctis, Rania Elalaily
November 2014, 18(7):39-47
DOI:10.4103/2230-8210.145073  PMID:25538876
Nutrition is one of the most important factors affecting pubertal development. Puberty entails a progressive nonlinear process starting from prepubescent to full sexual maturity through the interaction and cooperation of biological, physical, and psychological changes. Consuming an adequate and balanced healthy diet during all phases of growth (infancy, childhood and puberty) appears necessary both for proper growth and normal pubertal development. Girls begin puberty at an earlier age compared to past decades. Excessive eating of many processed, high-fat foods, may be the cause of this phenomenon. Overweight or obese children are more likely to enter puberty early. Some evidence suggests that obesity can accelerate the onset of puberty in girls and may delay the onset of puberty in boys. Moreover, the progression of puberty is affected by nutrition. On the other hand, puberty triggers a growth spurt, which increases nutritional needs including macro and micronutrients. Increased caloric, protein, iron, calcium, zinc and folate needs have to be provided during this critical period of rapid growth. Severe primary or secondary malnutrition also can delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Moreover, many environmental endocrine disruptors (EDs) have been identified that can significantly impair the normal course of puberty. This mini-review sums up some important findings in this important complex that link nutrition and pubertal development.
  33 7,840 1,700
Anemia and growth
Ashraf T Soliman, Vincenzo De Sanctis, Sanjay Kalra
November 2014, 18(7):1-5
DOI:10.4103/2230-8210.145038  PMID:25538873
  21 2,875 9,421
Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?
Ashraf Soliman, Vincenzo De Sanctis, Rania Elalaily, Said Bedair
November 2014, 18(7):53-62
DOI:10.4103/2230-8210.145075  PMID:25538878
Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS.
  16 13,925 967
Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond
Vincenzo De Sanctis, Salvatore Di Maio, Ashraf T Soliman, Giuseppe Raiola, Rania Elalaily, Giuseppe Millimaggi
November 2014, 18(7):63-71
DOI:10.4103/2230-8210.145076  PMID:25538880
Skeletal age assessment (SAA) is a clinical procedure which is used in determining the SA of children and adolescents. Bone development is influenced by a number of factors, including nutrition, hormonal secretions, and genetics. There are several factors to be borne in mind when using methods of assessing skeletal maturity. These include: Variability among methods, degree of variability in the estimation of skeletal maturation, sources of low accuracy, and dispersion of the values of skeletal maturation. Currently, the main clinical methods for SAA are the Greulich and Pyle (GP) and Tanner and Whitehouse (TW) methods. The GP method has the advantage of being quick and easy to use. A well-trained radiologist takes few minutes to determine the bone age (BA) from a single hand radiograph. The method of TW, however, seems to be more reliable than the GP method. In recent years, the increasing speed in computer sciences and reduction of their cost has given the opportunity to create and use computerized BA estimation system. Despite the fact that the number of automated systems for BAA have increased, most are still within the experimental phase. The use of automated BA determination system, cleared for clinical use in Europe (BoneXpert), has been validated for various ethnicities and children with endocrine disorders. Ultrasound imaging has some limitations that include operator dependence, lower intra-rater and inter-rater reliability of assessment and difficulties with standardization of documentation and imaging transfer. Magnetic resonance imaging (MRI) is noninvasive alternative tool for SA assessment in children. However, few studies have been reported on this topic, and further research is needed to evaluate the reliability and validity of MRI BAAs. In conclusion, at present radiographic methods for the assessment of BA remain the gold standards. Whatever method one adopts, it is essential to minimize the causes of imprecision by taking care to consider the quality of the X-ray. Moreover, it is imperative to assume a correct hand positioning because poor positioning can change the appearance of some bones. It is also preferable to employ scoring methods to these techniques and percentiles rather than BA in years and months. In addition, the possible differences in maturation among different population should be kept in mind.
  10 13,844 2,093
Linear growth and endocrine function in children with ataxia telangiectasia
Mohammad Ehlayel, Ashraf Soliman, Vincenzo De Sanctis
November 2014, 18(7):93-96
DOI:10.4103/2230-8210.145079  PMID:25538885
Introduction: Ataxia telangiectasia (AT) is a rare, genetic, primary immune deficiency disease characterized by immunodeficiency and neurological manifestations, with an increased tendency to infection, malignancy, and autoimmune diseases. Both growth delay and endocrine abnormalities are occasionally reported in these patients. Patients and Methods: We studied growth parameters height (Ht), weight, body mass index (BMI) and calculated the Ht standard deviation scores (HtSDS) of 13 patients (age 7.7 ± 3.5 years-age range: 3-14.5 years) with AT in relation to their mid-parental Ht SDS (MPHtSDS). We measured their serum calcium (Ca), phosphorus (PO4), alkaline phosphatase, alanine transferase (ALT), serum ferritin, creatinine and albumin concentrations. Endocrine investigations included the assessment of serum free thyroxine (FT4), thyrotropin (TSH), insulin-like growth factor-I (IGF-I) and morning cortisol. Complete blood count and serum immunoglobulins (IgG, IgM and IgA antibodies) were also measured. Growth data were correlated to hormonal and immune data. Results: About 31% of patients with AT had short stature (HtSDS <−2). However, their MPHtSDS denoted that their short stature was familial because four out of 13 had MPHtSDS <−2. They had low BMI, and two of them had low serum albumin and IGF-I, denoting malnutrition or disturbed growth hormone secretion. Elevated serum ALT and ferritin in some patients suggest immune-related inflammation in the liver. 30% of patients had high TSH, two of them had low FT4 diagnosing overt (15%) and sub-clinical (15%) hypothyroidism. Anti-thyroid peroxidase antibodies were high in two out of 13 patients denoting immune-related thyroid aggression. Eight out of 13 patients had Vitamin D deficiency (<20 ng/ml) however, their serum Ca and PO 4 levels were in the normal range. One adolescent girl (14.5 years) had hyper-gonadotropic hypogonadism (low estradiol and high follicle stimulating hormone). All patients had normal 8 AM cortisol and renal function. None of the growth parameters were correlated with the IgG, IgM or IgA levels. In summary: Patients with AT had a high prevalence of growth retardation and endocrine dysfunction in the form of low IGF-I, overt and subclinical hypothyroidism and hypogonadism. Physicians should be aware of these possible endocrinopathies for an early diagnosis and proper treatment.
  8 2,104 316
Vitamin D deficiency in adolescents
Ashraf T Soliman, Vincenzo De Sanctis, Rania Elalaily, Said Bedair, Islam Kassem
November 2014, 18(7):9-16
DOI:10.4103/2230-8210.145043  PMID:25538884
The prevalence of severe vitamin D deficiency (VDD) in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical presentations may be subtle and go unnoticed, thus making true prevalence studies difficult. Adolescents with severe VDD may present with vague manifestations including pain in weight-bearing joints, back, thighs and/or calves, difficulty in walking and/or climbing stairs, or running and muscle cramps. Adaptation includes increased parathormone (PTH) and deceased insulin-like growth factor-I (IGF-I) secretion. PTH enhances the tubular reabsorption of Ca and stimulates the kidneys to produce 1, 25-(OH) 2D3 that increases intestinal calcium absorption and dissolves the mineralized collagen matrix in bone, causing osteopenia and osteoporosis to provide enough Ca to prevent hypocalcaemia. Decreased insulin like growth factor-I (IGF-I) delays bone growth to economize calcium consumption. Radiological changes are not uncommon and include osteoporosis/osteopenia affecting long bones as well as vertebrae and ribs, bone cysts, decalcification of the metaphysis of the long bones and pseudo fractures. In severe cases pathological fractures and deformities may occur. Vitamin D treatment of adolescents with VDD differs considerably in different studies and proved to be effective in treating all clinical, biochemical, and radiological manifestations. Different treatment regiments for VDD have been discussed and presented in this mini-review for practical use. Adequate vitamin D replacement after treating VDD, improving calcium intake (milk and dairy products), encouraging adequate exposure to the sun and possible enrichment of the stable food with vitamin D in areas with high prevalence of VDD are important measures to prevent the harmful consequences of VDD.
  8 3,956 1,016
Onset of menstrual cycle and menses features among secondary school girls in Italy: A questionnaire study on 3,783 students
Vincenzo De Sanctis, Sergio Bernasconi, Luigi Bianchin, Gianni Bona, Mauro Bozzola, Fabio Buzi, Carlo De Sanctis, Franco Rigon, Luciano Tatò, Giorgio Tonini, Egle Perissinotto
November 2014, 18(7):84-92
DOI:10.4103/2230-8210.140251  PMID:25538883
Premise: Healthcare professionals need updated information about what is the range of "normal" variation of menstrual cycle features to support young girls and their parents in managing reproductive health, and to detect diseases early. Materials and Methods: This cross-sectional study aimed to provide an updated picture of age at menarche and main menstrual cycle characteristics and complaints in an Italian population-based sample of 3,783 adolescents attending secondary school. Girls filled in a self-administered anonymous questionnaire including questions about demography, anthropometry, smoking and drinking habits, use of contraceptive, socioeconomic status, age at menarche, menstrual pattern, and physical/psychological menstrual complaints. Mean age at menarche and prevalence of polymenorrhea (cycle length < 21 days), oligomenorrhea (cycle length > 35 days), irregularity, dysmenorrhea, and of physical/psychological complaints were computed. Factors associated with age at menarche and menstrual disturbances were explored by using multiple logistic models. Results: The girls' mean age was 17.1 years (SD 1.4 years) and the mean age at menarche was 12.4 years (SD 1.3 years); menarche occurred with two monthly peaks of frequency in July-September and in December-January (P < 0.0001). Age at menarche was significantly associated with geographic genetics (as expressed by parents' birth area), mother's menarcheal age, BMI, family size, and age at data collection. The prevalence of polymenorrhea was about 2.5%, oligomenorrhea was declared by 3.7%, irregular length by 8.3%, while long bleeding (>6 days) was shown in 19.6% of girls. Gynecological age was significantly associated with cycle length (P < 0.0001) with long cycles becoming more regular within the fourth year after menarche, while frequency of polymenorrhea stabilized after the second gynecological year. Oligomenorrhea and irregularity were both significantly associated with long menstrual bleeding (adjusted OR = 2.36; 95% CI = 1.55-3.60, and adjusted OR = 2.59; 95% CI = 1.95-3.44, respectively). Conclusions: The findings of the study support the levelling-off of secular trend in menarche anticipation in Italy and confirm the timing in menstrual cycle regularization. The study provides updated epidemiological data on frequency of menstrual abnormalities to help reproductive health professionals in managing adolescent gynecology.
  7 3,103 556
Determinants, consequences and prevention of childhood overweight and obesity: An Indian context
Harish Ranjani, Rajendra Pradeepa, TS Mehreen, Ranjit Mohan Anjana, Krishnan Anand, Renu Garg, Viswanathan Mohan
November 2014, 18(7):17-25
DOI:10.4103/2230-8210.145049  PMID:25538874
The prevalence of obesity in adolescents and children has risen to alarming levels globally, and this has serious public health consequences. Sedentary lifestyle and consumption of calorie-dense foods of low nutritional value are speculated to be two of the most important etiological factors responsible for escalating rate of childhood overweight in developing nations. To tackle the childhood obesity epidemic we require comprehensive multidisciplinary evidence-based interventions. Some suggested strategies for childhood obesity prevention and management include increasing physical activity, reducing sedentary time including television viewing, personalized nutrition plans for very obese kids, co-curriculum health education which should be implemented in schools and counseling for children and their parents. In developing countries like India we will need practical and cost-effective community-based strategies with appropriate policy changes in order to curb the escalating epidemic of childhood obesity.
  6 20,054 1,393
Endocrine check-up in adolescents and indications for referral: A guide for health care providers
Vincenzo De Sanctis, Ashraf T Soliman, Bernadette Fiscina, Heba Elsedfy, Rania Elalaily, Mohamed Yassin, Nicos Skordis, Salvatore Di Maio, Giorgio Piacentini, Mohamed El Kholy
November 2014, 18(7):26-38
DOI:10.4103/2230-8210.145055  PMID:25538875
The American Academy of Pediatrics recommends that young people between the ages of 11 and 21 years should be seen annually by their pediatricians, since annual checkups can be an important opportunity for health evaluation and anticipatory guidance. Parents of infants and young children are accustomed to regularly visiting a pediatrician for their child's checkups. Unfortunately, when children reach the teen years, these annual checkups may decrease in frequency. In routine check-ups and medical office visits, particular attention should be paid to the possibility of a developmental or endocrine disorder. Early diagnosis and treatment may prevent medical complications in adulthood and foster age-appropriate development. Our purpose is to acquaint readers with the concept, based on current scientific understanding, that some endocrine disorders may be associated with a wide range of deleterious health consequences including an increased risk of hypertension and hyperlipidemia, increased risk of coronary artery disease, type 2 diabetes, significant anxiety and lack of self-esteem. Understanding the milestones and developmental stages of adolescence is essential for pediatricians and all other health providers who care for adolescents. Treating adolescents involves knowledge of a variety of medical, social and legal information; in addition, close working relationships must be established within the adolescent's network to create an effective care system. In summary, we underline the importance of a periodic endocrine checkup in adolescents in order to identify endocrine problems early and develop an approach to treatment for those patients who need help during this time. Indications for endocrine referral for professional and other healthcare providers are also included. These lists are clearly not intended to be comprehensive, but will hopefully serve as a guide for specific clinical circumstances.
  6 3,398 981
Phenotypic variability of hyperandrogenemia in females heterozygous for CYP21A2 mutations
Vassos Neocleous, Christos Shammas, Alexia AP Phedonos, Leonidas A Phylactou, Nicos Skordis
November 2014, 18(7):72-79
DOI:10.4103/2230-8210.145077  PMID:25538881
Objectives: The objective was to seek evidence on the prevalence and consequences of heterozygous CYP21A2 mutations in girls, adolescent, and adult females with clinical manifestation of androgen excess. Patients and Methods: The study included 64 girls diagnosed with premature adrenarche (PA) in childhood and 141 females with clinical hyperandrogenemia manifested in adolescence or adulthood. Direct DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to identify mutations in the CYP21A2 gene. Results: (1) Thirty-four patients were diagnosed with nonclassical-congenital adrenal hyperplasia (NC-CAH) based on the 17-hydroxyprogesterone (17-OHP) levels and the presence of two mutations in CYP21A2 and therefore were excluded from the study, 66 were found to be heterozygotes and finally 105 had no identifiable mutations. The most frequent mutations among the carriers were the mild p.Val281 Leu and p.Qln318stop. Higher levels of mean stimulated 17-OHP were found in the carriers of the p.Val281 Leu. (2) A notable increased allelic frequency for the known p.Asn493 Ser polymorphism was observed in the pool of females with hyperandrogenemia in whom no mutation was identified. (3) In girls, who presented early with PA, 26.6% were diagnosed with NC-CAH and carried two mutations, 28.7% were identified as heterozygotes 43.7% had no identifiable genetic defect in the translated region of the CYP21A2 gene. On the contrary, in the group of 141 females with late onset hyperandrogenemia, the presence of 2 mutations was detected in 12%, 1 mutation in 33.4% and no mutation in 54.6%. Conclusions: The carrier status for 21-OHD, may be an important factor in the variable phenotype of hyperandrogenism and may be a contributing factor for the early manifestation of the disease.
  4 3,094 474
Does priming with sex steroids improve the diagnosis of normal growth hormone secretion in short children?
Ashraf Soliman, Ashraf Adel, Aml Sabt, Elkhansa Elbukhari, Hannah Ahmed, Vincenzo De Sanctis
November 2014, 18(7):80-83
DOI:10.4103/2230-8210.145078  PMID:25538882
Introduction: There is still controversy for priming with sex steroid before growth hormone (GH) testing. Objective: We studied GH response to stimulation in 92 children >9 years with idiopathic short stature (height standard deviation score [HtSDS]-2). They were divided randomly into two groups. Children in Group 1 (n = 50) were primed with premarin in girls and testosterone in boys and those in Group 2 were not primed (n = 42). All children were tested using standard clonidine test and their serum insulin-like growth factor-I concentration (IGF-I). Additionally the growth and GH-IGF-I data of the two groups of children were compared with those for 32 short children (HtSDS <−2) below the age 9 years who were non-primed before GH testing (Group 3). Results: Neither GH peak response to provocation nor IGF-I concentrations differed between the two groups with and without priming. Discussion: Taking a cut-level of 7 ng/ml for normal GH response to clonidine, priming with sex steroids did not significantly increase the percentage of patients with normal GH response (52%) versus nonpriming (47%). IGF-I level did not show any significant difference among the two studied groups >9 years. The peak GH response to clonidine provocation test did not differ before (n = 42) versus after 9 years (n = 32) of age. Conclusions: In this randomized study priming with sex steroids before GH testing did not significantly increase the yield of diagnosing short patients with normal GH secretion. In addition, GH response to provocation did not vary significantly between young (<9 years) and old (>9 years) short children.
  4 2,249 468
Agenesis and not ectopia is common in North Indian children with thyroid dysgenesis
Devi Dayal, L Sindhuja, Anish Bhattacharya, Kushaljit Singh Sodhi, Naresh Sachdeva
November 2014, 18(7):97-99
DOI:10.4103/2230-8210.145080  PMID:25538886
Context: Ectopic Thyroid Gland (ETG) is known to be the most common form of thyroid dysgenesis in children with permanent congenital hypothyroidism (CH). Recent reports indicate that agenesis or hypoplasia of thyroid gland may be commoner as compared to ETG in thyroid dysgenesis (TD). There is limited information available on the proportion of different variants of TD in Indian children. Aim: To characterize the different TD variants in a cohort of North Indian children with TD. Settings and Design: Endocrinology Unit of a large Multispecialty Pediatrics Center located in North India. Retrospective review of clinical records of children with CH due to TD diagnosed between April 2004 and March 2014. Results: Diagnoses of TD in 94 children (48 boys and 46 girls) were based on combined scanning with high-resolution ultrasonography, and technetium-99m pertechnetate thyroid scintigraphy. Thyroid agenesis, ectopia and hypoplasia were diagnosed in 74 (78.7%), 14 (14.8%) and 6 (6.4%) patients respectively. The mean initial serum total T4 and thyroid stimulating hormone concentrations at diagnosis were 3.03 ± 2.88 μg/dL (range 0.01-8.9) and 284.52 ± 300.67 mIU/L (range 10.03-1159.0) respectively. Patients with ETG were older at the time of diagnosis as compared to patients with hypoplasia or ectopia. The mean duration of follow-up was 3.7 ± 2.85 years (range 3 months-10 years). Conclusions : Thyroid agenesis was the most common form of TD in our children with permanent CH. Hypoplasia and ectopia were uncommon. Female preponderance, noted in many previous reports, was not seen in our patients with TD.
  1 1,205 238
Pediatric diabetes: Potential for insulin degludec
Sanjay Kalra, Ambika Gopalakrishnan Unnikrishnan, Rakesh Sahay
November 2014, 18(7):6-8
DOI:10.4103/2230-8210.145036  PMID:25538879
  - 1,653 2,771
Twins and endocrinology
K. V. S. Hari Kumar, KD Modi
November 2014, 18(7):48-52
DOI:10.4103/2230-8210.145074  PMID:25538877
Twins are two independent babies delivered during the same pregnancy and are divided as monozygotic or dizygotic based on their origin. Dizygotic twins are similar to two siblings and have different genetic information. In contrary, monozygotic twins have a similar genetic identity and provide a unique opportunity to evaluate the contribution of genetic and environmental factors of the disease. The endocrine and metabolic disorders affect a large number of the population including the twins. Diabetes, obesity, and autoimmune thyroid disease are the most common endocrine disorders in general practice. It is essential to understand the genetic basis of endocrine disorders for therapy, prognostication and risk assessment for future generations. In this article, we review the endocrine disorders in relation to their occurrence in monozygotic twins to highlight the genetic and environmental contribution.
  - 2,283 368