Review Nutritional interventions during adolescence and their possible effects.

Nutrition is one of the most important factors affecting pubertal development. Increasing demands for energy proteins and micronutrients are necessary to cope with the rapid linear pubertal growth and development, change in body composition, and increased physical activity. Adequate nutrition is a key permissive factor for the normal timing and tempo of pubertal development. Severe primary or secondary malnutrition also can adversely delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Here we provide an overview of nutritional requirements (macronutrients and micronutrients) necessary to cope with these changes. In addition, we discuss possible nutritional interventions trials and their effects on several aspects of growth and development in undernourished and stunted adolescents, in low- and middle-income countries (LMIC), who require nutritional rehabilitation. This mini-review sums up some important findings in this important complex that links between nutrition, nutritional interventions, and pubertal development.

COVID-19 virus case fatality rate: How to avoid errors in calculation of data during the outbreak?

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Prevalence, attitude and practice of self-medication among adolescents and the paradigm of dysmenorrhea self-care management in different countries.

Self-medication (SM) is an important worldwide public health issue affecting children and adolescents. The pattern of SM varies in different communities, affected by factors such as age, sex, income, expense, self-care orientation, educational level and medical knowledge. It is a fairly common practice: for minor health problems, it often provides cheap, rapid, and convenient solutions, outside of the health care system of many countries. Painkillers, antipyretics, cough medicines, cold preparations, dermatological products, nutritional supplements and antibiotics are the drugs most frequently used. Potential risks include incorrect self-diagnosis, improper dosage, inappropriate choice of therapy, masking of severe disease and drug interactions. Lack of awareness of warnings and precautions, storage conditions, the recommended shelf-life and adverse reactions increase the risk of side effects. Little is known about the SM of dysmenorrhea by adolescent girls. Attitudes towards treatment are influenced by cultural, ethnic, and religious factors. Some girls discuss dysmenorrhea with family and friends, and the majority may not seek medical advice. As dysmenorrhea is a common problem for adolescents, it is essential that these girls be aware of the normal and abnormal symptoms of menstruation. In the light of these findings, the roles of family, school, health professionals and health authorities are of utmost importance for the implementation of measures to approach this health problem in a more efficient way.

An adolescent with an asymptomatic adnexal cyst: To worry or not to worry? Medical versus surgical management options.

Paraovarian cysts or paratubal cysts (PTCs) arise from either the mesothelium or from paramesonephric remnants. These present as either adnexal mass or as an incidental finding. Diagnosis is usually established on ultrasound and it is important to differentiate these from ovarian cysts. Typically PCTs appear as simple cysts by ultrasound and are indistinguishable from ovarian cysts if one does not recognize the extraovarian location. Occasionally, PTCs have internal echoes due to hemorrhage. PTCs are usually asymptomatic and benign. The differential diagnosis includes a simple ovarian cyst, peritoneal inclusion cyst and hydrosalpinx. Malignant changes have been reported in about 2% to 3%, and it should be suspected if papillary projections are present. PTCs management depend upon the presence and severity of the symptoms, the cyst size and US characteristics, CA 125 results, age of the patient and the risk of malignancy. Simple PTCs can be expected to regress and may be managed expectantly. When surgery is indicated, a joint multidisciplinary management by the paediatric surgeons and trained paediatric gynaecologists should be the gold standard.

Is the Second to Fourth Digit Ratio (2D:4D) a Biomarker of Sex-Steroids Activity?

The second-to-fourth digit ratio (2D:4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, and has been reported to be smaller in males than in females. This gender difference in digit length ratios has been linked with the in utero balance of androgens to oestrogen. This sexual dimorphism in 2D:4D ratios is apparent by 2 years of age and seems to be established early in life, possibly by the 14th week of gestation. Digits in females attain their maximum length at about 2.2 years (dextral subjects) or 5.1 years (sinistral subjects) earlier than those in males and increase slightly with age. It has also been reported that the 2D:4D ratio is correlated negatively with prenatal testosterone levels. This tentative theory is partially supported by lower 2D:4D in girls with congenital adrenal hyperplasia (CAH), higher 2D:4D in individuals with complete androgen insensitivity syndrome (CAIS) and a relationship between 2D:4D and polymorphisms in the androgen receptor. In contrast, individuals with Klinefelter syndrome (KS), who have reduced testosterone secretion throughout life, have a mean 2D:4D value similar to those found in female population norms. Nevertheless, its validity has not yet been conclusively demonstrated and is currently debated. In this context, our aim was to review and debate the relationship between 2D:4D ratio and sex-steroids activity in children, adolescents and young adults.

Pros and cons for the medical age assessments in unaccompanied minors: a mini-review.

Unaccompanied minors refer to immigrants who are under the age of 18 and are not under the care of a parent or legal guardian. Age assessment is used in Europe mainly to establish whether or not an individual is under 18 years of age and therefore eligible for protection under the United Nations' Convention on the Rights of the Child (UN - CRC). EU Member States use a combination of techniques to determine the age of a minor and to certify minor status, including interviews and documentation, physical examinations (anthropometric assessment; sexual maturity assessment; dental observation); psychological and sociological assessment; radiological tests (carpal, dental or collarbone x-rays). All such techniques are criticized as they are often arbitrary, do not take into account ethnic variations, and are based on reference materials that are outdated, invasive and may procure harm to the individuals whose age is assessed. They also generate a margin of error that makes them inaccurate to use. There is a debate about the risks and ethics associated with the use of X-rays for non-medical purposes versus the benefits of more accurate age assessments in the interest of justice. It appears that in European countries many individuals carrying out age assessment do not have sufficient training or are not sufficiently independent enough to be carrying out such assessments. Moreover, there is a lack of standardized approach between countries or even within the same country. Only some countries clearly indicate a margin of error in the results of age assessment examinations but there is no consensus - within and among countries - about the width of such margins in relation to each exams applied. It has been advised that the expert report should give the degree of age probability to allow Magistrate to interpret the age assessment results on the 'balance of probabilities' and give the detainee the right to the rule of the 'benefit of the doubt'. It also addresses concerns rested in the convention of the Rights of the Child.

Cross-sectional observational study of nipple and areola changes during pubertal development and after menarche in 313 Italian girls.

UNLABELLED: Obiective: To describe the characteristics of nipple development during puberty in Italian females. In addition this is compared with Tanner criteria for breast and pubic hair development at different stages and correlated with body mass index (BMI) and the menstrual age. DESIGN: Cross-sectional observational study. SETTING: Italian children and adolescents consecutively assessed at the Endocrine and Adolescent Outpatient Clinic of Private Accredited Quisisana Hospital of Ferrara. Partecipants: Healthy females 2-20 years, belonging to Italian middle socio-economic class. Study duration: This study was conducted for a total period of 39 months from September 2012 to December 2015. METHODS: Demographic characteristics, age at menarche and menstrual duration, anthropometry (weight, height, BMI) and pubertal status (breast and pubic hair) were evaluated. The greatest diameters of the erect nipple and areola sizes were measured in all subjects in supine position using a plastic template with graduated circular cut-outs or a transparent graduated ruler. RESULTS: Significant increments in nipple diameter were noted between Tanner's stages B1, B2, B3, B4 and B5 but the differences between stages B1 vs B2, B3 vs B4, B4 were more significant (p<0.001) than the difference between B4 vs B5 (p<0.004).The same statistical pattern was documented between Tanner's stage PH1 and PH2, PH2 and PH3 and PH4 and PH5. The nipple diameter increased significantly in relation to BMI in all Tanner's stage groups (p: 0.021 for B1 vs B2; and p<0.001 for B3 vs B4 and B4 vs B5) but one (B2 vs B3=p: 0.518).A significant correlation was observed between duration of menses, nipple and areola sizes (r: 0.490; p=<0.001 and r: 0.252; p=0.012, respectively). CONCLUSIONS: The assessment of sexual maturation is important in population studies as well as for daily clinical encounter. In our subjects the mean age of onset of secondary sexual characteristics was 10.3±1.4 years and mean age at menarche was 12.02±1.5 years. The study provides the normative data for nipple and areola sizes in Italian girls. Change in nipple and areola sizes may represent an early marker for transition to puberty.

Endocrine profile of ß-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center.

AIM: Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40-50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists. OBJECTIVES: The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs. DESIGN: A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic. PARTICIPANTS: Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8-59.5 years; 23 females) were studied. PATIENTS AND METHODS: An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained. RESULTS: The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml). CONCLUSIONS: These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy.

INTRODUCTION: It is well known that the older generation of adult TM patients has a higher incidence of morbidities and co-morbidities. At present, little information is available on adult TM patients with multiple endocrine complications (MEC). The main objectives of this longitudinal retrospective survey were: 1) to establish the incidence and progression of MEC (3 or more) in TM patients; 2) to compare the clinical, laboratory and imaging data to a sex and age-matched group of TM patients without MEC; 3) to assess the influence of iron overload represented by serum ferritin (peak and mean annual value at the last endocrine observation). PATIENTS AND METHODS: The study was started in January 1974 and was completed by the same physician at the end of December 2015. The registry database of the regularly followed TM patients from diagnosis included 145 adults (> 18 years). All TM patients were of Italian ethnic origin. Eleven out of 145 patients (7.5 %) developed MEC. Twenty-four other patients (12 females and 12 males) had a normal endocrine function (16.5 %) and served as controls. RESULTS: In our survey, four important, relevant aspects emerged in the MEC group. These included the late age at the start of chelation therapy with desferrioxamine mesylate (DFO); the higher serum ferritin peak (8521.8 ± 5958.9 vs 3575.2 ± 1801.4 ng/ml); the upper proportion of splenectomized (81.8 % vs. 28.5%) patients and poor compliance registered mainly during the peripubertal and pubertal age (72.7 % vs.16.6 %) in TM patients developing MEC versus those without endocrine complications. Furthermore, a negative correlation was observed in all TM patients between LIC and final height (r: -0.424; p = 0.031). CONCLUSIONS: Our study supports the view that simultaneous involvement of more than one endocrine gland is not uncommon (7.5 %). It mainly occurred in TM patients who started chelation therapy with DFO late in life and who had irregular/poor compliance to treatment. Therefore, prevention of the endocrine complications through adopting early and regular chelation therapy appears mandatory for improving the quality of life and psychological outcome of these patients. When diagnosing and managing patients with MEC, it is of paramount importance that the multidisciplinary team have excellent knowledge relating to these complications. In ideal circumstances an endocrinologist with experience of TM will form part of the regular multidisciplinary team caring for such patients.

Thyroid Hemiagenesis from Childhood to Adulthood: Review of Literature and Personal Experience.

Thyroid hemiagenesis (TH) is a rare congenital abnormality of the thyroid gland, characterised by the absence of one lobe. The true prevalence of this congenital abnormality is not known because the absence of one thyroid lobe usually does not cause clinical symptoms by itself. Between 1970 and 2010, 329 cases of TH have been reported. It is interesting to note that most cases have an agenesis of the left lobe (80% of cases) followed by the isthmus (44-50% of cases). Although the female to male ratio was 1:1.4 in 24,032 unselected 11-to 14-yr-old schoolchildren from South-eastern Sicily, several other reports have documented a higher prevalence in women, which may indicate a possible gender association. Most cases of TH are diagnosed when patients present a lesion in the functioning lobe. The functioning lobe of the thyroid gland can be a site of pathological changes similar to a normally developed gland and may present a spectrum of diseases like multinodular goiter, colloid goiter, follicular adenoma, thyroiditis, hypothyroidism and hyperthyroidism. In three of our patients, TH was associated with Hashimoto thyroiditis (n = 1) and with subclinical hypothyroidism (n = 2). The frequency of thyroid abnormalities in patients with TH varies with age, due to the longer exposure of the hemi-agenetic gland to TSH overstimulation in older patients. This could explain the controversy about the benign character of this anomaly. Other extrathyroidal lesions, such as parathyroid adenoma or hyperplasia, cervical thymic cysts, ectopic sublingual thyroid gland and thyroglossal duct cyst have been reported with TH. Therefore, systematic follow-up of all identified cases is recommended.

Acquired Hypogonadotropic Hypogonadism (AHH) in Thalassaemia Major Patients: An Underdiagnosed Condition?

INTRODUCTION: In males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function, and strength, a worsened sense of well-being and degraded quality of life (QOL). PATIENTS AND METHODS: We studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy. Fasting venous blood samples were collected two weeks after transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*. Bone mineral density was measured at the lumbar spine (L1-L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine. RESULTS: The mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH showed azoospermia in 3 and oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml (severe iron load) was significantly higher in AHH patients compared to controls, 5/11 (45.4 %) versus1/12 (8.3%), p=0.043. Heart iron concentrations (T2* values) were significantly lower in AHH patients compared to controls (p=0.004). Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity. Heart T2* values were significantly reduced in the AHH group vs. the controls (p=0.004). On the other hand, liver iron concentration (mg/g dry weight) was not different between the two groups of TM patients. Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic, and 36.3 % (4/11) were osteopenic. CONCLUSIONS: In this cohort of thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH. Treatment of AHH in TM patients is a vital and dynamic field for improving their health and QOL. Early identification and management of AHH are very crucial to avoid long-term morbidity, including sexual dysfunction and infertility. Therapy aims to restore serum testosterone levels to the mid-normal range. Many exciting opportunities remain for further research and therapeutic development.

Methods for Rating Sexual Development in Girls.

Sexual maturity rating (SMR) is important in population studies and in clinical care. Pubertal staging allows doctors to assess the maturation of adolescents to correlate several pubertal phenomena such as age at menarche, growth spurt and final height, to advise and manage patients appropriately and to have sensitive "sensors" of the effects of environmental exposure on human populations. The commonly used markers of the timing of female puberty are thelarche and menarche. Appearance of the breast bud is the first indicator of puberty onset in 90% of girls. Assessment of thelarche may be performed by a physician with expertise in adolescents or by self-assessment, in which the adolescent identifies her stage of maturation based on Tanner's photographs/illustrations. The assessment of Tanner stages by professionals provides more reliable information than self-assessment but may involve variations between observers. Tanner self-assessment has been proposed as an alternative in various studies. Some studies have found reasonable agreement between self-assessment and examination by a physician whereas others found discrepancies. Measuring nipple and areola diameters is feasible for sexual maturation staging. Both sizes show a significant increase during pubertal development and after menarche. However, the ratings using nipple/areola method need to be analyzed to establish their degree of concordance with standard techniques and other markers of development in girls.

Precocious Puberty Following Traumatic Brain Injury in Early Childhood: A Review of the Literature.

AIMS OF THE REVIEW: The intent of the current manuscript is to review the cases of central precocious puberty (CPP) in early childhood following traumatic brain injury (TBI). SEARCH OF THE LITERATURE: The MEDLINE database was accessed through PubMed in April 2015. Results were not restricted to the date and language of the articles. For the first search we utilized MeSH terms "precocious puberty" in conjunction with "traumatic brain injury" and with "endocrine consequences". Reference lists were reviewed and relevant papers were also consulted to find additional studies and data. In selected cases the corresponding author was contacted by email. RESULTS: In our systematic review, only a few case reports or small case series have highlighted a link between TBI and hypothalamic-pituitary hormone abnormalities. Fourteen reported children were females and 8 were males. The majority of patients reported had severe TBI, assessed by Glasgow Coma Scale or structural injury (skull fractures, intracranial hemorrhage or cerebral injury) reported on computerized tomography or magnetic resonance imaging scans. The pathogenic mechanism of precocious puberty has not yet been determined. An increased pressure on the hypothalamic-pituitary area with loss of normal childhood hypothalamic inhibition of pituitary gonadotropins could be one of the factors responsible for CPP after TBI. CONCLUSIONS: The current review highlights the importance of close clinical follow-up to evaluate the rate of linear growth and pubertal development after TBI. Although, precocious puberty appears to be rare after TBI, prevalence should ideally be assessed by longitudinal follow-up of a large population. Therefore, further multicenter and multidisciplinary studies are required to explore in detail the true incidence and the possible mechanisms of CPP after TBI. Because precocious puberty can be detected on clinical assessment during childhood, a pragmatic approach would be for family physicians to monitor growth and development in children after TBI. Inasmuch as precocity is mediated through the hypothalamic-pituitary pathways, use of LH-RH analogue therapy should be effective in arresting pubertal progression.

Insulin-like growth factor- I and factors affecting it in thalassemia major.

Despite improvement of blood transfusion regimens and iron chelation therapy growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis still occur in good number of thalassemic patients. Decreased IGF-1 secretion occurs in the majority of the thalassemic patients particularly those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including disturbed growth hormone (GH) - insulin-like growth factor - I (IGF-I) axis. The possible factors contributing to low IGF-I synthesis in thalassemia and the possible interaction between low IGF-I secretion and the occurrence of these complications is discussed in this mini-review. Improvement of IGF-I secretion in thalassemic patients should be intended to improve linear growth and bone mineral accretion in thalassemic patients. This can be attained through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake), correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism at the proper time and treating GH deficiency. This review paper provides a summary of the current state of knowledge regarding IGF-I and factors affecting it in patients with thalassaemia major (TM). Search on PubMed and reference lists of articles with the term 'IGF-I, GH, growth, thalassemia, thyroxine, anemia, vitamin D, and zinc' was carried out. A hundred and forty-eight articles were found and used in the write up and the data analyzed was included in this report.

Endocrine check-up in adolescents and indications for referral: A guide for health care providers.

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.

Nutrition and pubertal development.

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.

Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

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.

Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond.

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.