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The article presents several abstracts related to hormone research including one on postnatal growth and intellectual performance among males born preterm, one on the clinical, endocrine and metabolic consequences of human acid labile subunit deficiency and one on three dimensional protein homology modelling for steroidogenic diseases.

The prevalence of obesity among children and adolescents is progressively increasing around the world. One of the important consequences of obesity is the development of insulin resistance (IR). This condition has a multifactorial pathogenesis and is associated with cardiovascular risk, diabetes, hypertension, polycystic-ovary syndrome and a shorter lifespan. IR during childhood may be diagnosed by physical examination or there may be clues in the histories of the patient and his/her family. When IR is suspected, tests on a blood sample (which are more reliable) are recommended. Most of the biochemical markers have been well defined in adults, but appropriate reference data for children are still lacking. Here we discuss the usefulness of various currently known biochemical markers to evaluate insulin sensitivity (homeostatic model assessment, the quantitative insulin sensitivity check index, the oral glucose tolerance test, Matsuda method and the whole-body insulin resistance index), hormones (leptin, adiponectin, resistin, glucocorticoids, the insulin-like growth factor-1-binding protein/growth hormone axis, ghrelin, sex hormone-binding globulin and retinol-binding protein-4) and inflammatory markers (C-reactive protein, IL-6, intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin), which can be used in the diagnosis of IR in children. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Glucocorticoid excess promotes visceral obesity and cardiovascular disease. Ligand availability to the glucocorticoid receptor is controlled by isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD) which converts endogenous cortisone to active cortisol. Aim: To evaluate the expression and activity of 11β-HSD1 in subcutaneous adipose tissue (SC) and visceral adipose tissue (VAT) in prepubertal children with normal weight. Methods: Fourteen patients (11 female/3 male) with a mean age of 6.9 ± 0.9 years and a body mass index (BMI) of 17.4 ± 0.61 underwent elective open abdominal surgery. Results: Expression of 11β-HSD1 mRNA in SC and VAT was similar (0.8 ± 0.15 vs. 0.61 ± 0.12 AU). The activity of this enzyme in SC was significantly lower compared to VAT (1.42 ± 0.39 vs. 2.79 ± 0.61 ng cortisol/g tissue/24 h, p < 0.05). In addition, we observed a significant direct correlation with the expression of 11β-HSD1 in VAT adipose tissue with the patient’s BMI (r = 0.825, p = 0.002). Conclusions: This correlation together with the increased activity of this enzyme in visceral adipose tissue might contribute to decreased hepatic insulin sensitivity due to increased portal cortisol when BMI increases. These observations appear to be particularly important in children born with low birth weight who develop rapid early weight gain. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A program is presented for the 5th Biennial Scientific Meeting of the Asia Pacific Pediatric Endocrine Society (APPES), scheduled to take place in Seoul, Korea, on October 29 through November 1, 2008. Discussions to take place include "Endocrinological Characteristics of Brain Tumor Survivors," "Thyroiditis in Paediatric and Adolescent Age," and "Central Precocious Puberty: Clinical Management and Consensus."

Abstracts of presentations from the 5th Biennial Scientific Meeting of the Asia Pacific Pediatric Endocrine Society (APPES) are presented, including "Modern Management of Type 1 Diabetes Mellitus," by William Tamborlane, "Central Precocious Puberty: Clinical Management and Consensus," by Erica Eugster, and Endocrinological Characteristics of Brain Tumor Survivors," by Choong-Ho Shin.

Background: Nine distinct genetic conditions have been identified in the last 12 years causing neonatal diabetes mellitus through failure of normal pancreatic development, islet cell dysfunction or β-cell destruction. This review will focus on the three conditions about which our understanding of the pathology – and in some cases the treatment options – has greatly increased: transient neonatal diabetes mellitus, permanent neonatal diabetes due to ‘channelopathies’ and immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome. Conclusions: Effective treatment of neonatal diabetes requires thorough understanding of the disease processes underlying this highly variable condition. As our knowledge of pancreatic development and physiology expands, so, too, do the treatment options for some patients. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The diagnosis in industrialized countries is usually made with population-based newborn screening that measures thyroid-stimulating hormone (TSH) or TSH and total thyroxine (T4) in dried blood spots in the first 3 days of life. In newborns with a screening result suspicious for hypothyroidism, the diagnosis of primary CH is confirmed when serum TSH levels are above and T4 (free T4) levels are below the age-related reference ranges. Hypothalamic-pituitary hypothyroidism is more difficult to diagnose. Most infants with this diagnosis are missed in screening programs unless T4 (free T4)/TSH or TSH/T4/thyroxine binding globulin is simultaneously measured. If hypothyroidism is confirmed by laboratory analysis, imaging studies should be performed immediately; however, it is not acceptable to delay hormone replacement therapy if imaging studies are not readily available. Conclusions: The goal of treatment of CH is to avoid disturbed mental development, and initial treatment can be adjusted to physiological conditions. To match the higher thyroid hormone concentrations in the first weeks of life, substitution with l-thyroxine should aim to achieve serum T4/free T4 levels in the upper half of the normal age-related reference range. Some newborns and infants will have persistently high TSH levels despite normalized T4/free T4 serum concentrations. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy of goserelin 10.8 mg (Zoladex LA – ZLA) administered 9–12 weekly with 3.6 mg (Zoladex – Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI). Methods: Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months’ treatment were compared. Results: To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04). Conclusion: Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Publishes abstracts submitted by endocrinologists for presentation at the 42nd Annual meeting of the European Society of Pediatric Endocrinology at Ljubljana, Slovenia. Goal to enrich the physician's knowledge of the etiology and treatment of endocrinological disorders; Note of thanks for all who submitted their abstracts and contributed to the scientific programming of the meeting; Plan to present the abstracts in different sessions of the meeting.

Aim: To optimize the workup of short-statured children by defining the most appropriate tools for diagnosing growth hormone (GH) deficiency. Methods: Patients were assigned to prepubertal (n = 113) or pubertal (n = 112, including 25 boys primed with testosterone) age groups. Mean plasma GH concentration during sleep, GH peak after provocative test, and insulin-like growth factor I (IGF-I) were measured in a single evaluation. Results: The mean GH concentration during sleep was more often normal (n = 155) than the GH peak after provocative tests (n = 105) or the IGF-I concentration (n = 88). Prepubertal patients with a normal body mass index (BMI) had mean GH concentrations during sleep that correlated positively with height, growth rate, GH peak after provocative tests, and IGF-I (p < 0.0005 for all) and negatively with the difference between target and patient heights (p = 0.01) and BMI (p < 0.05). Pubertal patients with a normal BMI had a mean GH concentration during sleep that correlated positively with GH after provocative tests (p < 0.0001) and IGF-I (p < 0.005). Mean GH concentration during sleep and IGF-I concentration for boys primed with testosterone were more often normal (n = 23) than the GH peak after provocative tests (n = 14). All 9 patients with pituitary stalk interruption had low IGF-I concentrations; 1 patient had a normal GH peak after provocative test, and 2 patients had normal mean GH concentrations during sleep. Conclusions: Measuring the GH concentration during sleep and priming boys with pubertal delay can help to exclude idiopathic GH deficiency. Magnetic resonance imaging is needed to exclude anatomic abnormalities when GH and/or IGF-I concentrations are low.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The efficacy of a 3-month depot preparation of the GnRH agonist leuprorelin acetate in central precocious puberty was studied. Methods: Treatment with a 3-month depot of leuprorelin acetate was performed subcutaneously in a 7.3-year-old girl with central precocious puberty. Results: During treatment the hormonal suppression was constant and complete as demonstrated by suppressed GnRH stimulation tests and prepubertal estradiol plasma levels. The size and volume of the uterus and ovaries returned to the normal range. The rate of bone maturation was significantly reduced with a ratio ΔBA/ΔCA of 0.58 for 3 treatment years. Thus, the effects of treatment were comparable to those reported for treatment with 1-month depot of GnRH agonists. Conclusion: Three-month depots have the advantage of a prolonged injection interval which is more convenient for the patients and reduces costs by necessitating fewer visits to the physician and being approximately 10% cheaper than the 1-month depot. We suggest that comparative and randomized studies be performed to make 3-month depots of GnRH agonists available for routine use in children with central precocious puberty.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The present survey among members of the ESPE on current practice in diagnosis and treatment of growth hormone (GH) deficiency (GHD) is of great clinical relevance and importance in the light of the recently published guidelines for diagnosis and treatment of GHD by the Growth Hormone Research Society. We have found much conformity but also numerous discrepancies between the recommendations of the Growth Hormone Research Society and the current practice in Europe. Results: We found that 80% of the pediatric endocrinologists included insulin-like growth factor I (IGF-I) in their initial evaluation of a short child suspected of having GHD, whereas only 22% used GH provocative testing alone in the initial evaluation of a short child. Sixty-eight percent confirmed the diagnosis of GHD using two separate provocative tests. In the present survey cutoff values for GH provocative testing clustered around two values; 10 ng/ml and 20 mU/l. Interestingly, these two values, differing by a factor of 2, were also the most prevalent cutoff values among those who reported their assay to be calibrated against the WHO International Reference Preparation 80/505 where the conversion factor between milligrams and milliunits is 2.6. This suggests that the selection of cutoff values is based on tradition rather than on specific GH assay characteristics. In addition, only 63% of the respondents actually knew what GH assay they were using, and only 57% knew how their GH assay was calibrated. Dosing of GH at the start of treatment was reported according to body surface by 39%, whereas 59% were dosing according to body weight. GH dose adjustment was primarily based on growth response and height during auxological assessment every 3–4 months (height velocity, change in height velocity or change in height standard deviation scores) as indicated by almost 70% of the respondents. However, dose adjustment according to body surface (38%) and body weight (44%) was also quite common. Sixty-five percent measures IGF-I regularly (at least once a year) during GH therapy in children, and to our surprise 17% reported that they adjust the GH dose according to the IGF-I levels. Summary: In summary, we have found large heterogeneity in the current practice of diagnosis and treatment of childhood GHD among European pediatric endocrinologists. Especially standardizations of GH assays and cutoff values are urgently required to ensure a uniform and correct diagnosis and therapy of GHD in the future.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To study the effects of growth hormone (GH) deficiency (GHD) and GH replacement therapy (GHRx) on bone mineral density (BMD) and body composition. Methods: 59 GHD children participated (age range 0.4–16.9 years); the follow-up period was 6 years. Lumbar spine BMD (BMD[sub LS] ), total-body BMD (BMD[sub TB] ), and body composition were measured prospectively using dual-energy X-ray absorptiometry. Results: Mean BMD[sub LS ] and BMD[sub TB] were significantly reduced at the time of the diagnosis. The bone mineral apparent density of the lumbar spine (BMAD[sub LS] ) was reduced to a lesser degree. The BMAD[sub LS] increased to normal values after 1 year; BMD[sub LS] and BMD[sub TB] normalized 1 year later. At the time of the diagnosis, the lean body mass was reduced and steadily increased during GHRx. Percentage of body fat was increased at baseline and normalized within 6 months. The severity of GHD was not associated with the BMD at diagnosis or the response to GHRx. Conclusion: Areal BMD[sub LS] and BMD[sub TB] and, to a lesser extent, BMAD[sub LS] are decreased in GHD children, but normalize within 1–2 years.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents the schedule of lectures and events of the international symposium on the binding proteins of insulin-like growth factors (IGFBP) being held by the Section for Pediatric Endocrinology of Tübingen University in Germany on November 1-3, 2002. Information on IGFBP; Highlights of the symposium.

Presents the consensus statement issued by the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society concerning congenital adrenal hyperplasia caused by hydroxylase deficiency. Evaluation of an infant with ambiguous genitalia; Mass screening of newborns for hydroxylase deficiency; Goals of the surgery for newborns with ambiguous genitalia.

The management of children and adolescents with congenital adrenal hyperplasia (CAH) remains difficult. To assess the current European practice in diagnosis and management of CAH, an ESPE (European Society for Paediatric Endocrinology) survey was circulated in 2000/2001. The questionnaire was answered by 34% of ESPE members, representing 125 institutions which cared for 6,553 CAH patients. Paediatric endocrinologists, surgeons, gynaecologists, geneticists, and psychologists are involved in the immediate care of the CAH neonate and his family. 44% of centres take part in neonatal screening programmes. In families at risk, prenatal dexamethasone therapy is started at a median gestational age of 6 weeks in a median dose of 20 μg/kg/day. 53% reported maternal adverse events, 8% observed adverse fetal events. Regarding feminizing surgery, 33% reported simultaneous clitoric reduction and vaginoplasty during infancy. However, clitoridectomy is still reported by 13% of centres, and vaginal dilatations have been performed by 27%. Although 71% of female CAH patients with psychosexual problems, only 17% undertake routine psychodiagnostics and counselling. Hydrocortisone is the substance used for the treatment of CAH during growth in 84%; the median dose (mg/m²/day) is 17.5 in infants, 15 in children and adolescents, and 13.75 in adults. The glucocorticoid dose is increased two- to sixfold during intercurrent stress. Mineralocorticoid is administered in cases of clinically manifest salt wasting and of elevated plasma renin activity, to decrease high glucocorticoid doses, or according to genotype. All participating ESPE members feel the need for further improvement in prenatal diagnosis and treatment, compliance during puberty, screening programmes, psychological aspects, and corrective surgery.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents abstracts of papers highlighted at the 41st Annual Meeting of the European Society for Paediatric Endocrinology. "When One Is Not Enough: Endocrine Consequences of Haploinsufficiency," by J. Parks; "Williams-Beuren Syndrome," by L.A. Pérez-Jurado; "Genetics of Congenital Hypothyroidism," by R. Di Lauro; "Epidemiology and Clinical Aspects of Neonatal Diabetes," by P. Czernichow; "Transgenic and Genomic Approaches to the Study of Female Puberty," by S.R. Ojeda et al.

Presents abstracts of papers featured at the 41st Annual Meeting of the European Society for Paediatric Endocrinology. "Genetic Epidemiology of Mody Diabetes in the Czech Republic," by S. Pruhova et al; "Insulin Pump Therapy First Experience in Latvia," by I. Dzivite; "Insulin Requirement at Diagnosis of Type 1 Diabetes Mellitus Is Age-Dependent," by A. Herbst et al; "Hypophosphatemic Bone Disease Needs Lifelong Treatment," by M.R. Azar; "Growth and Puberty After Treatment for Acute Lymphoblastic Leukaemia," by N. Setian et al.

Presents abstracts of papers highlighted at the 41st Annual Meeting of European Society for Paediatric Endocrinology. "Endothelial Dysfunction But Not Platelet Dysaggregability in Children and Adolescents With Type 1 Diabetes Mellitus," by A. Gerasimidi-Vazeou et al; "Height Weight and Body-Mass-Index in Patients With Type-1 Diabetes: From Pediatric to Adult Diabetes Care," by R.W. Holl et al; "Psychosocial Aspects, Self-Management of Diabetes in Adolescence in Relationship to the Age of Diagnosis," by A. Irune et al; "Transient Neonatal Diabetes Mellitus in Two Brothers," by C. Theodoridis et al.

Objective: To evaluate the long-term efficacy and possible side effects of low doses of iodized oil on iodine nutrition and thyroid function in endemic goiter in Romania. Methods: Random selection of 214 schoolchildren aged 6–14 years. Serial measurements of urinary iodine, thyroid volume with ultrasound, serum concentrations of thyrotropin, free thyroxine, thyroglobulin and thyroid autoantibodies before and up to 2 years after the oral administration of 200 mg iodine in iodized oil. Results: Urinary iodine concentrations indicated a moderate iodine deficiency before therapy, sharply increased soon after therapy and slowly decreased thereafter but remained within the normal range up to more than 1 year after therapy. The prevalence of goiter was 29% before the administration of iodized oil and 9% 1 year later. Thyroid function tests and autoantibodies were normal before and up to 2 years after therapy. Conclusion: A single dose of 200 mg iodine from oral Lipiodol[sup ®] appears adequate and safe for correcting moderate iodine deficiency in children.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The small number of boys present in most studies on final height (FH) after gonadotropin-releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP) offers difficulties in the evaluation of the effects of treatment on FH in males. Method: We therefore combined FH data from The Netherlands, Italy and France to study the effect of GnRHa treatment in a large group of 26 boys with CPP. Results: The mean chronological age at the start of treatment was 7.6 ± 2.0 (SD) years, bone age (BA) was 11.0 ± 2.1 years. All boys were treated with depot formulations of the GnRHa triptorelin with established gonadal suppression for a mean treatment period of 4.7 ± 2.1 years. FH was 172.9 ± 6.6 cm. FH standard deviation score (SDS) was –0.66 ± 1.22, not significantly different from the target height SDS of –0.23 ± 0.75. FH-SDS was significantly lower in the subgroup of 12 patients with organic CPP compared to patients with idiopathic CPP (–1.34 ± 1.06 vs. –0.08 ± 1.06, respectively; p = 0.01), but no difference in height gain was observed. The mean estimated height gain, defined as the difference between predicted and actual adult height was 6.2 ± 8.7 cm using the average tables of Bayley and Pinneau, and 0.3 ± 8.6 cm using the BA advance adjusted tables. Regional differences in height gain were observed between the different countries, reflecting different local practices. Conclusion: We conclude that GnRHa treatment in boys results in a FH close to target height.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents information on the consensus development symposium convened by the Bone Club of the European Society for Pediatric Endocrinology on July 6, 2001 concerning the supplementation of vitamin D. Background on vitamin D; Overview of vitamin D deficiency rickets; Risk of children of immigrants for rickets.

A girl aged 5 years and 6 months presented with premature thelarche in our outpatient clinic. During long-term observation, we recorded growth acceleration, advanced bone age, and elevated oestradiol levels which together were taken to confirm the diagnosis of precocious puberty. The patient was successfully treated with a gonadotropin-releasing hormone agonist, but in view of the poor growth prognosis, recombinant human growth hormone was administered concurrently. At the age of 9 years and 6 months a mild clitoris enlargement and conspicuous muscle development without any further signs of virilization were noticed. Laboratory findings showed high values for testosterone and normal basal values for 17-hydroxyprogesterone and dehydroepinadrosterone sulphate. Explorative laparotomy revealed a gonadoblastoma arising from testicular structures on the left, a female streak gonad on the right side, and normal uterus and fallopian tubes. The karyotype was 46,XY/45,X. These findings confirmed the diagnosis of mixed gonadal dysgenesis with testosterone-producing gonadoblastoma.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Epidemiologic and auxologic characteristics of patients treated with GH during childhood and adolescence and entered in a national registry in Catalonia were studied between 1988 and 1997. At the end of 1997, prevalence was 53.2 treatments/100,000 inhabitants aged 0–14 years. Maximum annual incidence rates were observed in 1990 and 1991 (34.0–35.6 cases/100,000 inhabitants aged 0–14 years). Study Design: Analysis of treatments terminated in 1993 (n = 548) revealed, for the three principal reasons for cessation of treatment (‘near-final height’, ‘adequate height but further growth potential’, and ‘poor growth response’), that males began and ended treatment at older ages with a better auxologic situation in SDS than girls at the beginning and end of therapy in the first two subgroups, with a similar duration of therapy. Severe GH deficiency (GHD) [both multiple pituitary hormone deficiency (MPHD) and the most severe isolated GHD (IGHD-A)] was more frequent in the group ending treatment at ‘near-final height’, whereas cessation of therapy because of ‘poor growth response’ was more frequent in the group with ‘other causes of short stature’ and no demonstrable GHD by routine tests. In the near-final height group, after excluding Turner’s syndrome, MPHD and GHD cases secondary to brain tumors and GH deficiencies associated with malformative syndromes, positive linear correlations were observed between HSDS at the end of treatment and HSDS at the beginning, predicted adult height SDS (PAHSDS) and target height SDS (THSDS). Multiple regression analysis showed that in this group of patients, 41.4% of the variability in HSDS increment can be explained by the equation: HSDS increment = –0.33 + 0.29 THSDS – 0.68 HSDS at the beginning of treatment. Results: The outcome showed a reasonable use of GH, since good-response cases generally continued treatment until final height whereas therapy was suspended in doubtful cases.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Diabetes is an evolving disease, with changing patterns seen in both type 1 and type 2 diabetes. A wide (over 400-fold) variation exists in worldwide incidence rates of type 1 diabetes, with the highest occurring in Finland (over 45 per 100,000 under the age of 15 years) and the lowest in parts of China. In many countries (e.g. in Europe, the Middle East, Australia) the incidence of autoimmune-mediated type 1 diabetes in children <15 years of age has risen by 2–5% per annum. Type 2 diabetes is also increasing rapidly globally and is occurring at a younger age, including in adolescence and childhood. In the USA, approximately one third of newly diagnosed in the adolescent age group is type 2, with up to 20% presenting with ketosis and ketoacidosis. The management of type 2 diabetes is especially difficult in the adolescent age group. Obesity is the single most obvious risk factor for type 2 diabetes. Lifestyle modification programmes starting in childhood are urgently needed and society needs to change its attitudes to childhood nutrition, play and exercise.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hypoglycaemia is particularly common in young children with type 1 diabetes mellitus yet the normal protective counterregulatory responses have been little studied in this age group. The studies reported have shown conflicting results, in part related to prior glycaemic control and also to the method of investigation used. Counterregulatory hormone responses during both spontaneous and experimentally induced episodes of nocturnal hypoglycaemia do appear to be blunted, which may be a function of sleep itself. Although studies of cognitive function have consistently shown defects in certain areas of neurocognitive performance, particularly in those children with early-onset diabetes or a prior history of severe hypoglycaemia, the contribution of nocturnal hypoglycaemia to the development of these impairments has not been evaluated. In young adults and adolescents, nocturnal hypoglycaemia has been linked to cardiac arrhythmia and the risk of sudden death. The development of new techniques for continuous subcutaneous glucose monitoring may allow detailed study of counterregulatory responses and symptom recognition in young children. Effective intensification of insulin therapy without an increased risk of hypoglycaemia may be possible using new insulin analogues or continued subcutaneous intravenous infusion (CSII), thus improving patient compliance and overall quality of clinical care.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Current data on rapid and long-acting insulin analogues in the paediatric age group is limited. While several studies indicate a benefit in reducing hypoglycaemia, particularly at night, with rapid or long-acting insulin analogue treatment, the effect on long-term glycaemic control remains controversial. The continuous glucose monitoring system offers a new option for tailoring treatment with insulin analogues to achieve optimal glycaemia. In 29 adolescents with diabetes this approach confirmed the non-inferiority of postprandial rapid-acting analogue administration compared to preprandial regular insulin, but revealed significant mealtime differences, with increased analogue requirement at breakfast and dinner. Although rapid- and long-acting insulin analogues may offer potential benefits for problems frequently encountered in paediatric diabetology, their value for the individual child still has to be tested in long-term observations in daily clinical practice.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Recent advances in diabetes care have facilitated the achievement and maintenance of excellent metabolic control. New insulin pumps and continuous glucose monitoring systems provide cause for optimism that an artificial pancreas may soon be developed. In addition, transplantation biology has advanced to the point where pancreas and islet transplants are being performed with increasing frequency. Recent reports suggest that improved techniques for isolation of islets and immune suppression may allow these procedures to become more commonplace. However, serious questions regarding long-term safety and efficacy need to be answered in older individuals before consideration is given to their more routine use in children and adolescents with diabetes.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Continuous subcutaneous insulin infusion (CSII) has been used in the paediatric age group for more than 20 years. The technique is not yet widely used in most countries but there has recently been increasing interest in pump therapy for young children and adolescents. In 1999, 7.5% of Swedish children and adolescents with diabetes used pumps, now the figure is approaching 12%. The indication for starting pump therapy has usually been a medical problem, but today quality of life issues are becoming increasingly important. One technique sometimes used is to start CSII by wearing the pump only at night. Daily insulin requirements are usually decreased compared with injection therapy. Studies have shown that it is possible to lower HbA[sub 1c] when using an insulin pump and that the risk of severe hypoglycaemia can be lowered. The use of CSII has also been successful in preventing recurrent admission for diabetic ketoacidosis. While starting pump therapy does take an extra effort from both the diabetes team and the family, routine visits are generally no more time-consuming than for patients on multiple injection therapy. CSII can be initiated during admission to hospital but most pumps are started on an outpatient basis. Our department has the patients on the day care ward for 3–4 days of ‘pump school’. Parents wear a saline pump for practice. The total daily insulin dose is usually lowered 15–20% compared with multiple injections; on average 40–50% (sometimes up to 60%) of the daily dose is given as basal rate. We start all pumps on rapid-acting analogues and use 40 IU/ml if the basal rate is <0.3 IU/h. In conclusion, the use of CSII in children and adolescents is well accepted and can be managed safely.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Most multicentre studies demonstrate that the outcome of diabetes therapy falls below the targets set up in recent guidelines. Applying quality control methodology may provide one means better to achieve such targets. Before setting up a quality circle, objective, standardized documentation of relevant quality indicators is necessary. Based on internal (for example longitudinal changes over time) and external quality control (comparison with other institutions), both favourable and unfavourable results achieved by each institution are identified. Such data provide the basis for intensive discussion among the members of diabetes care teams on how to remedy such deficits. In Germany, the working group on paediatric diabetology set up a system for external quality assessment in 1995: For 6 continuous years, quality indicators are compared twice yearly, and regional quality circles for more open discussions have been established, in addition to yearly nationwide meetings among all participants.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. Aim/Method: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. Results: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. Conclusion: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Method: We compared the growth hormone response to a modified exercise test – the treadmill exhausting test – to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. Results: The mean ± SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 ± 1.3 in the pharmacological tests vs. 5.0 ± 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean ± SEM peak GH concentrations (ng/ml) of 5.5 ± 0.5 in the pharmacological tests and 4.1 ± 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. Conclusion: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hyperinsulinism and hyperandrogenism have the capacity to increase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the sequence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described. Methods: Fifty-two non-obese PP girls were studied (age range 6.9–14.9 years). Serum leptin was also measured in 42 control girls, matched for age, body mass index and pubertal stage. Results: BMD SDS, measured by dual-energy X-ray absorptiometry, was elevated in PP girls compared to the population reference (0.39 ± 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, was significantly advanced compared to chronological age (1.2 ± 0.1 years; p < 0.0005). Conclusion: Compared to control girls, PP girls had higher leptin levels for degree of body mass index (PP girls: 9.4 ± 0.6 ng/ml; controls: 7.8 ± 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversely related to birthweight (r = –0.32, p = 0.01) and positively related to free androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = –0.26, p < 0.05) and positively related to serum leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insulin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). In multiple regression, MSI was the strongest determinant of BMD SDS (β = 0.50, p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyperandrogenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The role of IGF-I and IGFBP-3 measurements in the diagnostic work-up of short children is established but remains controversial. Little information exists on the value of IGFBP-2 measurements. Based on reference data established in 388 children we have reinvestigated the issue, using data from 392 short children who underwent the same diagnostic procedures between 1987 and 1998 (GHD, n = 187; non-GHD, n = 205, including patients with ISS, n = 76; IUGR, n = 46; and TS, n = 83). In comparing IGF-I, IGFBP-3 and IGFBP-2 serum levels of GHD and ISS children with reference data, we calculated the sensitivity, specificity, efficiency and positive predictive value for the diagnosis of GHD. The overall sensitivity of the parameters was high, the rank order being as follows: IGF-I >IGFBP-3 >IGFBP-2 (75, 67 and 62%, respectively). In contrast, the specificity was relatively low: IGFBP-3 >IGFBP-2 >IGF-I (50, 50 and 32%, respectively). The efficiency and positive predictive value of parameters was in the order of 40, 60 and 70–80%, respectively. In repeated measurements, the recorded basal levels of IGF-I and IGFBP-3 showed an overall narrow range of variation. We conclude that the determination of basal IGF parameters is, together with anthropometry and imaging techniques, an indispensable tool for differentiating between GHD and ISS; and that IGFBP-2 plays an additional role in this process.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p < 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (<7–139), inhibin B: 80 pg/ml (<20–294) (median, range)) compared to levels in age-matched healthy schoolgirls (inhibin A: all values <7 pg/ml, inhibin B: 21 pg/ml (<20–122) (median, range)), but were appropriate for Tanner stage. During treatment with GnRH agonist (intranasal buserelin and oral cyproterone acetate, treatment group 1, n = 23, or triptorelin depot injections, treatment group 2, n = 19) levels of both hormones fell significantly (p = 0.002). There was a significantly (p = 0.003) greater fall in inhibin B levels during treatment in group 2 compared to group 1, with inhibin B levels now lying below (group 2: <20 pg/ml (<20–68)) rather than within (group 1: 34.5 pg/ml (<20–93)) the age-appropriate range. It is concluded that levels of inhibin A and inhibin B are elevated and suppressed in concert with activation and suppression of the hypothalamo-pituitary-gonadal axis in girls with CPP, supporting the concept that ovarian inhibin secretion is dynamically regulated by gonadotropin stimulation.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 ± 0.10 vs. 0.80 ± 0.10 mm, p < 0.0001 for prepubertal children and 0.81 ± 0.10 vs. 0.94 ± 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 ± 57.3 vs. 113.09 ± 37 kPa, p < 0.0001 for prepubertal children and 172.5 ± 61.7 vs. 117.3 ± 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 ± 0.09 vs. 0.39 ± 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 ± 0.05 vs. 0.33 ± 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Much has been learned over the last two decades regarding the management of growth hormone deficiency (GHD) in children and adolescents. However, significant divergence and debate continue to exist on the ideal approach to the management of GHD. Despite active controversy, several paradigms have recently emerged which should guide the treatment of GHD patients as we head into the new millennium. The primary objectives of GH therapy remain the normalization of height in childhood and the attainment of normal adult height, but the recognition of the metabolic roles of GH define additional therapeutic benefits. A daily subcutaneous injection of recombinant human GH in a dose range of 25-50 µg/kg/ day has been established as the mainstay of therapy. Alternative modes of treatment including GH-releasing hormone (GHRH), GH secretagogues and depot GH have been developed, but evaluation of their clinical utility remains incomplete. Careful monitoring and follow-up of pediatric GHD patients by a pediatric endocrinologist are essential. Accurate determination of height velocity and interval height increases (expressed as the change in height z score) continue to be the most important parameters in monitoring the response to treatment. Monitoring serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 has gained utility in the assurance of compliance and safety, but does not always correlate well with the growth response. A clear role for a biochemical as well as an auxological monitoring approach has nonetheless been established. The comparison of attained growth response to that which has been calculated by various modeling approaches is also becoming a valuable monitoring tool. Significant side effects of GH therapy are quite rare and are easily identified and addressed during close follow-up. Despite previous concerns, it now appears that in the absence of additional risk factors there is no evidence that long-term recipients of GH are at any... [ABSTRACT FROM AUTHOR]

The cholesterol biosynthetic activity was assessed using [2-[sup 14] C]-acetate as substrate in the homogenates of amnion and chorion obtained from women (n = 6, age 26–39 years) after spontaneous labour at term (37–40 weeks of gestation) having uncomplicated pregnancies. Reverse-isotope dilution analysis gave positive identification of [[sup 14] C]-cholesterol acetate in all incubations of viable tissues. This metabolite was not evident in heat-denatured homogenates which served as controls. The extent of enzymic conversion for amnion at 2.6 × 10[sup –3] to 0.19% was persistently higher than that of the chorion at 1.7 × 10[sup –3] to 9.0 × 10[sup –3] %. The results indicate that human term fetal membranes possess the full complement of enzymes to catalyze the transformation of acetate to cholesterol. This study provides evidence that fetal membranes possess the capacity for de novo cholesterol biosynthesis, the sterol being essential for steroidogenesis as well as in embryo viability during pregnancy.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The relationship between perceptions versus measured height and children’s psychosocial adaptation in a sample of medically referred youth with short stature was investigated. All children referred for a growth evaluation to one regional pediatric endocrinology clinic received a psychosocial screening assessment as a routine component of their initial visit. Data were collected for patients ages 4–18 years (n = 620) with heights ranging from –4.0 to –1.1 SD for age- and gender-adjusted population norms. Patients (8 years and older) and in all cases a parent/guardian served as informant through paper-and-pencil questionnaires. Both children and parents overestimated the child’s height. Overestimations of height were associated with greater patient and parent satisfaction with stature. Perceived height was more strongly associated with psychosocial adaptation than was measured height. Clinical management decisions designed to enhance patient quality of life by increasing projected adult height through hormonal interventions should take into account both measured and perceived patient height.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The statural catch-up growth, defined as reaching at least tenth length/height percentile (P10) for normal population standards (–1.28 SD score, SDS), was studied in 73 infants short at birth (length < P10 for gestational age) admitted to NICU. Mean gestational age at birth was 35.2 weeks (range 29–41) and mean birth length standard deviation score –2.31 (–4.52/–1.46). Infants were measured at birth, at 3, 6, 12, 18, and 24 months corrected age and then once a year until 6 years chronological age. Statural catch-up growth was studied, with reference both to normal population standards and to individual genetic target. With reference to normal population standards, 44% of infants had caught-up at 3 months of age, 51% at 3 years, 66% at 4 years and 73% at 6 years. In the case of individual genetic targets, a similar trend was present, but the absolute values were slightly higher from 4 to 6 years (73 vs. 66% and 78 vs. 73%, respectively). Statistically significant changes in mean standard deviations score for chronological age were present from birth to 3 months, 3 to 12 months, 3 to 4 years and 5 to 6 years (p < 0.05). No differences were found in this trend of recovery when considering ponderal index (PI) at birth (symmetrical vs. asymmetrical), sex (male vs. female) or gestational age (p > 0.05). In the majority of cases infants with short stature at birth admitted to a NICU had a statural catch-up growth within the first years of life. This is more evident when considered in relation to individual genetic target rather than to normal population standards.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Insulin-like growth factors (IGFs) circulate in plasma as part of a 150-kD complex that also contains IGF-binding protein-3 (IGFBP-3), a protein that binds IGF-I and IGF-II with high affinity, and an acid-labile subunit (ALS) that does not directly bind IGFs. Because the ALS assay methods currently being used are relatively new, there is a need for updated normative reference data. We report the normative data in 17 preterm infants (10 males and 7 females), 30 normal full-term newborns (15 males and 15 females) and 150 normal children who where divided into 5 groups according to their Tanner stage (15 males and 15 females per group). Serum levels of total and free ALS were significantly lower in premature infants than in full-term newborns, but all newborns had significantly lower levels than Tanner stage-I children (p < 0.001, ANOVA). A significant increase was seen between Tanner stages I–III in both sexes (p < 0.001, ANOVA). No differences were found between sexes at any developmental age studied. Significant correlations (p < 0.001) were seen between total and free ALS concentrations and IGF-I (r = 0.50 and 0.60, respectively), free IGF-I (r = 0.37 and 0.36), IGF-II (r = 0.37 and 0.27), IGFBP-1 (r = –0.48 and –0.49), IGFBP-2 (r = –0.44 and –0.51) and IGFBP-3 (r = 0.67 and 0.59) at all Tanner stages. However, no correlation was found with IGFBP-1, -2 or -3 levels at birth. This study shows normal values in a population of preterm infants and healthy Spanish newborns and subjects of both sexes at all stages of pubertal development and indicate the different relationships between the components of the IGF system during intra- and extrauterine life.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Discusses several issues on hormones and paediatric endocrinology as highlighted by several studies presented at the 39th Annual Meeting of the European Society for Paediatric Endocrinology. "Genetic Basis of Chondrocyte Differentiation"; "Childhood's End: Growth Plate Senescence and Epiphyseal Fusion"; "Regulation of Apoptosis in Cells of the Epiphyseal Growth Plate."

Presents abstracts of studies on hormones, presented at the 39th Annual Meeting of the European Society for Paediatric Endocrinology in Brussels, Belgium. "Mutations in the LIM-Homeodomain LHX3 Gene Result in a New Syndrome Revealed by Combined Pituitary Hormone Deficiency"; "Transcriptional and Translational Regulation of the Splicing Isoforms of the GH Receptor by Glucocorticoids"; "Placental Growth Hormone: Relationship to Maternal and Fetal Serum Leptin and IGF-1."

Presents abstracts of studies on hormones, highlighted at the 39th Annual Meeting of the European Society for Paediatric Endocrinology in Brussels, Belgium. "Growth, Endocrine, Cytogenetic and Clinical Features of a Boy with Jacobsen Syndrome Including Primary Hypothyroidism and Growth Hormone Deficiency"; "Relative Contributions of Inferior Petrosal Sinus Sampling and Pituitary Imaging in the Investigation of Children and Adolescents with ACTH-Dependent Cushing's Syndrome."

Presents information on the awards given to researchers in endocrinology during the 38th meeting of the European Society of Pediatric Endocrinology in Warsaw, Poland. Zvi Laron; Eveline Francesca Gevers; Jean-Pierre Bourguignon.

Aim: To investigate the possible cardiac morphofunctional alterations inducd by prolonged and high-dose GH therapy in a group of 14 children with isolated GH deficiency. Patients and Methods: Patients were evaluated at phase 1, after 1.1 ± 0.6 years of treatment with GH 0.93 ± 0.13 U/kg/week, and at phase 2, after 5.5 ± 2.1 years of therapy 0.89 ± 0.11 U/kg/week. At each phase left ventricular volume, mass and systolic function were evaluated by two-dimensional guided M-mode echocardiography; left ventricular diastolic function was assessed by PW-Doppler sampling of transmitral flow. Results: Phase 1: diastolic blood pressure was lower (p < 0.05) and fractional shortening was not adequate for the level of afterload (stress shortening index p < 0.05) in patients compared to controls. Phase 2: diastolic blood pressure was lower (p < 0.01) and mass and mass/volume ratio were increased (mass index p < 0.05, mass/ volume ratio p < 0.05) in patients compared to controls. The increased mass/volume ratio, together with the normal systolic blood pressure, explains the reduction in peak systolic stress (p < 0.005). Among the parameters of left ventricular diastolic function, the peak E velocity/total area under mitral valve tracing and the area under E velocity/total area under mitral value tracing ratios were significantly decreased (p < 0.05). Conclusion: After a mean period of 5 years on high-dose GH treatment in GH-deficient children, subclinical morphofunctional alterations in the left ventricle were found.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In girls, pronounced adrenarche with precocious pubarche (PP) has been related to reduced fetal growth and to a cluster of endocrine-metabolic abnormalities. We examined whether these associations are also evident in boys with PP. The study population consisted of matched groups of boys (n = 58; age range 5–15 years) without or with a history of PP. After stratification for pubertal development, non-PP and PP boys displayed comparable results for the studied variables, including serum insulin-like growth factor I, sex hormone binding globulin, insulin-like growth factor binding proteins 1 and 3, indices of circulating glucose and insulin responsiveness to an oral glucose load, and birth weight SD score. In conclusion, the present results indicate that adrenarche-driven PP in boys is, in contrast to PP in girls, not associated with a cluster of endocrine-metabolic abnormalities and is not related to reduced fetal growth. These observations support the view that adrenarche-driven PP in boys may be regarded as a variant of normal development.Copyright © 1999 S.Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents a list of awards and activities at the 6th Joint Meeting of the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society from September 24 through 27, 1998 in Florence, Italy. Professional appointments; Gold Medal of the Finnish Diabetes Association award; Major research projects.

A 14.2-year-old prepubertal boy diagnosed with complete-type growth hormone deficiency and tertiary hypothyroidism, keeps growing in the height range between –1 and –2 SD. He has been treated with levothyroxine only. To understand the growth mechanism of this boy, we analyzed the serum growth hormone (GH) with a radioimmunoassay (RIA), serum GH bioactivity with Nb2 and erythroid progenitor cell bioassays, and growth hormone-binding protein (GHBP) with a ligand-mediated immunofunctional assay (LIFA). In addition, IGF-1 and free IGF-1 were analyzed by immunoradiometric assay (IRMA) and insulin-like growth factor-binding protein-3 (IGFBP-3) by Western immunoblot. Peak GH-RIA responses to insulin, arginine and GH-releasing factor, and nocturnal GH secretion, were low (0.5–2.3 ng/ml); bioactive GH was low (0.313 ng/ml), and GHBP was elevated (84 ng/ml). The serum levels of IGF-1 and free IGF-1 were continuously low, 17.1–39.3 and 0.17–0.26 ng/ml, respectively. Moreover, serum IGFBP-3 levels were low (1.68– 1.39 mg/l) and IGFBP-3 protease activity was negative. Prolactin and insulin were in the normal range. The result of the assay for growth-promoting activity showed that the patient’s serum stimulated normal erythroid progenitor cells twice as potently as did healthy thin adult control serum. These results suggest that GH and IGF-1 are not indispensable for maintaining physical growth in this boy. Thus, it appears that circulating GH and IGF-1 are not mandatory requirements for maintaining normal physical growth, and other, as yet uncharacterized, pathways or growth factors might be sufficiently compensatory under certain conditions. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) treatment of GH-deficient (GHD) children is to a certain extent standardized worldwide. Recombinant 22 kDa GH is injected once daily by the subcutaneous route, mostly in the evening. The amount of GH injected (calculated per kg body weight or body surface area, expressed in terms of IU or mg) in prepubertal children mimics the known production rate (approximately 0.02 mg [0.06 IU]/kg body weight per day). However, there is a wide variation in dosage, the reasons for which are partly unknown and partly due to national traditions and regimes imposed by authorities regulating reimbursement. The situation during puberty is less standardized, with most clinicians still not increasing the dosage according to known production rates. The results of these approaches in terms of adult height outcome are not always satisfactory. In order to achieve optimal height development during childhood, puberty and adulthood, strategies must be developed to individualize GH dosing according to set therapeutical goals taking into account efficacy, safety and cost. The implementation of prediction algorithms will help us to reach these goals. In addition, other response variables will have to be monitored during treatment in order to correct for deficits resulting from GHD.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]