Serum concentrations of insulin, insulin-like growth factor-I and insulin-like growth factor binding proteins are different between white and African American girls.

OBJECTIVES: To determine whether serum insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP) concentrations are different between African American and white girls. STUDY DESIGN: Serum glucose and hormone concentrations were measured in blood samples collected after a 12-hour fast from 79 white and 57 African American healthy girls between 9 and 17 years of age. Tanner stages of pubic hair development were evaluated by physical examination, and body composition by dual energy x-ray absorptiometry. RESULTS: The African American girls were older and sexually more mature and had higher fat mass, higher serum insulin and free IGF-I concentrations, higher serum free IGF-I to total IGF-I ratio, but lower serum IGFBP-1 concentrations than the white girls. After controlling for sexual maturation and fat mass, the serum concentrations of total IGF-I, bound IGF-I, and IGFBP-3 in the white girls became significantly higher than those in the African American girls. The higher concentrations of total IGF-I in the white girls were due to a proportional increase in the concentrations of bound IGF-I that coincided with a similar increase in serum IGFBP-3 concentrations. CONCLUSIONS: Higher serum insulin concentrations in the African American girls are associated with lower serum IGFBP-1 concentrations and increased bioavailability of free IGF-I, which may contribute to their accelerated growth compared with their white counterparts.     

Serum Levels of Free Insulin-Like Growth Factor (IGF)-I in Normal Children

Serum levels of free insulin-like growth factor (IGF)-I were measured by immunoradiometric assay (IRMA) in fasting sera of 137 normal boys and 120 normal girls aged from 8 to 15 yr to study relationships between free IGF-I levels and ages, total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit (ALS) levels. In both sexes, serum free IGF-I levels and the ratios of free IGF-I to total IGF-I were significantly higher in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-I showed a significant positive correlation with those of total IGF-I, IGFBP-3 and ALS, while they showed a significant negative correlation with those of IGFBP-1. These observations suggest that increase in serum free IGF-I levels during puberty is caused by a dramatic increase in total IGF-I, rather than IGFBP-3, and a decrease in IGFBP-1. Also, high free IGF-I levels may play an important role in pubertal growth spurt.     

Effect of hypothyroidism and its treatment on the IGF system in infants and children

We performed a study on infants and children with hypothyroidism to determine the effect of hypothyroidism and its correction on components of the IGF system. A total of 35 patients were subdivided into four groups based on age and severity of the disease. Serum concentrations of immunoreactive IGF-I, free IGF-I, IGFBP-2 and IGFBP-3 were measured before and after treatment and compared to controls matched for age, sex and puberty. Baseline total IGF-I (TIGF-I) concentrations were significantly lower prior to treatment in the infants with severe hypothyroidism and increased significantly after thyroxine therapy. Baseline free IGF-I (FIGF-I) concentration was significantly lower prior to treatment in infants with severe hypothyroidism when compared to controls but did not increase significantly after treatment. In infants with severe and compensated hypothyroidism, IGFBP-3 concentrations prior to treatment were lower when compared to controls. These concentrations increased during treatment. Baseline IGFBP-2 levels did not differ from the control values in both these groups but decreased significantly after correction of the hypothyroidism. Although these changes appeared to occur with thyroxine therapy, multiple regression analysis suggested that age was a more important determinant of the changes observed in these parameters than serum thyroxine concentration. In children with acquired hypothyroidism no difference in any of these parameters was noted between hypothyroid patients and controls. TIGF-I increased significantly on thyroxine therapy, but the difference was small. No significant differences were noted in other measured parameters with thyroxine therapy. In older children with compensated hypothyroidism no significant differences were noted in any of the measured parameters in the pretreatment, post-treatment and control groups. In conclusion, although changes appear in TIGF-I, IGFBP-3 and IGFBP-2 in infants with congenital hypothyroidism when they are treated with thyroxine, age appears to be the more important determinant of these changes than does thyroxine concentration. In older children with acquired hypothyroidism, TIGF-I and FIGF-I levels were not significantly lower than in age- and sex-matched controls. After treatment only TIGF-I levels increased.     

Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin like growth factor I

Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

Growth hormone and insulin-like growth factor I axis and growth of children with different sickle cell anemia haplotypes

BACKGROUND: The purpose of this study was to examine the relationships between growth in children with sickle cell anemia and the different beta-globin haplotypes, as well as components of the insulin-like growth factor (IGF)/insulin-like growth factor binding protein (IGFBP) axis. PATIENTS AND METHODS: Growth parameters and plasma concentrations of growth hormone (GH), IGF-I, and IGFBP-3 were studied in 41 children with sickle cell anemia whose haplotypes were defined. RESULTS: Plasma concentrations of IGF-I (total, free, and free/total fraction) and IGFBP-3 were significantly reduced in all patients with sickle cell anemia compared with the healthy children. Patients with the CAR/CAR haplotype had significantly lower mean growth velocity compared with those with Ben/Ben. When the GH/IGF axis elements were compared in relation with the different haplotypes, total IGF-I levels in CAR/CAR patients were significantly lower compared with levels in patients with Ben/Ben. A positive correlation was found between hematocrit and total IGF-I and between fetal hemoglobin percentages and the z-scores for total IGF-I and IGFBP-3. There was a positive correlation between age, weight, height, bone age, and the various elements of the GH/IGF-I axis when all groups were considered, although the correlation was lost when the auxologic data were expressed as standard deviation score for age. Growth velocity and the z-score for growth velocity were not correlated with any element of the axis. CONCLUSIONS: The positive relationship between hematocrit and fetal hemoglobin percentages with total IGF-I, free/total IGF-I, and IGFBP-3 in patients with sickle cell anemia could show that the delayed growth of these patients may be linked to intrinsic factors of the disease, which also determine the low circulating concentrations of the various elements of the GH/IGF-I axis. It is reasonable to assume that decrease of total IGF-I concentrations in patients with CAR/CAR haplotype is secondary to the severity of the disease.     

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-IL serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance. Finally, IGF-I administration suppresses GH secretion.     

Endocrine function in thai children infected with human immunodeficiency virus

Most children infected by HIV show manifestations which mimic the clinical features of endocrine dysfunction, such as failure to thrive and hyperpigmentation. Our cross-sectional study was designed to assess the endocrine function of Thai children infected with HIV and to determine any relationship between disease severity, height and endocrine function. Thirty-six prepubertal children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/- 2 years), were tested for thyroid function (serum T4, T3, TSH and free T4), morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T-lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five patients had euthyroid sick syndrome. Thyroid function tests indicated another five patients had a condition compatible with compensated hypothyroidism. Most patients had normal morning serum cortisol levels. Two-thirds and one-third of the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS), respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were classified as severely immune suppressed. A weak linear relationship was indicated between disease severity and endocrine function (r = -0.03 to 0.41). Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3 SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively. Nearly half (44%) the patients were below the third percentile for height of Thai children. There was also a weak correlation between height SDS and endocrine function (r = -0.03 to 0.41). Statistical significance was observed between height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01, respectively). We conclude that HIV-infected children with demonstrated growth failure and greater disease severity tend to have abnormal endocrine function, particularly disordered IGF-I levels.     

A study of anthropomorphic and biochemical characteristics in girls with central precocious puberty and thelarche variant

BACKGROUND: Premature thelarche in later childhood may progress to central precocious puberty (CPP), which does not spontaneously resolve. Thelarche variant (TV) is a slowly progressive variant of precocious puberty. AIM: To determine and compare levels of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and anthropomorphic measures in girls with TV and CPP. SUBJECTS: Prepubertal controls and girls with TV and CPP. METHODS: Chronological and bone age, weight, height, BMI, height velocity (HV), and serum IGF-I, IGFBP-3, leptin, follicle-stimulating hormone (FSH) and lutenizing hormone (LH) levels were assessed. RESULTS: Serum IGF-I levels, HV and IGF-I/ IGFBP-3 ratio were significantly higher in girls with CPP compared to both controls and girls with TV. IGFBP-3 values for bone age (IGFBP-3BA) were significantly higher in the TV group compared to both controls and girls with CPP. FSH and LH concentrations were significantly higher in the CPP group compared to TV. CONCLUSION: HV, IGF-I, LH and FSH levels and IGF-I/IGFBP-3 ratio are elevated in girls with CPP compared to those with TV.     

Insulin-like growth factor I, IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia.

OBJECTIVES: To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status. METHODS: Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [125I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS). RESULTS: The median (range) IGF-I SDS was significantly reduced in all patients (-1.1 (-5.1 to 1.2)) and lower in children who were malnourished (-2.5 (-3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness. CONCLUSIONS: IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.     

Insulin-like growth factors in childhood-onset Gaucher disease

There is a high prevalence of growth retardation in children with type 1 Gaucher disease. The cause of this poor growth is not yet known; however, studies have shown acceleration of growth with enzyme replacement therapy (ERT). IGF are recognized as important determinants of somatic growth. It has been proven that chronic diseases with liver involvement might cause IGF deficiency. The aim of this study was to assess the IGF system in patients with childhood-onset Gaucher disease, before and after ERT, and its association with other clinical and analytical parameters. Twenty-two patients with type I Gaucher disease were included. The diagnosis was established before 14 y of age in all patients. Baseline determinations of total IGF-I, free IGF-I, and IGF binding protein 3 (IGFBP-3) were obtained in 19 patients before starting ERT at a mean age of 13.8 +/- 11.2 y. A Spearman test was performed to establish the association with other clinical and analytical parameters. In a group of 13 patients receiving IGF, changes were evaluated during the initial 2 y of treatment. A Wilcoxon test was performed for the statistical analysis. Total IGF-I, free IGF-I, and IGFBP-3 were expressed as SD scores (SDS). We found low levels of IGF and its binding proteins before ERT. A significant association was found between the total IGF-I SDS before treatment and the age-adjusted severity score index: r = -0.62, p < 0.05. Total IGF-I and IGFBP-3 SDS correlated negatively with the presence of the L444P mutation (r = -0.53 and -0.5, respectively, p < 0.05). Height SDS correlated with total IGF-I and IGFBP-3 SDS in eight children (r = 0.84 and 0.78, respectively, p < 0.05). Total IGF-I SDS increased from -1.8 +/- 0.8 to -0.8 +/- 1.4 (p = 0.005) and free IGF-I increased from -1.2 +/- 1 to 1.1 +/- 2.1 after 12 +/- 6.8 mo (p = 0.011) of ERT. IGFBP-3 SDS increased from -1.3 +/- 0.6 to -0.2 +/- 1.2 (p = 0.012) after 12 +/- 4.5 mo of ERT. Type 1 Gaucher disease is associated with low levels of IGF and its binding proteins, which could be a consequence of liver involvement. Total IGF-I deficiency is associated with the severity of the illness. Growth retardation in pediatric patients with Gaucher disease is related to the alterations in IGF axis. Total IGF-I and IGFBP-3 are the two parameters that better correlate with height before treatment. ERT results in significant increase of total IGF-I, free IGF-I, and IGFBP-3 during the first year of treatment.     

Relation between serum Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 levels, clinical status and growth parameters in prepubertal cystic fibrosis patients

BACKGROUND: This study aims to determine the relation between anabolic hormones, Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3), growth parameters, and clinical status in prepubertal cystic fibrosis (CF) patients. This prospective study comprises age/sex-matched control subjects and was set in a tertiary care teaching hospital. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured in 37 CF and 23 healthy subjects, whose mean ages were 5.02 +/- 3.06 and 5.27 +/- 2.82, respectively. The results were analyzed in relation to body mass index standard deviation scores (BMISD), height standard deviation scores (HSD), growth velocity standard deviation scores (GVSD), and clinical status assessed by Shwachman scores and pulmonary function parameters. RESULTS: Serum IGFBP-3 of CF patients showed significantly lower concentrations than healthy subjects (2457 vs. 3249 ng/mL) (P < 0.05), whereas IGF-I levels did not (123.35 vs. 149.8 ng/mL). There was significant positive correlation between IGF-I and IGFBP-3 with HSD (r = 0.62; r = 0.79) and BMISD (r = 0.39; r = 0.50). The pulmonary function tests in 14 CF subjects were not statistically worse than in nine healthy cases. The mean HSD (-0.67, SD 1.06) and BMISD (-0.28, SD 0.71) of CF patients were not significantly lower than those of healthy subjects (-0.02, SD 0.86 and 0.03, SD 0.49), respectively. CONCLUSION: Decreased serum IGF-I and IGFBP-3 levels may reflect growth retardation in CF. IGFBP-3 seems like a more sensitive parameter than IGF-I for growth monitoring in this study. Growth parameters of Turkish prepubertal CF patients are not markedly below national standards. Different genetic backgrounds of relevant populations certainly play an important role for the variable clinical course.     

Insulin-like growth factor I,IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia

OBJECTIVES—To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status.METHODS—Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [¹²⁵I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS).RESULTS—The median (range) IGF-I SDS was significantly reduced in all patients (?1.1 (?5.1 to 1.2)) and lower in children who were malnourished (?2.5 (?3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness.CONCLUSIONS—IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.     

Growth hormone-IGF-I axis and growth velocity in Chinese children with type 1 diabetes mellitus

OBJECTIVE: To elucidate hormonal disturbances in patients with type 1 diabetes mellitus (DM1) with and without growth retardation. METHODS: Patients with DM1 were divided into two groups, group A consisted of 14 patients with poor growth, and group B consisted of 24 patients with normal growth. Serum IGF-I, IGFBP-3, basal and stimulated GH, and HbA1c were measured. RESULTS: Serum IGF-I and IGFBP-3 concentrations were significantly decreased in group A versus both groups B and controls in Tanner stages I-III; in addition, these measurements in group B were significantly lower compared to controls in Tanner stages II and III, but there was no significant difference in prepuberty. Both basal and peak serum GH were attenuated significantly in group A versus group B. Basal serum GH in group B (normal growth DM1) was significantly elevated versus the controls. There was an unambiguous negative linear regression between IGF-I and mean HbA1c in patients with DM1. CONCLUSIONS: Growth retardation in patients with DM1 is associated with an abnormal GH-IGF-I axis and poor glycemic control.     

Insulin-like growth factor binding protein-3 proteolysis and growth of athyreotic infants in the first weeks of life

To gain a better understanding of the growth of athyreotic newborns in the first weeks of life, we evaluated auxological parameters and determined the serum levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and free IGF-I, and IGF-binding protein-3 (IGFBP-3) in 15 hypothyroid infants (10 females) at a mean age of 25 d of life, immediately before the beginning of L-thyroxine therapy, and at 3 and 6 mo of life. Fourteen normal infants (9 females) of the same age were studied as controls. IGFBP-3 proteolytic activity was evaluated in 8 patients and in 8 controls at 25 d and 6 mo of life. There was no significant difference concerning weight and length between the patients and controls at birth, 25 d, 3 and 6 mo of life. The blood GH, IGF-I and IGFBP-3 levels were significantly lower in patients at diagnosis than in controls of the same age (p < 0.01 for all parameters), as well as IGFBP-3 studied by Western blotting. At diagnosis, the patients' free IGF-I level was within the control range, but the free IGF-I percentage of total IGF-I was higher than in the controls (p < 0.01). IGFBP-3 proteolytic activity was found to be greater in the patients (p < 0.01). At 6 mo of life, after therapy, none of these parameters was different from those of the controls. CONCLUSION: Increased IGFBP-3 proteolytic activity in our patients at diagnosis, favouring IGF-I bioavailability, could account for normal free IGF-I levels and in turn for their normal growth pattern during the first weeks of life and before the start of treatment.     

Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3), leptin levels and early postnatal growth in infants born asymmetrically small for gestational age

This study was planned to investigate the relationship between birth weight and insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and leptin levels in neonates with normal growth (appropriate for gestational age: AGA) and retarded growth (small for gestational age: SGA); and to evaluate these growth factors' effects in early postnatal growth. All newborns were full-term: gestational age 3,841 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and leptin levels were measured in maternal serum and venous cord blood at birth and at 15 days of life of neonates using specific RIAs. Maternal serum leptin concentrations were significantly higher than cord blood leptin concentrations (p < 0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show correlations with birth weight. In contrast, there were significantly positive correlations between birth weight and venous cord blood IGF-I, IGFBP-3 and leptin levels (p < 0.001). In the SGA group, the newborns with a slow postnatal growth pattern had lower umbilical cord serum IGF-I levels compared with newborns with a normal growth pattern. A similar result was also found in the AGA group. Similar results were not found for serum leptin and IGFBP-3. In conclusion, cord blood IGF-I, IGFBP-3 and leptin levels play an important role in the regulation of fetal and neonatal growth. It is likely that IGF-I has a more important role than the other factors in early postnatal growth.     

Endocrine abnormalities in Anorexia Nervosa

Anorexia Nervosa (AN) is a psychiatric disorder characterized by the classic triad: amenorrhea, weight loss, and behavioral changes. It is generally seen in young, white women under 25 and is particularly common in adolescence. The mortality of the disease varies between 5.1% and 13%. The endocrine changes associated with AN have been studied in depth and provide strong evidence for hypothalamic dysfunction. All are secondary and reverse with weight gain. In general, gonadotropin (FSH, LH) levels are decreased in patients with AN, as well as the response to Gonadotropin releasing hormone (GnRH). Fasting growth hormone levels are elevated, but the stimulated response of Growth hormone (GH) to Growth hormone releasing hormone (GHRH) is normal and inversely correlated to body weight. Serum Growth hormone binding protein (GHBP), insulin growth factor I (IGF-I) and IGF binding protein (IGFBP) - 3 levels are all significantly decreased in patients with AN and return to normal with refeeding. IGFBP-1 and 2 are increased and return also to normal with weight gain. Serum IGF-II is decreased but not significantly. The IGFBP-3 proteolytic activity is normal. Thyroxine (T4) and Triiodothyronine (T3) while reverse T3 (rT3) is elevated. Thyrotropin stimulating hormone (TSH). TSH levels are normal with a delayed response to thyrotropin releasing hormone (TRH). Cortisol levels are normal or elevated as well as urinary free cortisol. Corticotropin (ACTH) levels are normal with decreased response to Corticotropin releasing hormone (CRH). Dexamethasone suppression test is abnormal. Sex steroids are decreased. Finally leptin levels are decreased in patients with AN while ghrelin levels are elevated. Both leptin and ghrelin levels return to control values after renutrition.     

Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern. STUDY DESIGN: One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p < 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p < 0.001). There was a correlation between height SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01). CONCLUSION: Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.     

Autonomous thyroid nodules in adolescents: clinical characteristics and results of TRH testing

Seven adolescents with autonomous thyroid nodules were evaluated over a three-year period. They had hyperfunctioning nodules on radionuclide scan which failed to suppress with exogenous administration of thyroid hormone. They were clinically euthyroid and had normal T4, free T4, and basal TSH values. However, as a group they had elevated total serum T3 concentrations, blunted TSH response to TRH, and accelerated closure of cranial sutures, all of which suggested subtle hyperthyroidism. These patients have been followed for one to five years. Four have undergone partial thyroidectomy because of persistent elevation in the serum T3 concentration or enlargement of the nodule. The clinical presentation and laboratory findings in this group are similar to those found in adults with autonomous nodules.     

Reduced levels of growth hormone,insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

Accepted 25 March 1997
OBJECTIVE—Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern.
STUDY DESIGN—One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured.
RESULTS—The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p< 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p< 0.001). There was a correlation between height SD score and IGF-I levels in the total patientpopulation (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01).
CONCLUSION— Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.

• Prepubertal children with shunted hydrocephalus have reduced circulating IGF-I and IGFBP-3 concentrations • Pubertal children with shunted hydrocephalus have reduced basal serum growth hormone concentrations • Reduced growth hormone secretion may contribute to slow linear growth and reduced final height in hydrocephalic children • Carbamazepine treatment may increase IGF-I and IGFBP-3 concentrations in the peripheral circulation