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Sixteen girls with Turner's syndrome aged 7.9-15.2 years (bone ages 7.0-11.8 years) were given methionyl growth hormone (somatrem) 4 IU/m2 body surface daily, corresponding to 0.9 IU/kg/week. During one year of treatment their mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) cm/year and height prediction from 148.2 (4.4) to 150.0 (4.4) cm. All the girls except one had a height velocity increment of more than 2 cm/year and these velocities are above the age references for girls with Turner's syndrome. The girl with a low growth response had antibodies against growth hormone with high binding capacity (3.7 U/l). The height velocity increment was inversely correlated with age and bone age, but this might be partly due to the somewhat higher dosage/m2 body surface and kg body weight that the younger patients were given because of the rounding off of the dose. The better results of our study compared with those of other workers who used similar dosages but did not give the drug as often suggest that giving it daily might have increased the growth response as it does in children deficient in growth hormone. [ABSTRACT FROM AUTHOR]

Unlabelled: Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce., Objective: To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children., Design: Longitudinal 6-year GH study with a randomized controlled part for 3 years., Results: At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMAD(LS) SDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDS(height)) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMAD(LS) SDS. LBM SDS(height) remained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDS(height) rapidly normalized to values comparable with zero., Conclusion: During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDS(height )remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls.

Context: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks., Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses., Patients: Thirty-six prepubertal short SGA children were the subjects of this study., Intervention: Subjects received 1 (group A) or 2 (group B) mg GH/m(2).d., Main Outcome Measures: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured., Results: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P < 0.009). In group B, maximum GH levels increased from 43.9-161 mU/liter (P < 0.0002), and in group A, from 57.2-104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A., Conclusion: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.

Objective: As overweight is a major concern in many children with Turner syndrome, we studied the effect of growth-promoting treatment with human growth hormone (hGH) on body weight indices., Design: Longitudinal study of the effect of hGH on weight indices over time in a cohort of Turner girls of different ages., Subjects: An index group of 199 hGH treated girls and a reference group of 569 untreated girls., Methods: Turner-specific weight-for-age, weight-for-height and body mass index-for-age (BMI) values were computed. In order to take account of regression to the mean, we studied spontaneous changes of these variables in the reference group. References for spontaneous changes over 3, 6, 12 or 24 months were constructed. Observed changes in the index group were corrected by subtracting the expected spontaneous change. Corrected changes were compared between overweight, normal and underweight children., Results: Treatment with hGH leads to a temporary decrease of weight indices during the first six months. This decreasing effect was not seen in overweight children. Treatment increases BMI in overweight children over 24 months, but not in normal or underweight children. BMI at start of hGH treatment did not modify long-term growth response., Conclusion: hGH treatment does not help to improve BMI in Turner syndrome children with a tendency to overweight.

The shape of the craniofacial complex was established in 69 children with Turner syndrome aged between 3.5 and 16.6 years. The children had not been treated with growth hormone (GH) or anabolic steroids. On a standardized lateral roentgenencephalogram 13 linear and 7 angular variables were measured. Data of all variables were available from normal Dutch children for comparison. The main abnormalities were located in the cranial base and in the mandible and consisted of a short posterior cranial base, all increased cranial base angle and a short, retrognathic and posteriorly rotated mandible. The maxilla was smaller than normal and also slightly posteriorly rotated. The abnormalities were already present in young children with Turner syndrome. Indications were found that in Turner syndrome interstitially as well as appositionally growing cartilage is affected. The changes in the maxilla can be explained in various ways. They may be due to defective growth of the nasal cartilage or to a disorder in the intramembranous ossification of the maxilla or they may be adaptive to the changes in the cranial base and the mandible. From this study it can be concluded that patients with Turner syndrome exhibit several craniofacial abnormalities, probably due to a cartilage disorder.

Short stature is a feature in almost all cases with Turner syndrome. The etiology is unknown, but GH secretion appears to be normal. The treatment with anabolic steroids does not seem to increase final height. Oestrogens are needed for secondary sex characteristics, but should be given in a low dosage and at approximately 12-13 years of age, in order not to compromise final height. Growth hormone increases growth velocity and leads to an average gain of 5 cm in terms of final height. The addition of oxandrolone leads to an even higher growth rate, but final height is probably similar to that reached by growth hormone alone. The dosage, injection frequency, age and bone age at the start of therapy have influence on the efficacy. GH in the dosages given appears safe.

Study Objective: To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome., Design: Randomized study., Setting: Referral-based pediatric endocrinology departments of seven university medical centers., Patients: Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis., Treatment: Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen., Results: The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects., Conclusions: Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.

Immunologic studies of 14 girls with Turner syndrome were done before and during treatment with biosynthetic growth hormone (GH). Compared with control subjects, the patients before treatment had a decreased CD4/CD8 ratio and an increased number of cells bearing the natural killer cell marker CD16; serum immunoglobulin levels were within the normal range. During GH treatment some of the girls had a slight reduction in the percentage of CD20+ B cells, but we observed no impairment of B lymphocyte function as demonstrated by the normal in vivo antibody response to the primary antigen Helix Pomatia hemocyanin, administered 6 months after the start of GH treatment. The number of CD16+ natural killer cells returned to normal. Although the number of children with thyroid antibodies increased from two before treatment to five after 1 year, no conclusion about an adverse effect of GH is warranted, because the phenomenon might be part of the natural course of the disease. We conclude that girls with Turner syndrome have minor changes in some immunologic measurements and that GH treatment resulted in some alterations that have no effect on immune function.

The various causes of persisting hyperthyroxinemia without hyperthyroidism are discussed after short case histories of an infant with hyperthyroxinemia due to TBG excess, discovered by newborn screening for congenital hypothyroidism and a girl with peripheral resistance to thyroid hormones disclosed by investigation of a small goiter. The differentiation of these various causes by thyroid function-tests is indicated. Though the anomalies leading to euthyroid hyperthyroxinemia are usually harmless their timely recognition, also in other members of the family, will prevent erroneous diagnosis and treatment of hyperthyroidism.

Venous switch operations for simple transposition of the great arteries are being carried out in increasingly younger patients. To guarantee sufficient growth of the reconstructed atria into adulthood it is advantageous to use as little prosthetic material as possible. We therefore compared the results in 36 patients who underwent the Mustard operation in which a large amount of foreign material is used with the results in 36 patients who underwent the Senning operation in which a small amount, if any, foreign material is used. The Senning operation resulted in a lower hospital mortality and a lower incidence of dysrhythmias.

Seven patients with primary glucocorticoid or glucocorticoid and mineralocorticoid deficiency are described with emphasis on the clinical presentation and laboratory investigations. Two patients presented with irreversible shock and at autopsy adrenal tissue was recognized only microscopically. In 3 patients adrenal antibodies were present. One girl had the polyglandular autoimmune disorder type I and one boy had glucocorticoid deficiency only. The histories of the patients illustrate that the presenting symptoms of primary adrenocortical insufficiency are very insidious and that it may take several years before the correct diagnosis is made and hydrocortisone substitution therapy is instituted.