Ann J. Johanson

Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome

Seventy girls with Turner syndrome, verified by karyotype, were randomly assigned to observation or treatment with human growth hormone (hGH), oxandrolone, or a combination of hGH plus oxandrolone for a period of 12 to 24 months, to assess the effect of treatment on growth velocity and adult height. Subsequently, all subjects received either hGH alone or hGH plus oxandrolone. Data are presented for 62 subjects treated for a period of 3 to 6 years. When compared with the anticipated growth rate in untreated patients, the growth rate after treatment with hGH, both alone and in combination with oxandrolone, showed a sustained increase for at least 6 years. Treatment is continuing in over half of the subjects; at present, 14 (82%) of 17 girls receiving hGH alone and 41 (91%) of 45 girls receiving combination therapy exceeded their expected adult heights. Thirty girls have completed treatment; mean height for these 30 patients is 151.9 cm, compared with their mean original projected adult height of 143.8 cm. We conclude that therapy with hGH, alone and in combination with oxandrolone, can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome.

Three-year results of a randomized prospective trial of methionyl human growth hormone and oxandrolone in Turner syndrome

Seventy girls with Turner syndrome, 4 to 12 years of age, participated in a prospective, randomized study to determine the effects on growth of methionyl human growth hormone (met-hGH) or oxandrolone. Subjects were randomly assigned to receive either no treatment (control) or met-hGH (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination met-hGH plus oxandrolone. At the end of an initial period of 12 to 20 months, patients in the original control and oxandrolone groups were given combination met-hGH plus oxandrolone. At that time the dosage of oxandrolone was lowered to 0.0625 mg/kg/day. Sixty-five subjects have now completed the first 3 years of the study. Compared with the control growth rate for year 1 (3.8 cm/yr), significant increases in growth rate were seen in all 3 years of combination therapy (9.8, 7.4, and 6.1 cm/yr, respectively) and in the first 2 years of treatment with met-hGH alone (6.6, 5.4, and 4.6 cm/yr). When growth velocity was expressed as standard deviation for age in girls with Turner syndrome, significant increases relative to the control group for year 1 (-0.1 SD) were seen in all three years of both combination therapy and met-hGH alone (combination, +6.6, +4.3, +3.0 SD; met-hGH, +3.1, +2.0, +1.4 SD). After 3 years of treatment, predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group.

Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy

Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height. It is yet unknown whether therapy would alter pubertal development or affect final height. Three-year treatment results in a group of children with idiopathic short stature are reported. For year 1 of the study, 121 prepubertal children were randomly selected to receive somatotropin, 0.3 mg/kg per week, administered subcutaneously three times weekly (n = 63), or to be nontreatment control subjects (n = 58). After 1 year, all subjects were again randomly selected to receive either three-times-weekly or daily dosing at the same total dose. For the 92 subjects who completed 36 months of treatment, mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment. Daily dosing resulted in a significantly faster mean growth rate (9.0 cm/yr) than three-times-weekly dosing (7.8 cm/yr) (p = 0.0005). Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3, respectively, and did not differ by dosing group. Mean standardized height for all subjects improved from -2.7 to -1.6 after 3 years. When the growth rate was standardized for bone age, however, subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period (p < 0.02). Mean standardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset, but for individuals this score was more variable. Year-1 growth response, expressed as growth rate or change in height SD score, was the best predictor of growth in subsequent years. Responses to therapy could not be reliably predicted from baseline anthropometric variables, plasma insulin-like growth factor I SD score, growth hormone levels. Final height assessment will be needed to determine the ultimate benefit of therapy.

Carbohydrate and lipid metabolism in Turner syndrome: Effect of therapy with growth hormone, oxandrolone, and a combination of both

To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.

Brain tumor recurrence in children treated with growth hormone: The National Cooperative Growth Study experience☆☆☆★★★

As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.

Methionyl human growth hormone and oxandrolone in Turner syndrome: Preliminary results of a prospective randomized trial

Seventy girls with Turner syndrome, 4 to 12 years of age, were randomly assigned to receive either no treatment (control) or methionyl human growth hormone (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination hGH plus oxandrolone therapy. Baseline growth rates averaged 4.3 cm/yr, and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome. Sixty-seven girls remained in the study for a minimum of 1 year. Growth rates and growth velocity (in standard deviations for age in girls with Turner syndrome) were control 3.8 cm/yr (-0.1 SD), hGH 6.6 cm/yr (+2.3 SD), oxandrolone 7.9 cm/yr (+3.7 SD), and combination therapy 9.8 cm/yr (+5.4 SD). Mean bone ages advanced 1.0 years (hGH), 1.3 years (oxandrolone), and 1.6 years (combination). However, median increments in height age/bone age (delta HA/delta BA) ratios ranged from 1.0 to 1.1 for treatment groups, compared with 0.8 for the controls. Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or oxandrolone alone, and 3.2 cm for combination treatment. These data indicate that both hGH and oxandrolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome, and potentially increase final adult height.

Blood pressure and puberty

The purpose of this investigation was to study the relation of blood pressure to sexual maturation in 229 boys and 189 girls, 10 to 14 years of age. The results showed that there was no significant correlation between the systolic and diastolic pressure with the level of serum follicule-stimulating hormone and luteinizing hormone in either sex. Nor was there a significant correlation with the stage of pubic hair development in the boys nor with the stage of breast development, menarche, and duration since menarche in the girls. Therefore the presence of hypertension during 10 to 14 years of age should not be regarded as a physiologic response to pubertal development, but rather as a suspicious finding which deserves careful follow-up examinations.

Congenital lipodystrophy: An endocrine study in three siblings

Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...

Congenital lipodystrophy. II. Association with polycysticovarian disease

cultures were obtained from air-conditioning systems, patient rooms, or other rooms to confirm environmental contamination. As a result, no definite conclusions can be drawn as to the route of transmission of infection in our five patients. Previous reports have attempted to correlate the presence of airborne spore contamination and simultaneous occurrences of aspergillosis in compromised patients. 7-~ Elimination of sources of contamination resulted in the disappearance of cases of aspergillosis. Other reports suggest endogenous routes of transmission, such as the gastrointestinal tract and nasopharynx7 There is no information suggesting the incubation period for infection. In view of the limited ep idemiologic information concerning Aspergillus infections, outbreaks of disease in susceptible populations may warrant Careful environmental investigation, including culture confirmation. Specific recommendations for management of contaminated areas can only follow from a better understanding of the transmission o f disease,

Results from the first 2 years of a clinical trial with recombinant DNA-derived human growth hormone (somatrem) in Turner's syndrome.

A total of 70 subjects with Turners syndrome from 11 centres were enrolled in a study of somatrem. After an initial observation period, they were randomly assigned to one of four groups, receiving no treatment (Group 1, control); oxandrolone, 0.125 mg/kg/day (Group 2); somatrem, 0.125 mg/kg 3 times/week (Group 3); or a combination of somatrem and oxandrolone on the above dose regimens (Group 4). After 12–20 months, Groups 1 (control), 2 (oxandrolone) and 4 (combination) were treated with somatrem, 0.125 mg/kg 3 times/week, and oxandrolone, 0.0625 mg/kg/day; Group 3 remained on somatrem, 0.125 mg/kg 3 times/week. All three treatment groups showed a statistically significant increase during year 1 in growth velocity over both their pretreatment growth rates and the control group growth rate. These increases were slightly less in year 2 for the somatrem and combination therapy groups, but remained significantly higher than the year 1 control group growth rate. Plasma IGF‐1 levels were elevated in years 1 and 2 in the somatrem and combination groups. Adverse events were few with the somatrem group, though mild virilization occurred with oxandrolone, alone or in combination. Bone age advancement was observed with all treatments but was greater with combination therapy; it was accompanied by height age advancement. The effect of this therapy on predicted adult height was also evaluated.