Barry M. Sherman

Recombinant human growth hormone treatment of children following renal transplantation

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6–30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5±2.1 vs 5.7±2.7;P<0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potiental adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P<0.009) and 12 months (P<0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.

Growth hormone testing in short children and their response to growth hormone therapy

Because current concepts of growth hormone (GH) testing and GH treatment have become controversial, we investigated the GH secretory patterns in children with normal and short stature. Twenty-four-hour serum GH levels were evaluated in three groups of children. Group 1 was composed of children with normal height (mean height = 0.02 SD, n = 33); group 2 was composed of short children (less than 5th percentile, n = 63) with normal results on provocative GH testing; and group 3 was composed of short children (less than 5th percentile, n = 7) with subnormal results on provocative GH testing. Mean +/- SD (range) GH levels during 24-hour studies of GH secretion were 1.6 +/- 1.1 (0.5 to 5.6), 1.8 +/- 1.2 (0.6 to 6.3), and 0.9 +/- 0.4 (0.5 to 1.7) ng/ml in groups 1, 2, and 3, respectively. No statistical difference existed in mean GH levels between groups 1 and 2 or between groups 1 and 3. The mean GH concentration from 24-hour studies in group 2 children did not correlate with chronologic age, height standard deviation, growth rates, or insulin-like growth factor 1 levels. The linear growth rate of 26 of 28 children in group 2 who received GH therapy for 6 months improved by 2 cm/yr or more; the mean +/- SD growth rate was 4.0 +/- 1.3 and 8.8 +/- 2.0 cm/yr during control and treatment periods, respectively, for these 28 children. Mean GH levels from testing did not predict response to GH during 6 months of therapy. Children with slower growth rates responded better to GH therapy (p less than 0.05). We conclude that (1) in 24-hour studies, GH levels in normal children overlapped with those of short children, including those with classic GH deficiency, (2) in 24-hour studies, GH levels did not predict responses of linear growth to short-term GH treatment, nor did they correlate with childrens heights or growth velocities, and (3) the majority of short children in group 2 treated with GH for 6 months had an increase in linear growth velocity, the mean +/- SD change being 4.8 +/- 2.0 cm/yr.

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

ABSTRACT: Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 ± 0.3 versus 3.4 ± 0.2 μg/L); group 2 had significantly lower GH concentrations (1.6 ± 0.2 μg/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 ± 2.6 nmol/L, p < 0.001) than in groups 2 and 3 (2.6 ± 0.5 and 5.5 ± 0.7 nmol/L, respectively). Urinary GH (mean ± SEM) standardized for body weight (μg/kg) in group 1 (0.31 ± 0.02) was significantly greater than in group 2 (0.14 ± 0.01) and group 3 (0.20 ± 0.01). However, when expressed as μg/mol creatinine, the output of GH was similar in group 1 (4.0 ± 0.3) and group 3 (3.4 ± 0.3); both groups had significantly greater output compared to group 2 (1.3 ± 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 ± 0.02) was significantly greater than in group 2 (0.12 ± 0.01) or group 3 (0.07 ± 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p < 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.

Accelerated Growth Following Treatment of Children with Chronic Renal Failure with Recombinant Human Growth Hormone (Somatrem): a Preliminary Report

Five male children with chronic renal failure (CRF) and growth retardation were treated with recombinant human GH (somatrem) three times weekly for 6 months. The patients ranged in age from 35 to 91 months and had a mean SD score for height of ‐3.03 ± 1.0 at initiation of therapy. Their mean pretreatment height velocity was 4.94 ± 1.40 cm/year for the year prior to somatrem treatment. Following 6 months of treatment all children had a significant increase in annual height velocity, with the mean annual value for the group being 10.08 ± 1.97 cm/year (p <0.01). Glucose tolerance was monitored and was not significantly affected nor were there any other complications of note. These data indicate that somatrem can produce short‐term accelerated height velocity in the child with growth retardation associated with CRF, The long‐term benefits of therapy in this group of children is under investigation.

Urinary Growth Hormone and Insulin-like Growth Factor I Effects of Growth-Hormone Injection Schedule

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-1) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.