Treatment of Short Stature in Children and Adolescents with Human Pituitary Growth Hormone (Raben)

101

A B S T R A C T The effects of administered human growth hormone (HGH) were evaluated in dwarfed, prepubertal children who were receiving long-term corticosteroid therapy for a chronic disease. During 11 complete metabolic balance studies, the eight corticosteroid-treated children demonstrated impaired response to large doses of HGH with minimal nitrogen and no phosphorus retention. In contrast, two hypopituitary subjects and two asthmatic children not receiving corticosteroid responded to the same preparations of HGH with nitrogen, potassium, and phosphorus retention. Six corticosteroid-treated children were given large doses of HGH (40-120 mg/wk for 4 to 8 months and showed no improvement in their retarded rate of growth, whereas the hypopituitary subjects showed accelerated growth during administration of 10-15 mg of HGH/wk. It is concluded that dwarfism in steroid-treated children results from corticosteroid-induced antagonism of the effects of HGH at the peripheral tissue level.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic effects of human growth hormone in corticosteroid-treated children

Morris¹,

Jørgensen²,

Elrick³

et al. 1968

101

“…It is reasonable to speculate that the inflection in the growth curve at 3-6 mo may be a manifestation of such a loss of responsiveness. This inference is supported by the fact that non-GH-deficiernt children, in whom dose B-C of HGH has little effect on elemental balances (1), show little or no accelera- tion of linear growth in response to long-term treatment with these doses (11,12). When the precise timing and relationships of these two events, change in slope of the growth curve and loss of anabolic responsiveness to HGH, have been defined, it may be possible to design a new schedule of intermittent HGH treatment which will maintain a higher average rate of growth during long-term treatment.…”

Section: Resultsmentioning

confidence: 96%

Responsiveness of Growth Hormone-Deficient Children to Human Growth Hormone EFFECT OF REPLACEMENT THERAPY FOR ONE YEAR

Rudman¹,

Patterson²,

Gibbas³

1973

A B S T R A C T Previous studies have shown that growth hormone (GH) -deficient children are more responsive to exogenous human growth hormone (HGH) than non-GH-deficient children. In six GH-deficient children, velocity of linear growth was less than 2.5 cm/yr. By the metabolic balance study technique, anabolic responses (increments in elemental balances) were measured to a 7 day course of 0.0532 U HGH/kg body weight (BW)81' per day (dose B) and to 0.168 U/kg BW"/' per day (dose C). They were then treated for 1 yr with HGH at a dose intermediate between B and C. Velocity of linear growth accelerated to 15-25 cm/yr for the first 4-7 mo, then declined to 0-8 cm/yr. At 12 mo, responsiveness to doses B and C was measured again; the responses were only 20-60% as great as before treatment. After 3 mo without HGH treatment, responsiveness to the anabolic effects of doses B and C returned to the magnitudes observed before treatment. A low titer of plasma antibodies to HGH was detected in two of the six children at the end of the year's treatment; these titers showed little change after 3 mo without HGH, Thus the hyperresponsiveness of GH-deficient subjects to exogenous HGH, compared to non-GH-deficient individuals, declines during long-term HGH treatment and is restored by 3 mo interruption of treatment. These changes in peripheral responsiveness may be related to the decline in velocity of linear growth which occurs after 4-7 mo of continuous treatment.When HGH was withdrawn after 12 mo, all six patients exhibited negative balances of N, P, Na, and K about half extracellular fluid. These observations indicate a role of GH in the continuing regulation of nitrogen and mineral metabolism in addition to its function as a growth-promoting hormone.

“…In 2-wk metabolic balance studies, normal children and adults show little or no anabolic response to doses up to 0.15 U/kg body weight (BW)"4 but generally respond to 0.5 U/kg BW"/' (1-B). Daily injection of about 0.05-0.15 U/kg BW"'4 (the usual dose in long-term treatment of growth retardation) in short children with normal endogenous GH generally does not accelerate growth (9,10). GH deficient children are more responsive; doses between 0.015 and 0.15 U/kg BW"4 usually elicit an acute anabolic response (1).…”

Section: Introductionmentioning

confidence: 99%

Diurnal Variation in the Responsiveness of Human Subjects to Human Growth Hormone

Rudman¹,

Freides²,

Patterson³

et al. 1973

A B S T R A C T The objective of this study was to compare the responsiveness of human subjects to the anabolic effects of human growth hormone (HGH) administered at 8 a.m. or at 11 p.m. Three doses of HGH were used: A, 0.0168 U/kg body weight (BW)"'4 per day; B, 0.0532 U/kg BW"/' per day; C, 0.168 U/kg BW"'4 per day. The effect of each dose on daily balances of N, P, Na, and K and on BW was measured. The subjects were of two groups: (a) seven GH-deficient children, of whom three were deficient in ACTH; and (b) three patients with limb-girdle dystrophy. ACTHdeficient patients in group (a) received exogenous cortisol at 7 a.m. In all 10 subjects, the anabolic effects of dose C, and sometimes of B and A, administered at 11 p.m. were significantly (P < 0.05) greater than when administered at 8 a.m. In these experiments plasma cortisol concentration averaged 3 times greater at 8 a.m. than at 11 p.m.In the next experiments, exogenous cortisol was administered to the three ACTH-deficient patients at 10 p.m. and the responsiveness to HGH injected at 11 p.m. vs. 8 a.m. was again compared. Under these conditions, when plasma cortisol concentration averaged 3 times greater at 11 p.m. than at 8 a.m., HGH injected at 8 a.m. caused significantly greater anabolic responses than HGH injected at 11 p.m.These findings indicate that the magnitude of the anabolic response to exogenous HGH is inversely related to the plasma cortisol concentration at the time of HGH injection.