Growth Hormone (GH) Dose-Response in Young Adults with Childhood-Onset GH Deficiency: A Two-Year, Multicenter, Multiple-Dose, Placebo-Controlled Study

Abstract

GH replacement therapy has been shown to improve abnormalities in body composition, bone mineral density (BMD), lipid profile, and other changes resulting from GH deficiency (GHD) in adults. There is, however, need to determine appropriate dosing in young adults who were treated for GHD as children, to bridge the interval between childhood (in which relatively high doses are used) and older adulthood (in which only lower doses are tolerated). This multicenter, randomized, double-blind, placebo-controlled study compares the safety and efficacy of two doses of GH (25 and 12.5 microg/kg.d) with placebo, maintained for 2 yr, in adults with GHD who were treated as children and were off GH for at least 1 yr (mean, 5.6 yr). The 64 treated subjects were less than 35 yr of age (mean, 23.8 yr) and had maximum serum GH responses, on retesting less than 5 microg/liter (mean, 0.7 micro g/liter). At baseline, 22% had spine BMD below -2 SD, 59% were overweight or obese, and 45% had serum total cholesterol more than 200 mg/dl. A significant dose response was seen for percent increase in spine BMD at 24 months (mean of 1.3%, 3.3%, and 5.2% in the placebo, 12.5-, and 25- microg/kg.d groups, respectively, P = 0.018). Both GH-treated groups had similar changes in body composition at 6 months (decreased fat mass, increased lean mass); however, some gains were subsequently lost in the lower dose group. A significant decrease in low-density lipoprotein cholesterol was seen only in the higher GH dose group. Significant changes were not observed in quality of life and echocardiographic measures. The groups were similar with regard to adverse events and laboratory measurements, except for a higher incidence of edema in the GH-treated groups. We conclude that this dose-response study confirms the benefits of GH-replacement therapy in GHD adults and indicates that, to achieve treatment goals in younger adults, higher doses may be needed than those generally used in older adults.

Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency

“…No increase in total body BMD was detected in our study. Several recent studies have assessed the effects of GH replacement on BMD at completion of linear growth in children (36)(37)(38)(39). Consistent with our findings, in a smaller study involving 24 adolescents with severe GHD, 12 months' GH therapy was associated with a 4.7% increase in mean lumbar spine BMD from baseline compared with a 2.7% change in those who discontinued treatment, while the median whole body BMC increased by 6% in GH-treated patients and remained unchanged in untreated patients (36).…”

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy

“…Studies in these patients have particularly been investigating if continuous GH therapy results in a progressive increase in BMD after epiphyseal closure and final height (8,9,(29)(30)(31)(32) and whether stopping GH therapy causes a negative change in BMD. The longest follow-up in these patients is 2 years (9, 30-32), and five studies included a control group of non-GH-treated patients who had been off GH therapy for 1 week to 5 years before enrolment (8,9,(30)(31)(32). BMD increased between 5 and 8% on GH therapy and between 1 and 5% in the non-GH-treated patients (8,9,30,32), and in one study, no difference between groups was recorded (31).…”

“…The longest follow-up in these patients is 2 years (9, 30-32), and five studies included a control group of non-GH-treated patients who had been off GH therapy for 1 week to 5 years before enrolment (8,9,(30)(31)(32). BMD increased between 5 and 8% on GH therapy and between 1 and 5% in the non-GH-treated patients (8,9,30,32), and in one study, no difference between groups was recorded (31). One problem with these studies is the carry-over effect of previous GH therapy on BMD that will last for 1-2 years after stopping GH therapy (9).…”

“…One problem with these studies is the carry-over effect of previous GH therapy on BMD that will last for 1-2 years after stopping GH therapy (9). Furthermore, higher GH doses were used and some even used paediatric doses (9,30), and particularly females needed the higher doses (32), as they are less sensitive to standard GH doses (32,33). GH-deficient ALL patients are, however, different from patients in the above-mentioned studies, as most of the ALL patients are GH naïve and have changed from partial GHD to insufficient and more severely GHD later in life.…”

Análise densitométrica da região femoral de homens acima de 50 anos oriundos de um ambulatório de urologia

“…9,[22][23][24][25] The use of testosterone and/or growth hormone replacement (GH) remains only in cases of deficiency (hypogonadism and GH deficiency). 26,27 In our study, the men came from an urology outpatient clinic and were older. Probably it was the reason for a higher frequency of osteoporosis secondary to drugs for treatment of prostate cancer and other chronic diseases.…”