The Effects of Treatment and the Individual Responsiveness to Growth Hormone (GH) Replacement Therapy in 665 GH-Deficient Adults

Abstract

Data from 665 adults with GH deficiency (GHD; 332 women; 169 childhood-onset GHD; mean age, 44 yr) were analyzed to determine the efficacy of and individual responsiveness to GH replacement therapy. GH replacement was started at enrolment into KIMS (Pharmacia & Upjohn, Inc. International Metabolic Database). Mean maintenance doses of GH after 6 and 12 months were 0.43 and 0.53 mg/day (1.3 and 1.6 IU/day) for men and women, respectively. Serum insulin-like growth factor I (IGF-I) SD score increased from -2.2 and -4.2 in men and women, respectively, to 1.8 and -0.9 at 6 months and 0.8 and -0.7 at 12 months. The waist/hip ratio decreased after 6 and 12 months, with the changes more pronounced in men. The waist/hip ratio was not influenced by age of onset of GHD, severity of hypopituitarism, or gonadal status. Total cholesterol decreased significantly in men, and high density lipoprotein cholesterol increased in women. Systolic blood pressure was unchanged during GH therapy, but diastolic blood pressure decreased in women. Quality of life, determined by a specific questionnaire for assessment of GHD in adults, improved after 6 and 12 months of GH therapy; this was more pronounced in adult-onset than in childhood-onset GHD, but was not influenced by gender, severity of hypopituitarism, or gonadal status. In 80% of patients, the starting dose of GH was 0.27 mg/day or less. This and the absence of a correlation between body weight and change in IGF-I were consistent with a dose-titration approach, which would tend to obscure individual variations in responses (determined by IGF-I levels). Nonetheless, the increase in IGF-I was significantly higher in men than in women on similar mean GH doses. Weak correlations were observed between the maintenance dose of GH and the change in IGF-I in men and women receiving sex steroid replacement, but not in patients with untreated hypogonadism or an intact gonadotropin reserve. Similarly, the increment in IGF-I was not related to the severity of GHD, as determined by the number of additional pituitary hormone deficiencies. Differences in IGF-I generation may partly explain the gender differences in reduction of central adiposity. These data highlight the value of large longitudinal surveillance databases in defining the optimum dose regimen for GH replacement and indicate that women may need a higher replacement dose of GH than men.

Adult GH deficiency throughout lifetime

“…GH replacement was associated with significant improvements in TC, LDL-C and HDL-C but no change in triglycerides (38). Similar findings have been found in other studies (29,39). Older patients also demonstrate lipid benefits with GH replacement.…”

“…Poor baseline QoL-AGHDA score predicts a greater psychosocial response to GH replacement (65). There seems to be no difference in improvement in QoL in adult patients of different ages, with older patients deriving as much benefit from GH replacement as those who are younger (27,36,39) (Fig. 4).…”

“…GH replacement is usually associated with a neutral effect on blood pressure (BP) (38); the antinatriuretic and possible chronotropic actions of GH are offset by vasodilation arising from increased generation of endothelial nitrous oxide. In studies where changes have been reported, these tend to reflect improvements in diastolic BP (27,36,39,51). These findings may be less apparent in older patients.…”

“…Some of the QoL improvements seen with GH replacement may arise from improvements in physical factors, such as increased circulating volume, exercise tolerance and muscle strength. Aetiology-specific differences in QoL are seen: craniopharyngioma (65), female gender (6,39,59), Sheehan's syndrome (66) and cranial irradiation (33) are all associated with worse baseline QoL, although it should be noted that all of these, with the exception of irradiation, are associated with particularly low IGF1 levels. Patients with isolated GHD reported in the KIMS database showed no difference in QoL between childhood and adult-onset disease using QoL-AGHDA questionnaires (59).…”

Deficiência de GH em adultos: resultados do estudo multicêntrico brasileiro

“…A experiência acumulada nos últimos anos tem mostrado que existe uma grande variabilidade individual na resposta à reposição com GH, que depende da idade, sexo, IMC e IGF-1 basal, que foi responsável por 51% da variação na dose de GH necessária para normalizar o IGF-1 SD escore em um estudo (57). Pacientes com maior IMC apresentam menor redução na gordura corporal, jovens exibem um maior aumento na massa corporal magra, enquanto que os homens demonstram aumento mais pronunciado nos níveis séricos de IGF-1, bem como na água corporal total do que as mulheres (58)(59)(60)(61)(62). Neste estudo, encontramos uma cor-…”