Continued Growth Hormone (GH) Treatment after Final Height Is Necessary to Complete Somatic Development in Childhood-Onset GH-Deficient Patients

Abstract

Lean body mass (LBM), fat mass (FM), and total bone mineral content are significantly reduced in adult GHD subjects who had received pediatric GH. To test the hypothesis that continued GH therapy after final height is necessary to attain adult body composition, we performed a prospective, multinational, randomized, controlled, 2-yr study in patients who completed pediatric GH treatment at final height. Patients were randomized to GH at 25.0 microg/kg x d (pediatric dose; n = 58) or 12.5 microg/kg x d (adult dose; n = 59) or no GH treatment (control; n = 32). LBM and FM were measured by dual energy x-ray absorptiometry and were centrally evaluated. IGF-I, IGF-binding protein-3, and lipid concentrations were also measured centrally. During the 2 yr, GH-treated patients gained a significant amount of LBM compared with controls (P < 0.001), but the change with the higher pediatric dose (14.2 +/- 11.7%) was not different from that seen with the lower adult dose (12.7 +/- 9.4%; P = 0.970). Similarly, the decrease in FM was significantly (P = 0.029) influenced by treatment, but with no dose effect (adult dose, -7.1 +/- 22.8%; pediatric dose, -6.0 +/- 26.6%; P = 0.950). When the GH treatment effect was analyzed by gender, males gained 15.6 +/- 9.8% and 14.3 +/- 11.7% LBM (P = 0.711) and lost 12.4 +/- 22.2% and 11.0 +/- 27.1% FM (P = 0.921) with the low and high doses, respectively. Females gained 8.3 +/- 7.3% and 12.5 +/- 12.8% LBM with the two doses (P = 0.630), but increased their FM by 3.5 +/- 16.2% with the lower dose and lost only 1.2 +/- 23.2% FM with the higher dose (P = 0.325). A similar pattern was seen in IGF-I sd score; the 2-yr GH dose response was significantly higher with the pediatric than with the adult dose in females (P = 0.008), but not males (P = 0.790). The divergent pattern of change in LBM and FM in males and females is consistent with normal developmental sexual dimorphism and indicates that GH-dependent progress to target body composition continues after the age at which GH treatment is usually terminated. Dose requirements may have to be adjusted by gender, with females requiring a higher dose than males.

Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy

“…Their age at operation and time since operation was 13 (7-18) years and 36 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) years respectively.…”

“…Thus, the exact benefit of GH therapy cannot be elucidated based on the present study design, as no control group of CO craniopharyngioma patients without GH therapy is available in Sweden. Further, recent consensus statements (29) suggest that GH therapy should be recommended in patients with reconfirmed GHD to at least their mid-20s as there are negative consequences on somatic maturation if GH replacement is interrupted (30). Positive effects of continued treatment on fat distribution, muscle mass, cardiac function, and bone mass have been shown (31,32).…”

Consensus and Discordance in the Management of Growth Hormone-Treated Patients: Results of a Knowledge, Attitudes, Beliefs, and Practices Survey

“…However, following diagnosis of GHD based upon an abnormal GHST, it has been recommended that further functional testing of pituitary function and a brain MRI be performed [2, 4]. Brain MRI with focus on the pituitary has been proposed as an alternative to GHST for diagnosis of GHD [20].…”

“…To develop the survey content, we reviewed the most recent guidelines from the American Association of Clinical Endocrinologists (AACE) [2], the Endocrine Society (ES) [3], the Growth Hormone Research Society (GHRS) [4], and the Lawson Wilkins Pediatric Endocrine Society (LWPES) [5] and extracted specific recommendations for diagnosis and treatment. In addition, a Medline search was conducted on the terms “growth hormone,” “growth hormone deficiency,” “Turner syndrome,” “craniopharyngioma,” and “Prader-Willi syndrome.” The search was limited to papers published since the most recent updates of the guidelines (2003–2006).…”

Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto

“…A massa e a força muscular aumentam gradativamente após o fechamento das cartilagens de crescimento, porquanto o pico de massa muscular ocorre entre os 20 e 30 anos de idade (8). A suspensão do tratamento com GH, quando o paciente com DGH atinge a estatura final, reduz a massa e a força muscular (5,(8)(9)(10), comprometendo a capacidade para a atividade física (11). Estas alterações são reversíveis com a reposição de GH (5,12).…”