Predictors of Insulin-Like Growth Factor-I Responses to Growth Hormone Replacement in Young Adults with Growth Hormone Deficiency

Abstract

Background/Aims: Physiological growth hormone (GH) secretion and insulin-like growth factor-I (IGF-I) levels are greater in young compared to older adults. We evaluated IGF-I levels and predictors of IGF-I responses in young adults on GH replacement. Design: From the KIMS database, 310 young adults (age 15-26 years) with severe GH deficiency related to childhood-onset disease and commenced on ‘adult GH replacement' were identified. ‘IGF-I responses' were estimated from first-year increments in IGF-I standard deviation scores (SDS) and adjusted for GH dose. Body composition was assessed by bioimpedance in 143 patients. Results: IGF-I levels increased markedly from baseline to 1 year of replacement (-3.75 ± 1.94 vs. -1.36 ± 1.86 SDS, p < 0.0001), but remained low compared to normative data despite dose titration. In multivariate models, IGF-I responses were positively associated with age [B (SE) SDS/(mg/m²); 0.52 (0.15), p = 0.0007] and BMI SDS [1.06 (0.25), p < 0.0001] and inversely associated with female gender [-4.45 (0.79), p < 0.0001] and baseline IGF-I SDS [-1.44 (0.20), p < 0.0001]. IGF-I responses were positively associated with first-year increases in lean body mass (r = 0.19, p = 0.003) and haemoglobin A1c (r = 0.15, p = 0.031). Conclusions: Low IGF-I levels in young adults on treatment may reflect suboptimal GH replacement. Identification of predictors for IGF-I responses could lead to a more appropriate replacement strategy. Association between IGF-I responses and lean body mass suggests that maintaining age-appropriate IGF-I levels is important during therapy.

Approach to the Patient: Management of Pituitary Hormone Replacement Through Transition

“…IGF-I should be used to titrate GH dose, and this is lower than those used in childhood, (0.2-0.5 mg/d) ( 56 ). Younger patients ( 57 ), especially women on oral estrogen, may require higher doses ( 35 ) because oral estrogens cause hepatic GH resistance resulting from a first-pass effect in the liver ( 58 , 59 ).…”

Short-Term Effects of Growth Hormone on Lipolysis, Glucose and Amino Acid Metabolism Assessed in Serum and Microdialysate of Healthy Young Men

“…Data after the administration of a single subcutaneous dose of GH have less frequently been investigated [1,2,8]. The majority of studies on GH replacement in young adults used 0.01-0.025 mg/kg/day [16,17]. Considerably higher GH doses are commonly used in children and adolescents.…”

Appropriate management of growth hormone deficiency during the age of transition: an Italian Delphi consensus statement

“…IGF-1 responses are a marker of GH replacement outcomes in young adults, are associated with increases in lean body mass and HbA1c during rhGH therapy and are dependent on age, gender, BMI and baseline IGF-1 levels [10,40]. Indicators of severe GHD, such as low GH peak levels, young age at diagnosis and severe short stature, are associated with low-serum IGF-1 levels [7].…”