Growth hormone (GH) deficiency (GHD) of childhood onset: Reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults

GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 +/- 3.2 yr in 35 young adults with childhood-onset GH deficiency ( GHD). The patients were subdivided into 4 groups according to their first p ituitary magnetic resonance imaging (MRI) findings: group I, 11 patients wi th isolated GHD (IGHD) and normal pituitary volume (280 +/- 59.4 mm(3)); gr oup II, 7 patients Kith IGHD and small pituitary gland(163.1 +/- 24.4 mm(3) ; P = 0.0009 us. group I); group III, 13 patients (5 with IGHD and 8 with m ultiple pituitary hormone deficiency) with congenital hypothalamic-pituitar y abnormalities such as pituitary hypoplasia (95.8 +/- 39.3 mm(3); P < 0.00 001 vs. group I and P = 0.003 vs. group II, pituitary stalk agenesis, and p osterior pituitary ectopia; and group IV, 4 patients with multiple pituitar y hormone deficiency secondary to craniopharyngioma. Pituitary MRI and GH s ecretory status were reevaluated after GH withdrawal using arginine, insuli n induced-hypoglycemia, and sequential arginine-insulin tests. Serum insuli n-like growth factor I(IGF-T) and IGF-binding protein-3 (IGFBP-3) were dete rmined at the time of retesting and 6, 12, and 24 months after discontinuat ion of treatment in the patients with permanent GHD and after 6 months in t hose with normal GH responses to stimulation. The patients in groups I and II showed a normal response to stimulation after completion of GH treatment regardless of pituitary size, whereas all patients in groups III and IV st ill had a GH response of less than 3 mu g/L to any of the tests. Pituitary volume normalized in 6 of 7 patients in group II, whereas in all patients i n group III MRI studies confirmed the initial findings. Mean IGF-I and IGFB P-3 concentrations at the time of retesting were significantly higher in gr oups I and II than in groups III and IV. In patients of groups III and IV, mean IGF-I was significantly decreased after 6 and 12 months, whereas IGFBP -3 was significantly decreased 12 months alter treatment withdrawal. Our re sults confirm that a high proportion of children with IGHD and normal or sm all pituitary show normalization of GH secretion at the completion of GH tr eatment. whereas GHD is permanent in all patients with pituitary hypoplasia , pituitary stalk agenesis, and posterior pituitary ectopia. IGF-I and IGFB P-3 determinations shortly after GH withdrawal had limited value in the dia gnosis of GHD of childhood onset associated with congenital hypothalamic-pi tuitary abnormalities, but became accurate after 6-12 months. We suggest th at patients with GHD and congenital hypothalamic-pituitary abnormalities do not require further investigation of GH secretion, whereas patients with I GHD and normal or small pituitary gland should be retested well before the attainment of adult height.