Growth Hormone (GH) Deficiency (GHD) of Childhood Onset: Reassessment of GH Status and Evaluation of the Predictive Criteria for Permanent GHD in Young Adults

Abstract

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 pituitary magnetic resonance imaging (MRI) findings: group I, 11 patients with isolated GHD (IGHD) and normal pituitary volume (280 ± 59.4 mm3); group II, 7 patients with IGHD and small pituitary gland (163.1 ± 24.4 mm3; P = 0.0009 vs. group I); group III, 13 patients (5 with IGHD and 8 with multiple pituitary hormone deficiency) with congenital hypothalamic-pituitary abnormalities such as pituitary hypoplasia (95.8 ± 39.3 mm3; P < 0.00001 vs. group I and P = 0.003 vs. group II), pituitary stalk agenesis, and posterior pituitary ectopia; and group IV, 4 patients with multiple pituitary hormone deficiency secondary to craniopharyngioma. Pituitary MRI and GH secretory status were reevaluated after GH withdrawal using arginine, insulin induced-hypoglycemia, and sequential arginine-insulin tests. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were determined at the time of retesting and 6, 12, and 24 months after discontinuation of treatment in the patients with permanent GHD and after 6 months in those 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 still had a GH response of less than 3 μg/L to any of the tests. Pituitary volume normalized in 6 of 7 patients in group II, whereas in all patients in group III MRI studies confirmed the initial findings. Mean IGF-I and IGFBP-3 concentrations at the time of retesting were significantly higher in groups 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 after treatment withdrawal. Our results confirm that a high proportion of children with IGHD and normal or small pituitary show normalization of GH secretion at the completion of GH treatment, whereas GHD is permanent in all patients with pituitary hypoplasia, pituitary stalk agenesis, and posterior pituitary ectopia. IGF-I and IGFBP-3 determinations shortly after GH withdrawal had limited value in the diagnosis of GHD of childhood onset associated with congenital hypothalamic-pituitary abnormalities, but became accurate after 6–12 months. We suggest that patients with GHD and congenital hypothalamic-pituitary abnormalities do not require further investigation of GH secretion, whereas patients with IGHD and normal or small pituitary gland should be retested well before the attainment of adult height.