Idiopathic growth hormone deficiency: presentation, diagnostic and treatment during childhood

The clinical and biological presentation of idiopathic growth hormone (GH) deficiency (GHD) varies greatly, demonstrating the variety of its pathogenic features and explaining why it is difficult to diagnose. We examined 48 patients (26 males) with certain idiopathic GHD diagnosed at 4.8 +/- 0.7 yr. The symptoms that led to the diagnosis of GHD were low growth rate (33 cases), hypoglycemia (12 cases), microphallus (1 case) and in 2 cases the GHD was diagnosed from magnetic resonance imaging (MRI) performed for delayed mental development (1 case), or congenital blindness (1 case). The 2 other cases were diagnosed from routine GH evaluation performed at birth because of idiopathic GHD in siblings. Thirteen had congenital malformation. Twenty three cases (48%) had features suggesting that the GHD was of antenatal origin. Six of them were born by breech delivery. Twenty one cases (44%) had features suggesting a hypothalamic origin. The decrease in growth rate occurred before 0.5 year in 21 (55%), before 1 year in 27 (71%) and before 2 years in 30 (79%): 8 patients (21%) maintained a normal growth rate after this age. Among these 8 patients, 5 had signs suggesting an antenatal origin and 4 had severe episodes of hypoglycemia from birth. The mean GH peak after the pharmacological stimulation test was 3.6 +/- 0.5 micrograms/l. The mean plasma insulin-like growth factor 1 (IGFI) was 0.1 +/- 0.02 U/ml. The GH deficiency was associated with deficiencies of thyrotropin in 26 (54%) and of adrenocorticotrophic hormone in 17 (35%) patients. Among the 15 patients of pubertal age, 9 (60%) had gonadotrophin deficiency. No patient had diabetes insipidus. The MRI showed pituitary stalk interruption syndrome in 39 patients and normal pituitary anatomy in 6 patients. GH treatment reduced the difference between target and actual heights from 3.5 SD (before) to I SD (after 3 years) in the 39 more recently seen patients given 0.5-0.6 U/kg/w GH in 6 or 7 weekly injections. Height gain during the first year and cumulative height gain over 3 years (SD) was correlated negatively with height (SD) at the start of treatment (p < 0.01). We conclude that most of the patients with GHD have features suggesting an antenatal origin. Despite this early origin, the decreased growth rate may occur after 2 years.