148
Effect of a long-term methionyl growth hormone treatment on growth hormone releasing hormone-induced growth hormone secretion in patients with constitutional growth delay A . Sartorio 1,2, A . C o n t i 1'2, F. M o r a b i t o 1, and G . Faglia 2 1Centro Auxologico Italiano, Via Lodovico Ariosto 13, 1-20145 Milano, Italy 2Istituto di Scienze Endocrine, Ospedale Policlinico, Via Francesco Sforza 35, 1-20122 Milano, Italy
Sir: The blunting of growth hormone (GH) secretion during exogenous GH administration has been observed after short-term [4] or intermediate-term [2, 5] administration of GH, while few studies have been performed on the effects of long-term GH treatment. In this respect, it has been recently reported that GH treatment over 12 months is not associated with an attenuation of the 24 h GH secretion [7, 8]. In order to verify the effects of long-term GH treatment on GH responsiveness to an acute provocative stimulus, we studied GH responses to 1 gg/kg growth hormone releasing hormone (GHRH) iv bolus (UCB Bioproducts, Belgium) before and after 3-6 months of methionyl growth hormone (met-GH) (Somatonorm, Kabi, Sweden, 4 I U x 3 / w e e k , sc, average amount/m2 per week: 11.7 + 0.6 IU) treatment in 6 patients (3 males, 3 females, age range 7-14 years, Tanner stage I-III) with constitutional growth delay (CGD), diagnosed as previously reported [6]. G H R H test was performed after a 36 h washout period from the last administration of met-GH. GH levels were determined at 0, 15, 30, 60 and 120 rain after GHRH Abbreviations: C G D = constitutional growth delay; G H = growth hormone; G H R H = growth hormone releasing hormone; IGF-I = insulin-like growth factor I; m e t - G H = methio w l growth hormone
50"
GHRH
GHRH
administration using a commercial RIA kit (Sorin, Italy). GH responses were calculated as the net incremental area under the curve (GH nAUC/h) by the trapezoidal method. Serum insulin-like growth factor-I (IGF-I) levels were determined by a commercial RIA kit (Nichols Institute, San Juan Capistrano, CA, USA). GH responses to GHRH administration before and after 3 and 6 months of met-GH treatment are shown in Fig. 1. Under basal conditions, the mean GH nAUC after GHRH was 787 + 122 ng/ml/hour (range: 309-1164 ng/ml/hour). A reduction of GH responses to GHRH was evident after 3 and 6 months of met-GH treatment (GH nAUC, 3rd month: 515 + 176 ng/ml/hour vs basal NS, 6th month: 299 + 41 ng/ml/hour, P < 0.01, respectively). During the period of treatment, plasma IGF-I levels increased significantly from 0.9 + 0.06 to 1.35 + 0.08 (3rd month, P < 0.005) and to 1.4 + 0.1 units/ml after 6 months (P < 0.001) of met-GH treatment; height velocity significantly increased (P
Effect of a long-term methionyl growth hormone treatment on growth hormone releasing hormone-induced growth hormone secretion in patients with constitutional growth delay A . Sartorio 1,2, A . C o n t i 1'2, F. M o r a b i t o 1, and G . Faglia 2 1Centro Auxologico Italiano, Via Lodovico Ariosto 13, 1-20145 Milano, Italy 2Istituto di Scienze Endocrine, Ospedale Policlinico, Via Francesco Sforza 35, 1-20122 Milano, Italy
Sir: The blunting of growth hormone (GH) secretion during exogenous GH administration has been observed after short-term [4] or intermediate-term [2, 5] administration of GH, while few studies have been performed on the effects of long-term GH treatment. In this respect, it has been recently reported that GH treatment over 12 months is not associated with an attenuation of the 24 h GH secretion [7, 8]. In order to verify the effects of long-term GH treatment on GH responsiveness to an acute provocative stimulus, we studied GH responses to 1 gg/kg growth hormone releasing hormone (GHRH) iv bolus (UCB Bioproducts, Belgium) before and after 3-6 months of methionyl growth hormone (met-GH) (Somatonorm, Kabi, Sweden, 4 I U x 3 / w e e k , sc, average amount/m2 per week: 11.7 + 0.6 IU) treatment in 6 patients (3 males, 3 females, age range 7-14 years, Tanner stage I-III) with constitutional growth delay (CGD), diagnosed as previously reported [6]. G H R H test was performed after a 36 h washout period from the last administration of met-GH. GH levels were determined at 0, 15, 30, 60 and 120 rain after GHRH Abbreviations: C G D = constitutional growth delay; G H = growth hormone; G H R H = growth hormone releasing hormone; IGF-I = insulin-like growth factor I; m e t - G H = methio w l growth hormone
50"
GHRH
GHRH
administration using a commercial RIA kit (Sorin, Italy). GH responses were calculated as the net incremental area under the curve (GH nAUC/h) by the trapezoidal method. Serum insulin-like growth factor-I (IGF-I) levels were determined by a commercial RIA kit (Nichols Institute, San Juan Capistrano, CA, USA). GH responses to GHRH administration before and after 3 and 6 months of met-GH treatment are shown in Fig. 1. Under basal conditions, the mean GH nAUC after GHRH was 787 + 122 ng/ml/hour (range: 309-1164 ng/ml/hour). A reduction of GH responses to GHRH was evident after 3 and 6 months of met-GH treatment (GH nAUC, 3rd month: 515 + 176 ng/ml/hour vs basal NS, 6th month: 299 + 41 ng/ml/hour, P < 0.01, respectively). During the period of treatment, plasma IGF-I levels increased significantly from 0.9 + 0.06 to 1.35 + 0.08 (3rd month, P < 0.005) and to 1.4 + 0.1 units/ml after 6 months (P < 0.001) of met-GH treatment; height velocity significantly increased (P
