PAOLA DURAN, MD PEDIATRIC ENDOCRINOLOGIST CENPA, FCI COLOMBIA

PAOLA DURAN, MD PEDIATRIC ENDOCRINOLOGIST CENPA, FCI COLOMBIA

GH has important effects on the intermediary metabolism of Carbohydrates Lipids Proteins Acute effects similar to insulin: hypoglycemia enhances transport, metabolism and storing of glucose and a.a. Increases synthesis of proteins and lypogenesis

Long term effects hyperglycemia hyperinsulinemia increased lypolisis decreased transport of glucose increase in the level of non sterified fatty acids decreased metabolism of glucose insulin resistance.

Adults with GHD show Dyslipidemia Increased total fat mass Early atherosclerosis Decreased fibrinolytic activity Increased in peripheral insulin resistance Increased glucose intolerance Altered cardiac structure and function Changes in body mass composition, increased visceral fat Decreased physical performance Low adiponectin levels

Treatment with GH has shown to: Decrease BMI and total fat mass after 6 months Increase muscle mass after 2 years in both genders. Improved lipid profile fasting and postprandial (LDL and Triglycerides). Lanes R. metabolic abnormalities induced by growth hormone Deficiency: Improvement with Growth Hormone Treatment. Lanes R, Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormonetreated and untreated patients. Horm Res. 2003;60(6):291-6. Twickler TB. Induction of postprandial inflammatory response in adult onset growth hormone deficiency is related to plasma remnant-like particle-cholesterol concentration. J Clin Endocrinol Metab. 2003;88(3):1228-33

FACTS IN GHD: Increase in non traditional inflammatory markers like homocisteine. Endothelial function deteriorates Inferior Quality of life Elevation of activator factor of tissular plasminogen inhibitor 1, fibrinogen and factor VII. Decreased cardiac function with decreased left ventricular mass, ejection fraction and altered in diastolic feel Increase in atheromatose plaques Increase in media thickness Decrease aortic distensibility

Treatment with GH has shown Improvement of lipid profile increase the left function and ventricular mass. Reverts early atherosclerotic changes measured by intima thickness. Decreases fibrinogen Ameliorates cardiac function Stopping treatment showed Worsen of dyslipidemia

Lanes R, Paoli M, Carrillo E, Villaroel O, Palacios A. Peripheral inflammatory and fibrinolytic markers in adolescents with growth hormone deficiency: Relation to postprandial dyslipidemia Journal of Pediatrics 2004;145: 657-661 Lanes R, Soros A, Gunczler P, Paoli M, Carrillo E, Villaroel O, Palacios A. Growth hormone deficiency, low levels of adiponectin, and unfavorable plasma lipid and lipoproteins. Journal of Pediatrics 2006;149:324-329 Lanes R, Paoli M, Carrillo E, Villaroel O, Palacios A. Cardiovascular risk of young growthhormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients. Horm Res. 2003;60(6):291-6. Capaldo B, Patti L, Oliviero U, Longobardi S, Pardo F, Vitale F, Fazio S, Di Rella F, Biondi B, Lombardi G, Saccà L. Increased arterial intima-media thickness in childhood-onset growth hormone deficiency. J Clin Endocrinol Metab. 1997 May;82(5):1378-81. Colao A, di Somma C, Cuocolo A, Spinelli L, Tedesco N, Pivonello R, Bonaduce D, Salvatore M, Lombardi G. Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency. J Clin Endocrinol Metab. 2001 May;86(5):1874-81. Johannsson G, Albertsson-Wikland K, Bengtsson BA. Discontinuation of growth hormone (GH) treatment: metabolic effects in GH-deficient and GH-sufficient adolescent patients compared with control subjects. Swedish Study Group for Growth Hormone Treatment in Children. J Clin Endocrinol Metab. 1999 Dec;84(12):4516-24. Lanes R, Gunczler P, Lopez E, Esaa S, Villaroel O, Revel-Chion R. Cardiac mass and function, carotid artery intima-media thickness, and lipoprotein levels in growth hormonedeficient adolescents. J Clin Endocrinol Metab. 2001 Mar;86(3):1061-5

GH also helps the bone mineral density, controlling bone turn over and helps peak bone mass. Gh treatment has shown to increase bone mineral density in GHD with improvement of bone turnover markers Two years of GH at 12,5 mcg/kg/day (n=58) o 25 mcg/kg/day (n=59) compared to control group (n=32) patients with GHD. There was a significant increase in bone mineral density in patients receiving GH. (Shalet et al).

SGA children without catch up have decreased GH secretion over 24 hrs, low IGF1 and IGFBP3. SGA children have decreased glucose captation mediated by insulin, and less suppression of free fatty acid, as well as insulin resistance. GH produces a significant improvement of the intellectual coefficient in those patients.

Gh improves neurocognitive and behavioral function in SGA children. Improves body composition, blood pressure and lipid profile also in SGA. 378 SGA patients that received GH for 3 years showed significant improvement in muscle mass17.

Lanes R, Gunczler P, Lopez E, Esaa S, Villaroel O, Revel-Chion R. Cardiac mass and function, carotid artery intima-media thickness, and lipoprotein levels in growth hormone-deficient adolescents. J Clin Endocrinol Metab. 2001 Mar;86(3):1061-5. Rapaport R. Growth and growth hormone in children born small for gestational age. Growth Horm IGF Res. 2004 Jun;14Suppl A:S3-6. Hokken-Koelega A, van Pareren Y, Arends N. Effects of growth hormone treatment on cognitive function and head circumference in children born small for gestational age. Horm Res. 2005;64Suppl 3:95-9. Noeker M. Neurocognitive development in children experiencing intrauterine growth retardation and born small for gestational age: pathological, constitutional and therapeutic pathways. Horm Res. 2005;64Suppl 3:83-8 Saenger P, Czernichow P, Hughes I, Reiter EO. Small for gestational age: short stature and beyond. Endocr Rev. 2007 Apr;28(2):219-51.

GH not only improves final height in GHD, SGA an TS. It prevents cardiovascular disease and metabolic complications in GHD and SGA patients. Improves bone mineral density in TS patients. Improves quality of life overall in those indications.