Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.
Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).


METHODS
We performed a longitudinal study (1 year) in a tertiary care center.


METHODS
23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.


RESULTS
In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).


CONCLUSIONS
In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy ; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy ; I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy.
Flavia
F
Prodam
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy.
Silvia
S
Savastio
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy.
Giulia
G
Genoni
Laboratory of Human Genetics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Deepak
D
Babu
I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy ; Laboratory of Human Genetics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Mara
M
Giordano
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy.
Roberta
R
Ricotti
Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy.
Gianluca
G
Aimaretti
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy ; I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy.
Gianni
G
Bona
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy ; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy ; I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy.
Simonetta
S
Bellone
D000293:Adolescent; D002352:Carrier Proteins / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000188:drug therapy*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D020249:Hormone Replacement Therapy / Q000379:methods; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use
D002352:Carrier Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D005947:Glucose; C051815:somatotropin-binding protein