Revaluation of the clinical and metabolic behavior of children with isolated growth hormone deficiency during GH treatment according to newly proposed note 39 of the Italian Medicines Agency (AIFA)
- 144 Downloads
This study aimed at evaluating the clinical and metabolic behavior of children with isolated growth hormone (GH)-deficiency (GHD), grouped according to the new AIFA criteria for the appropriateness of use and reimbursement of GH treatment in children.
The clinical and metabolic data of 310 prepubertal children (220 M, 90 F; mean age 10.8 years) grouped, according to new AIFA note 39, into Group A (No. 181 with a peak of GH <8 µg/l), Group B (No. 103 with a peak of GH ≥8 and <10 µg/l) and Group C (No. 26 with a peak of GH >10 µg/l) were retrospectively analyzed. Group A and B, diagnosed as having GHD, were treated with GH for at least 24 months, while Group C was analyzed only at baseline.
At baseline, Group A showed higher waist circumference than B (p = 0.031) and C (p = 0.041), while no difference in metabolic parameters was found between the three groups. After 12 and 24 months of treatment, Group B showed lower height velocity (p < 0.001 and p = 0.049, respectively) than Group A. As regards the metabolic parameters, both after 12 and 24 months of treatment, in Group B we found higher fasting glucose (p < 0.001 and p = 0.020), insulin (p = 0.002 and p = 0.011), Homa-β (p = 0.020 and p = 0.015) and Homa-IR (both p = 0.001) than Group A, with concomitant lower QUICKI (both p < 0.001) and HDL cholesterol (p = 0.020 and p = 0.011), without difference in other lipid parameters. The HbA1c levels, although always within the normal range, were found higher in Group B than Group A after 12 months (p = 0.015).
According to the new AIFA criteria, the reduction of GH cut-off for GHD diagnosis can be supported by auxological and metabolic data. The real benefits from GH therapy in children with higher stimulated GH levels at diagnosis remains to be better understand.
KeywordsGrowth hormone deficiency Children Italian Medicines Agency (AIFA)
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards
Informed consent for the scientific use of the data was obtained from all individual participants included in the study and from their parents.
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
- 1.Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. (1995) Guidelines for the use of growth hormone in children with short stature. A report by the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. J Pediatr 127(6):857–867Google Scholar
- 3.Saggese G, Ranke MB, Saenger P, Rosenfeld RG, Tanaka T, Chaussain JL, Savage MO (1998) Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Ten years after the Availability of Recombinant Human Growth Hormone Workshop held in Pisa, Italy, 27–28 March 1998. Horm Res 50(6):320–340Google Scholar
- 4.Growth Hormone Research Society (2000) Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 85:3990–3993Google Scholar
- 11.Di Somma C, Ciresi A, Amato MC, Savastano S, Savanelli MC, Scarano E, Colao A, Giordano C (2014) Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index. Endocrine Nov 9 (Epub ahead of print)Google Scholar
- 14.Kriström B, Aronson AS, Dahlgren J, Gustafsson J, Halldin M, Ivarsson SA, Nilsson NO, Svensson J, Tuvemo T, Albertsson-Wikland K (2009) Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature. J Clin Endocrinol Metab 94(2):483–490CrossRefPubMedGoogle Scholar
- 26.Ciresi A, Amato MC, Giordano C (2014) Reduction in insulin sensitivity and inadequate β-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment. J Endocrinol Invest Oct 2 (Epub ahead of print)Google Scholar
- 27.Salerno M, Esposito V, Farina V, Radetti G, Umbaldo A, Capalbo D, Spinelli L, Muzzica S, Lombardi G, Colao A (2006) Improvement of cardiac performance and cardiovascular risk factors in children with GH deficiency after two years of GH replacement therapy: an observational, open, prospective, case-control study. J Clin Endocrinol Metab 91(4):1288–1295CrossRefPubMedGoogle Scholar
- 28.Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, Severi F (1999) Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab 84(4):1324–1328CrossRefPubMedGoogle Scholar
- 29.Zucchini S, Pirazzoli P, Baronio F, Gennari M, Bal MO, Balsamo A, Gualandi S, Cicognani A (2006) Effect on adult height of pubertal growth hormone retesting and withdrawal of therapy in patients with previously diagnosed growth hormone deficiency. J Clin Endocrinol Metab 91(11):4271–4276CrossRefPubMedGoogle Scholar
- 30.Secco A, di Iorgi N, Napoli F, Calandra E, Calcagno A, Ghezzi M, Frassinetti C, Fratangeli N, Parodi S, Benassai M, Leitner Y, Gastaldi R, Lorini R, Maghnie M, Radetti G (2009) Reassessment of the growth hormone status in young adults with childhood-onset growth hormone deficiency: reappraisal of insulin tolerance testing. J Clin Endocrinol Metab 94(11):4195–4204CrossRefPubMedGoogle Scholar
- 31.Arafat AM, Möhlig M, Weickert MO, Schöfl C, Spranger J, Pfeiffer AF (2010) Improved insulin sensitivity, preserved beta cell function and improved whole-body glucose metabolism after low-dose growth hormone replacement therapy in adults with severe growth hormone deficiency: a pilot study. Diabetologia 53(7):1304–1313CrossRefPubMedGoogle Scholar