Home Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
Article
Licensed
Unlicensed Requires Authentication

Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential

  • Meropi Toumba EMAIL logo , Vasilis Kokotsis , Savvas C. Savva and Nicos Skordis
Published/Copyright: October 25, 2013

Abstract

Objective: The combination therapy of gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) has been used to increase growth in children with premature sexual maturation and attenuated growth. The aim of this report was to study the benefit over cost of combined treatment in girls with central precocious puberty (CPP) and poor height prognosis and in girls with idiopathic short stature (ISS) and early puberty. Should this expensive treatment be given to such patients?

Subjects and methods: Two patient groups were included: five girls with central precocious puberty (CPP) who reached final height (FH) at 16.3±1.2 years and eight girls with ISS who reached FH at 14.7±0.8 years. Patients were treated for 3.5±0.6 years.

Results: In both groups, FH improved significantly; in CPP from –1.3 to –0.5 standard deviation score (SDS) (p=0.030) and in ISS from –2.6 to –1.7 SDS (p=0.012). Only girls with CPP reached their target height (–0.5 vs. –0.6 SDS) (p=0.500).

Conclusions: Both groups had a total height gain of 5 cm. Each centimetre cost about €2700 per patient. This treatment should be considered only in patients with extremely low height prediction and very early pubertal onset.


Corresponding author: Meropi Toumba, MD, IASIS Hospital, 8, Voreiou Ipeirou, Paphos, Cyprus, Phone: +357 99573633, Fax: +357 26848300, E-mail: ; and Paediatric Endocrine Unit, Makarios III Hospital, Nicosia, Cyprus

References

1. Job JC, Toublanc JE, Landier F. Growth of short normal children in puberty treated for 3 years with growth hormone alone or in association with gonadotropin-releasing hormone agonist. Horm Res 1994;41:177–84.Search in Google Scholar

2. Saggese G, Pasquino AM, Bertelloni S, Baroncelli GI, Battini R, et al. Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis. Acta Pediatr 1995;84:299–304.Search in Google Scholar

3. Pasquino AM, Municchi G, Pucarelli I, Segni M, Mancini MA. Combined treatment with gonadotropin-releasing hormone analogue and growth hormone in central precocious puberty. J Clin Endocrinol Metab 1999;81:948–51.Search in Google Scholar

4. Tuvemo T, Gustafsson J, Proos LA. Growth hormone treatment during suppression of early puberty in adopted girls. Swedish Growth Hormone Advisory Group. Acta Paediatr 1999;88:928–32.Search in Google Scholar

5. Pucarelli I, Segni M, Ortore M, Arcadi E, Pasquino AM. Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution. J Pediatr Endocrinol Metab 2003;16:1005–10.Search in Google Scholar

6. Mul D, Oostdijk W, Waelkens JJ, Schulpen TW, Drop SL. Gonadotropin releasing hormone agonist treatment with or without recombinant human GH in adopted children with early puberty. Clin Endocrinol (Oxf) 2005;55:121–9.Search in Google Scholar

7. Maniati-Christidi M, Livadas S, Voutetakis A, Tolis G, Dacou-Voutetakis C. Human growth hormone and gonadotropin releasing hormone analog combination therapy increases predicted height in short normal girls. Clin Pediatr (Phila) 2003;42:59–65.Search in Google Scholar

8. Tato L, Saggese G, Cavallo L, Antoniazzi F, Corrias A, et al. Use of combined Gn-RH agonist and rhGH therapy for better attaining the goals in precocious puberty treatment. Horm Res 1995;44:49–54.Search in Google Scholar

9. Volta C, Bernasconi S, Tondi P, Salvioli V, Ghizzoni L, et al. Combined treatment with growth hormone and luteinizing hormone releasing hormone-analogue (LHRHa) of pubertal children with familial short stature. J Endocrinol Invest 1993;16:763–7.Search in Google Scholar

10. Saggese G, Cesaretti G, Barsanti S, Rossi A. Combination treatment with growth hormone and gonadotropin-releasing hormone analogues in short normal girls. J Paediatr 1995;126:468–73.Search in Google Scholar

11. Tanaka T, Satoh M, Yasunaga T, Horikawa R, Tanae A, et al. GH and GnRH analog treatment in children who enter puberty at short stature. J Clin Endocrinol Metab 1997;10:623–8.Search in Google Scholar

12. Lanes R, Gunczler P. Final height after combined growth hormone and gonadotropin-releasing analogue treatment in short healthy children entering into normally timed puberty. Clin Endocrinol (Oxf) 1998;49:197–202.Search in Google Scholar

13. Pasquino AM, Pucarelli I, Roggini M, Segni M. Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone. J Clin Endocrinol Metab 2000;85:619.Search in Google Scholar

14. Balducci R, Toscano V, Mangiantini A, Municchi G, Vaccaro F, et al. Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analogue and growth hormone. J Clin Endocrinol Metab 1995;80:3596–600.Search in Google Scholar

15. Kamp GA, Waelkens JJ, de Muinck Keizer-Schrama SM, Delemarre-van de Waal HA, Verhoeven-Wind L, et al. High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature. Arch Dis Child 2002;87:215–20.Search in Google Scholar

16. van Gool SA, Kamp GA, Visser-van Balen H, Mul D, Waelkens JJ, et al. Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty. J Clin Endocrinol Metab 2007;92:1402–8.Search in Google Scholar

17. Walvoord EC, Pescovitz OH. Combined use of growth hormone and gonadotropin-releasing hormone analogues in precocious puberty: theoretic and practical considerations. Pediatrics 1999;104:1010–4.Search in Google Scholar

18. Toumba M, Bacopoulou I, Savva SC, Skordis N. Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height. Indian Pediatr 2007;44:497–502.Search in Google Scholar

19. Carel JC, Eugster EA, Rogol A, Ghizzoni L, ESPE-LWPES GnRH Analogs Consensus Conference Group, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:752–62.Search in Google Scholar

20. Klein O, Barnes M, Jones V, Feuillan P, Cutler BJ. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J Clin Endocrinol Metab 2001;86:4711–6.Search in Google Scholar

21. Carel JC. Management of short stature with GnRH agonist and co-treatment with growth hormone: a controversial issue. Mol Cell Endocrinol 2006;25:254–5.Search in Google Scholar

22. Wit JM, Rekers-Mombarg LT. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 2002;87:604–11.Search in Google Scholar

23. Wit JM, Rekers-Mombarg LT, Cutler GB, Crowe B, Beck TJ, et al. Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect. J Pediatr 2005;146:45–53.Search in Google Scholar

24. Stanhope R, Preece MA, Grant DB, Brook CG. New concepts of the growth spurt of puberty. Acta Pediatr Scand 1988;347:30–7.Search in Google Scholar

25. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Stanford: Stanford University Press, 1959.Search in Google Scholar

26. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich and Pyle hand standards. J Pediatr 1952;40:423–41.Search in Google Scholar

27. Tanner JM, Goldstein H, Whitehouse RH. Standards for children’s height at ages 2-9 allowing for height of parents. Arch Dis Child 1970;45:755–62.Search in Google Scholar

28. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.Search in Google Scholar

29. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–24.Search in Google Scholar

30. Brito V, Latronico A, Cukier P, Teles M, Silveira L, et al. Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs. J Clin Endocrinol Metab 2008;93:2662–9.Search in Google Scholar

31. Lazar L, Padoa A, Philip M. Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity. J Clin Endocrinol Metab 2007;92:3483–9.Search in Google Scholar

32. Heger S, Sippell W, Partsch C. Gonadotropin-releasing hormone analogue treatment for precocious puberty. Twenty years of experience. Endocr Dev 2005;8:94–125.Search in Google Scholar

33. Proos LA, Lönnerholm T, Jonsson B, Tuvemo T. Can the TW3 bone age determination method provide additional criteria for growth hormone treatment in adopted girls with early puberty? A comparison of the Tanner-Whitehouse 3 method with the Greulich-Pyle and the Tanner-Whitehouse 2 methods. Horm Res Paediatr 2010;73:35–40.Search in Google Scholar

34. Cohen S, Cosgrove C. Normal at any cost: tall girls, short boys, and the medical industry’s quest to manipulate height. New York: Jeremy P. Tarcher/Penguin, 2009.Search in Google Scholar

Received: 2013-5-26
Accepted: 2013-8-30
Published Online: 2013-10-25
Published in Print: 2014-03-01

©2014 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Images in pediatric endocrinology
  4. Leprechaunism (Donohue syndrome): report of a case in a newborn
  5. Original articles
  6. Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
  7. Age of onset of pubertal maturation of Thai boys
  8. Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
  9. Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
  10. Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
  11. Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
  12. Insulin resistance in young adults born small for gestational age (SGA)
  13. The effect of childhood obesity on cardiac functions
  14. Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
  15. Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
  16. Health-related quality of life in Turner syndrome and the influence of key features
  17. Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
  18. The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
  19. Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
  20. Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
  21. The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
  22. A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
  23. Heterozygous GHR gene mutation in a child with idiopathic short stature
  24. A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
  25. A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
  26. Patient reports
  27. Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
  28. Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
  29. Pituitary stalk lesion in a 13-year-old female
  30. Radiologic manifestation of a BCS1L-mutated patient
  31. Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
  32. NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
  33. A teenage boy with hypocalcemia after radioablation for Graves’ disease
  34. Short communication
  35. A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
  36. Letter to the Editor
  37. Endometriosis and migraine: what is there behind the scenes?
  38. 10.1515/jpem-2014-0999
Downloaded on 20.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2013-0210/pdf
Scroll to top button