Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

Roderick de Lind van Wijngaarden; Elbrich  Siemensma; Dederieke Festen; B.J. Otten; Edgar van Mil; J. Rotteveel; R.J. Odink; Karen Bindels-de Heus; Mariette van Leeuwen; Danny Haring; Gianni Bocca; E. C.A. Mieke Houdijk; Gera Hoorweg-Nijman; R.C. Vreuls; Petr E. Jira; A. S. Paul Van Trotsenburg; Boudewijn Bakker; E.J. Schroor; Jan Willem Pilon; Jan M. Wit; Stenvert L S Drop; Anita C.S. Hokken-Koelega

doi:10.1210/jc.2009-0454

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

Roderick de Lind van Wijngaarden
, Elbrich Siemensma
, Dederieke Festen
, B.J. Otten
, Edgar van Mil
, J. Rotteveel
, R.J. Odink
, Karen Bindels-de Heus
, Mariette van Leeuwen
, Danny Haring
, Gianni Bocca
, E. C.A. Mieke Houdijk
, Gera Hoorweg-Nijman
, R.C. Vreuls
, Petr E. Jira
, A. S. Paul Van Trotsenburg
, Boudewijn Bakker
, E.J. Schroor
, Jan Willem Pilon
, Jan M. Wit

Stenvert L S Drop, Anita C.S. Hokken-Koelega

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.

Objectives: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.

Setting: We conducted a multicenter prospective trial.

Design: Fifty-five children with a mean ± SD age of 5.9 ± 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m2 · d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. SD scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDSPWS).

Results: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean ± SD height normalized from −2.27 ± 1.2 SDS to −0.24 ± 1.2 SDS (P < 0.0001). Head circumference SDS increased from −0.79 ± 1.0 at start to 0.07 ± 1.1 SDS after 4 yr. BMISDSPWS significantly decreased. Mean ± SD IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 ± 1.1 and 2.32 ± 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.

Conclusions: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m2 · d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Long-term growth hormone treatment is effective and safe in children with Prader-Willi syndrome.

Original language	Undefined/Unknown
Pages (from-to)	4205-4215
Number of pages	11
Journal	The Journal of clinical endocrinology and metabolism
Volume	94
Issue number	11
DOIs	https://doi.org/10.1210/jc.2009-0454
Publication status	Published - Nov 2009
Externally published	Yes

Access to Document

10.1210/jc.2009-0454

http://doi.org/10.1210/jc.2009-0454

Cite this

de Lind van Wijngaarden, R., Siemensma, E., Festen, D., Otten, B. J., van Mil, E., Rotteveel, J., Odink, R. J., Bindels-de Heus, K., van Leeuwen, M., Haring, D., Bocca, G., Mieke Houdijk, E. C. A., Hoorweg-Nijman, G., Vreuls, R. C., Jira, P. E., Paul Van Trotsenburg, A. S., Bakker, B., Schroor, E. J., Pilon, J. W., ... Hokken-Koelega, A. C. S. (2009). Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. The Journal of clinical endocrinology and metabolism, 94(11), 4205-4215. https://doi.org/10.1210/jc.2009-0454

@article{8e52229d0ffb4db5942bebd1052c4f26,

title = "Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.",

abstract = "Background: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. Objectives: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. Setting: We conducted a multicenter prospective trial. Design: Fifty-five children with a mean ± SD age of 5.9 ± 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m2 · d). Data were annually obtained in one center: fat percentage (fat\%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. SD scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDSPWS). Results: Fat\%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean ± SD height normalized from −2.27 ± 1.2 SDS to −0.24 ± 1.2 SDS (P < 0.0001). Head circumference SDS increased from −0.79 ± 1.0 at start to 0.07 ± 1.1 SDS after 4 yr. BMISDSPWS significantly decreased. Mean ± SD IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 ± 1.1 and 2.32 ± 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Conclusions: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m2 · d) improves body composition by decreasing fat\%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS. Long-term growth hormone treatment is effective and safe in children with Prader-Willi syndrome.",

author = "\{de Lind van Wijngaarden\}, Roderick and Elbrich Siemensma and Dederieke Festen and B.J. Otten and \{van Mil\}, Edgar and J. Rotteveel and R.J. Odink and \{Bindels-de Heus\}, Karen and \{van Leeuwen\}, Mariette and Danny Haring and Gianni Bocca and \{Mieke Houdijk\}, \{E. C.A.\} and Gera Hoorweg-Nijman and R.C. Vreuls and Jira, \{Petr E.\} and \{Paul Van Trotsenburg\}, \{A. S.\} and Boudewijn Bakker and E.J. Schroor and Pilon, \{Jan Willem\} and Wit, \{Jan M.\} and Drop, \{Stenvert L S\} and Hokken-Koelega, \{Anita C.S.\}",

year = "2009",

month = nov,

doi = "10.1210/jc.2009-0454",

language = "Undefined/Unknown",

volume = "94",

pages = "4205--4215",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "11",

}

de Lind van Wijngaarden, R, Siemensma, E, Festen, D, Otten, BJ, van Mil, E, Rotteveel, J, Odink, RJ, Bindels-de Heus, K, van Leeuwen, M, Haring, D, Bocca, G, Mieke Houdijk, ECA, Hoorweg-Nijman, G, Vreuls, RC, Jira, PE, Paul Van Trotsenburg, AS, Bakker, B, Schroor, EJ, Pilon, JW, Wit, JM, Drop, SLS & Hokken-Koelega, ACS 2009, 'Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.', The Journal of clinical endocrinology and metabolism, vol. 94, no. 11, pp. 4205-4215. https://doi.org/10.1210/jc.2009-0454

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. / de Lind van Wijngaarden, Roderick; Siemensma, Elbrich; Festen, Dederieke et al.
In: The Journal of clinical endocrinology and metabolism, Vol. 94, No. 11, 11.2009, p. 4205-4215.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

AU - de Lind van Wijngaarden, Roderick

AU - Siemensma, Elbrich

AU - Festen, Dederieke

AU - Otten, B.J.

AU - van Mil, Edgar

AU - Rotteveel, J.

AU - Odink, R.J.

AU - Bindels-de Heus, Karen

AU - van Leeuwen, Mariette

AU - Haring, Danny

AU - Bocca, Gianni

AU - Mieke Houdijk, E. C.A.

AU - Hoorweg-Nijman, Gera

AU - Vreuls, R.C.

AU - Jira, Petr E.

AU - Paul Van Trotsenburg, A. S.

AU - Bakker, Boudewijn

AU - Schroor, E.J.

AU - Pilon, Jan Willem

AU - Wit, Jan M.

AU - Drop, Stenvert L S

AU - Hokken-Koelega, Anita C.S.

PY - 2009/11

Y1 - 2009/11

N2 - Background: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. Objectives: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. Setting: We conducted a multicenter prospective trial. Design: Fifty-five children with a mean ± SD age of 5.9 ± 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m2 · d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. SD scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDSPWS). Results: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean ± SD height normalized from −2.27 ± 1.2 SDS to −0.24 ± 1.2 SDS (P < 0.0001). Head circumference SDS increased from −0.79 ± 1.0 at start to 0.07 ± 1.1 SDS after 4 yr. BMISDSPWS significantly decreased. Mean ± SD IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 ± 1.1 and 2.32 ± 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Conclusions: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m2 · d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS. Long-term growth hormone treatment is effective and safe in children with Prader-Willi syndrome.

AB - Background: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. Objectives: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. Setting: We conducted a multicenter prospective trial. Design: Fifty-five children with a mean ± SD age of 5.9 ± 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m2 · d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. SD scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDSPWS). Results: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean ± SD height normalized from −2.27 ± 1.2 SDS to −0.24 ± 1.2 SDS (P < 0.0001). Head circumference SDS increased from −0.79 ± 1.0 at start to 0.07 ± 1.1 SDS after 4 yr. BMISDSPWS significantly decreased. Mean ± SD IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 ± 1.1 and 2.32 ± 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Conclusions: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m2 · d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS. Long-term growth hormone treatment is effective and safe in children with Prader-Willi syndrome.

U2 - 10.1210/jc.2009-0454

DO - 10.1210/jc.2009-0454

M3 - Article

SN - 0021-972X

VL - 94

SP - 4205

EP - 4215

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 11

ER -