Published online May 1, 2006
PEDIATRICS
Vol. 117
No. 5
May 2006, pp.
1868-1869
(doi:10.1542/peds.2006-0022)
Effects of Growth Hormone Treatment on Neutrophil Count in Children Born Small for Gestational Age
Lourdes Ibáñez, MD, PhD
Endocrinology Unit
Hospital Sant Joan de Deu
University of Barcelona
08950 Esplugues, Barcelona, Spain
Ken Ong, MD
Epidemiology Unit
Medical Research Council
Cambridge CB2 2QQ, United Kingdom
Department of Paediatrics
Addenbrooke's Hospital
University of Cambridge
Cambridge CB2 2QQ, United Kingdom
David B. Dunger, MD, PhD
Department of Paediatrics
Addenbrooke's Hospital
University of Cambridge
Cambridge CB2 2QQ, United Kingdom
Francis de Zegher, MD, PhD
Department of Pediatrics
University of Leuven
3000 Leuven, Belgium
To the Editor.
In January 2005, we submitted that high-dose growth hormone (GH) treatment (
60 µg/kg per day for 6 months) raises the neutrophil count and that metformin treatment (425 mg/day for 6 months) lowers it in children born small for gestational age (SGA) with short stature or precocious pubarche.1 At the end of that report, we expressed the need to verify whether the GH-associated rise and the metformin-associated fall of the neutrophil count persist over time and whether they are specific for SGA children and/or for high-dose GH therapy.
Our own subsequent studies have since confirmed the hyperneutrophilia-lowering effect of metformin in adolescents with hyperinsulinemic hyperandrogenism2 and also in low birth weight girls with early-normal puberty.3 A high neutrophil count was also found to emerge by the age of 4 years in SGA children with spontaneous catch-up growth, in parallel with the development of insulin resistance.4 Between January and November 2005, independent groups linked a high neutrophil count to hyperinsulinemia,3,5,6 and Sohmiya et al7 showed in GH-deficient Japanese adults (mean: 52 years old) that exogenous GH (12 µg/kg per day) raises the neutrophil count by 50% within 2 months.
We now have longer-term follow-up data from our studies with high-dose GH therapy (60 µg/kg per day) or metformin treatment (Table 1), and we also provide new data in short SGA children using a lower-dose GH therapy as suggested by a recent meta-analysis (33 µg/kg per day, with a possible starting dose of 50 µg/kg per day in very short and/or late-starting children [so-called 50 
33 µg/kg per day algorithm]).8 In short SGA children, the neutrophil count remains elevated after 2 years on high-dose GH therapy; in contrast, the first experience with the 50 33 µg/kg per day algorithm in clinical practice is reassuring, at least with regard to neutrophilia. In SGA girls with precocious pubarche, the neutrophil count remains lowered after 2 years on metformin.
View this table:
[in this window]
[in a new window]
|
TABLE 1 Neutrophil Counts Before and During GH or Metformin Treatment in SGA Children With Short Stature or Precocious Pubarche
|
|
This update suggests that: - The neutrophilia-promoting effect of exogenous GH
- is not specific for short SGA children;
- is not observed in short SGA children receiving GH at a dose of 40 µg/kg per day, which is 33% above replacement level; and
- persists over 2 years in short SGA children receiving GH at a dose of 60 µg/kg per day, which is 100% above replacement level.
- The neutrophilia-decreasing effect of metformin persists over 2 years in SGA girls with precocious pubarche.
REFERENCES
- Ibáñez L, Fucci A, Valls C, Ong K, Dunger D, de Zegher F. Neutrophil count in small-for-gestational age children: contrasting effects of metformin and growth hormone therapy.
J Clin Endocrinol Metab. 2005;90
:3435
–3439[Abstract/Free Full Text]
- Ibáñez L, Jaramillo AM, Ferrer A, de Zegher F. High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception.
Hum Reprod. 2005;20
:2457
–2462[Abstract/Free Full Text]
- Ibáñez L, Valls C, Ong K, Dunger D, de Zegher F. Metformin therapy during puberty delays menarche, prolongs pubertal growth, and augments adult height: a randomized study in low-birthweight girls with early-normal onset of puberty.
J Clin Endocrinol Metab. 2006; In press
- Ibáñez L, Ong K, Dunger D, de Zegher F. Early development of adiposity and insulin resistance following catch-up weight gain in small-for-gestational-age children.
J Clin Endocrinol Metab. 2006; In press
- Orio F Jr, Palomba S, Cascella T, et al. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome.
J Clin Endocrinol Metab. 2005;90(1)
:2
–5
- Puder JJ, Varga S, Kraenzlin M, De Geyter C, Keller U, Muller B. Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance.
J Clin Endocrinol Metab. 2005;90
:6014
–6021[Abstract/Free Full Text]
- Sohmiya M, Kanazawa I, Kato Y. Effect of recombinant human GH on circulating granulocyte colony-stimulating factor and neutrophils in patients with adult GH deficiency.
Eur J Endocrinol. 2005;152
:211
–215[Abstract/Free Full Text]
- de Zegher F, Hokken-Koelega A. Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term.
Pediatrics. 2005;115(4)
. Available at: www.pediatrics.org/cgi/content/full/115/4/e458
- Ibáñez L, Valls C, Marcos MV, Ong K, Dunger D, de Zegher F. Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin.
J Clin Endocrinol Metab. 2004;89
:4331
–4337[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
