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Patterns of GH Output and Their Synchrony with Short-Term Height Increments Influence Stature and Growth Performance in Normal Children

Endocrine Sciences Research Group (M.S.G., V.T., P.E.C.), Academic Unit of Child Health, University of Manchester, Manchester M13 9PT, United Kingdom; and Department of Medicine (J.D.V.), General Clinical Research Center, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Peter Clayton, Endocrine Sciences Research Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. E-mail: pclayton{at}man.ac.uk

Abstract

GH is the principal hormone driving growth throughout childhood, but the mechanism by which changing GH secretion is translated into height (Ht) remains undefined. We previously demonstrated that variability in urinary GH (uGH) output over weeks is an important statistical determinant of stature in normal children. We now examine the relationship between the temporal pattern of uGH output and growth using approximate entropy (ApEn) in 29 healthy prepubertal children, monitored serially three times a week from September to June [13 males and 16 females; age, 5.7–7.8 yr; Ht SD score, -2.9 to +2.3; median, 85 measurements per subject]. ApEn is a measure of process irregularity, with low values indicating strong regularity or subpattern persistence and high values indicating greater irregularity. The bivariate extension of this method, cross (X)-ApEn, provides a measure of the strength of interaction between two paired time series (joint signal synchrony). Low values of X-ApEn indicate synchrony, whereas high values indicate asynchrony.

Weekly Ht gain, weight (Wt) gain, and uGH output showed significant orderliness in 20 of 29, 26 of 29, and 29 of 29 subjects, respectively, with weekly changes in uGH output being significantly more ordered than Ht gain (P < 0.001) and Wt gain (P < 0.01). ApEn(GH) was positively correlated with Ht gain over the whole year (r = 0.42) and Ht velocity SD score (r = 0.42; both, P < 0.05). Thus, increased irregularity in successive weekly GH output was associated with increased Ht gain and growth rate. There was significant synchrony between Ht and uGH, Wt and uGH, and Ht and Wt in 16 of 29, 22 of 29, and 25 of 29 subjects, respectively, as measured by X-ApEn. The degree of synchrony between Ht and GH output [X-ApEn(Ht:GH)] was inversely correlated with Ht SD score (r = -0.45) and Ht velocity SD score (r = -0.40; both P < 0.05), indicating that increased joint signal synchrony between Ht and GH accompanies tall stature and increased growth rate.

These results extend the concept that variability in GH output over time is an important determinant of growth in normal children by indicating that an irregular temporal pattern of GH contributes to growth. Furthermore, synchrony between GH output and short-term Ht increments is associated with tall stature and good growth.

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