The Midgrowth Spurt in Healthy Children Is Not Caused by Adrenarche

Abstract

A small transient increase in growth, the midgrowth spurt, has been observed in several growth studies in healthy children around the age of 7 yr. During this time adrenarche (the physiological increase in adrenal androgen secretion) also occurs. Although it is now well established that estrogen, not androgen, has a critical role in the male (and female) pubertal growth spurt, a direct effect of androgens on growth cannot be excluded. In accordance with published observations that growth is frequently accelerated in infants and young children with late-diagnosed 21-hydroxylase deficiency (before adequate androgen suppression), it has been speculated that the adrenarchal increase in adrenal androgen secretion in healthy children could be responsible for the midgrowth spurt. To test this hypothesis we studied long-term serial changes in urinary 24-h excretion rates of dehydroepiandrosterone sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identification of a midgrowth spurt. Annual measurements of standing height were performed over periods of 6-9 yr before the onset of puberty. All children collected five to seven serial 24-h urine samples (1-yr intervals) each at the time of anthropometric examination. The peak of the midgrowth spurt was found to occur at a mean age of 6.8 +/- 1.0 yr. The average height of the midgrowth peak, i.e. average maximum gain in height velocity, was 0.9 cm/yr. In a peak-centered examination of individual 24-h excretion rates of dehydroepiandrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr changes in adrenal androgens were observed until the peak was attained. Only after the peak did increments in urinary adrenal androgen output become more pronounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17-ketosteroid sulfate excretion rates revealed a highly significant overall increase in adrenal androgen secretion from 2 yr before to 2 yr after the midgrowth spurt. After multiple testing, however, significant increments, when compared with the respective preceding androgen excretion levels, were for the first time seen 1 yr after the midgrowth spurt (dehydroepiandrosterone sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our longitudinal analysis of prepubertal growth and urinary adrenal androgen excretion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secretion. However, the present results do not rule out a growth-accelerating effect of clearly higher androgen levels, as in premature adrenarche.

Adrenarche and Middle Childhood

“…In normal children DHEA is related to the development of bone diameter in prepubertal children (Remer et al 2003(Remer et al , 2009, but see Remer et al 2004) but has little effect on skeletal growth (Reinehr et al 2006). Furthermore, adrenarche occurs approximately a year after the mid-childhood spurt (Remer and Manz 2001), ruling out increases in DHEA/S as a cause of such a growth spurt.…”

DHEAS and nutritional status among Sidama, Ngandu, and Aka children: Effects of cortisol and implications for adrenarche

“…Physically, the mid‐childhood growth spurt was thought to correspond with adrenarche (Bogin, 1997; Parker, 1991), but Remer and Manz (2001) demonstrated that this growth spurt, if it occurs at all, is typically a year before levels of DHEA/S are detectable in circulation. DHEA/S is involved in the functioning of the immune system and may be protective against disease; specifically, elevated DHEAS levels are associated with decreased malaria density among pubertal girls (Leenstra et al, 2003), as well as increased resistance and lower density among pubertal males (Kurtis et al, 2001).…”