The midgrowth spurt in healthy children is not caused by adrenarche

A small transient increase in growth, the midgrowth spurt, has been observe d in several growth studies in healthy children around the age of 7 yr. Dur ing this time adrenarche (the physiological increase in adrenal androgen se cretion) also occurs. Although it is now well established that estrogen, no t androgen, has a critical role in the male (and female) pubertal growth sp urt, a direct effect of androgens on growth cannot be excluded. In accordan ce with published observations that growth is frequently accelerated in inf ants and young children with late-diagnosed 21-hydroxylase deficiency (befo re adequate androgen suppression), it has been speculated that the adrenarc hal increase in adrenal androgen secretion in healthy children could be res ponsible for the midgrowth spurt. To test this hypothesis we studied long-t erm serial changes in urinary 24-h excretion rates of dehydroepiandrosteron e sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identificatio n of a midgrowth spurt. Annual measurements of standing height were perform ed over periods of 6-9 yr before the onset of puberty. All children collect ed five to seven serial 24-h urine samples (1-yr intervals) each at the tim e 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 midgrow th 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 dehydroepia ndrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr change s in adrenal androgens were observed until the peak was attained. Only afte r the peak did increments in urinary adrenal androgen output become more pr onounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17- ketosteroid sulfate excretion rates revealed a highly significant overall i ncrease in adrenal androgen secretion from 2 yr before to 2 yr after the mi dgrowth spurt. After multiple testing, however, significant increments, whe n compared with the respective preceding androgen excretion levels, were fo r the first time seen I yr after the midgrowth spurt (dehydroepiandrosteron e sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our long itudinal analysis of prepubertal growth and urinary adrenal androgen excret ion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secreti on. However, the present results do not rule out a growth-accelerating effe ct of clearly higher androgen levels, as in premature adrenarche.