Early, discontinuous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years.

Most children born small for gestational age (SGA) normalize their size through spontaneous catch-up growth within the first 2 yr after birth. Some SGA children fail to do so and maintain an abnormally short stature throughout childhood. We have previously reported that high dose GH treatment (66 or 100 microg/kg x day s.c. over 2 yr; age at start, 2-8 yr; n = 38) induces pronounced catch-up growth in short children born SGA, thereby normalizing their height and weight in childhood. Here, we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early, high dose GH treatment. Of the 38 treated children, none developed precocious puberty, and 22 remained prepubertal. Mean age of the latter at start of GH was 4.4 yr, height was -3.7 SD score, and height after adjustment for midparental height was -2.9 SD score. Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD, respectively, during the first and second year after GH withdrawal. Subsequently, when stature was not extremely short at the start (mean adjusted height SD score, -2.7; n = 13), no further GH treatment was given, and the adjusted height was stabilized around -1.0 SD score; when stature was very short at the start (mean adjusted height, -3.3 SD score; n = 9), a second course of GH treatment (66 microg/kg x day s.c.) was initiated either 2 yr (n = 5) or 3 yr (n = 4) after initial GH withdrawal. This second course was associated with renewed catch-up growth and also resulted in a mean adjusted height of -1.0 SD score. In each subgroup, the pattern of the weight course paralleled that of the height course; GH treatment was well tolerated. In conclusion, early, discontinuous, high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children. It remains to be examined whether the normalized stature will be maintained during pubertal development, either with or without further GH treatment.

Postpartum hyperprolactinemia and hyporesponsiveness of growth hormone (GH) to GH-releasing peptide.

Human PRL and GH as well as their respective receptors have closely related origins. In peripartal women, physiological hyperprolactinemia is associated with a pronounced hyposomatotropism that remains to be fully characterized. Through paracrine mechanisms, PRL-secreting "pregnancy cells" may modulate the secretory function of somatotropes, which are known to express PRL receptors. Within a randomized, placebo-controlled design, we examined GH responsiveness in 10 nonpregnant women and in 58 mothers either in early (median, 48 h; range, 42-54 h after delivery; all lactating) or late postpartum (median, 10 weeks; range, 3-25 weeks; lactating and nonlactating subgroups), using GH-releasing peptide-1 (GHRP-1; 100-micrograms i.v. bolus) as the GH secretagogue. Baseline serum PRL concentrations were low and similar (median, 5 micrograms/L) in nonpregnant controls and nonlactating, late postpartum women and were elevated in lactating women, particularly in the early postpartum period (median, 102 micrograms/L), compared to those in the late postpartum period (median, 27 micrograms/L). GHRP-1 elicited GH responses in all study groups; lactation was associated with lower and slower GH responses. Serum GH concentrations (20 min after GHRP-1 treatment) in controls (median, 78 micrograms/L) were 7- and 5-fold higher than those in lactating women studied, respectively, early or late postpartum. Baseline prolactinemia presented an inverse correlation with GH responsiveness; the higher baseline PRL concentration, the lower and the slower the GH response to GHRP-1. GH hyporesponsiveness in postpartum women is herewith further characterized to include the GHRP pathway. The inverse relationship between baseline prolactinemia and GH responsiveness is consistent with the concept that pregnancy cells may exert, either directly or indirectly, an inhibitory effect on the secretory capacity of somatotropes.