Effect of the Long‐Acting Somatostatin Analogue SMS 201‐995 on Growth Rate and Reduction of Predicted Adult Height in Ten Tall Adolescents

Abstract

Ten adolescents (four boys and six girls) aged 11.5 to 17 years, presenting with constitutionally tall stature were treated with twice daily subcutaneous injections of 250 micrograms of SMS 201-995 (Sandostatin). Results are reported after 6 and 12 months of therapy. Reduction of growth rate was obtained in 9 patients and correlated with the reduction of 24-hour growth hormone pulsatility and with the decrease of plasma Somatomedin-C values. Moreover, acceleration of bone maturation on SMS 201-995 therapy occurred in seven patients, and mean bone age increased from 13.3 years to 14.5 and 15.8 years after 6 and 12 months of SMS therapy. The mean reduction of predicted adult height was 4.9 cm at the last evaluation after 6 or 12 months of therapy. The dual effect of SMS 201-995 on growth rate and bone maturation suggests that it may be an alternative treatment to reduce adult height.

Treatment of tall stature in boys with somatostatin analogue 201–995: effect on final height

“…Given the baseline mean GH levels, the clearly negative effect of SMS on mean GH and IGF-I levels, and the limited effect of SMS on reducing final height, GH action seems less important in the 'pathogenesis' of constitutional tall stature. We did not observe accelerated bone maturation as reported by Tauber et al (11) who treated ten pubertal adolescents with a high dose of SMS. We found a sustained and reversible effect on free thyroxine levels as expected in treatment with SMS and reported previously with suppression of TSH levels by SMS (21).…”

“…Furthermore, it is hypothesized that the somatostatin analogue 201 -995 (SMS) has local regulatory effects on bone growth and metabolism (9 -10). Several groups have reported on the role of SMS for the management of tall stature with a beneficial reduction in short-term growth in a number of children (11)(12)(13). Long-term effects of SMS therapy on growth velocity and final height are not available however.…”

Sex Steroid Treatment of Constitutionally Tall Stature*

“…Somatostatin is a neurohormone produced at the hypothalamic level that has potent inhibitory properties on GH release in the pituitary via the vascular network of the portal system (214). Preliminary data revealed an effective suppression of GH secretion in small groups of tall children and a significant reduction in growth rate and predicted adult height (215)(216)(217)(218). In addition, plasma IGF-I levels decreased whereas bone maturation accelerated in many of the treated children (216).…”

“…Preliminary data revealed an effective suppression of GH secretion in small groups of tall children and a significant reduction in growth rate and predicted adult height (215)(216)(217)(218). In addition, plasma IGF-I levels decreased whereas bone maturation accelerated in many of the treated children (216). The effect of somatostatin on bone maturation suggests that somatostatin acts not only by systemic hormonal effects on GH and/or IGFs but also by local regulatory effects on bone growth and metabolism.…”

Somatostatin Effects on Cultured Human Fetal Epiphyseal Chondrocytes

“…Long-term somatostatin analog treatment of children with excessive adult height prediction has shown a significant reduction in growth velocity during therapy, and this has been attributed to the somatostatin-induced decrease in growth hormone secretion (22,23). However, according to several experimental data that show that somatostatin binds to and exerts biologic effects on neonatal rat calvaria ( I 7) and neonatal rat long bones (24), that somatostatin inhibits proliferation and differentiation of cartilage and bone cells (25), and that the administration of somatostatin to mice inhibits longitudinal bone growth (26), it has been suggested that the somatostatin effect on the reduction of growth velocity in these children might in part be due to a direct effect of somatostatin on skeletal growth (27).…”