Background: Children with Silver Russell syndrome (SRS) suffer from severe intrauterine growth retardation. During infancy, short stature and delayed bone maturation are common features. A majority of these children initially have a good growth response to GH treatment. A catch-up period of skeletal maturation is often seen in early puberty. Later in puberty poor height acceleration may be seen.
Objective and hypothesis: The objective of this study was to evaluate the association between prepubertal and pubertal estrogen levels and final height (FH) out-come in GH treated boys with SRS. The hypothesis was that altered adrenal activity with increased dehydroepiandrosterone (DHEA) secretion stimulates skeletal maturation through the conversion to estrogens.
Method: Serum concentrations of estrone (E1) and estradiol (E2) were determined by gas chromatography-tandem mass spectrometry at different ages and compared to auxological measures including FH in 11 boys with SRS. Subjects with FH ≤ −1 SDS from target height (TH) were considered responders and subjects with FH > −1 SDS from TH were considered non-responders.
Results: At the age of 10 all subjects were prepubertal. The majority had entered puberty at the age of 12. Non-responders had significantly higher levels of E2 (median 2 versus 1 pmol/l, P<0.05 and 23.1 versus 1.6 pmol/l, P<0.01) at the age 10 and 12, and lower E1/E2 ratio (3.2 versus 26.1, P<0.01) at the age of 12 compared to responders.
Conclusion: There is an association between high levels of E2 at the age of 10-12 and low E1/E2 ratio at the age of 12 leading to impaired final height out-come. An increase in E2 secretion before puberty is most likely derived from the adrenal gland. The E2 levels may be sufficient to accelerate skeletal maturation but far lower than what is normally seen during puberty which explains why there is no enhanced growth prepubertally in the non-responder group.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology