Hyperestrogenism Affects Adult Height Outcome in Growth Hormone Treated Boys With Silver-Russell Syndrome

• Background: Intrauterine growth retardation and short stature are common features in Silver-Russell syndrome (SRS). Despite recombinant growth hormone (rGH) treatment, poor pubertal height gain, affecting adult height (AH), is common. This study investigated whether growth patterns and estrogen concentrations are associated with AH outcome in rGH treated SRS males. Methods: In this retrospective longitudinal single-center study, 11 males with SRS were classified as non-responders (NR = 6) or responders (R = 5), depending on AH adjusted for midparental height. Epigenetic analysis and longitudinal growth measures, including bone age, rGH related parameters, pubertal development, gonadotropins and estrogen concentrations, were analyzed until AH. Results: Pubarche before 9 years was only observed in one NR. At 10 years of age, there was no difference in gonadotropins between NR and R. However, estradiol (E2) concentrations at 10 years of age showed a strong association to AH adjusted for MPH (r = -0.78, p < 0.001). Serum E2 (pmol/L) was significantly higher in NR at ages 10 years [median (range) 2 (<2-5) vs. <2 (<2)], 12 years [23 (10-57) vs. 2 (<2-2)] and 14 years [77 (54-87) vs. 24 (<2-38)] but not at 16 years. Birth weight standard deviation score (SDS) was lower in NR [-4.1 (-4.7 to -2.1) vs. -2.7 (-3.3 to -1.7)]. Weight gain (SDS) until pubertal onset was greater in NR [2.4 (1.4-3.5) vs. 0.8 (-0.4 to 1.7)] and pubertal height gain (SDS) was lower in NR [-1.0 (-2.7-0.4) vs. 0.1 (-0.1 to 1.1)]. At AH, a number of NR and R had high E2 concentrations and small testes. Conclusion: Increased E2 concentrations at age 10, 12, and 14 years were associated to less pubertal height gain, thus affecting AH. Due to the small number of patients, the results need to be confirmed in larger cohorts. The finding of impaired testicular development stresses the need of hormonal evaluation as a complement to clinical and radiological assessment when predicting AH in males with SRS.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

small for gestational age

estrogens

puberty

mass spectrometry

hypogonadism

gonadotropins

Silver-Russell syndrome

adult height

for-gestational-age

mass-spectrometry assay

reference values

children

weight

birth

management

statement

estrone

srs

Endocrinology & Metabolism

small for gestational age; estrogens; puberty; mass spectrometry; hypogonadism; gonadotropins; Silver-Russell syndrome; adult height

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)