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Growth Hormone Therapy in Children after Cranial/Craniospinal Radiation Therapy: Sexually Dimorphic Outcomes

Division of Pediatric Endocrinology (S.E.L., G.J.M.H., S.E.O.), Children’s Hospital of New York-Presbyterian, New York, New York 10032; Division of Endocrinology (D.M.), New York Presbyterian Hospital, New York, New York 10032; and Division of Pediatric Endocrinology (C.A.S.), Memorial Sloan Kettering Cancer Center, New York, New York 10021

Address all correspondence and requests for reprints to: Dr. Sharon E. Oberfield, Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, 630 West 168th Street, PH-5E-522, New York, New York 10032. E-mail: seo8{at}columbia.edu.

Radiation therapy (RT) to the craniospinal region in childhood affects final height. The use of GH treatment (GHRx) in children after cranial or craniospinal RT results in variable improvement in final height. Nineteen children (12 males and 7 females) with tumors of the head, treated with cranial or craniospinal RT and subsequently with GHRx, were assessed for final height. Two outcome measures of efficacy of GHRx were used: Y1 = final height SD score (SDS) corrected for genetic potential, using midparental sex-adjusted target height (SATH) SDS, and Y2 = change in height SDS from predicted final height SDS pre-GHRx to actual final height SDS post-GHRx. The median age at diagnosis was 5.4 yr, the median RT to the hypothalamic-pituitary axis was 40 Gy, the median spinal RT dose in 13 of 19 of the subjects treated was 36 Gy, and the median years post-RT to GHRx was 4.8 yr. Adjuvant chemotherapy was used in 12 of 19 patients. All but one (optic glioma) had a lesion anatomically distant from the suprasellar region. The effects of age at diagnosis, sex, L-T₄ or GnRH agonist use, conventional vs. hyperfractionated RT, spinal RT, dose of spinal or cranial RT, chemotherapy, peak stimulated GH, dose and duration of GHRx, age at GHRx, time interval between RT and GHRx initiation, bone age, and height SDS at the start of GHRx were also assessed. Y1_girls best correlated with younger age at diagnosis and im vs. sc GHRx. Y2_girls best correlated with delayed bone age and younger age at diagnosis [Y1_girls = –9.95 + 0.38 (age in years at diagnosis) + 3.11[GH method (1 = im; 2 = sc)]; r² = 0.898; P = 0.02; Y2_girls = –3.54 + 1.8 (bone age – age in years) + 0.334 (age at diagnosis in years); r²= 0.956; P = 0.02]. Both Y1_boys and Y2_boys were strongly associated with spinal RT and younger age at diagnosis or treatment [Y1_boys = –11.22 + 4.65 [spinal RT (1 = yes; 2 = no)] + 0.396 (age in years at diagnosis); r²= 0.64, P = 0.01; Y2_boys = –6.32 + 0.23 (age in years at GH start) + 1.75 [spinal RT (1 = yes; 2 = no)]; r²= 0.646; P < 0.01]. This small historical cohort underscores that final stature is significantly reduced when immature bones are exposed to ionizing radiation. Intramuscular vs. sc use of GHRx is likely to be simply a surrogate marker for earlier methods of treatment. Of note, spinal RT did not significantly impact girls’ final heights, whereas in boys, spinal RT strongly predicted ultimate short stature and a reduced response to GHRx. This sexually dichotomous response may be due in part to the greater percentage of spinal growth remaining for boys vs. girls throughout childhood.