Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review.

BACKGROUND: Aromatase inhibitors (AIs) have been used off-label to increase adult height in short adolescent males. Studies have shown that AIs increase the predicted adult height (PAH) while delaying bone age (BA) maturation. We sought to determine whether AI therapy increases PAH in boys with short stature or rapid pubertal progression, and to evaluate any untoward effects. METHODS: The charts of 27 boys with BA ≥ 13 and short stature [height ≥ 2 standard deviation (SD) below the mean or ≥ 2 SD below mid-parental target height (MPTH)] or rapid pubertal progress, treated with anastrozole were reviewed. Outcome measures included anthropomorphic, hormonal, and metabolic data. RESULTS: The AI therapy averaged 21 months (range 14-30 months) for all, with Rx group 1 receiving <18 months therapy (n=7) and Rx group 2 receiving 18-30 months therapy (n=20). Post-therapy, in Rx group 1 and all subjects, there was no significant change in the PAH, height SDS, or BA/chronological age (CA). In Rx group 2, there was a small, nonsignificant increase in PAH, no change in height SDS, and a small decrease in BA/CA. Post-therapy PAH was different from MPTH in all and in both Rx groups 1 and 2, p<0.02. Eight of them achieved near-final height, averaging 6.73 ± 1.40 cm less than MPTH and 1.91 ± 0.86 cm less than the pre-therapy PAH. Post-therapy, the initially decreased estradiol did not persist but mildly increased testosterone and decreased high-density lipoprotein were noted, as was an increase in hematocrit, and decrease in growth velocity. CONCLUSIONS: We suggest that although bone age progression may be slightly delayed with longer duration of therapy, an overall short-term AI therapy does not lead to a final height that is greater than the predicted pre-therapy height.

Growth hormone therapy in children after cranial/craniospinal radiation therapy: sexually dimorphic outcomes.

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. Y1girls best correlated with younger age at diagnosis and im vs. sc GHRx. Y2girls best correlated with delayed bone age and younger age at diagnosis [Y1girls = -9.95 + 0.38 (age in years at diagnosis) + 3.11[GH method (1 = i.m.; 2 = s.c.)]; r2 = 0.898; P = 0.02; Y2girls = -3.54 + 1.8 (bone age - age in years) + 0.334 (age at diagnosis in years); r2= 0.956; P = 0.02]. Both Y1boys and Y2boys were strongly associated with spinal RT and younger age at diagnosis or treatment [Y1boys = -11.22 + 4.65 [spinal RT (1 = yes; 2 = no)] + 0.396 (age in years at diagnosis); r2= 0.64, P = 0.01; Y2boys = -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.