Pediatr Blood Cancer 2014;61:1140

LETTER TO THE EDITOR Slipped Capital Femoral Epiphyses after Total Body Irradiation To the Editor: Mostoufi-Moab et al.[1] have identified a significantly increased risk of slipped capital femoral epiphysis (SCFE) in childhood cancer survivors treated with recombinant growth hormone (rhGH) after receiving total body irradiation (TBI) for hematopoietic stem cell transplantation (HSCT). We reviewed our cohort of 104 children who received TBI conditioning over the past 30 years and identified 4 children who developed SCFE. In contrast to Mostoufi-Moab and of note, 3 were rhGH naı¨ve at the time of presentation. The children presented 4.8–10.3 years after 12Gy TBI conditioning for autologous HSCT. Presentation was atypical compared to idiopathic SCFE [2]: younger age (6.9–12.2 years), all prepubertal and only one overweight (BMI z-score 2.4 to 1.7). Two were bilateral at presentation, and three of the four patients presented with the uncommon valgus variant of SCFE. Overall time from symptom onset to radiological diagnosis was 5–27 months. The only child presenting with SCFE (unilateral) whilst on rhGH was a 12.2-year old female with unreplaced hypogonadism. She was diagnosed 11 months after commencing rhGH though had experienced X-ray negative transient hip pain 7 months prior. Upon review of her original radiographs, by Yngve’s criteria [3], there was subtle evidence of valgus slip. Pelvic radiation has previously been associated with an increased risk of SCFE [4]. There are several proposed reasons for this pathogenesis including direct irradiation effect on the physis and surrounding bone structure and a postulated role of chemotherapy radiosensitization [5]. There is no obvious explanation for the demographic differences compared to idiopathic SCFE including age, weight, and pre-pubertal status. Both data sets identify a greater incidence of valgus SCFE in the post TBI population. In addition, the risk after TBI may be increased further compared to localized irradiation alone because of concomitant subtle endocrinopathies, including hypothyroidism and hypogonadism, common in this population [6]. SFCE is a well recognized but uncommon complication of rhGH therapy [7]. Mostoufi-Moab et al. have identified a substantially higher rate of SCFE in children receiving rhGH after TBI compared to any other group receiving rhGH, including those on higher doses (e.g., Turner syndrome and chronic renal failure) [8]. Our data suggest that this increased risk may be inherently due to TBI rather than rhGH per se, but it is unclear from either study whether treatment with rhGH is additive or synergistic to this risk. Both these cohorts are an important reminder that TBI alone is a significant risk factor for SCFE, with delays in diagnosis due to the atypical clinical and radiological presentation being common [9]. Valgus slips are frequently subacute in presentation [3] with standard radiology inadequate. The radiological parameters described by Yngve are a more sensitive method of screening initial radiographs in children with hip symptoms. However, if standard radiological techniques are negative or equivocal, other modalities such as ultrasound and/or MRI must be considered and early orthopedic referral mandatory. Furthermore, poor growth is almost universal in this population and rhGH therapy frequently considered. The risk of developing

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2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.24895 Published online 10 January 2014 in Wiley Online Library (wileyonlinelibrary.com).

SCFE must be carefully considered by clinicians and clearly explained to families before embarking on rhGH therapy. Dr. Aditi Vedi, MBBS, MMed (Clin Epi) Kids Cancer Centre, Sydney Children’s Hospital School of Women’s and Children’s Health, University of NSW, Randwick, New South Wales, Australia Kristen Neville, MBBS, FRACP School of Women’s and Children’s Health, University of NSW, Endocrine Department, Sydney Children’s Hospital, Randwick, New South Wales, Australia Karen Johnston Kids Cancer Centre, Sydney Children’s Hospital, Randwick, New South Wales, Australia Davor Saravanja, MBBS, FRACS Orthopaedic Department, Sydney Children’s Hospital, Randwick, New South Wales, Australia Richard Jules Cohn, MBChB, FRACP Kids Cancer Centre, Sydney Children’s Hospital, School of Women’s and Children’s Health, University of NSW, Randwick, New South Wales, Australia

REFERENCES 1. Mostoufi-Moab S, Isaacoff EJ, Spiegel D, et al. Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy. Pediatr Blood Cancer 2013;60:1766–1771. 2. Loder RT. The demographics of slipped capital femoral epiphysis. An international multicenter study. Clin Orthop Relat Res 1996; 8–27. 3. Yngve DA, Moulton DL, Burke Evans E. Valgus slipped capital femoral epiphysis. J Pediatr Orthop B 2005;14:172–176. 4. Loder RT, Hensinger RN, Alburger PD, et al. Slipped capital femoral epiphysis associated with radiation therapy. J Pediatr Orthop 1998;18:630–636. 5. Ryan BR, Walters TR. Slipped capital femoral epiphysis following radiotherapy and chemotherapy. Med Pediatr Oncol 1979;6:279–283. 6. Burrow SR, Alman B, Wright JG. Short stature as a screening test for endocrinopathy in slipped capital femoral epiphysis. J Bone Joint Surg Br 2001;83:263–268. 7. Fidler MW, Brook CG. Slipped upper femoral epiphysis following treatment with human growth hormone. J Bone Joint Surg Am 1974;56:1719–1722. 8. Bell J, Parker KL, Swinford RD, et al. Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab 2010;95:167–177. 9. Kocher MS, Bishop JA, Weed B, et al. Delay in diagnosis of slipped capital femoral epiphysis. Pediatrics 2004;113:e322–e325.

 Correspondence to: Dr. Aditi Vedi, 102/155 Missenden Road, Newtown NSW, Australia 2042. E-mail: [email protected]

Received 3 October 2013; Accepted 4 November 2013

Slipped capital femoral epiphyses after total body irradiation.

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