<p><strong>BACKGROUND: </strong>Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.</p>

<p><strong>PROCEDURE: </strong>Retrospective cohort study (1980-2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.</p>

<p><strong>RESULTS: </strong>Median survivor follow-up since rhGH initiation was 4.8 (range 0.2-18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P &lt; 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.</p>

<p><strong>CONCLUSIONS: </strong>The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.</p>

<p><strong>BACKGROUND/AIMS: </strong>Pediatric Graves' disease (GD) accounts for 10-15% of all thyroid disorders in patients ≤18 years and is treated with antithyroid medication or definitive therapy [radioactive iodine (RAI) ablation vs. surgery]. Patients with GD may have concurrent differentiated thyroid cancer (DTC). DTC prevalence in pediatric GD is not well established. We examined the prevalence of DTC in pediatric GD and the role of preoperative thyroid ultrasound (US) in selecting the appropriate definitive therapy.</p>

<p><strong>METHODS: </strong>This is a single-institution, retrospective, cross-sectional study of 32 GD patients with a median age of 11 years (range 3-18) who underwent total thyroidectomy as the definitive treatment between 2005 and 2014.</p>

<p><strong>RESULTS: </strong>DTC was identified in 22% of the GD patients. A total of 97% completed preoperative thyroid US, and thyroid nodules were identified in 13/32 patients (41%). Preoperative fine needle aspiration (FNA) biopsy was performed in 6/13 patients, accounting for four preoperative diagnoses of concurrent DTC. Extra-thyroidal extension was present in 4/7 (63%), regional lymph node metastasis in 3/7 (43%), and lung metastasis in 2/7 patients (29%).</p>

<p><strong>CONCLUSIONS: </strong>Concurrent DTC occurs in pediatric GD patients. Thyroid US is an efficient tool for selecting patients for thyroidectomy. For patients with a nodule on US before definitive therapy, FNA should be performed to appropriately select thyroidectomy versus RAI ablation. © 2015 S. Karger AG, Basel.</p>

<p>Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p &lt; 0.001) and greater VAT (p &lt; 0.01), MAT (p &lt; 0.001), and fat infiltration of muscle (p = 0.04) independent of WB-FM, versus matched controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure versus controls (all p = 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT, and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p &lt; 0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p &lt; 0.01), and positively correlated with WB-FM and VAT (both p &lt; 0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.</p>