Vitamin D deficiency and hypocalcemia in an infant with newly diagnosed AML.

We report a 4-month-old male presenting with hypocalcemia, hyperleukocytosis, and newly diagnosed acute myeloid leukemia. He received chemical leukoreduction through low-dosed cytarabine, with appropriate decrease in his white blood cell count and development of subsequent symptomatic hypocalcemia, which did not normalize until the underlying vitamin D deficiency was addressed. A single dose of cholecalciferol raised the serum calcium concentration to an appropriate level within 48 hours. For infants with newly diagnosed leukemia and prolonged hypocalcemia, vitamin D deficiency should be considered in the differential diagnosis and managed appropriately.

Neoplastic causes of abnormal puberty.

BACKGROUND: Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. METHODS: We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. RESULTS: Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. CONCLUSIONS: Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis.

Growth effects of methylphenidate among childhood cancer survivors: a 12-month case-matched open-label study.

BACKGROUND: To investigate the effect of stimulant medication [methylphenidate (MPH)] on growth patterns among survivors of childhood cancer (acute lymphoblastic leukemia or brain tumor). PROCEDURE: Using a case-matched comparison design, childhood cancer survivors participating in a 12-month open-label MPH trial (n = 51) were compared with childhood cancer survivors not taking MPH (n = 51). Measures of body mass index (BMI), height, and weight were obtained at hospital visits and corrected for gender and age using Centers for Disease Control normative data. RESULTS: Significant deceleration of BMI and weight, but not height, was observed during the 12-month MPH trial for those children taking MPH. CONCLUSIONS: Childhood cancer survivors taking MPH experience significant, though modest, deceleration of BMI and weight across the first year of MPH intervention. The absence of height deceleration, and the presence of only modest BMI and weight deceleration, suggests that MPH is reasonably well tolerated by childhood cancer survivors with respect to growth. Such findings are encouraging in light of increasing evidence that MPH mitigates some of the cognitive late-effects of cancer treatments. Nevertheless, on a case-by-case basis, clinicians should balance the intended benefits of MPH with potential growth effects in this vulnerable population.

The use of bone age for bone mineral density interpretation in a cohort of pediatric brain tumor patients.

BACKGROUND: Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children. OBJECTIVE: To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion. MATERIALS AND METHODS: A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed. RESULTS: No significant difference between CA and BA Z-scores was detected in the overall cohort (P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort. CONCLUSION: Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males.

Implementing an intervention to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia: BONEII, a prospective placebo-controlled double-blind randomized interventional longitudinal study design.

The BONEII study is a large two-phase study. The baseline study (Study 1) aims to estimate the prevalence of diminished bone mineral density (BMD) in patients treated for childhood acute lymphoblastic leukemia (ALL) and identify risk factors for BMD deficits. The interventional phase (Study 2) of BONEII has a placebo-controlled double-blind randomized longitudinal design to evaluate the effects of nutritional counseling and calcium and vitamin D supplementation on changes in BMD and serum and urine markers of bone metabolism. The extensive information being collected through this large study will serve as a repository of relational data about BMD and bone turnover and will support further investigations to assess the association of calcium metabolism, bone turnover, nutritional intake, lifestyle factors (such as exercise and the use of alcohol and tobacco), and the specific agents used in ALL therapy in this rapidly increasing population of childhood cancer survivors.

Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial.

PURPOSE: To estimate the cumulative incidence of specific hormone deficiencies and the influence of hypothalamic-pituitary (HP) axis radiation dose in a cohort of children with embryonal brain tumors treated with risk-adapted craniospinal irradiation (CSI), conformal primary site irradiation, and high-dose chemotherapy. PATIENTS AND METHODS: Clinical data and HP axis radiation dosimetry data were obtained from 88 eligible children. All patients received regular endocrine follow-up that included screening tests of thyroid function and stimulation testing for growth hormone deficiency (GHD), and adrenocorticotropin hormone deficiency. RESULTS: The cumulative incidence of GHD, thyroid-stimulating hormone (TSH) deficiency, adrenocorticotropic hormone deficiency, and primary hypothyroidism at 4 years from diagnosis was 93% +/- 4%, 23% +/- 8%, 38% +/- 6%, and 65% +/- 7%, respectively. Radiation dosimetry to the HP axis was associated only with the development of TSH deficiency; the 4-year cumulative incidence was 44% +/- 19% and 11% +/- 8% (P = .014) for those receiving more or less than the median dose to the hypothalamus (>or= 42 v < 42 Gy), respectively. The median dose of CSI for the average-risk (AR) patients was 23.4 and 39.6 Gy (36 to 40.5 Gy) for the high-risk patients. The estimated mean decline in height Z-score after radiation therapy was greater in high-risk patients (-0.65 units/yr) when compared with AR patients (-0.54 units/yr; P = .039). CONCLUSION: Pediatric patients with CNS embryonal tumors are at high risk for treatment-related hormone deficiencies. GHD and primary hypothyroidism were diagnosed in a majority of subjects relatively soon after the completion of therapy. Radiation dose to the hypothalamus in excess of 42 Gy was associated with an increase in the risk of developing TSH deficiency.

Diabetic ketoacidosis during therapy for pediatric acute lymphoblastic leukemia.

BACKGROUND: Hyperglycemia is common during therapy for acute lymphoblastic leukemia (ALL), but diabetic ketoacidosis (DKA) occurs rarely. Morbidity due to DKA in children with ALL has not been systematically studied. PROCEDURES: We reviewed risk factors and clinical consequences of DKA in patients undergoing therapy for ALL at SJCRH between 1991 and 2006. RESULTS: DKA occurred in 6 of 797 evaluable patients. Only older age at diagnosis of ALL was a risk factor for DKA. Four of six patients with DKA as compared to 232 of the other 791 patients were older than 10 years (P = 0.03). Race, sex, body mass index, leukemia immunophenotype, ALL risk category, white blood cell count at diagnosis, and treatment protocol were not associated with DKA. All patients were managed with intravenous fluids, dietary modification, and short-term use of insulin. Patients were hospitalized for 4-12 days, with a median ICU stay of 1 day. In two patients, correction of hyperglycemia was too rapid, and two others experienced hypoglycemia due to insulin therapy. There were no permanent complications of DKA or its treatment. No patient required long-term insulin use. No patient had recurrent DKA; only one of the six patients had a subsequent hyperglycemia episode. All six patients are alive in remission 6-13 years after diagnosis. CONCLUSIONS: Patients with hyperglycemia during treatment for ALL should be screened for clinical evidence of DKA, which may require more intensive supportive care than those without ketoacidosis. The occurrence of DKA should not lead to alteration of ALL treatment.

White race as a risk factor for hypothyroidism after treatment for pediatric Hodgkin's lymphoma.

PURPOSE: Hypothyroidism frequently occurs after treatment for pediatric Hodgkin's lymphoma, but race has not been investigated as a risk factor for this delayed toxicity. The aim of this study was to determine whether race is an independent risk factor for hypothyroidism in survivors of pediatric Hodgkin's lymphoma. PATIENTS AND METHODS: To identify differences between black and white patients in the development of hypothyroidism after treatment for Hodgkin's lymphoma, we conducted a retrospective study of consecutively treated pediatric patients with newly diagnosed Hodgkin's lymphoma treated at St Jude Children's Research Hospital (Memphis, TN) from January 1980 through December 2002. Clinical or biochemical hypothyroidism was defined by an above normal thyroxine-stimulating hormone concentration or by the need for thyroid hormone replacement therapy. RESULTS: The 461 patients (388 white patients, 73 black patients) where followed for a median of 11.3 years (range, 1.8 to 24.9 years). Hypothyroidism developed in 196 (43%) of 461 patients after a median of 2.9 years (range, 0.7 to 11.3 years) after diagnosis of Hodgkin's lymphoma. Hypothyroidism developed in 47% of white patients but in only 21% of black patients (hazard ratio = 2.7; 95% CI, 1.6 to 4.6). After adjusting for other risk factors for hypothyroidism (thyroid radiation dose, sex, and nodular sclerosis histology), the risk of hypothyroidism in white patients was 2.5 times (95% CI, 1.5 to 4.3 times) the risk in black patients (P < .001). CONCLUSION: White patients have a higher risk of hypothyroidism after neck irradiation for pediatric Hodgkin's lymphoma than black patients.

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.