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Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.
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Estatura , Transtornos do Crescimento/patologia , Desnutrição/patologia , Neoplasias/complicações , Estado Nutricional , Redução de Peso , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Transtornos do Crescimento/etiologia , Humanos , Lactente , Masculino , Desnutrição/etiologia , Neoplasias/patologia , Neoplasias/terapia , Prognóstico , Estudos RetrospectivosRESUMO
Involvement of the pituitary gland by leukemic infiltration is exceedingly rare. Here, we describe a very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor and review the literature for previously reported cases. Our female patient presented 13 years after completion of therapy for B-ALL with headache, amenorrhea, galactorrhea and a pituitary mass. Subsequent studies revealed recurrence of her leukemia, and the pituitary lesion resolved after induction chemotherapy. Our case highlights the importance of considering leukemic infiltrate in the differential diagnosis of pituitary mass, particularly in a patient with a history of hematologic malignancy, sparing unnecessary surgical intervention and informing endocrine evaluation. In addition, the case also highlights difficulties with characterizing this recurrence as a very late relapse or clonal evolution of the original leukemia.
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Infiltração Leucêmica/diagnóstico , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Diagnóstico Diferencial , Feminino , Galactorreia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Hipófise/diagnóstico por imagem , Prolactina/sangue , Recidiva , Tireotropina/sangue , Adulto JovemRESUMO
BACKGROUND: Providers often rely on self-reported ovarian function in adolescent and young adult (AYA)-aged childhood cancer survivors when making clinical decisions. This study described reported menstrual patterns and the agreement between respondent-reported and biochemical premature ovarian insufficiency (POI) in this population. PROCEDURE: This was a cross-sectional study of survivors (or their parent proxy) aged 13-21.9 years who received gonadotoxic therapy and were enrolled in a longitudinal health survey. Participants reported menstrual regularity, hormone-replacement therapy (HRT) use, and ovarian dysfunction. Respondent-reported POI was defined as the survivor taking HRT for ovarian failure or having been told she had ovarian failure. Biochemical POI was defined as follicle-stimulating hormone (FSH) level ≥40 mIU/mL. The agreement between respondent-reported and biochemical POI was determined using Cohen's kappa coefficient (κ) and analyzed by demographic and clinical factors. RESULTS: Among 182 AYA-aged survivors (72.5% non-Hispanic White, 46.7% leukemia survivors), 14.8% reported requiring HRT to have menses but 55.5% reported regular menses without HRT use. Among survivors with FSH measurements (n = 130), 17.7% reported POI whereas 18.5% had FSH ≥40 mIU/mL (κ = 0.66, sensitivity 70.8%, specificity 94.3%). The highest agreement between respondent-reported and biochemical POI was with young adult self-report (κ = 0.78) and survivors with >5 survivor clinic (κ = 0.83) and/or >5 endocrinologist (κ = 1.00) visits. CONCLUSIONS: The majority of AYA-aged survivors reported having regular menses without HRT support. The accuracy of respondent-reported POI increased with repeated survivor clinic or endocrinologist visits, highlighting the importance of continued education. Survivors must be informed about their ovarian function to enable them to advocate for their reproductive health.
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Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias/terapia , Pais , Medidas de Resultados Relatados pelo Paciente , Insuficiência Ovariana Primária/diagnóstico , Adolescente , Adulto , Terapia Combinada , Estudos Transversais , Feminino , Seguimentos , Georgia/epidemiologia , Humanos , Incidência , Neoplasias/patologia , Insuficiência Ovariana Primária/epidemiologia , Prognóstico , Procurador , Saúde Reprodutiva , Adulto JovemRESUMO
Chronic myeloid leukemia (CML) accounts for 2-3% of leukemias in children under 15 and 9% in adolescents aged 15-19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.
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Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Abnormalities in BMI are well documented in childhood cancer survivors. Perceptions of BMI status in cancer survivors have been understudied. This study determines the accuracy of parent/survivor and provider reporting of BMI status in a cancer survivor program. PROCEDURE: This is a retrospective study. Parent/survivor assessment of BMI status was obtained from a baseline questionnaire of subjects enrolled in Children's Healthcare of Atlanta-Childhood, Adolescent, and Young Adult Cancer Survivor Study (CHOA-CAYACSS). Provider reporting of BMI was obtained from a clinic visit close in date to completion of the survey. Perceptions of BMI were compared to actual BMI status calculated from clinic visits and categorized based on the Centers for Disease Control and Prevention (CDC) BMI guidelines. RESULTS: Perceptions of BMI were collected from 290 survivors of pediatric cancer or their parents (range, 4.3-22.9 years). Nearly 5% of survivors were underweight, 19.7% overweight and 16.2% obese. High BMI was the BMI state least likely to be correctly identified by parents, survivors, and providers. Among survivors with high BMI, parents, survivors, and providers failed to identify the problem 49.4%, 66.7%, and 26.9% of the time, respectively. Providers were less likely to correctly identify overweight compared to obese status (P < 0.0001). Accuracy of BMI recognition was independent of gender of survivor, ethnicity, or primary cancer diagnosis. CONCLUSION: Abnormal BMI states, especially overweight, are frequently not correctly perceived by parents/survivors or providers. Assessment of BMI status and discussion about steps to normalize BMI is needed to prevent weight related morbidities in this population.
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Índice de Massa Corporal , Pessoal de Saúde , Neoplasias , Sobreviventes , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Estudos RetrospectivosRESUMO
OBJECTIVES: Transient hypocalcemia is a common complication after pediatric total thyroidectomy, while permanent hypoparathyroidism (PH) is relatively uncommon. To date there is no model to predict which patients will develop PH based on post-operative makers. We aim to identify pediatric patients who are at high risk of PH following thyroidectomy based on 6 h post-operative parathyroid hormone (PTH) value. METHODS: A retrospective review of 122 pediatric patients undergoing total thyroidectomy between 2016 and 2022 following implementation of a multidisciplinary team was performed. Outcome of interest was permanent hypoparathyroidism, defined as need for calcium supplementation at 6 months postoperatively. Receiver operating characteristic (ROC) analysis was used to determine PTH value at 6 h post-operative that was predictive of permanent hypoparathyroidism. RESULTS: Rates of permanent hypoparathyroidism reported are similar to those described in the literature with 12 patients (10.9%) developing PH. In patients who developed PH, mean 6 h postoperative PTH was 5.12 pg/mL. Mean 6 h postoperative PTH level in those who did not develop PH was 31.34 pg/mL (p<0.0001). The 6 h post-operative PTH value predictive for PH was ≤11.3 pg/mL. PTH cutoff of ≤11.3 pg/mL had a sensitivity of 100%, specificity of 72.2%, positive predictive value (PPV) of 27.0%, and negative predictive value (NPV) of 100%. CONCLUSIONS: 6 h postoperative PTH values were found to be predictive of permanent hypoparathyroidism in pediatric total thyroidectomy: a 6 h postoperative PTH level of >11.3 pg/mL excludes permanent hypoparathyroidism, but if PTH is ≤11.3 pg/mL at 6 h, approximately 1/3 of patients may persist with permanent hypoparathyroidism.
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Hipocalcemia , Hipoparatireoidismo , Humanos , Criança , Projetos Piloto , Tireoidectomia/efeitos adversos , Hormônio Paratireóideo , Hipoparatireoidismo/etiologia , Valor Preditivo dos Testes , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , CálcioRESUMO
PURPOSE: Pediatric total thyroidectomy is an uncommon procedure. Higher rates of complication are reported for pediatric patients compared to adults which may be secondary to lower case volume. In this study, we examine the effect of a two-surgeon operative approach on outcomes in pediatric total thyroidectomy. METHODS: A retrospective review of 152 pediatric patients undergoing total thyroidectomy at a single institution was performed. A control group of 89 patients, with one attending surgeon present, was compared to a cohort of 63 pediatric patients who underwent total thyroidectomy with two attendings present. Primary outcomes included rates of permanent hypoparathyroidism and recurrent laryngeal nerve (RLN) injury. The secondary outcomes included postoperative hematoma, length of stay (LOS), LOS greater than 1 day (>1d) secondary to hypocalcemia, and readmissions secondary to hypocalcemia. RESULTS: One RLN injury was documented in each cohort and no postoperative hematomas were documented. Rates of permanent hypoparathyroidism decreased in the two-surgeon cohort (11.48%) when compared to the control group (15.73%) but was not significant. There was a statistically significant decrease in LOS >1d secondary to hypocalcemia in the two-surgeon cohort. LOS >1d attributable to hypocalcemia was seen in 38.2% in the control group versus 15.87% in the 2-surgeon cohort (p = 0.003). CONCLUSIONS: Implementation of a two-surgeon operative approach was shown to lead to a significant decrease in length of stay >1d attributable to hypocalcemia. However, this change was in the setting of multidisciplinary thyroid team and postoperative protocol implementation, and concentration of surgeons performing the operation. Further studies are needed to investigate the effects of the two-surgeon operative approach further.
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Hipocalcemia , Hipoparatireoidismo , Traumatismos do Nervo Laríngeo Recorrente , Cirurgiões , Adulto , Humanos , Criança , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Estudos Retrospectivos , Traumatismos do Nervo Laríngeo Recorrente/etiologiaRESUMO
CONTEXT: Transgender and gender diverse (TGD) individuals often seek gender-affirming hormone therapy (GAHT). While receipt of GAHT has been associated with improved well-being, the risk of GAHT discontinuation and its reasons are not well known. OBJECTIVE: There were two main objectives: (1) To investigate the proportion of TGD individuals who discontinue therapy after an average of 4 years (maximum 19 years) since GAHT initiation; and (2) to explore reasons for GAHT discontinuation. This was a retrospective cohort study at academic centers providing care to TGD adolescents and adults. TGD individuals prescribed estradiol or testosterone between January 1, 2000, and January 1, 2019, were included. GAHT continuation was ascertained using a 2-phase process. In phase 1, Kaplan-Meier survival analyses were used to examine likelihood of GAHT discontinuation and compare discontinuation rates by age and sex assigned at birth. In phase 2, reasons for stopping GAHT were investigated by reviewing records and by contacting study participants who discontinued therapy. The main outcome measures were incidence and determinants of GAHT discontinuation. RESULTS: Among 385 eligible participants, 231 (60%) were assigned male at birth and 154 (40%) were assigned female at birth. Less than one-third of participants (n = 121) initiated GAHT prior to their 18th birthday, constituting the pediatric cohort (mean age 15 years), and the remaining 264 were included in the adult cohort (mean age 32 years). In phase 1, 6 participants (1.6%) discontinued GAHT during follow-up, and of those only 2 discontinued GAHT permanently (phase 2). CONCLUSION: GAHT discontinuation is uncommon when therapy follows Endocrine Society guidelines. Future research should include prospective studies with long-term follow-up of individuals receiving GAHT.
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Pessoas Transgênero , Recém-Nascido , Adulto , Adolescente , Feminino , Masculino , Humanos , Criança , Estudos Prospectivos , Estudos Retrospectivos , Cognição , EstradiolRESUMO
The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to â¼5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.
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Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Criança , Antineoplásicos/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológicoRESUMO
Summary: Insulinomas are a rare cause of persistent hypoglycemia in a previously healthy child. In addition to symptoms of hypoglycemia, individuals with insulinomas usually present with a history of incessant caloric intake and weight gain due to a constant need to counter hypoglycemia. In addition to an extensive review of the literature, we report the first case of an insulinoma coexisting with reduced appetite secondary to anorexia nervosa in an adolescent female. Learning points: Eliciting a detailed family history is important in hypoglycemia cases. Obtaining a thorough dietary intake, weight history, and menstrual cycles (in females) and considering a psychiatric consultation for an eating disorder when indicated. Although rare in the pediatric population, multiple endocrine neoplasia type 1 syndrome should be considered in the evaluation of children and adolescents with hypoglycemia who also have a family history of pituitary, pancreatic, and/or parathyroid endocrinopathies.
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Introduction: To illustrate how quality improvement can produce unexpected positive outcomes. Methods: We compared a retrospective review of perioperative management and outcomes of baseline 122 pediatric total thyroidectomies to 121 subsequent total thyroidectomies managed by an Electronic Medical Record protocol in a large, free-standing children's healthcare system. Process measures included serum calcium measurement 6-12 hours postoperatively; parathyroid hormone measurement 6 hours postoperatively; preoperative iodine for Graves disease, and postoperative prophylactic calcium carbonate administration. In addition, we completed 4 Plan-Do-Study-Act (PDSA) cycles, focusing on implementation, refinement, usage, education, and postoperative calcitriol administration. The primary outcome included transient hypocalcemia during admission. Results: All perioperative process measures improved over PDSA cycles. Measurement of postoperative serum calcium increased from 42% at baseline to 100%. Measurement of postoperative PTH increased from 11% to 97%. Preoperative iodine administration for Graves disease surgeries improved from 72% to 94%. Postoperative calcium carbonate administration increased from 36% to 100%. There was a trend toward lower rates of severe hypocalcemia during admission over the subsequent PDSA cycles starting at 11.6% and improving to 3.4%. With the regular review of outcomes, surgical volume consolidated among high-volume providers, associated with a decrease in a permanent hypoparathyroid rate of 20.5% at baseline to 10% by the end of monitoring. Conclusions: In standardizing care at 1 large pediatric institution, implementing a focused quality improvement project involving the perioperative management of transient hypocalcemia in total thyroidectomy pediatric patients resulted in additional, unanticipated improvements in patient care.
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Growth hormone deficiency (GHD) is common in childhood cancer survivors (CCS). Major risk factors for GHD include radiation therapy, both cranial and total body irradiation, and tumor location. Some newer anti-cancer therapies may impact growth and the GH-IGF-1 axis as well. While untreated childhood-onset GHD adversely impacts adult height in CCS, longstanding GHD can cause or exacerbate multiple metabolic and skeletal health problems. This chapter discusses considerations in the diagnosis and treatment of GHD in CCS and discusses long-term outcomes in survivors of childhood cancer who have GHD.
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Sobreviventes de Câncer , Hormônio do Crescimento Humano , Neoplasias , Adulto , Criança , Hormônio do Crescimento , Terapia de Reposição Hormonal , Humanos , Fator de Crescimento Insulin-Like IRESUMO
BACKGROUND: Various measures and definitions for undernutrition are used in pediatrics. Younger children treated for cancer are at high risk, but lack well-defined risk-based screening and intervention. METHODS: A retrospective study collected weight longitudinally for patients less than three years-old over two years after initiating cancer treatment. We included those diagnosed 2007-2015 at a large pediatric cancer center. Exclusion criteria included treatment starting outside our system, secondary or relapsed malignancy, or incomplete information. A decrease ≥1 in weight-for-age or weight-for-height z-score signified clinically significant weight loss. Univariate and multivariate models assessed hazards for developing first episode of clinically significant weight loss. RESULTS: Of 372 patients, only 24.6% of patients lost 10% of weight, but 58.6% lost weight-for-age z-score ≥1 and 64.8% lost ≥1 weight-for-height z-score within two years of treatment initiation. Patients who lost weight were younger (median age 15 vs. 24 months, p < 0.001). Compared to patients diagnosed in the first year of life, those diagnosed 24-35 months were less likely to lose weight (HR 0.62, p < 0.001) and lost weight later (median time to weight loss 144 vs. 35 days). Higher treatment intensity increased weight loss risk (HR 2.30, p < 0.001) and decreased time to weight loss (35 vs. 154 days). No differences were found based on sex, diagnosis, enteral or parenteral nutrition, gastroenterology consults, or intensive care admissions. CONCLUSIONS: Using normalized z-scores is more sensitive for identifying weight loss. Younger children are more likely to lose weight with higher intensity cancer therapy. Patient and treatment specific information should be used in risk stratifying weight loss screening and nutritional interventions.
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Desnutrição , Recidiva Local de Neoplasia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Desnutrição/diagnóstico , Desnutrição/terapia , Nutrição Parenteral , Estudos Retrospectivos , Redução de PesoRESUMO
BACKGROUND: Central adrenal insufficiency is observed after cranial radiation therapy for cancer. Screening at risk patients is recommended, but the best screening strategy is unknown. METHODS: A retrospective review of pediatric cancer survivors who underwent hypothalamic/pituitary/adrenal axis testing was conducted. Data included: cancer diagnosis, radiotherapy dose, other endocrinopathies, and adrenal function testing. Adrenal testing included sequential low-dose corticotropin test (LDCT) and standard-dose corticotropin test (SDCT). 8 a.m. serum cortisol levels were compared to LDCT results. LDCT results were compared by radiotheroapy dose and according to the presence of endocrine comorbidities. RESULTS: Seventy-eight subjects (56% male, mean age at diagnosis 6.5 years) underwent testing. 67.9% had been treated with radiotherapy to the hypothalamus/pituitary. Mean time to diagnosis of adrenal insufficiency was 6.8 years after cancer diagnosis. Adequate adrenal function was found in 65% of patients by LDCT and 89% by SDCT. Only 21% of patients had basal serum cortisols collected at 8 a.m. Agreement between 8 a.m. baseline cortisol and LDCT was fair. Agreement between random baseline cortisol and LDCT was poor. Prevalence of central adrenal insufficiency diagnosed by LDCT increased with radiotherapy dose (8% for 10-19.9 Gy; 83% for >or=40 Gy) and the number of endocrine comorbidities. CONCLUSIONS: In pediatric cancer survivors, central adrenal insufficiency was common even in patients receiving <40 Gy to the hypothalamus/pituitary. We recommend use of LDCT, not 8 a.m. serum cortisol to screen patients who received >30 Gy of radiotherapy and those with other central endocrinopathies.
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Testes de Função do Córtex Suprarrenal/estatística & dados numéricos , Insuficiência Adrenal/diagnóstico , Irradiação Craniana/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos da radiação , Neoplasias/radioterapia , Testes de Função Adreno-Hipofisária/estatística & dados numéricos , Lesões por Radiação/complicações , Sobreviventes , Adolescente , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Hormônio Adrenocorticotrópico/administração & dosagem , Adulto , Criança , Relação Dose-Resposta a Droga , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Doenças Hipotalâmicas/complicações , Sistema Hipotálamo-Hipofisário/fisiopatologia , Doenças da Hipófise/complicações , Sistema Hipófise-Suprarrenal/fisiopatologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Risco , Sobreviventes/estatística & dados numéricos , Adulto JovemRESUMO
Endocrine complications are highly prevalent in childhood cancer survivors. Approximately 50% of survivors will experience at least one hormonal disorder over the course of their lives. Endocrine complications often are observed in survivors previously treated with radiation to the head, neck, or pelvis. We provide an overview the most common endocrine late effects seen in survivors, including hypothalamic-pituitary dysfunction, primary thyroid dysfunction, obesity, diabetes mellitus, metabolic syndrome, and decreased bone mineral density. Primary gonadal injury is discussed elsewhere in this series. Given a variable latency interval, a systematic approach where individuals are periodically screened on the basis of their risk factors can help to improve health outcomes by prompt diagnosis and treatment of evolving endocrinopathies. These recommendations must be revised in the future given changes and improvements in cancer treatment over time.
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Sobreviventes de Câncer/estatística & dados numéricos , Doenças do Sistema Endócrino/epidemiologia , Criança , Doenças do Sistema Endócrino/diagnóstico , Humanos , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/terapiaRESUMO
STUDY OBJECTIVE: To obtain anti-Müllerian hormone (AMH) levels in female childhood cancer survivors and determine the association of therapeutic exposures with diminished ovarian reserve (DOR). DESIGN: Cross-sectional study. SETTING: Academic medical center. PARTICIPANTS: Forty-nine survivors (mean age = 14.9 years, SD = 3.3 years; mean time without therapy = 7.5 years, SD = 3.6 years) who received alkylator/heavy metal chemotherapy, and/or radiation exposure to the ovaries with 2 or more years without therapy were recruited. INTERVENTIONS: None. MAIN OUTCOME MEASURES: AMH, follicle stimulating hormone (FSH) levels (random), and therapeutic characteristics such as cyclophosphamide equivalent dose (CED), heavy metal exposure, and bilateral ovarian radiation exposure were determined for each subject. DOR was defined as a low AMH (less than the fifth percentile for age-matched controls), and premature ovarian insufficiency as an FSH greater than 40 IU/L with AMH less than the fifth percentile. RESULTS: Fourteen subjects (28.6%) had DOR, and 5 (10.2%) had premature ovarian insufficiency. Those with a low AMH were more likely exposed to a higher CED (P = .001) and/or bilateral ovarian radiation exposure (P = .048). In the multivariate model of DOR adjusted for age at diagnosis, DOR was associated with bilateral radiation (odds ratio = 39.9; 95% confidence interval 2.1-759.7; P = .04). There was a nonsignificant trend with increasing odds of low AMH with increased CED. CONCLUSION: DOR, defined by an AMH less than the fifth percentile, was observed in more than one-quarter of pediatric cancer survivors exposed to gonadotoxic cancer therapy and was significantly associated with bilateral ovarian irradiation. Identifying risk factors for low AMH prompts AMH and FSH surveillance in the early years after cancer therapy and, if needed, early referral to a reproductive specialist.
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Hormônio Antimülleriano/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/terapia , Insuficiência Ovariana Primária/sangue , Lesões por Radiação/sangue , Adolescente , Antineoplásicos Alquilantes/efeitos adversos , Estudos Transversais , Ciclofosfamida/efeitos adversos , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Metais Pesados/efeitos adversos , Ovário/efeitos dos fármacos , Ovário/efeitos da radiação , Insuficiência Ovariana Primária/etiologia , Lesões por Radiação/etiologia , SobreviventesRESUMO
CONTEXT: GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed. EVIDENCE ACQUISITION: A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. EVIDENCE SYNTHESIS: In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms. CONCLUSIONS: In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms.
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Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/epidemiologia , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias/epidemiologia , Neoplasias/etiologia , Criança , Predisposição Genética para Doença/epidemiologia , Transtornos do Crescimento/genética , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Neoplasias/genética , Fatores de Risco , Sobreviventes/estatística & dados numéricos , SíndromeRESUMO
BACKGROUND: Anti-Mullerian Hormone (AMH), a proposed indicator of ovarian follicle reserve in adults, has not been characterized in pediatric and adolescent females by race and/or ethnicity. OBJECTIVES: To describe AMH levels in healthy American girls and determine the influence of age and race/ethnicity on AMH. SUBJECTS: SUBJECTS aged 10-21 years were recruited from primary care settings and emergency departments. Race/ethnicity was characterized as White, Black or Hispanic. METHODS: Serum for AMH levels (ng/mL) was measured using an enzyme-linked immunosorbent assay. RESULTS: Thirty-one White, 60 Black and 24 Hispanic subjects were recruited. Mean AMH levels were 3.19 ng/mL (22.8 pmol/L) (SD 2.12) for Whites, 3.25 ng/mL (23.2 pmol/L) (SD 2.23) for Blacks and 2.97 ng/mL (21.2 pmol/L) (SD 1.75) for Hispanics. ANCOVA showed no difference in AMH levels among race/ethnicities, controlling for age (p=0.91). Age was significantly associated with AMH (p<0.001, R²=0.12). CONCLUSION: AMH levels do not vary by race/ethnicity, and AMH levels increase with age.
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Hormônio Antimülleriano/sangue , Etnicidade/estatística & dados numéricos , Reserva Ovariana/fisiologia , Grupos Raciais/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Humanos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
CONTEXT: Cranial radiation therapy (CRT) predisposes to GH deficiency and subsequent neoplasms (SNs) of the central nervous system (CNS). Increased rates of SNs have been reported in GH-treated survivors. OBJECTIVE: The objective of the study was to evaluate the association between GH treatment and the development of CNS-SNs. DESIGN: The study was designed with a retrospective cohort with longitudinal follow-up. SETTING: The setting of the study was multiinstitutional. PARTICIPANTS: A total of 12 098 5-year pediatric cancer survivors from the Childhood Cancer Survivor Study, diagnosed with cancer prior to age 21 years, of whom 338 self-reported GH treatment, which was verified through medical record review. INTERVENTIONS: INTERVENTIONS included subject surveys, medical records abstraction, and pathological review. OUTCOME MEASURES: Incidence of meningioma, glioma, and other CNS-SNs was measured. RESULTS: Among GH-treated survivors, 16 (4.7%) developed CNS-SN, including 10 with meningioma and six with glioma. Two hundred three survivors without GH treatment (1.7%) developed CNS-SN, including 138 with meningioma, 49 with glioma, and 16 with other CNS-SNs. The adjusted rate ratio in GH-treated compared with untreated survivors for development of any CNS-SN was 1.0 [95% confidence interval (CI) 0.6-1.8, P = .94], for meningiomas, 0.8 (95% CI 0.4-1.7, P = .61), and for gliomas, 1.9 (95% CI 0.7-4.8, P = .21). Factors associated with meningioma development included female gender (P = .001), younger age at primary cancer diagnosis (P < .001), and CRT/longer time since CRT (P < .001). Glioma was associated with CRT/shorter time since CRT (P < .001). CONCLUSIONS: There was no statistically significant increased overall risk of the occurrence of a CNS-SN associated with GH exposure. Specifically, occurrence of meningiomas and gliomas were not associated with GH treatment.
Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Hormônio do Crescimento Humano/efeitos adversos , Segunda Neoplasia Primária/epidemiologia , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Idade de Início , Neoplasias do Sistema Nervoso Central/etiologia , Criança , Pré-Escolar , Irradiação Craniana/efeitos adversos , Irradiação Craniana/estatística & dados numéricos , Feminino , Glioma/epidemiologia , Glioma/etiologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/epidemiologia , Lactente , Recém-Nascido , Masculino , Meningioma/epidemiologia , Meningioma/etiologia , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
CONTEXT: Many pediatric cancer survivors have endocrine conditions. Surveillance for late effects is recommended by national guidelines. Endocrine surveillance is recommended after alkylating agents, steroids, methotrexate, and radiation. OBJECTIVE: The objective of the study was to describe the endocrine outcomes in patients followed up in a program that uses national screening guidelines. DESIGN: The design of the study was a medical records review. SETTING: The study was conducted in the Comprehensive Cancer Survivor Program, an academic pediatric oncology program. PARTICIPANTS: The study included 519 pediatric and young adult survivors of noncentral nervous system childhood malignancies between January 1, 2001, and December 15, 2005. INTERVENTION: Patients were evaluated with history, physical examinations, and evaluations recommended in the Children's Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. OUTCOME MEASURES: The frequency and types of endocrine conditions were measured. RESULTS: Four hundred eighty endocrine conditions were observed in 299 survivors (57.6% of survivors). The most common types of endocrine conditions were problems with weight and gonadal function. In a Cox regression model, stem cell transplant, radiation, and older age at cancer diagnosis were associated with higher hazard of an endocrine condition. Radiation, stem cell transplant, and sarcoma diagnosis were associated with growth problems. CONCLUSIONS: Endocrine disorders were common after pediatric cancers. Endocrinologists should be aware of national guidelines, anticipate referral of pediatric cancer survivors, and participate in further research to optimize screening for and treatment of endocrine effects of cancer therapy.