Late endocrine effects of childhood cancer

Nature Reviews Endocrinology

Volumn 12, Issue 6, 2016, Pages 319-336

  Rose, Susan R ^a   Horne, Vincent E ^a   Howell, Jonathan ^a   Lawson, Sarah A ^a   Rutter, Meilan M ^a   Trotman, Gylynthia E ^a   Corathers, Sarah D ^a  

^a UNIVERSITY OF CINCINNATI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLATING AGENT; ANTIMETABOLITE; CORTICOSTEROID; ANTINEOPLASTIC AGENT; CORTICOTROPIN;

ACUTE MYELOBLASTIC LEUKEMIA; BONE DENSITY; BONE TUMOR; BRAIN RADIATION; BRAIN TUMOR; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER HORMONE THERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER SCREENING; CANCER SURVIVOR; CHILD; CHILDHOOD CANCER; CORTICOTROPIN DEFICIENCY; CYTOTOXICITY; DIABETES INSIPIDUS; DIABETES MELLITUS; FEMALE FERTILITY; FERTILITY PRESERVATION; GONADOTROPIN DEFICIENCY; GROWTH HORMONE DEFICIENCY; HODGKIN DISEASE; HORMONE DEFICIENCY; HUMAN; HYPERPROLACTINEMIA; HYPOGONADISM; HYPOTHYROIDISM; METABOLIC SYNDROME X; NEUROBLASTOMA; OBESITY; OSTEOPOROSIS; OVARY INSUFFICIENCY; PRECOCIOUS PUBERTY; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; RHABDOMYOSARCOMA; SEXUAL DYSFUNCTION; SEXUAL FUNCTION; SKULL IRRADIATION; ADULT; ADVERSE EFFECTS; BONE DISEASES, METABOLIC; DEFICIENCY; ENDOCRINE SYSTEM DISEASES; FEMALE; GROWTH DISORDERS; INFERTILITY; MALE; NEOPLASMS; PUBERTY, DELAYED; PUBERTY, PRECOCIOUS; RADIOTHERAPY; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SURVIVOR;

ADRENOCORTICOTROPIC HORMONE; ADULT; ANTINEOPLASTIC AGENTS; BONE DISEASES, METABOLIC; CHILD; CRANIAL IRRADIATION; DIABETES INSIPIDUS; ENDOCRINE SYSTEM DISEASES; FEMALE; GROWTH DISORDERS; HUMANS; HYPERPROLACTINEMIA; HYPOGONADISM; HYPOTHYROIDISM; INFERTILITY; MALE; METABOLIC SYNDROME X; NEOPLASMS; OBESITY; PUBERTY, DELAYED; PUBERTY, PRECOCIOUS; RADIOTHERAPY; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SURVIVORS;

EID: 84962074499     PISSN: 17595029     EISSN: 17595037     Source Type: Journal    
DOI: 10.1038/nrendo.2016.45     Document Type: Review

References (238)

1. CureSearch Children's Oncology Group. Childhood cancer survivor statistics. CureSearch [online], www. curesearch.org/childhood-cancer-statistics (2015).
2. Robison L. L, & Hudson M. M. Survivors of childhood and adolescent cancer: life-long risks and responsibilities. Nat. Rev. Cancer. 14, 61-70 (2014).
3. Hudson M. M, et al. Clinical ascertainment of health outcomes among adults treated for childhood cancer. J. Am. Med. Assoc. 309, 2371-2381 (2013).
4. Bhatia S. Cancer survivorship - pediatric issues. Hematology Am. Soc. Hematol. Educ. Program 507-515 (2005).
5. Landier W, & Bhatia S. Cancer survivorship: a pediatric perspective. Oncologist. 13, 1181-1192 (2008).
6. Nandagopal R, et al. Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. Horm. Res. 69, 65-74 (2008).
7. Leung W, et al. A prospective cohort study of late sequelae of pediatric allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore). 86, 215-224 (2007).
8. Rutter M. M, & Rose S. R. Long-Term endocrine sequelae of childhood cancer. Curr. Opin. Pediatr. 19, 480-487 (2007).
9. Chemaitilly W, & Sklar C. A. Endocrine complications in long-Term survivors of childhood cancers. Endocr. Relat. Cancer. 17, R141-R159 (2010).
10. Patterson B. C, et al. Endocrine health problems detected in 519 patients evaluated in a pediatric cancer survivor program. J. Clin. Endocrinol. Metab. 97, 810-818 (2012).
11. Dickerman J. D. The late effects of childhood cancer therapy. Pediatrics. 119, 554-568 (2007).
12. Savage L. J, & Murray R. D. Late effects of cancer therapy on growth and GH. Int. Growth Monitor. 16, 2-7 (2006).
13. Schwartz C. L, Hobbie W. L, Constine L. S, & Ruccione K. S. (eds) in Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach 3rd edn 1-13; 151-166; 253-281; 339-351; 369-384 (Springer-Verlag, 2015).
14. Couto-Silva A. C, Brauner R, & Adan L. F. Endocrine sequelae after radiotherapy in childhood and adolescence. Arq. Bras. Endocrinol. Metabol. 49, 825-832 (2005).
15. Van Dorp W. Long-Term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review. Hum. Reprod. Update. 18, 12-28 (2012).
16. Francis G. L, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 25, 716-759 (2015).
17. Landier W, et al. Long-Term follow up guidelines for survivors of childhood, adolescent, and young adult cancers. Children's Oncology Group [online], www. survivorshipguidelines.org (2015).
18. Tulandi T. G, & Gosden R. G. (eds) Preservation of Fertility (Taylor &Francis, 2004).
19. Wallace W. H, Anderson R. A, & Irvine D. S. Fertility Preservation for Young Patients with Cancer: Who Is at Risk and What Can Be Offered? Lancet Oncol. 6, 209-218 (2005).
20. Servitzoglou M, et al. Dose-effect relationship of alkylating agents on testicular function in male survivors of childhood lymphoma. Pediatr. Hematol. Oncol. 32, 613-623 (2015).
21. Kobayashi H, et al. Testicular morphological changes in children with acute lymphoblastic leukemia following chemotherapy. Acta Paediatr. Jpn. 38, 640-643 (1996).
22. Molina J. R, Barton D. L, & Loprinzi C. L. Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf. 28, 401-416 (2005).
23. Committee on Adolescent Health Care. Primary ovarian insufficiency in adolescents and young women. Obstet. Gynecol. 124, 193-197 (2014).
24. Levine J. in Oncofertility Medical Practice: Clinical Issues and Implementation (eds Gracia C, & Woodruff T. K.) 3-14 (Springer, 2012).
25. Lee S. J, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. 24, 2917-2931 (2006).
26. Haddy T. B, Mosher R. B, Nunez S. B, & Reaman G. H. Growth hormone deficiency after chemotherapy for acute lymphoblastic leukemia in children who have not received cranial radiation. Pediatr. Blood Cancer. 46, 258-261 (2006).
27. Hogler W, et al. Incidence of skeletal complications during treatment of childhood acute lymphoblastic leukemia: comparison of fracture risk with general practice research database. Pediatr. Blood Cancer. 48, 21-27 (2007).
28. Thomas I. H, et al. Bone mineral density in young adult survivors of acute lymphoblastic leukemia. Cancer. 113, 3248-3256 (2008).
29. Muszynska-Roslan K, et al. Little evidence of low bone mass in acute lymphoblastic leukemia survivors. J. Clin. Densitom. 15, 108-115 (2012).
30. Alikasifoglu A, et al. Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: comparison of megadose methylprednisolone and conventional-dose prednisolone treatments. Am. J. Hematol. 80, 113-118 (2005).
31. Hochberg J, El Mallawany N. K, & Cairo M. S. Humoral and cellular immunotherapy in ALL in children, adolescents, and young adults. Clin. Lymphoma Myeloma Leuk. 14, S6-S13 (2014).
32. Torino F, et al. Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses. Eur. J. Endocrinol. 169, R153-R164 (2013).
33. Ishida Y, et al. Late effects and quality of life of childhood cancer survivors: part 2. Impact of radiotherapy. Int. J. Hematol. 92, 95-104 (2010).
34. Chow E. J, et al. Differential effects of radiotherapy on growth and endocrine function among acute leukemia survivors: a childhood cancer survivor study report. Pediatr. Blood Cancer. 60, 110-115 (2013).
35. Rizzo J. D, et al. Recommended screening and preventive practices for long-Term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation. Biol. Blood Marrow Transplant. 12, 138-151 (2006).
36. Felicetti F, et al. Endocrine late effects after total body irradiation in patients who received hematopoietic cell transplantation during childhood: a retrospective study from a single institution. J. Cancer Res. Clin. Oncol. 137, 1343-1348 (2011).
37. van Dijk I. W, et al. Dose-effect relationships for adverse events after cranial radiation therapy in long-Term childhood cancer survivors. Int. J. Radiat. Oncol. Biol. Phys. 85, 768-775 (2013).
38. Wessel T, et al. Age at menarche in childhood cancer survivors: results of a nationwide survey in Germany. Horm. Res. Paediatr. 77, 108-114 (2012).
39. Shalitin S, et al. Endocrine outcome in long-Term survivors of childhood brain tumors. Horm. Res. Paediatr. 76, 113-122 (2011).
40. Rose S. R, Danish R. K, Kearney N. S, Schreiber R. E, & Hudson M. M. ACTH deficiency in childhood cancer survivors. Pediatr. Blood Cancer. 45, 808-813 (2005).
41. Patterson B. C, et al. Adrenal function testing in pediatric cancer survivors. Pediatr. Blood Cancer. 53, 1302-1307 (2009).
42. Haller M. J, & Schatz D. A. Endocrine complications of childhood cancer therapy: evaluation and management. Pediatr. Endocrinol. Rev. 4, 196-204 (2007).
43. Byrne J, et al. Fertility in women treated with cranial radiotherapy for childhood acute lymphoblastic leukemia. Pediatr. Blood Cancer. 42, 589-597 (2004).
44. Rose S. R, Lawson S, Burns K, & Merchant T. E. in Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach 3rd edn (eds Schwartz C. L, et al.) 65-94 (Springer-Verlag, 2015).
45. Vinchon M, et al. Craniopharyngioma and hypothalamic obesity in children. Childs Nerv. Syst. 25, 347-352 (2009).
46. Lustig R. H, et al. Risk factors for the development of obesity in children surviving brain tumors. J. Clin. Endocrinol. Metab. 88, 611-616 (2003).
47. Rose S. R. Clinical utility of time of day normal ranges for TSH. J. Pediatr. 157, 662-667 (2010).
48. Patterson B. C, et al. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J. Clin. Endocrinol. Metab. 99, 2030-2037 (2014).
49. Chow E. J, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr. Blood Cancer. 53, 432-437 (2009).
50. Sklar C, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab. 85, 3227-3232 (2000).
51. Bhatti P, et al. Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat. Res. 174, 741-752 (2010).
52. Cooper D. S, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 19, 1167-1214 (2009).
53. McMullen T, et al. Hyperparathyroidism after irradiation for childhood malignancy. Int. J. Radiat. Oncol. Biol. Phys. 73, 1164-1168 (2009).
54. Wilson S. D, et al. Primary hyperparathyroidism with a history of head and neck irradiation: the consequences of associated thyroid tumors. Surgery. 150, 869-877 (2011).
55. Taylor A. J, et al. Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study. Int. J. Cancer. 125, 2400-2405 (2009).
56. Chen S. H, et al. Surgical correction of postradiation spinal deformity. Chang Gung Med. J. 26, 160-169 (2003).
57. Hovi L, et al. Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation. Bone Marrow Transplant. 24, 1131-1136 (1999).
58. Xu W, Janss A, & Moshang T. Adult height and adult sitting height in childhood medulloblastoma survivors. J. Clin. Endocrinol. Metab. 88, 4677-4681 (2003).
59. Stava C. J, Jimenez C, & Vassilopoulou-Sellin R. Endocrine sequelae of cancer and cancer treatments. J. Cancer Surviv. 1, 261-274 (2007).
60. Byrne J, et al. Fertility of long-Term male survivors of acute lymphoblastic leukemia diagnosed during childhood. Pediatr. Blood Cancer. 42, 364-372 (2004).
61. Klose M, et al. From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum - A KIMS analysis. Eur. J. Endocrinol. 161, S75-S83 (2009).
62. Green D. M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the childhood cancer survivor study. J. Clin. Oncol. 27, 2374-2381 (2009).
63. Vantyghem M. C, et al. Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation. Orphanet J. Rare Dis. 9, 162 (2014).
64. Perkins J. L, et al. Long-Term follow up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr. Blood Cancer. 49, 958-963 (2007).
65. Lucchini G, & Bader P. Hematopoietic stem cell transplantation and immunotherapy for pediatric acute myeloid leukemia: an open challenge. Expert Rev. Hematol. 7, 291-300 (2014).
66. Blijdorp K, et al. Endocrine sequelae and metabolic syndrome in adult long-Term survivors of childhood acute myeloid leukemia. Leuk. Res. 37, 367-371 (2013).
67. Leung W, et al. A prospective cohort study of late sequelae of pediatric allogenic hematopoietic stem cell transplantation. Medicine. 86, 215-224 (2007).
68. Mulder R. L, et al. Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat. Rev. 35, 616-632 (2009).
69. Vinchon M, Baroncini M, Leblond P, & Delestret I. Morbidity and tumor-related mortality among adult survivors of pediatric brain tumors: a review. Childs Nerv. Syst. 27, 697-704 (2011).
70. Hamre H, et al. Gonadal function and parenthood 20 years after treatment for childhood lymphoma: a cross-sectional study. Pediatr. Blood Cancer. 59, 271-277 (2012).
71. van Dorp W, et al. Long-Term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review. Hum. Reprod. Update. 18, 12-28 (2012).
72. Green D. M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J. Clin. Oncol. 27, 2374-2381 (2009).
73. Wikström A. M, Hovi L, Dunkel L, & Saarinen- Pihkala U. M. Restoration of ovarian function after chemotherapy for osteosarcoma. Arch. Dis. Child. 88, 428-431 (2003).
74. Gaspar N, et al. Ewing sarcoma: current management and future approaches through collaboration. J. Clin. Oncol. 33, 3036-3046 (2015).
75. Kubota M, et al. Long-Term follow up status of patients with neuroblastoma after undergoing either aggressive surgery or chemotherapy - A single institutional study. J. Pediatr. Surg. 39, 1328-1332 (2004).
76. Martin A, et al. Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma. Pediatr. Blood Cancer. 61, 1350-1356 (2014).
77. Clement S. C, et al. Long-Term follow up of the thyroid gland after treatment with 131I Metaiodobenzylguanidine in children with neuroblastoma: importance of continuous surveillance. Pediatr. Blood Cancer. 60, 1833-1838 (2013).
78. Punyko J. A, et al. Long-Term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study. Pediatr. Blood Cancer. 44, 643-653 (2005).
79. Lam K. S, et al. Effects of cranial irradiation on hypothalamic-pituitary function - A 5 year longitudinal study in patients with nasopharyngeal carcinoma. Q. J. Med. 78, 165-176 (1991).
80. Liamis G, Milionis H. J, & Elisaf M. Endocrine disorders: causes of hyponatremia not to neglect. Ann. Med. 43, 179-187 (2011).
81. Diederich S, Franzen N. F, Bähr V, & Oelkers W. Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases. Eur. J. Endocrinol. 148, 609-617 (2003).
82. Sklar C. A, & Constine L. S. Chronic neuro-endocrinological sequelae of radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 31, 1113-1120 (1995).
83. Laughton S. J, et al. 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. J. Clin. Oncol. 26, 1112-1118 (2008).
84. Brennan B. M, et al. Growth hormone status in adults treated for acute lymphoblastic leukemia in childhood. Clin. Endocrinol. (Oxf.). 48, 777-783 (1998).
85. Robinson I. C, Fairhall K. M, Hendry J. H, & Shalet S. M. Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat. J. Endocrinol. 169, 519-526 (2001).
86. Darzy K. H. Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat. Clin. Pract. Endocrinol. Metab. 5, 88-99 (2009).
87. Blatt J, et al. Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia. J. Pediatr. 104, 182-186 (1984).
88. Merchant T. E, et al. Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J. Clin. Oncol. 29, 4776-4780 (2011).
89. Gilchrist F. J, Murray R. D, & Shalet S. M. The effect of long-Term untreated growth hormone deficiency (GHD) and 9 years of GH replacement on the quality of life (QoL) of GH deficient adults. Clin. Endocrinol. (Oxf.). 57, 363-370 (2002).
90. Sklar C. A. Growth and neuroendocrine dysfunction following therapy for childhood cancer. Pediatr. Clin. North Am. 44, 489-503 (1997).
91. Leung W, et al. Late effects of treatment in survivors of childhood acute myeloid leukemia. J. Clin. Oncol. 18, 3273-3279 (2000).
92. Leung W, et al. Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. J. Clin. Oncol. 20, 2959-2964 (2002).
93. Shalet S. M. Growth hormone deficiency after treatment of acute leukemia in children. Arch. Dis. Child. 51, 489-493 (1976).
94. Shalet S. M. Radiation and pituitary dysfunction. N. Engl. J. Med. 328, 131-133 (1993).
95. Schmiegelow M, et al. Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors. Horm. Res. 54, 53-59 (2000).
96. Darzy K. H, Pezzoli S. S, Thorner M. O, & Shalet S. M. The dynamics of growth hormone (GH) secretion in adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors: evidence for preserved pulsatility and diurnal variation with increased secretory disorderliness. J. Clin. Endocrinol. Metab. 90, 2794-2803 (2005).
97. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J. Clin. Endocrinol. Metab. 85, 3990-3993 (2000).
98. Wilson T. A, et al. Update of guidelines for the use of growth hormone in children: The Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J. Pediatr. 143, 415-421 (2003).
99. Rose S. R, et al. The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency. N. Engl. J. Med. 319, 201-207 (1988).
100. Sklar C, Sarafoglou K, & Whittam E. Efficacy of insulin-like growth factor binding protein 3 in predicting the growth hormone response to provocative testing in children treated with cranial irradiation. Acta Endocrinol. (Copenh.). 129, 511-515 (1993).
101. Cummings D. E, & Merriam G. R. Growth hormone therapy in adults. Annu. Rev. Med. 54, 513-533 (2003).
102. Adan L, et al. GH deficiency caused by cranial irradiation during childhood: factors and markers in young adults. J. Clin. Endocrinol. Metab. 86, 5245-5251 (2001).
103. Molitch M. E, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1587-1609 (2011).
104. Cook D. M, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr. Pract. 15 (Suppl. 2), 1-29 (2009).
105. Darendeliler F, et al. Recurrence of brain tumours in patients treated with growth hormone: analysis of KIGS (Pfizer International Growth Database). Acta Paediatr. 95, 1284-1290 (2006).
106. Chung T. T, et al. Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement. Clin. Endocrinol. (Oxf.). 63, 274-279 (2005).
107. Ferry R. J. Jr, Cohen P, & Levitt Katz L. E. Pharmacodynamic considerations with recombinant human insulin-like growth factor I in children. Horm. Res. 63, 220-227 (2005).
108. Appelman-Dijkstra N. M, et al. Pituitary dysfunction in adult patients after cranial irradiation for head and nasopharyngeal tumours. Radiother. Oncol. 113, 102-107 (2014).
109. Hovi L, Saarinen-Pihkala U. M, Vettenranta K, Lipsanen M, & Tapanainen P. Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation. Bone Marrow Transplant. 24, 1131-1136 (1999).
110. Follin C, Thilén U, Ahrén B, & Erfurth E. M. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH deficient adult survivors of childhood-onset acute lymphoblastic leukemia. J. Clin. Endocrinol. Metab. 91, 1872-1875 (2006).
111. Maiter D, et al. Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database. Eur. J. Endocrinol. 155, 253-260 (2006).
112. Child C. J, et al. Incidence of primary cancers and intracranial tumour recurrences in GH treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study. Eur. J. Endocrinol. 172, 779-790 (2015).
113. van den Heijkant S, et al. Effects of growth hormone therapy on bone mass, metabolic balance, and well-being in young adult survivors of childhood acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol. 33, e231-e238 (2011).
114. Brod M, et al. Impact of adult growth hormone deficiency on daily functioning and well-being. BMC Res. Notes. 7, 813 (2014).
115. Rose S. R. Isolated central hypothyroidism in short stature. Pediatr. Res. 38, 967-973 (1995).
116. Baloch Z, et al. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 13, 3-126 (2003).
117. Rose S. R, et al. Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. J. Clin. Endocrinol. Metab. 84, 4472-4479 (1999).
118. Ferretti E, et al. Evaluation of the adequacy of levothyroxine replacement in patients with central hypothyroidism. J. Clin. Endocrinol. Metab. 84, 924-929 (1999).
119. Kazlauskaite R, et al. Corticotropin tests for hypothalamic-pituitary adrenal insufficiency: a metaanalysis. J. Clin. Endocrinol. Metab. 93, 4245-4253 (2008).
120. Rose S. R, et al. ACTH deficiency in childhood cancer survivors. Pediatr. Blood Cancer. 45, 808-813 (2005).
121. Bornstein S. R, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 101, 364-389 (2016).
122. Constine L. S, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N. Engl. J. Med. 328, 87-94 (1993).
123. Yanovski J. A, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N. Engl. J. Med. 348, 908-917 (2003).
124. Oberfield S. E, et al. Age at onset of puberty following high-dose central nervous system radiation therapy. Arch. Pediatr. Adolesc. Med. 150, 589-592 (1996).
125. Armstrong G. T, et al. Abnormal timing of menarche in survivors of central nervous system tumors: a report from the Childhood Cancer Survivor Study. Cancer. 115, 2562-2570 (2009).
126. Ogilvy-Stuart A. L, Clayton P. E, & Shalet S. M. Cranial irradiation and early puberty. J. Clin. Endocrinol. Metab. 78, 1282-1286 (1994).
127. Walvoord E. The timing of puberty: is it changing? Does it matter? J. Adolesc. Health. 47, 433-439 (2010).
128. Carel J. C, & Leger J. Precocious puberty. N. Engl. J. Med. 358, 2366-2377 (2008).
129. Berberoglu M. Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. J. Clin. Res. Pediatr. Endocrinol. 1, 164-174 (2009).
130. Carel J. C, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 123, e752-e762 (2009).
131. Cassorla F, et al. Effects of luteinizing hormone-releasing hormone analog-induced pubertal delay in growth hormone (GH)-deficient children treated with GH: preliminary results. J. Clin. Endocrinol. Metab. 82, 3989-3992 (1997).
132. Cafasso M, et al. Clinical efficacy of three month depot GnRH agonist in suppression of central puberty. J. Nurse Pract. 11, 686-694 (2015).
133. Hirsch H. J, et al. The histrelin implant: a novel treatment for central precocious puberty. Pediatrics 116, e798-e802 (2005).
134. Leader A, Lishner M, Michaeli J, & Revel A. Fertility considerations and preservation in haemato-oncology patients undergoing treatment. Br. J. Haematol. 15, 291-308 (2011).
135. [No authors listed.] Committee opinion no. 607. Gynecologic concerns in children and adolescents with cancer. Obstet. Gynecol. 124, 403-408 (2014).
136. Waimey K. E, et Al. Understanding Fertility in Young Female Cancer Patients J. Womens Health. 24, 812-818 (2015).
137. Knobf M. T. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors. Oncologist. 11, 96-110 (2006).
138. Nieman C. L, et al. Cancer survivors and infertility: a review of a new problem and novel answers. J. Support. Oncol. 4, 171-178 (2006).
139. Green D. M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J. Clin. Oncol. 27, 2374-2381 (2009).
140. Sadri-Ardekani H, & Atala A. Testicular tissue cryopreservation and spermatogonial stem cell transplantation to restore fertility: from bench to bedside. Stem Cell Res. Ther. 5, 68 (2014).
141. Rowley M. J, Leach D. R, Warner G. A, & Heller C. G. Effect of graded doses of ionizing radiation on the human testis. Radiat. Res. 59, 665-678 (1974).
142. Izard M. A. Leydig cell function and radiation: a review of the literature. Radiother. Oncol. 34, 1-8 (1995).
143. Faddy M. J. Follicle dynamics during ovarian ageing. Mol. Cell. Endocrinol. 163, 43-48 (2000).
144. Committee on Gynecologic Practice. Committee opinion no. 618. Ovarian reserve testing. Obstet. Gynecol. 125, 268-273 (2015).
145. Nelson L. M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 360, 606-614 (2009).
146. Welt C. K. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin. Endocrinol. (Oxf.). 68, 499-509 (2008).
147. Chemaitilly W, et al. Acute ovarian failure in the childhood cancer survivor study. J. Clin. Endocrinol. Metab. 91, 1723-1728 (2006).
148. Sklar C. A, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J. Natl Cancer Inst. 98, 890-896 (2006).
149. Metzger M. L, et al. Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J. Clin. Oncol. 31, 1239-1247 (2013).
150. Levi M, et al. Anti-Müllerian hormone is a marker for chemotherapy-induced testicular toxicity. Endocrinology. 156, 3818-3827 (2015).
151. Pfaff T, et al. Inhibin B as a marker of sertoli cell damage and spermatogenic disturbance in the rat. Birth Defects Res. B. Dev. Reprod. Toxicol. 98, 91-103 (2013).
152. Tuttelmann F, et al. Anti-Müllerian hormone in men with normal and reduced sperm concentration and men with maldescended testes. Fertil. Steril. 91, 1812-1819 (2009).
153. DiVasta A. D, & Gordon C. M. Hormone replacement therapy for the adolescent patient. Ann. NY Acad. Sci. 1135, 204-211 (2008).
154. Han T. S, & Bouloux P. M. What is the optimal therapy for young males with hypogonadotrophic hypogonadism? Clin. Endocrinol. (Oxf.). 72, 731-737 (2010).
155. Davenport M. L. Moving toward an understanding of hormone replacement therapy in adolescent girls: looking through the lens of Turner syndrome. Ann. NY Acad. Sci. 1135, 126-137 (2008).
156. Van Kasteren Y. M, & Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum. Reprod. Update. 5, 483-492 (1999).
157. Ethics Committee of American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: a committee opinion. Fertil. Steril. 100, 1224-1231 (2013).
158. Gracia C. R, et al. Ovarian tissue cryopreservation for fertility preservation in cancer patients: successful establishment and feasibility of a multidisciplinary collaboration. J. Assist. Reprod. Genet. 29, 495-502 (2012).
159. Marchak J. G, et al. Perceptions of infertility risks among female pediatric cancer survivors following gonadotoxic therapy. J. Pediatr. Hematol. Oncol. 37, 368-372 (2015).
160. Loren A. W, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J. Clin. Oncol. 31, 2500-2510 (2013).
161. Blumenfeld Z, Katz G, & Evron A. 'An ounce of prevention is worth a pound of cure': the case for and against GnRH-Agonist for fertility preservation. Ann. Oncol. 25, 1719-1728 (2014).
162. Milsom S, et al. Treatment of infertility with hypogonadotropic hypogonadism: 10 year experience in Auckland, New Zealand. Aust. N. Z. J. Obstet. Gynaecol. 52, 293-298 (2012).
163. Dwyer A. A, Raivio T, & Pitteloud N. Gonadotrophin replacement for induction of fertility in hypogonadal men. Best Pract. Res. Clin. Endocrinol. Metab. 29, 91-103 (2015).
164. Critchley H. O, et al. Abdominal irradiation in childhood: the potential for pregnancy. Br. J. Obstet. Gynaecol. 99, 392-394 (1992).
165. Ben-Nagi J, & Penay N, et al. Premature ovarian insufficiency: how to improve reproductive outcome? Climacteric. 17, 22-26 (2014).
166. Blumenfeld Z, & von Wolff M. GnRH-Analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum. Reprod. Update. 14, 543-552 (2008).
167. Turner N. H, et al. Utility of gonadotropin-releasing hormone agonists for fertility preservation in young breast cancer patients: the benefit remains uncertain. Ann. Oncol. 24, 2224-2235 (2013).
168. Westphal L. M, & Massie J. A. M. in Oncofertility Medical Practice: Clinical Issues and Implementation (eds Gracia C, & Woodruff T. K.) 51-61 (Springer, 2012).
169. Cardozo E. R, et al. Ovarian stimulation and in vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17 year experience. J. Assist. Reprod. Genet. 32, 587-596 (2015).
170. Society for Assisted Reproductive Technology. Clinic summary report 2013. sart cors [online], https://.www.sartcorsonline.com/rptCSR-PublicMultYear.aspx? ClinicPKID=0 (2013).
171. Mahajan N. Fertility preservation in female cancer patients: an overview. J. Hum. Reprod. Sci. 8, 3-13 (2015).
172. Uzelac P, Christensen G, & Nakajima S. in Oncofertility Medical Practice: Clinical Issues and Implementation (eds Gracia C, & Woodruff T. K.) 77-89 (Springer, 2012).
173. Salama M, & Woodruff T. K. New advances in ovarian autotransplantation to restore fertility in cancer patients. Cancer Metastasis Rev. 34, 807-822 (2015).
174. Oktay K, & Sonmezer M. Ovarian tissue banking for cancer patients: fertility preservation, not just ovarian cryopreservation. Hum. Reprod. 19, 477-480 (2004).
175. Knopman J. M, & Noyes N. in Oncofertility Medical Practice: Clinical Issues and Implementation (eds Gracia C, & Woodruff T. K.) 91-104 (Springer, 2012).
176. Clough K. B, et al. Laparoscopic unilateral ovarian transposition prior to irradiation: a prospective study of 20 cases. Cancer. 77, 2638-2645 (1996).
177. Cutillo G, et al. Conservative treatment of reproductive and sexual function in young woman with squamous carcinoma of the vagina. Gynecol. Oncol. 103, 234-237 (2006).
178. Trost L, & Branningan R. in Oncofertility Medical Practice: Clinical Issues and Implementation (eds Gracia C, & Woodruff T. K.) 27-50 (Springer, 2012).
179. Muller J, et al. Cryopreservation of semen from pubertal boys with cancer. Med. Pediatr. Oncol. 34, 191-194 (2000).
180. Bober S. L, et al. Sexual function in childhood cancer survivors: a report from project REACH. J. Sex. Med. 10, 2084-2093 (2013).
181. Zebrack B. J, et al. Sexual functioning in young adult survivors of childhood cancer. Psychooncology. 19, 814-822 (2010).
182. Schover L. R, et al. Sexual dysfunction and infertility as late effects of cancer treatment. EJC Suppl.12, 41-53 (2014).
183. Markey K. A, Macdonald K. P, & Hill G. R. The biology of graft versus host disease: experimental systems instructing clinical practice. Blood. 124, 354-362 (2014).
184. Hirsch P, et al. Female genital chronic graft-versus-host disease: importance of early diagnosis to avoid severe complications. Transplantation. 93, 1265-1269 (2012).
185. Rosen R. C. Assessment of sexual dysfunction in patients with benign prostatic hyperplasia. BJU Int. 97 (Suppl. 2), 29-33 (2006).
186. Meston C. M, & Derogatis L. R. Validated instruments for assessing female sexual function. J. Sex. Marital. Ther. 28 (Suppl. 1), 155-164 (2002).
187. Wasilewski-Masker K, et al. Bone mineral density deficits in survivors of childhood cancer: long-Term follow up guidelines and review of the literature. Pediatrics 121, e705 (2008).
188. Wilson C. L, et al. Fractures among long-Term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer. 118, 5920-5928 (2012).
189. Cummings E. A, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J. Clin. Endocrinol. Metab. 100, 408-3417 (2015).
190. Kaste S. C, et al. Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development. Leukemia. 15, 728-734 (2001).
191. Polgreen L. E, et al. Modifiable risk factors associated with bone deficits in childhood cancer survivors. BMC Pediatr. 12, 40 (2012).
192. Choudhary A, Chou J, Heller G, & Sklar C. Prevalence of vitamin D insufficiency in survivors of childhood cancer. Pediatr. Blood Cancer. 60, 1237-1239 (2013).
193. Wallace G, et al. Vitamin D deficiency and survival in children after hematopoietic stem cell transplant. Biol. Blood Marrow Transplant. 21, 1627-1631 (2015).
194. Neville K. A, & Cohn R. J. Bone health in survivors of childhood cancer. Lancet Diabetes Endocrinol. 3, 496-497 (2015).
195. Kalkwarf H. J, et al. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J. Clin. Endocrinol. Metab. 92, 2087-2099 (2007).
196. Zemel B. S, et al. Height adjustment in assessing dual energy x ray absorptiometry measurements of bone mass and density in children. J. Clin. Endocrinol. Metab. 95, 1265-1273 (2010).
197. The International Society for Clinical Densitometry. 2013 ISCD combined official positions. [online], https://iscd.app.box.com/OP-ISCD-2013-Adult-Ped- Eng (2013).
198. Kanis J. A, et al. The diagnosis of osteoporosis. J. Bone Miner. Res. 9, 1137-1141 (1994).
199. Holick M. F, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1911-1930 (2011).
200. Fan C, Foster B. K, Wallace W. H, & Xian C. J. Pathobiology and prevention of cancer chemotherapy-induced bone growth arrest, bone loss, and osteonecrosis. Curr. Mol. Med. 11, 140-151 (2011).
201. Neville K. A, et al. Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors. J. Clin. Endocrinol. Metab. 91, 4401-4407 (2006).
202. Talvensaari K. K, Lanning M, Tapanainen P, & Knip M. Long term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome. J. Clin. Endocrinol. Metab. 81, 3051-3055 (1996).
203. Nottage K. A, et al. Metabolic syndrome and cardiovascular risk among long-Term survivors of acute lymphoblastic leukaemia - from the St. Jude Lifetime Cohort. Cancer. 120, 2742-2750 (2014).
204. Van Waas M, Neggers S. J, Pieters R, & Van den Heuvel-Eibrink M. M. Components of metabolic syndrome in 500 adult survivors. Ann. Oncol. 21, 1121-1126 (2010).
205. de Haas E. C, et al. The metabolic syndrome in cancer survivors. Lancet Oncol. 11, 193-203 (2010).
206. Wei C, et al. Reduced β-cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation. Clin. Endocrinol. 82, 59-67 (2015).
207. Meacham L. R, et al. Diabetes mellitus in long-Term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the childhood cancer survivor study. Arch. Intern. Med. 169, 1381-1388 (2009).
208. De Vathaire F, et al. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 13, 1002-1010 (2012).
209. Ehrhardt M. J, & Mulrooney D. A. Metabolic syndrome in adult survivors of childhood cancer: the intersection of oncology, endocrinology and cardiology. Lancet Diabetes Endocrinol. 3, 494-496 (2015).
210. Kim J. H, & Choi J. H. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents. Ann. Pediatr. Endocrinol. Metab. 18, 161-167 (2013).
211. Lustig R. H. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment. Front. Endocrinol. (Lausanne). 2, 60 (2011).
212. Elowe-Gruau E, et al. Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J. Clin. Endocrinol. Metab. 98, 2376-2382 (2013).
213. Haliloglu B, & Bereket A. Hypothalamic obesity in children: pathophysiology to clinical management. J. Pediatr. Endocrinol. Metab. 28, 503-513 (2015).
214. Inoue S, et al. Role of the efferent and afferent vagus nerve in the development of ventromedial hypothalamic (VMH) obesity. Brain Res. Bull. 27, 511-515 (1991).
215. King B. M, & Frohman L. A. The role of vagally-medicated hyperinsulinemia in hypothalamic obesity. Neurosci. Biobehav. Rev. 6, 205-214 (1982).
216. Inoue S, & Bray G. A. The effects of subdiaphragmatic vagotomy in rats with ventromedial hypothalamic obesity. Endocrinology. 100, 108-114 (1977).
217. De Silva A, & Bloom S. R. Gut hormones and appetite control: a focus on PYY and GLP 1 as therapeutic targets in obesity. Gut Liver. 6, 10-20 (2012).
218. O'Gorman C. S, Simoneau-Roy J, Pencharz M. P, Adeli K, & Hamilton J. Delayed ghrelin suppression following oral glucose tolerance test in children and adolescents with hypothalamic injury secondary to craniopharyngioma compared with obese controls. Int. J. Pediatr. Obes. 6, 285-288 (2011).
219. Rakhshani N, et al. Evaluation of a comprehensive care clinic model for children with brain tumor and risk for hypothalamic obesity. Obesity (Silver Spring). 18, 1768-1774 (2010).
220. Lustig R. H, et al. Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J. Pediatr. 135, 162-168 (1999).
221. Deepak D, Furlong N. J, Wilding J. P. H, & MacFarlane I. Cardiovascular disease, hypertension, dyslipidaemia and obesity in patients with hypothalamic-pituitary disease. Postgrad. Med. J. 83, 277-280 (2007).
222. Elfers C. T, & Roth C. L. Effects of methylphenidate on weight gain and food intake in hypothalamic obesity. Front. Endocrinol. (Lausanne). 2, 78 (2011).
223. Mason P. W, Krawiecki N, & Meacham L. R. The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch. Pediatr. Adolesc. Med. 156, 887-892 (2002).
224. Hamilton J. K, et al. Hypothalamic obesity following craniopharyngioma surgery: results of a pilot trial of combined diazoxide and metformin therapy. Int. J. Pediatr. Endocrinol. 2011, 417949 (2011).
225. Lustig R. H, et al. Insulin dynamics predict body mass index and z score response to insulin suppression or sensitization pharmacotherapy in obese children. J. Pediatr. 148, 23-29 (2006).
226. Zoicas F, et al. GLP 1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. Eur. J. Endocrinol. 168, 699-706 (2013).
227. Laferré B, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 93, 2479-2485 (2008).
228. Sarson D. L, Scopinaro N, & Bloom S. R. Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity. Int. J. Obes. 5, 471-480 (1981).
229. Lustig R. H, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J. Clin. Endocrinol. Metab. 88, 2586-2592 (2003).
230. Inge T. H, et al. Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy. Nat. Clin. Pract. Endocrinol. Metab. 3, 606-609 (2007).
231. Rottembourg D, et al. Outcome after bariatric surgery in two adolescents with hypothalamic obesity following treatment of craniopharyngioma. J. Pediatr. Endocrinol. Metab. 22, 867-872 (2009).
232. Blum R. W, et al. Transition from child-centered to adult health-care systems for adolescents with chronic conditions: a position paper of the Society for Adolescent Medicine. J. Adolesc. Health. 14, 570-576 (1993).
233. McManus M. A, et al. Current status of transition preparation among youth with special needs in the United States. Pediatrics. 131, 1090-1097 (2013).
234. Cooley W. C, & Sagerman P. J. Supporting the health care transition from adolescence to adulthood in the medical home. Pediatrics. 128, 182-200 (2011).
235. Gan H. W, & Spoudeas H. A. Long-Term follow up of survivors of childhood cancer (SIGN Clinical Guideline 132). Arch. Dis. Child. Educ. Pract. Ed. 99, 138-143 (2014).
236. Overholser L. S, et al. Development of a primary care based clinic to support adults with a history of childhood cancer: The Tactic Clinic. J. Pediatr. Nurs. 30, 724-731 (2015).
237. Tonorezos E. S, et al. Screening and management of adverse endocrine outcomes in adult survivors of childhood and adolescent cancer. Lancet Diabetes Endocrinol. 3, 545-555 (2015).
238. Brignardello E, et al. Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow up clinics. Eur. J. Endocrinol. 168, 465-472 (2013).