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Pituitary

, Volume 12, Issue 1, pp 40–50 | Cite as

Hypopituitarism following radiotherapy

  • Ken H. DarzyEmail author
  • Stephen M. Shalet
Article

Abstract

Deficiencies in anterior pituitary hormones secretion ranging from subtle to complete occur following radiation damage to the hypothalamic–pituitary (h–p) axis, the severity and frequency of which correlate with the total radiation dose delivered to the h–p axis and the length of follow up. Selective radiosensitivity of the neuroendocrine axes, with the GH axis being the most vulnerable, accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h–p axis with doses less than 30 Gy. With higher radiation doses (30–50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50–100%. Compensatory hyperstimulation of a partially damaged h–p axis may restore normality of spontaneous GH secretion in the context of reduced but normal stimulated responses; at its extreme, endogenous hyperstimulation may limit further stimulation by insulin-induced hypoglycaemia resulting in subnormal GH responses despite normality of spontaneous GH secretion in adults. In children, failure of the hyperstimulated partially damaged h–p axis to meet the increased demands for GH during growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction and, unlike in adults, the ITT remains the gold standard for assessing h–p functional reserve. Thyroid-stimulating hormone (TSH) and ACTH deficiency occur after intensive irradiation only (>50 Gy) with a long-term cumulative frequency of 3–6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30–50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30–60% after 10 years) occur after more intensive irradiation (>60 Gy) used for nasopharyngeal carcinomas and tumors of the skull base, and following conventional irradiation (30–50 Gy) for pituitary tumors. The frequency of hypopituitarism following stereotactic radiotherapy for pituitary tumors is mostly seen after long-term follow up and is similar to that following conventional irradiation. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy.

Keywords

Hypopituitarism Growth hormone deficiency GHD ACTH deficiency TSH deficiency Gonadotropin deficiency Precocious puberty Hyperprolactinemia Hypothalamus h–p axis Cranial radiotherapy Cranial irradiation Stereotactic radiotherapy Gamma knife surgery GKS Cancer survivors Late effects 

References

  1. 1.
    Thames HD, Hendry JH (1987) Response of tissues to fractionated irradiation: effect of repair, in fractionation in radiotherapy. Taylor & Francis, London. pp 53–99Google Scholar
  2. 2.
    Withers HR (1994) Biology of radiation oncology. In: Tobias JS, Thomas PRM (eds) Current radiation oncology. Edward Arnold, London. pp 5–23Google Scholar
  3. 3.
    Chieng PU, Huang TS, Chang CC, Chong PN, Tien RD, Su CT (1991) Reduced hypothalamic blood flow after radiation treatment of nasopharyngeal cancer: SPECT studies in 34 patients. AJNR Am J Neuroradiol 12:661–665 MedlinePubMedGoogle Scholar
  4. 4.
    Robinson IC, Fairhall KM, Hendry JH, Shalet SM (2001) Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat. J Endocrinol 169:519–526 Medline. doi: 10.1677/joe.0.1690519 PubMedGoogle Scholar
  5. 5.
    Hochberg Z, Kuten A, Hertz P, Tatcher M, Kedar A, Benderly A (1983) The effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells. Radiat Res 94:508–512 Medline. doi: 10.2307/3575908 PubMedGoogle Scholar
  6. 6.
    Constine LS, Woolf PD, Cann D et al (1993) Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 328:87–94 Medline. doi: 10.1056/NEJM199301143280203 PubMedGoogle Scholar
  7. 7.
    Clayton PE, Shalet SM (1991) Dose dependency of time of onset of radiation-induced growth hormone deficiency. J Pediatr 118:226–228 Medline. doi: 10.1016/S0022-3476(05)80487-1 PubMedGoogle Scholar
  8. 8.
    Littley MD, Shalet SM, Beardwell CG, Robinson EL, Sutton ML (1989) Radiation-induced hypopituitarism is dose-dependent. Clin Endocrinol (Oxf) 31:363–373 MedlineGoogle Scholar
  9. 9.
    Lam KS, Tse VK, Wang C, Yeung RT, Ho JH (1991) Effects of cranial irradiation on hypothalamic-pituitary function—a 5-year longitudinal study in patients with nasopharyngeal carcinoma. Q J Med 78:165–176 MedlinePubMedGoogle Scholar
  10. 10.
    Duffner PK, Cohen ME, Voorhess ML et al (1985) Long-term effects of cranial irradiation on endocrine function in children with brain tumors. A prospective study. Cancer 56:2189–2193 Medline. doi: 10.1002/1097–0142(19851101)56:92189::AID-CNCR2820560909≥3.0.CO;2-I PubMedGoogle Scholar
  11. 11.
    Pai HH, Thornton A, Katznelson L et al (2001) Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: demonstration of a dose-effect relationship using dose-volume histogram analysis. J Radiat Oncol Biol Phys 49:1079–1092 doi: 10.1016/S0360-3016(00)01387-0 Google Scholar
  12. 12.
    Samaan NA, Vieto R, Schultz PN et al (1982) Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck. Int J Radiat Oncol Biol Phys 8:1857–1867 MedlinePubMedGoogle Scholar
  13. 13.
    Chen MS, Lin FJ, Huang MJ et al (1989) Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation. Jpn J Clin Oncol 19:265–270 MedlinePubMedGoogle Scholar
  14. 14.
    Shalet SM, Beardwell CG, Pearson D, Jones PH (1976) The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clin Endocrinol (Oxf) 5:287–290 MedlineGoogle Scholar
  15. 15.
    Brauner R, Czernichow P, Rappaport R (1986) Greater susceptibility to hypothalamopituitary irradiation in younger children with acute lymphoblastic leukemia. J Pediatr 108:332 Medline. doi: 10.1016/S0022-3476(86)81027-7 PubMedGoogle Scholar
  16. 16.
    Samaan NA, Schultz PN, Yang KP et al (1987) Endocrine complications after radiotherapy for tumors of the head and neck. J Lab Clin Med 109:364–372 MedlinePubMedGoogle Scholar
  17. 17.
    Ogilvy-Stuart AL, Clark DJ, Wallace WH et al (1992) Endocrine deficit after fractionated total body irradiation. Arch Dis Child 67:1107–1110 MedlinePubMedGoogle Scholar
  18. 18.
    Littley MD, Shalet SM, Morgenstern GR, Deakin DP (1991) Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. Q J Med 78:265–274 MedlinePubMedGoogle Scholar
  19. 19.
    Agha A, Sherlock M, Brennan S et al (2005) Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults. J Clin Endocrinol Metab 90:6355–6360 Medline. doi: 10.1210/jc.2005-1525 PubMedGoogle Scholar
  20. 20.
    Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML (1989) Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 70:145–160 MedlinePubMedGoogle Scholar
  21. 21.
    Schmiegelow M, Lassen S, Poulsen HS et al (2000) 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 Medline. doi: 10.1159/000053232 PubMedGoogle Scholar
  22. 22.
    Spoudeas HA, Hindmarsh PC, Matthews DR, Brook CG (1996) Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study. J Endocrinol 150:329–342 Medline. doi: 10.1677/joe.0.1500329 PubMedGoogle Scholar
  23. 23.
    Achermann JC, Brook CG, Hindmarsh PC (2000) The GH response to low-dose bolus growth hormone-releasing hormone (GHRH(1-29)NH2) is attenuated in patients with longstanding post-irradiation GH insufficiency. Eur J Endocrinol 142:359–364 Medline. doi: 10.1530/eje.0.1420359 PubMedGoogle Scholar
  24. 24.
    Darzy KH, Aimaretti G, Wieringa G, Gattamaneni HR, Ghigo E, Shalet SM (2003) The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab 88:95–102 Medline. doi: 10.1210/jc.2002-021094 PubMedGoogle Scholar
  25. 25.
    Brada M, Rajan B, Traish D et al (1993) The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol (Oxf) 38:571–578 MedlineGoogle Scholar
  26. 26.
    Rush S, Cooper PR (1997) Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas. Int J Radiat Oncol Biol Phys 37:1031–1034 Medline. doi: 10.1016/S0360-3016(96)00586-X PubMedGoogle Scholar
  27. 27.
    Shalet SM, Beardwell CG, Morris-Jones PH, Pearson D (1975) Pituitary function after treatment of intracranial tumours in children. Lancet 2:104–107 Medline. doi: 10.1016/S0140-6736(75)90006-9 PubMedGoogle Scholar
  28. 28.
    Costin G (1988) Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function. Am J Dis Child 142:847–852PubMedGoogle Scholar
  29. 29.
    Kirk JA, Raghupathy P, Stevens MM et al (1987) Growth failure and growth-hormone deficiency after treatment for acute lymphoblastic leukaemia. Lancet 1:190–193 Medline. doi: 10.1016/S0140-6736(87)90004-3 PubMedGoogle Scholar
  30. 30.
    Brennan BM, Rahim A, Mackie EM, Eden OB, Shalet SM (1998) Growth hormone status in adults treated for acute lymphoblastic leukaemia in childhood. Clin Endocrinol (Oxf) 48:777–783 Medline. doi: 10.1046/j.1365-2265.1998.00438.x Google Scholar
  31. 31.
    Giorgiani G, Bozzola M, Locatelli F et al (1995) Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone. Blood 86:825–831 MedlinePubMedGoogle Scholar
  32. 32.
    Brauner R, Adan L, Souberbielle JC et al (1997) Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation. J Pediatr 130:785–792 Medline. doi: 10.1016/S0022-3476(97)80022-4 PubMedGoogle Scholar
  33. 33.
    Papadimitriou A, Urena M, Hamill G, Stanhope R, Leiper AD (1991) Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation. Arch Dis Child 66:689–692 MedlinePubMedGoogle Scholar
  34. 34.
    Olshan JS, Willi SM, Gruccio D, Moshang T Jr (1993) Growth hormone function and treatment following bone marrow transplant for neuroblastoma. Bone Marrow Transplant 12:381–385 MedlinePubMedGoogle Scholar
  35. 35.
    Gleeson HK, Gattamaneni HR, Smethurst L, Brennan BM, Shalet SM (2004) Reassessment of growth hormone status is required at final height in children treated with growth hormone replacement after radiation therapy. J Clin Endocrinol Metab 89:662–666 Medline. doi: 10.1210/jc.2003-031224:PubMedGoogle Scholar
  36. 36.
    Shalet SM, Toogood AA, Rahim A, Brennan BMD (1998) The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 19:203–223 Medline. doi: 10.1210/er.19.2.203 PubMedGoogle Scholar
  37. 37.
    Lustig RH, Schriock EA, Kaplan SL, Grumbach MM (1985) Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency. Pediatrics 76:274–279 MedlinePubMedGoogle Scholar
  38. 38.
    Grossman A, Savage MO, Blacklay A et al (1985) The use of growth hormone-releasing hormone in the diagnosis and treatment of short stature. Horm Res 22:52–57 MedlinePubMedGoogle Scholar
  39. 39.
    Oberfield SE, Kirkland JL, Frantz A, Allen JC, Levine LS (1987) Growth hormone response to GRF 1-44 in children following cranial irradiation for central nervous system tumors. Am J Pediatr Hematol Oncol 9:233–238 Medline. doi: 10.1097/00043426-198724000-00010 PubMedGoogle Scholar
  40. 40.
    Crosnier H, Brauner R, Rappaport R (1988) Growth hormone response to growth hormone-releasing hormone (hp GHRH1-44) as an index of growth hormone secretory dysfunction after prophylactic cranial irradiation for acute lymphoblastic leukemia (24 grays). Acta Paediatr Scand 77:681–687 MedlinePubMedGoogle Scholar
  41. 41.
    Lissett CA, Saleem S, Rahim A, Brennan BM, Shalet SM (2004) The impact of irradiation on growth hormone responsiveness to provocative agents is stimulus dependent: results in 161 individuals with radiation damage to the somatotropic axis. J Clin Endocrinol Metab 86:663–668 Medline. doi: 10.1210/jc.86.2.663 Google Scholar
  42. 42.
    Ahmed SR, Shalet SM, Beardwell CG (1986) The effects of cranial irradiation on growth hormone secretion. Acta Paediatr Scand 75:255–260 MedlinePubMedGoogle Scholar
  43. 43.
    Romshe CA, Zipf WB, Miser A, Miser J, Sotos JF, Newton WA (1984) Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature. J Pediatr 104:177–181 Medline. doi: 10.1016/S0022-3476(84)80988-9 PubMedGoogle Scholar
  44. 44.
    Dickinson WP, Berry DH, Dickinson L et al (1978) Differential effects of cranial radiation on growth hormone response to arginine and insulin infusion. J Pediatr 92:754–757 Medline. doi: 10.1016/S0022-3476(78)80143-7 PubMedGoogle Scholar
  45. 45.
    Chrousos GP, Poplack D, Brown T, O’Neill D, Schwade J, Bercu BB (1982) Effects of cranial radiation on hypothalamic-adenohypophyseal function: abnormal growth hormone secretory dynamics. J Clin Endocrinol Metab 54:1135–1139 MedlinePubMedCrossRefGoogle Scholar
  46. 46.
    Darzy K, Pezzoli S, Thorner M, Shalet S (2005) The dynamics of GH secretion in adult cancer survivors with severe GH deficiency acquired following brain irradiation in childhood for non-pituitary brain tumors: evidence for preserved pulsatility and diurnal variation with increased secretory disorderliness. J Clin Endocrinol Metab 90:2794–2803 Medline. doi: 10.1210/jc.2004-2002 PubMedGoogle Scholar
  47. 47.
    Toogood AA, Nass RM, Pezzoli SS, O’Neill PA, Thorner MO, Shalet SM (1997) Preservation of growth hormone pulsatility despite pituitary pathology, surgery, and irradiation. J Clin Endocrinol Metab 82:2215–2221 Medline. doi: 10.1210/jc.82.7.2215 PubMedGoogle Scholar
  48. 48.
    Reutens AT, Veldhuis JD, Hoffman DM, Leung KC, Ho KK (1996) A highly sensitive growth hormone (GH) enzyme-linked immunosorbent assay uncovers increased contribution of a tonic mode of GH secretion in adults with organic GH deficiency. J Clin Endocrinol Metab 81:1591–1597 Medline. doi: 10.1210/jc.81.4.1591 PubMedGoogle Scholar
  49. 49.
    Baum HB, Biller BM, Katznelson L et al (1996) Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men–a clinical research center study. J Clin Endocrinol Metab 81:84–92 Medline. doi: 10.1210/jc.81.1.84 PubMedGoogle Scholar
  50. 50.
    Roelfsema F, Biermasz NR, Veldhuis JD (2002) Pulsatile, nyctohemeral and entropic characteristics of GH secretion in adult GH-deficient patients: selectively decreased pulsatile release and increased secretory disorderliness with preservation of diurnal timing and gender distinctions. Clin Endocrinol (Oxf) 56:79–87 Medline. doi: 10.1046/j.0300-0664.2001.01433.x Google Scholar
  51. 51.
    Jessup SK, Malow BA, Symons KV, Barkan AL (2004) Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep. Eur J Endocrinol 151:561–566 Medline. doi 10.1530/eje.0.1510561:PubMedGoogle Scholar
  52. 52.
    Ocampo-Lim B, Guo W, DeMott-Friberg R, Barkan AL, Jaffe CA (1996) Nocturnal growth hormone (GH) secretion is eliminated by infusion of GH-releasing hormone antagonist. J Clin Endocrinol Metab 81:4396–4399 Medline. doi: 10.1210/jc.81.12.4396 PubMedGoogle Scholar
  53. 53.
    Wehrenberg WB, Brazeau P, Luben R, Bohlen P, Guillemin R (1982) Inhibition of the pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF). Endocrinology 111:2147–2148 MedlinePubMedGoogle Scholar
  54. 54.
    Darzy KH, Pezzoli SS, Thorner MO, Shalet SM (2007) Cranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal. J Clin Endocrinol Metab 92:1666–1672 Medline. doi: 10.1210/jc.2006-2599 PubMedGoogle Scholar
  55. 55.
    Sklar CA, Constine LS (1995) Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113–1121 Medline. doi: 10.1016/0360-3016(94)00427-M PubMedGoogle Scholar
  56. 56.
    Kashio Y, Chihara K, Kita T et al (1987) Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue. J Clin Endocrinol Metab 64:92–97 MedlinePubMedGoogle Scholar
  57. 57.
    Masuda A, Shibasaki T, Hotta M et al (1990) Insulin-induced hypoglycemia, L-dopa and arginine stimulate GH secretion through different mechanisms in man. Regul Pept 31:53–64 Medline. doi: 10.1016/0167-0115(90)90195-3 PubMedGoogle Scholar
  58. 58.
    Koppeschaar HP, ten Horn CD, Thijssen JH, Page MD, Dieguez C, Scanlon MF (1992) Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion. Clin Endocrinol (Oxf) 36:487–490 MedlineGoogle Scholar
  59. 59.
    Hanew K, Utsumi A (2002) The role of endogenous GHRH in arginine-, insulin-, clonidine- and l-dopa-induced GH release in normal subjects. Eur J Endocrinol 146:197–202 Medline. doi: 10.1530/eje.0.1460197 PubMedGoogle Scholar
  60. 60.
    Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797 Medline. doi: 10.1210/er.19.6.717 PubMedGoogle Scholar
  61. 61.
    Veldhuis JD, Farhy L, Weltman AL, Kuipers J, Weltman J, Wideman L (2005) Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults. J Clin Endocrinol Metab 90:2874–2881 Medline. doi: 10.1210/jc.2004-1363 PubMedGoogle Scholar
  62. 62.
    Soares-Welch C, Farhy L, Mielke KL et al (2005) Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults. J Clin Endocrinol Metab 90:2225–2232 Medline. doi: 10.1210/jc.2004-1365 PubMedGoogle Scholar
  63. 63.
    Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P (1995) Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 133:305–312PubMedGoogle Scholar
  64. 64.
    Diamond MP, Jones T, Caprio S et al (1993) Gender influences counterregulatory hormone responses to hypoglycemia. Metabolism 42:1568–1572 Medline. doi: 10.1016/0026-0495(93)90152-E PubMedGoogle Scholar
  65. 65.
    Osterman PO, Wide L (1976) The insulin tolerance test after pre-treatment with dexamethasone. Acta Endocrinol (Copenh) 83:341–356 MedlineGoogle Scholar
  66. 66.
    Biller BM, Samuels MH, Zagar A et al (2002) Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87:2067–2079 Medline. doi: 10.1210/jc.87.5.2067 PubMedGoogle Scholar
  67. 67.
    Hirvonen E, Seppala M, Karonen SL, Adlercreutz H (1977) Luteinizing hormone responses to luteinizing hormone releasing hormone, and growth hormone and cortisol responses to insulin induced hypoglycaemia in functional secondary amenorrhoea. Acta Endocrinol (Copenh) 84:225–236 MedlineGoogle Scholar
  68. 68.
    Blatt J, Lee P, Suttner J, Finegold D (1988) Pulsatile growth hormone secretion in children with acute lymphoblastic leukemia after 1800 cGy cranial radiation. Int J Radiat Oncol Biol Phys 15:1001–1006 MedlinePubMedGoogle Scholar
  69. 69.
    Crowne EC, Moore C, Wallace WH et al (1992) A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation. Clin Endocrinol (Oxf) 36:59–68 MedlineGoogle Scholar
  70. 70.
    Stubberfield TG, Byrne GC, Jones TW (1995) Growth and growth hormone secretion after treatment for acute lymphoblastic leukemia in childhood. 18-Gy versus 24-Gy cranial irradiation. J Pediatr Hematol Oncol 17:167–171 Medline. doi: 10.1097/00043426-199505000-00012 PubMedGoogle Scholar
  71. 71.
    Lannering B, Rosberg S, Marky I, Moell C, Albertsson-Wikland K (1995) Reduced growth hormone secretion with maintained periodicity following cranial irradiation in children with acute lymphoblastic leukaemia. Clin Endocrinol (Oxf) 42:153–159 MedlineGoogle Scholar
  72. 72.
    Blatt J, Bercu BB, Gillin JC, Mendelson WB, Poplack DG (1984) Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia. J Pediatr 104:182–186 Medline. doi: 10.1016/S0022-3476(84)80989-0 PubMedGoogle Scholar
  73. 73.
    Moell C, Garwicz S, Westgren U, Wiebe T, Albertsson-Wikland K (1989) Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia. Arch Dis Child 64:252–258 MedlinePubMedGoogle Scholar
  74. 74.
    Ryalls M, Spoudeas HA, Hindmarsh PC et al (1993) Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia. J Endocrinol 136:331–338 MedlinePubMedGoogle Scholar
  75. 75.
    Lannering B, Albertsson-Wikland K (1987) Growth hormone release in children after cranial irradiation. Horm Res 27:13–22 MedlinePubMedGoogle Scholar
  76. 76.
    Moell C (1988) Disturbed pubertal growth in girls after acute leukaemia: a relative growth hormone insufficiency with late presentation. Acta Paediatr Scand Suppl 343:162–166 MedlinePubMedGoogle Scholar
  77. 77.
    Pasqualini T, Escobar ME, Domene H, Muriel FS, Pavlovsky S, Rivarola MA (1987) Evaluation of gonadal function following long-term treatment for acute lymphoblastic leukemia in girls. Am J Pediatr Hematol Oncol 9:15–22 Medline. doi: 10.1097/00043426-198721000-00004 PubMedGoogle Scholar
  78. 78.
    Sanders JE, Buckner CD, Leonard JM et al (1983) Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation. Transplantation 36:252–255 Medline. doi: 10.1097/00007890-198309000-00005 PubMedGoogle Scholar
  79. 79.
    Rappaport R, Brauner R, Czernichow P et al (1982) Effect of hypothalamic and pituitary irradiation on pubertal development in children with cranial tumors. J Clin Endocrinol Metab 54:1164–1168 MedlinePubMedGoogle Scholar
  80. 80.
    Yoshimoto Y, Moridera K, Imura H (1975) Restoration of normal pituitary gonadotropin reserve by administration of luteinizing-hormone-releasing hormone in patients with hypogonadotropic hypogonadism. N Engl J Med 292:242–245 MedlinePubMedCrossRefGoogle Scholar
  81. 81.
    Hall JE, Martin KA, Whitney HA, Landy H, Crowley WF Jr (1994) Potential for fertility with replacement of hypothalamic gonadotropin-releasing hormone in long term female survivors of cranial tumors. J Clin Endocrinol Metab 79:1166–1172 Medline. doi: 10.1210/jc.79.4.1166 PubMedGoogle Scholar
  82. 82.
    Brauner R, Rappaport R (1985) Precocious puberty secondary to cranial irradiation for tumors distant from the hypothalamo-pituitary area. Horm Res 22:78–82 MedlinePubMedGoogle Scholar
  83. 83.
    Leiper AD, Stanhope R, Kitching P, Chessells JM (1987) Precocious and premature puberty associated with treatment of acute lymphoblastic leukaemia. Arch Dis Child 62:1107–1112 MedlinePubMedGoogle Scholar
  84. 84.
    Ogilvy-Stuart AL, Clayton PE, Shalet SM (1994) Cranial irradiation and early puberty. J Clin Endocrinol Metab 78:1282–1286 Medline. doi: 10.1210/jc.78.6.1282 PubMedGoogle Scholar
  85. 85.
    Lannering B, Jansson C, Rosberg S, Albertsson-Wikland K (1997) Increased LH and FSH secretion after cranial irradiation in boys. Med Pediatr Oncol 29:280–287 Medline. doi: 10.1002/(SICI)1096-911X(199710)29:4≤280::AID-MPO8≥3.0.CO;2-I PubMedGoogle Scholar
  86. 86.
    Roth C, Schmidberger H, Schaper O et al (2004) Cranial irradiation of female rats causes dose-dependent and age-dependent activation or inhibition of pubertal development. Pediatr Res 47:586–591 Medline. doi: 10.1203/00006450-200005000-00005 Google Scholar
  87. 87.
    Roth C, Schmidberger H, Lakomek M, Witt O, Wuttke W, Jarry H (2001) Reduction of gamma-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats. Neurosci Lett 297:45–48 Medline. doi: 10.1016/S0304-3940(00)01663-3 PubMedGoogle Scholar
  88. 88.
    Quigley C, Cowell C, Jimenez M et al (1989) Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia. N Engl J Med 321:143–151 MedlinePubMedCrossRefGoogle Scholar
  89. 89.
    Livesey EA, Hindmarsh PC, Brook CG et al (1990) Endocrine disorders following treatment of childhood brain tumours. Br J Cancer 61:622–625 MedlinePubMedGoogle Scholar
  90. 90.
    Darzy KH, Shalet SM (2005) Absence of adrenocorticotropin (ACTH) neurosecretory dysfunction but increased cortisol concentrations and production rates in ACTH-replete adult cancer survivors after cranial irradiation for nonpituitary brain tumors. J Clin Endocrinol Metab 90:5217–5225 Medline. doi: 10.1210/jc.2005-0830 PubMedGoogle Scholar
  91. 91.
    Mohn A, Chiarelli F, Di Marzio A, Impicciatore P, Marsico S, Angrilli F (1997) Thyroid function in children treated for acute lymphoblastic leukemia. J Endocrinol Invest 20:215–219 MedlinePubMedGoogle Scholar
  92. 92.
    Lando A, Holm K, Nysom K et al (2001) Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation. Clin Endocrinol (Oxf) 55:21–25 Medline. doi: 10.1046/j.1365-2265.2001.01292.x Google Scholar
  93. 93.
    Carter EP, Leiper AD, Chessells JM, Hurst A (1989) Thyroid function in children after treatment for acute lymphoblastic leukaemia. Arch Dis Child 64:631 MedlinePubMedGoogle Scholar
  94. 94.
    Oberfield SE, Sklar C, Allen J et al (1992) Thyroid and gonadal function and growth of long-term survivors of medulloblastoma/PNET. In: Green DM, D’Angio GJ (eds) Late effects of treatment for childhood cancer. Wiley-Liss Inc, New York. pp 55–62Google Scholar
  95. 95.
    Rose SR, Lustig RH, Pitukcheewanont P et al (1999) Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. J Clin Endocrinol Metab 84:4472–4479 Medline. doi: 10.1210/jc.84.12.4472 PubMedGoogle Scholar
  96. 96.
    Schmiegelow M, Feldt-Rasmussen U, Rasmussen AK, Poulsen HS, Muller J (2003) A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor. J Clin Endocrinol Metab 88:136–140 Medline. doi: 10.1210/jc.2002-020380 PubMedGoogle Scholar
  97. 97.
    Darzy KH, Shalet SM (2005) Circadian and stimulated thyrotropin secretion in cranially irradiated adult cancer survivors. J Clin Endocrinol Metab 90:6490–6497 Medline. doi: 10.1210/jc.2005-1593 PubMedGoogle Scholar
  98. 98.
    Coke C, Andrews DW, Corn BW et al (1997) Multiple fractionated stereotactic radiotherapy of residual pituitary macroadenomas: initial experience. Stereotact Funct Neurosurg 69:183–190 Medline. doi: 10.1159/000099872 PubMedGoogle Scholar
  99. 99.
    Mitsumori M, Shrieve DC, Alexander E III et al (1998) Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas. Int J Radiat Oncol Biol Phys 42:573–580 Medline. doi: 10.1016/S0360-3016(98)00256-9 PubMedGoogle Scholar
  100. 100.
    Paek SH, Downes MB, Bednarz G et al (2005) Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas. Int J Radiat Oncol Biol Phys 61:795–808 Medline. doi: 10.1016/j.ijrobp.2004.07.688 PubMedGoogle Scholar
  101. 101.
    Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2006) Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas. Clin Endocrinol (Oxf) 64:542–548 Medline. doi: 10.1111/j.1365-2265.2006.02506.x Google Scholar
  102. 102.
    Milker-Zabel S, Debus J, Thilmann C, Schlegel W, Wannenmacher M (2001) Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland. Int J Radiat Oncol Biol Phys 50:1279–1286 Medline. doi: 10.1016/S0360-3016(01)01535-8 PubMedGoogle Scholar
  103. 103.
    Colin P, Jovenin N, Delemer B et al (2005) Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients. Int J Radiat Oncol Biol Phys 62:333–341 Medline. doi: 10.1016/j.ijrobp.2004.09.058 PubMedGoogle Scholar
  104. 104.
    Hayashi M, Izawa M, Hiyama H et al (1999) Gamma Knife radiosurgery for pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1):111–118 Medline. doi: 10.1159/000056446 PubMedGoogle Scholar
  105. 105.
    Muacevic A, Uhl E, Wowra B (2004) Gamma knife radiosurgery for nonfunctioning pituitary adenomas. Acta Neurochir Suppl (Wien) 91:51–54Google Scholar
  106. 106.
    Jane JA Jr, Vance ML, Woodburn CJ, Laws ER Jr (2003) Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach. Neurosurg Focus 14:e12 MedlinePubMedCrossRefGoogle Scholar
  107. 107.
    Vladyka V, Liscak R, Simonova G et al (2000) [Radiosurgical treatment of hypophyseal adenomas with the gamma knife: results in a group of 163 patients during a 5-year period]. Cas Lek Cesk 139:757–766 MedlinePubMedGoogle Scholar
  108. 108.
    Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD (2002) Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg 97:408–414 MedlinePubMedGoogle Scholar
  109. 109.
    Kong DS, Lee JI. Lim do H, Kim KW, Shin HJ, Nam DH, Park K, Kim JH (2007) The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution. Cancer 110:854–860 Medline. doi: 10.1002/cncr.22860 PubMedGoogle Scholar
  110. 110.
    Losa M, Valle M, Mortini P et al (2004) Gamma knife surgery for treatment of residual nonfunctioning pituitary adenomas after surgical debulking. J Neurosurg 100:438–444 MedlinePubMedGoogle Scholar
  111. 111.
    Pollock BE, Carpenter PC (2003) Stereotactic radiosurgery as an alternative to fractionated radiotherapy for patients with recurrent or residual nonfunctioning pituitary adenomas. Neurosurgery 53:1086–1091. discussion 1091–1094 Medline. doi: 10.1227/01.NEU.0000088661.81189.66 Google Scholar
  112. 112.
    Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Steiner L, Vance ML (2007) Gamma Knife surgery for Cushing’s disease. J Neurosurg 106:980–987 MedlinePubMedGoogle Scholar
  113. 113.
    Mingione V, Yen CP, Vance ML et al (2006) Gamma surgery in the treatment of nonsecretory pituitary macroadenoma. J Neurosurg 104:876–883 MedlinePubMedGoogle Scholar
  114. 114.
    Attanasio R, Epaminonda P, Motti E et al (2003) Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J Clin Endocrinol Metab 88:3105–3112 Medline. doi: 10.1210/jc.2002-021663 PubMedGoogle Scholar
  115. 115.
    Wowra B, Stummer W (2002) Efficacy of gamma knife radiosurgery for nonfunctioning pituitary adenomas: a quantitative follow up with magnetic resonance imaging-based volumetric analysis. J Neurosurg 97:429–432 MedlinePubMedGoogle Scholar
  116. 116.
    Jezkova J, Marek J, Hana V et al (2006) Gamma knife radiosurgery for acromegaly–long-term experience. Clin Endocrinol (Oxf) 64:588–595 Medline. doi: 10.1111/j.1365-2265.2006.02513.x Google Scholar
  117. 117.
    Feigl GC, Bonelli CM, Berghold A, Mokry M (2002) Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function. J Neurosurg 97:415–421 MedlinePubMedGoogle Scholar
  118. 118.
    Iwai Y, Yamanaka K, Yoshioka K (2005) Radiosurgery for nonfunctioning pituitary adenomas. Neurosurgery 56:699–705. discussion 699–705 Medline. doi 10.1227/01.NEU.0000156836.42945.28:PubMedGoogle Scholar
  119. 119.
    Hoybye C, Grenback E, Rahn T, Degerblad M, Thoren M, Hulting AL (2001) Adrenocorticotropic hormone-producing pituitary tumors: 12- to 22-year follow-up after treatment with stereotactic radiosurgery. Neurosurgery 49:284–291. Discussion 291–292 Medline. doi: 10.1097/00006123-200108000-00008 PubMedGoogle Scholar
  120. 120.
    Vladyka V, Liscak R, Novotny J Jr, Marek J, Jezkova J (2003) Radiation tolerance of functioning pituitary tissue in gamma knife surgery for pituitary adenomas. Neurosurgery 52:309–316. Discussion 316–317 Medline. doi: 10.1227/01.NEU.0000043709.53906.31:PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Diabetes and EndocrinologyEast & North Hertfordshire NHS TrustWelwyn Garden CityUK
  2. 2.Department of EndocrinologyChristie Hospital NHS Trust ManchesterUK

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