Pituitary

, Volume 14, Issue 3, pp 276–283

Excess mortality for patients with residual disease following resection of pituitary adenomas

  • Michael E. Sughrue
  • Edward F. Chang
  • Rodney A. Gabriel
  • Manish K. Aghi
  • Lewis S. Blevins
Article

Abstract

The importance of achieving tumor control in pituitary adenoma surgery is not entirely established. This manuscript reviews the literature linking residual pituitary tumor and hormonal hypersecretion to increases in long term mortality. When possible, we utilized meta-analysis methods to estimate a pooled standardized mortality ratio (SMR), which relates the risk of mortality for a cohort of patients compared to a similar age and gender matched cohort in the general population, for patients with endocrinologic evidence of residual disease. When this was not possible, we review the existing literature in the results and discussion section of this review. We identified 10 articles regarding acromegaly and three articles regarding Cushing’s disease which presented SMR data for adult patients undergoing transphenoidal surgery with data divided into subgroups based on post-operative growth hormone levels. Using growth hormone levels of 2.5 μg/l as a cutoff, the mortality rate ratio was 1.83 (95% CI = 1.03–3.24) for patients with persistent acromegaly. Similarly, patients with persistent Cushing’s disease experienced a marked increase in mortality rate ratio compared to those experiencing initial cure (mortality rate ratio = 3.25 (95% CI = 1.54–6.84). For other tumor subtypes, (i.e. Endocrine inactive adenomas, Prolactinomas, and TSH secreting tumors) there were not enough studies identified to allow for rigorous statistical analysis. There is an increasing body of data suggesting that treatment refractory acromegaly and Cushing’s disease puts patients at risk for early mortality, suggesting that aggressive efforts to normalize hormone levels in these patients are justified.

Keywords

Mortality Pituitary tumors 

References

  1. 1.
    Levy A, Lightman S (2003) Molecular defects in the pathogenesis of pituitary tumours. Front Neuroendocrinol 24(2):94–127PubMedCrossRefGoogle Scholar
  2. 2.
    Melmed S (2008) Update in pituitary disease. J Clin Endocrinol Metab 93(2):331–338PubMedCrossRefGoogle Scholar
  3. 3.
    Chang EF, Sughrue ME, Zada G, Wilson CB, Blevins LS Jr, Kunwar S (2010) Long term outcome following repeat transsphenoidal surgery for recurrent endocrine-inactive pituitary adenomas. Pituitary 13(3):223–229PubMedCrossRefGoogle Scholar
  4. 4.
    Sughrue ME, Chang EF, Tyrell JB, Kunwar S, Wilson CB, Blevins LS Jr (2009) Pre-operative dopamine agonist therapy improves post-operative tumor control following prolactinoma resection. Pituitary 12(3):158–164PubMedCrossRefGoogle Scholar
  5. 5.
    DerSimonian R (1990) Combining evidence from clinical trials. Anesth Analg 70(5):475–476PubMedCrossRefGoogle Scholar
  6. 6.
    Der Simonian R (1996) Meta-analysis in the design and monitoring of clinical trials. Stat Med 15(12):1237–1248 discussion 1249–1252CrossRefGoogle Scholar
  7. 7.
    Der Simonian R, Charette LJ, McPeek B, Mosteller F (1982) Reporting on methods in clinical trials. N Engl J Med 306(22):1332–1337CrossRefGoogle Scholar
  8. 8.
    Der Simonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefGoogle Scholar
  9. 9.
    Abosch A, Tyrrell JB, Lamborn KR, Hannegan LT, Applebury CB, Wilson CB (1998) Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 83(10):3411–3418PubMedCrossRefGoogle Scholar
  10. 10.
    Arita K, Kurisu K, Tominaga A et al (2003) Mortality in 154 surgically treated patients with acromegaly: a 10-year follow-up survey. Endocr J 50(2):163–172PubMedCrossRefGoogle Scholar
  11. 11.
    Bates AS, Van’t Hoff W, Jones JM, Clayton RN (1993) An audit of outcome of treatment in acromegaly. Q J Med 86(5):293–299PubMedGoogle Scholar
  12. 12.
    Beauregard C, Truong U, Hardy J, Serri O (2003) Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol 58(1):86–91CrossRefGoogle Scholar
  13. 13.
    Biermasz NR, Dekker FW, Pereira AM et al (2004) Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab 89(6):2789–2796PubMedCrossRefGoogle Scholar
  14. 14.
    Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89(2):667–674PubMedCrossRefGoogle Scholar
  15. 15.
    Kauppinen-Makelin R, Sane T, Reunanen A et al (2005) A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab 90(7):4081–4086PubMedCrossRefGoogle Scholar
  16. 16.
    Orme SM, McNally RJ, Cartwright RA, Belchetz PE (1998) Mortality and cancer incidence in acromegaly: a retrospective cohort study. UK acromegaly study group. J Clin Endocrinol Metab 83(8):2730–2734PubMedCrossRefGoogle Scholar
  17. 17.
    Swearingen B, Barker FG II, Katznelson L et al (1998) Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83(10):3419–3426PubMedCrossRefGoogle Scholar
  18. 18.
    Trepp R, Stettler C, Zwahlen M, Seiler R, Diem P, Christ ER (2005) Treatment outcomes and mortality of 94 patients with acromegaly. Acta Neurochir 147(3):243–251 discussion 250–241CrossRefGoogle Scholar
  19. 19.
    Dekkers OM, Biermasz NR, Pereira AM et al (2007) Mortality in patients treated for Cushing’s disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab 92(3):976–981PubMedCrossRefGoogle Scholar
  20. 20.
    Hammer GD, Tyrrell JB, Lamborn KR et al (2004) Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab 89(12):6348–6357PubMedCrossRefGoogle Scholar
  21. 21.
    Lindholm J, Nielsen EH, Bjerre P et al (2006) Hypopituitarism and mortality in pituitary adenoma. Clin Endocrinol 65(1):51–58CrossRefGoogle Scholar
  22. 22.
    Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS (2004) Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab 89(4):1613–1617PubMedCrossRefGoogle Scholar
  23. 23.
    Etxabe J, Vazquez JA (1994) Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol 40(4):479–484CrossRefGoogle Scholar
  24. 24.
    Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK (1994) Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol 41(1):95–102CrossRefGoogle Scholar
  25. 25.
    Bengtsson BA, Eden S, Ernest I, Oden A, Sjogren B (1988) Epidemiology, long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223(4):327–335PubMedCrossRefGoogle Scholar
  26. 26.
    Mestron A, Webb SM, Astorga R et al (2004) Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish acromegaly registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol 151(4):439–446PubMedCrossRefGoogle Scholar
  27. 27.
    Bihan H, Espinosa C, Valdes-Socin H et al (2004) Long-term outcome of patients with acromegaly and congestive heart failure. J Clin Endocrinol Metab 89(11):5308–5313PubMedCrossRefGoogle Scholar
  28. 28.
    Holdaway IM, Bolland MJ, Gamble GD (2008) A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol 159(2):89–95PubMedCrossRefGoogle Scholar
  29. 29.
    Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R (1980) Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol 12(1):71–79CrossRefGoogle Scholar
  30. 30.
    Nabarro JD (1987) Acromegaly. Clin Endocrinol 26(4):481–512CrossRefGoogle Scholar
  31. 31.
    Welbourn RB (1985) Survival and causes of death after adrenalectomy for Cushing’s disease. Surgery 97(1):16–20PubMedGoogle Scholar
  32. 32.
    Watson RG, van Heerden JA, Northcutt RC, Grant CS, Ilstrup DM (1986) Results of adrenal surgery for Cushing’s syndrome: 10 years experience. World J Surg 10(4):531–538PubMedCrossRefGoogle Scholar
  33. 33.
    Grabner P, Hauer-Jensen M, Jervell J, Flatmark A (1991) Long-term results of treatment of Cushing’s disease by adrenalectomy. Eur J Surg 157(8):461–464PubMedGoogle Scholar
  34. 34.
    Favia G, Boscaro M, Lumachi F, D’Amico DF (1994) Role of bilateral adrenalectomy in Cushing’s disease. World J Surg 18(4):462–466PubMedCrossRefGoogle Scholar
  35. 35.
    Hoybye C, Grenback E, Rahn T, Degerblad M, Thoren M, Hulting AL (2001) Adrenocorticotropic hormone-producing pituitary tumors: 12–22-year follow-up after treatment with stereotactic radiosurgery. Neurosurgery 49(2):284–291 discussion 291–282PubMedCrossRefGoogle Scholar
  36. 36.
    Kobayashi T, Kida Y, Mori Y (2002) Gamma knife radiosurgery in the treatment of Cushing’s disease: long-term results. J Neurosurg 97(5 Suppl):422–428PubMedGoogle Scholar
  37. 37.
    Nagesser SK, van Seters AP, Kievit J et al (2000) Treatment of pituitary-dependent Cushing’s syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery. Clin Endocrinol 52(4):427–435CrossRefGoogle Scholar
  38. 38.
    Sheehan JM, Vance ML, Sheehan JP, Ellegala DB, Laws ER Jr (2000) Radiosurgery for Cushing’s disease after failed transsphenoidal surgery. J Neurosurg 93(5):738–742PubMedCrossRefGoogle Scholar
  39. 39.
    Swearingen B, Biller BM, Barker FG II et al (1999) Long-term mortality after transsphenoidal surgery for Cushing’s disease. Ann Intern Med 130(10):821–824PubMedGoogle Scholar
  40. 40.
    Pikkarainen L, Sane T, Reunanen A (1999) The survival and well-being of patients treated for Cushing’s syndrome. J Intern Med 245(5):463–468PubMedCrossRefGoogle Scholar
  41. 41.
    Barker FG II, Klibanski A, Swearingen B (2003) Transsphenoidal surgery for pituitary tumors in the US, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88(10):4709–4719PubMedCrossRefGoogle Scholar
  42. 42.
    Chang EF, Zada G, Kim S et al (2008) Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. J Neurosurg 108(4):736–745PubMedCrossRefGoogle Scholar
  43. 43.
    Tomlinson JW, Holden N, Hills RK et al (2001) Association between premature mortality and hypopituitarism. West midlands prospective hypopituitary study group. Lancet 357(9254):425–431PubMedCrossRefGoogle Scholar
  44. 44.
    Bates AS, Bullivant B, Sheppard MC, Stewart PM (1999) Life expectancy following surgery for pituitary tumours. Clin Endocrinol 50(3):315–319CrossRefGoogle Scholar
  45. 45.
    Sanno N, Teramoto A, Osamura RY (2000) Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma. J Neurosurg 93(2):194–200PubMedCrossRefGoogle Scholar
  46. 46.
    Teramoto A, Sanno N, Tahara S, Osamura YR (2004) Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment. Acta Neuropathol 108(2):147–153PubMedCrossRefGoogle Scholar
  47. 47.
    Beck-Peccoz P, Persani L (2006) TSH-induced hyperthyroidism caused by a pituitary tumor. Nat Clin Pract Endocrinol Metab 2(9):524–528 quiz following p 528PubMedCrossRefGoogle Scholar
  48. 48.
    Sanno N, Teramoto A, Osamura RY (2001) Thyrotropin-secreting pituitary adenomas. Clinical and biological heterogeneity and current treatment. J Neurooncol 54(2):179–186PubMedCrossRefGoogle Scholar
  49. 49.
    Chanson P, Weintraub BD, Harris AG (1993) Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas. A follow-up of 52 patients. Ann Intern Med 119(3):236–240PubMedGoogle Scholar
  50. 50.
    Caron P, Arlot S, Bauters C et al (2001) Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 86(6):2849–2853PubMedCrossRefGoogle Scholar
  51. 51.
    Kuhn JM, Arlot S, Lefebvre H et al (2000) Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide. J Clin Endocrinol Metab 85(4):1487–1491PubMedCrossRefGoogle Scholar
  52. 52.
    Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P (1996) Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 81(8):3084–3090PubMedCrossRefGoogle Scholar
  53. 53.
    Socin HV, Chanson P, Delemer B et al (2003) The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol 148(4):433–442PubMedCrossRefGoogle Scholar
  54. 54.
    Brucker-Davis F, Oldfield EH, Skarulis MC, Doppman JL, Weintraub BD (1999) Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 84(2):476–486PubMedCrossRefGoogle Scholar
  55. 55.
    Gesundheit N, Petrick PA, Nissim M et al (1989) Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of 9 patients. Ann Intern Med 111(10):827–835PubMedGoogle Scholar
  56. 56.
    McCutcheon IE, Weintraub BD, Oldfield EH (1990) Surgical treatment of thyrotropin-secreting pituitary adenomas. J Neurosurg 73(5):674–683PubMedCrossRefGoogle Scholar
  57. 57.
    Gancel A, Vuillermet P, Legrand A, Catus F, Thomas F, Kuhn JM (1994) Effects of a slow-release formulation of the new somatostatin analogue lanreotide in TSH-secreting pituitary adenomas. Clin Endocrinol 40(3):421–428CrossRefGoogle Scholar
  58. 58.
    Hankinson SE, Willett WC, Michaud DS et al (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 91(7):629–634PubMedCrossRefGoogle Scholar
  59. 59.
    Clayton RN, Stewart PM, Shalet SM, Wass JA (1999) Pituitary surgery for acromegaly. Should be done by specialists. BMJ 319(7210):588–589PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Michael E. Sughrue
    • 1
  • Edward F. Chang
    • 1
  • Rodney A. Gabriel
    • 1
  • Manish K. Aghi
    • 1
  • Lewis S. Blevins
    • 1
  1. 1.California Center for Pituitary DisordersUniversity of CaliforniaSan FranciscoUSA

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