Improving Quality of Life in Patients with Pituitary Tumours

US Endocrinology, 2014;10(1):79–83 DOI: http://doi.org/10.17925/USE.2014.10.01.79

Abstract:

Evaluation of health-related quality of life (QoL) in people with pituitary tumours has received much attention over the last 10–15 years. Most of them show impaired QoL, but little is known about how to prevent impairment or how to improve QoL. Our aim is to review what is known about QoL in pituitary tumours patients and to highlight the areas worth improving, for the patient’s well being. The article has four sections: acromegaly, Cushing’s syndrome, prolactinomas and non-functioning adenomas. Control of comorbidities is usually an important factor to prevent QoL impairment; however, each disease has specific characteristics that should be properly addressed in order to obtain full patient recovery after successful therapy.
Keywords: Quality of life, acromegaly, Cushing
Disclosure: The authors have no conflicts of interest to declare.
Received: January 10, 2013 Accepted January 29, 2013
Correspondence: Susan M Webb, Department of Endocrinology, Hospital de Sant Pau, C. S. Antoni Maria Claret n.167, 08025 Barcelona, Spain. E: swebb@santpau.cat
An erratum to this article can be found below.

Pituitary tumours are associated with pituitary dysfunction, either hypersecretion (mainly prolactinomas, acromegaly or Cushing’s disease [CD]) or hypopituitarism, due to compression or destruction of normal pituitary cells. They may also cause headache or visual disturbances due to pressure on surrounding structures. Health-related quality of life (QoL) is a concept that refers to individual wellbeing. It is based on how a particular individual feels, responds and functions in daily life. Subjects will value their QoL, taking into account their expectations, standards and goals, as well as the emotional, physical and social aspects of their lives, which may be affected if a disease is present.1 There are two kinds of tools normally used to measure QoL: generic and specific questionnaires. In both, patients answer questions related to their perception of their health status. Answers can be rated in yes/no questions, a Likert scale (i.e. always, often, sometimes, rarely, never) or in a range (i.e. 0–100). Generic questionnaires are useful in different populations, including healthy subjects. They can help to compare QoL in different diseases, for instance. Examples of generic questionnaires used in pituitary tumours are the Nottingham Health Profile (NHP),2 Short-Form 36 (SF-36),3 the EuroQoL4–6 or the Psychological General Wellbeing Scale (PGWBS)7 (see Table 1). However, they are often not sensitive enough to appreciate particular problems that may be related to a certain disease. That is why diseasespecific questionnaires have been developed, more sensitive to detect subtle changes in QoL in a determined disease (for instance, improvement after treatment). For pituitary adenomas, questionnaires often used are AcroQoL for acromegaly,8 CushingQoL for Cushing’s syndrome (CS)9,10 and Adult Growth Hormone Deficiency Assessment (AGHDA)11 or Questions on Life Satisfaction-Hypopituitarism (QLS-H) for growth hormone (GH) deficiency12,13 (see Table 1). The following section reviews what is known about QoL in patients with pituitary tumours, both at diagnosis and after treatment, highlighting what may be helpful to improve QoL. Acromegaly Acromegaly is a syndrome caused by chronic exposure to elevated levels of GH and peripheral insulin-like growth factor 1 (IGF-I). It is associated with morphological changes (including soft tissue swelling, excessive sweating and change in patients’ voice), often not completely reversible, with physical and psychological limitations (including joint pains, headache, low energy and libido). Due to the insidious nature of the disease, the diagnosis of acromegaly is significantly delayed, being undiagnosed for years, despite the presence of signs and symptoms, thus, the impact of the disease and its treatment on the patients’ QoL can be great.14–18 When compared with the general population, SF-36 questionnaire scores are lower in acromegaly, reflecting impairment of perceived QoL in physical function dimensions, but not in the mental ones.19 Successful surgery or medical treatment may be followed by marked improvement in the patient’s overall health, often, but not always, accompanied by improvement or normalisation of biochemical parameters such as GH and IGF-I. Since comorbidities occur after many years of exposure to excessive GH, an earlier diagnosis would benefit patients’ perceived health and QoL.20,21 The availability of a questionnaire, specifically designed to evaluate the problems typical of acromegaly (AcroQoL), has favoured research in this area. This is particularly important in consideration of the fact that GH and IGF-I do not always correlate with subjective and clinical improvements experienced by patients and physicians after treatment.22 With AcroQoL, lower scores in active disease have persistently been observed in different countries, compared with patients in remission after successful therapy, with appearance being the most affected dimension and the personal relations area the least affected.23–26 However, impairments in QoL, as assessed by the generic questionnaire PGWBS, persist in ‘cured’ acromegaly compared with the normal population and patients treated for a non-functioning pituitary adenoma, mainly in the domains of general health and vitality, and similarly bad or worse than adults with GH deficiency.27
References:
  1. Webb SM, Resmini E, Santos A, et al., Quality of Life in acromegaly and Growth Hormone Deficiency. In: Ken Ho (editor), Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician, New York City: Humana Press, 2011;201;237–50.
  2. Hunt SM, McKenna SP, McEwen J, et al., The Nottingham Health profile: Subjective health status and medical consultations, Soc Sci Med, 1981;15A:221–9.
  3. Ware JE, Snow KK, Kosinski M, et al., SF-36 Health Survey. Manual and Interpretation Guide. Boston: The Health Institute, New England Medical Center, 1993.
  4. Dolan P, Modelling valuations for EuroQol health states, Medical Care, 1997;35(11):1095–108.
  5. Badia X, Herdman M, Schiaffino A, A determining correspondence between scores on the EQ-5D “thermometer” and a 5-point categorical rating scale, Medical Care, 1999;37(1):671–7.
  6. Brooks R, EuroQol: the current state of play, Health Policy, 1996;37:53–7.
  7. Gray LC, Goldsmith HF, Livieratos BB, et al., Individual and contextual social-status contributions to psychological wellbeing, Soc & Soc Res,1983;68(1):78–95.
  8. Webb SM, Prieto L, Badia X, et al. Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties, Clin Endocrinol, 2002;57(2):251–8.
  9. Webb SM, Badia X, Barahona MJ, et al., Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire, Eur J Endocrinol, 2008;158(5):623–30.
  10. Santos A, Resmini E, Martínez-Momblán MA, et al., Psychometric performance of the CushingQoL questionnaire in conditions of clinical practice, Eur J Endocrinol, 2012;167(3):337–42.
  11. McKenna SP, Doward LC, Alonso J, et al., The QoL.AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency, Qual Life Res, 1999;8(4):373–83.
  12. Blum WF, Shavrikova EP, Edwards DJ, et al., Decreased quality of life in adult patients with growth hormone deficiency compared with general populations using the new, validated, self-weighted questionnaire, questions on life satisfaction hypopituitarism module, J Clin Endocrinol Metab, 2003;88:4158–67.
  13. Rosilio M, Blum WF, Edwards DJ, et al., Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by QLS-H, J Clin Endocrinol Metab, 2004;89(9):1684–93.
  14. Biermasz NK, Pereira AM, Smit JWA,et al., Morbidity after long-term remission for acromegaly: Persisting joint-related complaints cause reduced quality of life, J Clin Endocrinol Metab, 2005(4);90:2731–9.
  15. Cappola A, Disorders of the Anterior Pituitary and Hipothalamus. In: Kasper DL, Braunwald E, Fauci AS, et al., (eds), Harrison’s Manual of Medicine, New York City: McGrawHill, 2005; 807–13.
  16. Melmed S, Acromegaly pathogenesis and treatment, J Clin Invest, 2009;119(5):3189–202.
  17. Vanucci L, Luciani P, Gagliardi E, et al., Assessment of sleep apnea syndrome in treated acromegalic patients and correlation of its severity with clinical and laboratory parameters, J Endocrinol Invest, 2012; Epub ahead of print.
  18. Unubol M, Eryilmaz U, Guney E, et al., QT dispersion in patients with acromegaly, Endocrine, 2012; Epub ahead of print.
  19. Johnson MD, Woodburn CJ, Vance ML, Quality of life in patients with a pituitary adenoma, Pituitary, 2003;6(2):81–7.
  20. Melikoglu MA, Sezer I, Kocabas H, et al., Acromegalic arthropathy of the hip: a case report, Acta Rumatol Port, 2008;33(3):357–9
  21. Siegel S, Streetz-van der Werf C, Schott JS, et al., Diagnostic delay is associated with psychosocial impairment in acromegaly, Pituitary, 2012; Epub ahead of print.
  22. Neggers SJ, van Aken MO, de Herder WW, et al., Quality of life in acromegalic patients during long-term somatostatin analog treatment with and without pegvisomant, J Clin Endocrinol Metab, 2008;93(10):3853–9.
  23. Webb SM, Badia X, Surinach NL, et al., Validity and clinical applicability of the acromegaly quality of life questionnaire AcroQoL: a 6-month prospective study, Eur J Endocrinol, 2006;155(2):269–77.
  24. Matta MP, Couture E, Cazals L, et al., Impaired quality of life of patients with acromegaly: control of GH/IGF-1 excess improves psychological subscale appearance, Eur J Endocrinol, 2008;158(3):305–10.
  25. Trepp R, Everts R, Stettler C, et al., Assessment of quality of life in patients with uncontrolled versus controlled acromegaly using the acromegaly quality of life questionnaire (AcroQoL), Clin Endocrinol, 2005;63(1):103–10.
  26. Deyneli O, Yavuz D, Gozu H, et al. Evaluation of quality of life in Turkish patients with acromegaly (abstract P3-508). In: Programs and abstracts of the 84th Annual Meeting of the Endocrine Society, Philadelphia, 2003.
  27. Rowles SV, Prieto L, Badia X, et al., Quality of life (QOL) in patients with acromegaly is severely impaired: Use of a novel measure of QOL: Acromegaly quality of life questionnaire, J Clin Endocrinol Metab, 2005;90(6):3337–41.
  28. Galdiero M, Pivonello R, Grasso LF, et al., Growth hormone, prolactin, and sexuality, J Endocrinol Invest, 2012;35(8):782–94.
  29. Ruchala M, Stangierska I, Gurgul E, et al., The effect of octreotide treatment on somatic and psychological symptoms of acromegaly, Neuro Endocrinol Lett, 2010;31(2):265–9.
  30. Sardella C, Lombardi M, Rossi G, et al., Short and long-term changes of quality of life in patients with acromegaly, results from a prospective study, J Endocrinol Invest, 2010;33(1):20–25.
  31. Sievers C, Brübach K, Saller B, et al., Change of symptoms and perceived health in acromegalic patients on pegvisomant therapy: a retrospective cohort study within the German Pegvisomant Observational Study (GPOS), Clin Endocrinol (Oxf), 2010;73(1):89–94.
  32. Lombardi G, Minuto F, Tamburrano G, et al., Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in somatostatin analogue-naive patients with acromegaly, J Endocrinol Invest, 2009;32(3):202–9.
  33. Postma MR, Netea-Maiter RT, Van den Berg G, et al., Quality of life is impaired in association with the need for prolenged postoperative therapy by somatostatin analogs in patients with acromegaly, Eur J Endocrinol, 2012;166(4):585–92.
  34. Biermasz NK, Van Thiel SW, Pereira AM, et al., Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess, J Clin Endocrinol Metab, 2004;89(11):5369–76.
  35. Van der Klaauw AA, Biermasz NR, Hoftijzer HC, et al., Previous radiotherapy negatively influences quality of life during 4 years of follow-up in patients cured from acromegaly, Clin Endocrinol (Oxf), 2008;69(1):123–8.
  36. Miller A, Doll H, David J, Wass J, Impact of musculoskeletal disease on quality of life in long-standing acromegaly, Eur J Endocrinol, 2008;158(5):587–93.
  37. Melmed S, Colao A, Barkan A, et al., Guidelines for acromegaly management: an update, J Clin Endocrinol Metab, 2009;94(5):1509–17.
  38. Ciric I, Ragin A, Baumgartner C, et al., Complications of transsphenoidal surgery: results of a national survey, review of the literature and personal experience, Neurosurgery, 1997;40(2):225–36.
  39. Ahmed E, Stratton P, Adams W, Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience, Clin Endocrinol (Oxf), 1999;50(5):561–67.
  40. Gittoes NJ, Sheppard MC, Johnson AP, Stewart PM, Outcome of surgery for acromegaly-the experience of a dedicated pituitary surgeon, QJM, 1999;92(12):741–5.
  41. 41. Bates PR, Carson MN, Trainer PJ, et al., Wide variation in surgical outcomes for acromegaly in the UK, Clin Endocrinol (Oxf), 2008;68(1):136–142.
  42. Sievers C, Ising M, Pfister H, et al., Personality in patients with pituitary adenomas is characterised by increased anxiety related traits: comparison of 70 Acromegalic patients to patients with non-functioning pituitary adenomas and age and gender matched controls, Eur J Endocrinol, 2009;160:367–73.
  43. Van der Klaauw AA, Kars M, Biermasz NR, et al., Diseasespecific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas, Clin Endocrinol, 2008;69(5):775–84.
  44. Kauppinen-Mäkelin R, Sane T, Sintonen H, et al., Quality of Life in Treated Patients with Acromegaly, J Clin Endocrinol Metab, 2006;91:3891–6.
  45. Wexler T, Gunnell L, Omer Z, et al., Growth hormone deficiency is associated with decreased quality of life in patients with prior acromegaly, J Clin Endocrinol Metab, 2009;94:2471–7.
  46. Van der Klaauw AA, Bax JJ, Roelfsema F, et al., Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly, Pituitary, 2009;12(4):339–46.
  47. Lindsay JR, Nansel T, Baid S, et al., Long-term impaired quality of life in Cushing’s syndrome despite initial improvement after surgical remission, J Clin Endocrinol Metab, 2006;91:447–53.
  48. Lindholm J, Juul S, Jorgensen JO, et al., Incidence and late prognosis of Cushing’s syndrome: a population-based study, J Clin Endocrinol Metab, 2001;86:117–23.
  49. Hawn MT, Cook D, Deveney C, et al., Quality of life after laparoscopic bilateral adrenalectomy for Cushing’s disease, Surgery, 2002;132(6):1064–8.
  50. Wagenmakers MA, Netea-Maier RT, Prins JB, et al., Impaired quality of life in patients in long-term remission of Cushing’s syndrome of both adrenal and pituitary origin: a remaining effect of long-standing hypercortisolism?, Eur J Endocrinol, 2012;167(5):687–95.
  51. Van Aken MO, Pereira AM, Biermasz NR, et al., Quality of Life in Patients After Long-term Biochemical Cure of Cushing’s Disease, J Clin Endocrinol Metab, 2002;90(6):3279–86.
  52. Heald AH, Ghosh S, Bray S, et al., Long-term negative impact on quality of life in patients with successfully treated Cushing’s disease, Clin Endocrinol, 2004;61:458–65.
  53. Sonino N, Navarrini C, Ruini C, et al., Persistent psychological distress in patients treated for endocrine disease, Psychother Psychosom, 2004;73:(4)78–83.
  54. Gotch PM, Cushing’s syndrome from the patient’s perspective, Endocrinol Metab Clin North Am, 1994;23(3):607–17
  55. Pikkarainen L, Sane T, Reunanen A, The survival and wellbeing of patients treated for Cushing’s syndrome, J Intern Med, 1999;245(5):463–8.
  56. Valassi E, Santos A, Yaneva M, et al., The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics, Eur J Endocrinol, 2011;165(3):383–92.
  57. Sonino N, Fava GA, Psychosomatic aspects of Cushing’s disease, Psychother Psychosom, 1998;67(3):140–46.
  58. Bourdeau I, Bard C, Noel B, et al., A loss of brain volume in endogenous Cushing’s syndrome and its reversibility after correction of hypercortisolism, J Clin Endocrinol Metab, 2002;87(5):1949–54.
  59. Dorn LD, Burgess ES, Friedman TC, et al., The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism, J Clin Endocrinol Metab, 1997;82:(3)912–919.
  60. O’Riordain DS, Farley DR, Young WF Jr, et al., Long-term outcome of bilateral adrenalectomy in patients with Cushing’s syndrome, Surgery, 1994;116(6):1088–94.
  61. Nagesser SK, van Seters AP, Kievit J, et al., Long-term results of total adrenalectomy for Cushing’s disease, World J Surg, 2000;24(1):108–13.
  62. Thompson SK, Hayman AV, Ludlam WH, et al., Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing’s disease: a 10-year experience, Ann Surg, 2007;245(5):790–94
  63. Sippel RS, Elaraj DM, Kebebew E, et al., Waiting for change: Symptom resolution after adrenalectomy for Cushing’s syndrome, Surgery, 2008;144(6):1054–61.
  64. Smith PW, Turza KC, Carter CO, et al., Bilateral adrenalectomy for refractory Cushing’s Disease: A safe and definitive therapy, J Am Coll Surg, 2009;208(6):1059–64.
  65. Dekkers OM, van der Klaauw AA, Pereira AM, et al., Quality of life is decreased after treatment for nonfunctioning pituitary macroadenomas, J Clin Endocrinol Metab, 2006;91:3364–69.
  66. Capatina C, Christodoulides C, Fernandez A, et al., Current treatment protocols can offer a normal or near normal quality of life in the majority of patients with non-functioning pituitary adenomas, Clin Endocrinol, 2013;78(1):86–93.
  67. Page RC, Hammersley MS, Burke CW, et al., An account of the quality of life of patients after treatment for non-functioning pituitary tumours, Clin Endocrinol, 1997;46(4):401–6.
  68. Nielsen EH, Lindholm J, Laurberg P, et al., Non-functioning pituitary adenomas: incidence, causes of death and quality of life in relation to pituitary function, Pituitary, 2007;10(1):67–73.
  69. Degerblad M, Grunditz R, Hall K, et al., Substitution therapy with recombinant growth hormone (Somatrem) in adults with growth hormone deficiency, Acta Paediatr Scand, 1987;337(Suppl.):170–1.
  70. Salomon F, Cuneo R, Hesp R, et al., The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency, N Engl J Med, 1989;321(26):1797–803.
  71. Cuneo R, Salomon F, McGauley G, et al., The growth hormone deficiency syndrome in adults, Clin Endocrinol, 1992;37(5):387–97.
  72. McGauley GA, Cuneo RC, Salomon F, et al., Psychological wellbeing before and after growth hormone treatment in adults with growth hormone deficiency, Horm Res, 1990;33(Suppl. 4):52–4.
  73. Koltowska-Häggström M, Kind P, Monson, et al., Growth hormone (GH) replacement in hypopituitary adults with GH deficiency evaluated by a utility-weighted quality of life index: a precursor to cost–utility analysis, Clin Endocrinol, 2008;68:122–9.
  74. Höybye C, Ragnarsson O, Jönsson PJ, et al., Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing’s disease, Eur J Endocrinol, 2010;162(4):677–84.
  75. Miller KK, Wexler T, Fazeli P, et al., Growth hormone deficiency after treatment of acromegaly: a randomised, placebocontrolled study of growth hormone replacement, J Clin Endocrinol Metab, 2010;95:567–77.
  76. Lombardi G, di Somma C, Grasso LF, et al., The Cardiovascular System in GH excess and GH deficiency, J Encocrinol Invest, 2012;35(11):1021–9.
  77. Giavoli C, Profka E, Verrua E, et al., GH Replacement Improves Quality of Life and Metabolic Parameters in Cured Acromegalic Patients with Growth Hormone Deficiency, J Clin Endocrinol Metab, 2012;97(11):3983–8.
  78. Spielhagen C, Schwahn C, Möller K, et al., The benefit of long-term growth hormone (GH) replacement therapy in hypopituitary adults with GH deficiency: results of the German KIMS database, Growth Horm IGF Res, 2011;21(1);1–10.
  79. Kann PH, Growth Hormone therapy in adult patients: a review, Wien Klin Wochenschr, 2011;123(9–10:259–67.
  80. Koltowska-Häggström M, Mattsson AF, Shalet SM, Assessment of quality of life in adult patients with GH deficiency: KIMS contribution to clinical practice and pharmacoeconomic evaluations, Eur J Endocrinol, 2009;161(Suppl. 1):S51–64.
  81. Attanasio AF, Shavrikova EP, Blum WF, et al., Quality of life in childhood onset growth hormone-deficient patients in the transition phase from childhood to adulthood, J Clin Endocrinol Metab, 2005;90:4525–9.
  82. Biermasz NR, Joustra SD, Donga E, et al., Patients previously treated for non-functioning pituitary macroadenomas have disturbed sleep characteristics, circadian movement rhythm and subjective sleep quality, J Clin Endocrinol Metab, 2011;96(5):1524–32.
  83. Reddy R, Cudlip S, Byrne JV, et al., Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma?, Eur J Endocrinol, 2011;165(5):739–44.
  84. Van Beek AP, van den Bergh AC, van den Berg LM, et al., Radiotherapy is not associated with reduced quality of life and cognitive function in patients treated for nonfunctioning pituitary adenoma, Int J Radiat Oncol Biol Phys, 2007;68:986–91.
  85. Cesar de Oliveira Naliato E, Dutra Violante AH, Caldas D, et al., Quality of life in women with microprolactinoma treated with dopamine agonists, Pituitary, 2008;11(3):247–54.
  86. Kars M, van der Klaauw AA, Onstein CS, et al., Quality of life is decreased in female patients treated for microprolactinoma, Eur J Endocrinol, 2007;157(2):133–9.
  87. Athanasoulia AP, Ising M, Pfister H, et al., Distinct dopaminergic personality patterns in patients with prolactinomas: A comparison with non-functioning pituitary adenoma patients and age- and gender-matched controls, Neuroendocrinology, 2012;96(3):204–11.
  88. Kars M, Dekkers OM, Pereira AM, et al., Update in prolactinomas, Neth J Med, 2010;68(3):104–12.
  89. Ciccarelli A, Guerra E, De Rosa M, et al., PRL secreting adenomas in male patients, Pituitary, 2005;8:39–42.
Keywords: Quality of life, acromegaly, Cushing