Abstract
Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (p < 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (p = 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.
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Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M (2003) Diagnosis and complications of cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88:5593–5602
Sonino N, Fava GA (2001) Psychiatric disorders associated with Cushing’s syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs 15:361–373
De Martin M, ecori Giraldi PF, Cavagnini F (2006) Cushing’s disease. Pituitary 9:279–287
Kelly WF (1996) Psychiatric aspects of Cushing’s syndrome. QJM 89:543–551
Sonino N, Fava GA (1998) Psychosomatic aspects of Cushing’s disease. Psychother Psychosom 67:140–146
Sonino N, Fava GA, Belluardo P, Girelli ME, Boscaro M (1993) Course of depression in cushing’s syndrome: response to treatment and comparison with graves’ disease. Horm Res 39:202–206
van Aken MO, Pereira AM, Biermasz NR, van Thiel SW, Hoftijzer HC, Smit JW, Roelfsema F, Lamberts SW, Romijn JA (2005) Quality of life in patients after long-term biochemical cure of Cushing’s disease. J Clin Endocrinol Metab 90:3279–3286
Boscaro M, Barzon L, Fallo F, Sonino N (2001) Cushing’s syndrome. Lancet 357:783–791
Santos A, Resmini E, Martinez MA, Marti C, Ybarra J, Webb SM (2009) Quality of life in patients with pituitary tumors. Curr Opin Endocrinol Diabetes Obes 16:299–303
Lindsay JR, Nansel T, Baid S, Gumowski J, Nieman LK (2006) Long-term impaired quality of life in Cushing’s syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab 91:447–453
Webb SM, Badia X, Barahona MJ, Colao A, Strasburger CJ, Tabarin A, van Aken MO, Pivonello R, Stalla G, Lamberts SW, Glusman JE (2008) Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur J Endocrinol 158:623–630
Johnson MD, Woodburn CJ, Vance ML (2003) Quality of life in patients with a pituitary adenoma. Pituitary 6:81–87
Keil MF, Merke DP, Gandhi R, Wiggs EA, Obunse K, Stratakis CA (2009) Quality of life in children and adolescents 1-year after cure of cushing syndrome: a prospective study. Clin Endocrinol 71:326–333
Johnston DG, Alberti KG, Nattrass M, Barnes AJ, Bloom SR, Joplin GF (1980) Hormonal and metabolic rhythms in Cushing’s syndrome. Metabolism 29:1046–1052
Friedman TC, Garcia-Borreguero D, Hardwick D, Akuete CN, Doppman JL, Dorn LD, Barker CN, Yanovski JA, Chrousos GP (1994) Decreased delta-sleep and plasma delta-sleep-inducing peptide in patients with Cushing syndrome. Neuroendocrinology 60:626–634
Veldman RG, Frolich M, Pincus SM, Veldhuis JD, Roelfsema F (2000) Apparently complete restoration of normal daily adrenocorticotropin, cortisol, growth hormone, and prolactin secretory dynamics in adults with Cushing’s disease after clinically successful transsphenoidal adenomectomy. J Clin Endocrinol Metab 85:4039–4046
Atkinson AB, Kennedy A, Wiggam MI, McCance DR, Sheridan B (2005) Long-term remission rates after pituitary surgery for Cushing’s disease: the need for long-term surveillance. Clin Endocrinol 63:549–559
Estrada J, Boronat M, Mielgo M, Magallon R, Millan I, Diez S, Lucas T, Barcelo B (1997) The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing’s disease. N Engl J Med 336:172–177
de Bruin C, Pereira AM, Feelders RA, Romijn JA, Roelfsema F, Sprij-Mooij DM, van Aken MO, van der Lelij AJ, de Herder WW, Lamberts SW, Hofland LJ (2009) Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas. J Clin Endocrinol Metab 94:1118–1124
Feelders RA, de Bruin C, Pereira AM, Romijn JA, Netea-Maier RT, Hermus AR, Zelissen PM, van Heerebeek R, de Jong FH, van der Lely AJ, de Herder WW, Hofland LJ, Lamberts SW (2010) Pasireotide alone or with cabergoline and ketoconazole in Cushing’s disease. N Engl J Med 362:1846–1848
Nieman LK (2002) Medical therapy of Cushing’s disease. Pituitary 5:77–82
Heald AH, Ghosh S, Bray S, Gibson C, Anderson SG, Buckler H, Fowler HL (2004) Long-term negative impact on quality of life in patients with successfully treated Cushing’s disease. Clin Endocrinol 61:458–465
de Bos Kuil MJ, Endert E, Fliers E, Prummel MF, Romijn JA, Wiersinga WM (1998) Establishment of reference values for endocrine tests. I: Cushing’s syndrome. Neth J Med 53:153–163
Hunt SM, McKenna SP, McEwen J, Backett EM, Williams J, Papp E (1980) A quantitative approach to perceived health status: a validation study. J Epidemiol Community Health 34:281–286
Hinz A, Klaiberg A, Schumacher J, Brahler E (2003) The psychometric quality of the Nottingham health profile (nhp) in the general population. Psychother Psychosom Med Psychol 53:353–358
Spinhoven P, Ormel J, Sloekers PP, Kempen GI, Speckens AE, Van Hemert AM (1997) A validation study of the hospital anxiety and depression Scale (hads) in different groups of Dutch subjects. Psychol Med 27:363–370
Smets EM, Garssen B, Bonke B, De Haes JC (1995) The multidimensional fatigue inventory (mfi) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 39:315–325
Smets EM, Visser MR, Willems-Groot AF, Garssen B, Schuster-Uitterhoeve AL, de Haes JC (1998) Fatigue and radiotherapy: (b) experience in patients 9 months following treatment. Br J Cancer 78:907–912
Brazier JE, Harper R, Jones NM, O’Cathain A, Thomas KJ, Usherwood T, Westlake L (1992) Validating the sf-36 health survey questionnaire: new outcome measure for primary care. BMJ 305:160–164
VanderZee KI, Sanderman R, Heyink J (1996) A comparison of two multidimensional measures of health status: the Nottingham health profile and the rand 36-item health survey 1.0. Qual Life Res 5:165–174
Krieger DT, Allen W, Rizzo F, Krieger HP (1971) Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab 32:266–284
Liu JH, Kazer RR, Rasmussen DD (1987) Characterization of the twenty-four hour secretion patterns of adrenocorticotropin and cortisol in normal women and patients with Cushing’s disease. J Clin Endocrinol Metab 64:1027–1035
Pereira AM, Tiemensma J, Romijn JA (2010) Neuropsychiatric disorders in Cushing’s syndrome. Neuroendocrinology 92(Suppl 1):65–70
Lindholm J, Juul S, Jorgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jorgensen J, Kosteljanetz M, Kristensen L, Laurberg P, Schmidt K, Weeke J (2001) Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 86:117–123
Sonino N, Bonnini S, Fallo F, Boscaro M, Fava GA (2006) Personality characteristics and quality of life in patients treated for Cushing’s syndrome. Clin Endocrinol 64:314–318
van der Klaauw AA, Kars M, Biermasz NR, Roelfsema F, Dekkers OM, Corssmit EP, van Aken MO, Havekes B, Pereira AM, Pijl H, Smit JW, Romijn JA (2008) Disease-specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas. Clin Endocrinol 69:775–784
Santos A, Resmini E, Martinez-Momblan MA, Crespo I, Valassi E, Roset M, Badia X, Webb S (2012) Psychometric performance of the cushingqol questionnaire in conditions of real clinical practice. Eur J Endocrinol 167:337–342
Tiemensma J, Biermasz NR, Middelkoop HA, van der Mast RC, Romijn JA, Pereira AM (2010) Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing’s disease. J Clin Endocrinol Metab 95:E129–E141
Conflict of interest
A. J. van der Lely, W. W. de Herder, S. W. J. Lamberts and R. A. Feelders have performed consultancy activities for Novartis. This is an investigator-initiated trial sponsored by Novartis Pharma, Basel, Switzerland.
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Clinical Trial Registration Number: Dutch Trial Registry (No. 1379).
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van der Pas, R., de Bruin, C., Pereira, A.M. et al. Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease. Pituitary 16, 536–544 (2013). https://doi.org/10.1007/s11102-012-0452-2
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DOI: https://doi.org/10.1007/s11102-012-0452-2