Skip to main content

Advertisement

SpringerLink
Log in

Characterization of persistent and recurrent Cushing’s disease

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

A case of possible recurrent Cushing’s disease (CD) is presented and data on current definitions of CD remission, persistence, and recurrence are reviewed. While prevailing guidelines recommend the use of serum cortisol in the first post-operative week for defining initial remission and predicting sustained remission, with the use of 24 h urinary free cortisol measurements if serum cortisol values are equivocal, there is debate as to which methods and thresholds best define CD remission and predict successful outcomes. Other methods used to define remission (and hence persistence and recurrence) include restoration of cortisol suppression after dexamethasone and physiologic diurnal cortisol rhythm as measured by midnight salivary free cortisol. However, the number and degree of abnormal test results needed to define recurrence, and the determination of which biochemical test has more significance when there are discrepancies between markers is inconsistent among studies. Further inquiry is warranted to examine if patients in apparent CD remission who have subtle hypothalamic pituitary adrenal (HPA) axis abnormalities represent distinctive remission subtypes versus mild or early recurrence. Additional investigation could also explore the degree to which these HPA axis abnormalities, such as alterations in cortisol circadian rhythm or partial resistance to dexamethasone, are associated with persistence of CD morbidities, including neuropsychiatric impairments, alterations in body composition, and cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ambrosi B, Faglia G, the Multicenter Pituitary umor Study Group, Lombardia Region (1991) Epidemiology of pituitary tumors. In: Faglia G, Beck-Peccoz P, Ambrosi B, Travaglini P, Spada A (eds) Pituitary adenomas: new trends in basic and clinical research. Excerpta Medica, Amsterdam, pp 159–168

    Google Scholar 

  2. Etxabe J, Vazquez JA (1994) Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf) 40(4):479–484

    Article  CAS  Google Scholar 

  3. Plotz CM, Knowlton AI, Ragan C (1952) The natural history of Cushing’s syndrome. Am J Med 13(5):597–614

    Article  CAS  PubMed  Google Scholar 

  4. Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stella GK, Swearingen B, Vance ML, Wass JA, Boscaro M (2008) Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93(7):2454–2462

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Boscaro M, Barzon L, Fallo F, Sonino N (2001) Cushing’s syndrome. Lancet 357(9258):783–791

    Article  CAS  PubMed  Google Scholar 

  6. Newell-Price J, Trainer P, Besser M, Grossman A (1998) The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 19(5):647–672

    CAS  PubMed  Google Scholar 

  7. Findling JW, Raff H (2006) Cushing’s Syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab 91(10):3746–3753

    Article  CAS  PubMed  Google Scholar 

  8. Starkman MN, Schteingart DE (1981) Neuropsychiatric manifestations of patients with Cushing’s syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. Arch Intern Med 141(2):215–219

    Article  CAS  PubMed  Google Scholar 

  9. Dorn LD, Burgess ES, Dubbert B, Simpson SE, Friedman T, Kling M, Gold PW, Chrousos GP (1995) Psychopathology in patients with endogenous Cushing’s syndrome: “atypical” or melancholic features. Clin Endocrinol (Oxf) 43(4):433–442

    Article  CAS  Google Scholar 

  10. Chee GH, Mathias DB, James RA, Kendall-Taylor P (2001) Transsphenoidal pituitary surgery in Cushing’s disease: can we predict outcome? Clin Endocrinol (Oxf) 54(5):617–626

    Article  CAS  Google Scholar 

  11. Estrada J, Garcia-Uria J, Lamas C, Alfaro J, Lucas T, Diez S, Salto L, Barcelo B (2001) The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 86(12):5695–5699

    CAS  PubMed  Google Scholar 

  12. Pereira AM, van Aken MO, van Dulken H, Schutte PJ, Biermasz NR, Smit JW, Roelfsema F, Romijn JA (2003) Long-term predictive value of postsurgical cortisol concentrations for cure and risk of recurrence in Cushing’s disease. J Clin Endocrinol Metab 88(12):5858–5864

    Article  CAS  PubMed  Google Scholar 

  13. Carrasco CA, Coste J, Guignat L, Groussin L, Duque MA, Gaillard S, Bertagna X, Betherat J (2008) Midnight salivary cortisol determination for assessing the outcome of transsphenoidal surgery in Cushing’s disease. J Clin Endocrinol Metab 93(12):4728–4734

    Article  CAS  PubMed  Google Scholar 

  14. Valero R, Vallette-Kasic S, Conte-Devolx B, Jaquet P, Brue T (2004) The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing’s disease. Eur J Endocrinol 151(6):727–733

    Article  CAS  PubMed  Google Scholar 

  15. Salem V, Dhillo WS, Meeran K, Donaldson M, Martin NM (2010) Dexamethasone-suppressed corticotrophin-releasing hormone-stimulation test does not reliably diagnose or predict recurrence of Cushing disease. Clin Chem 56(6):1031–1034

    Article  CAS  PubMed  Google Scholar 

  16. Schrell U, Fahlbusch R, Buchfelder M, Riedl S, Stalla GK, Muller OA (1987) Corticotropin-releasing hormone stimulation test before and after transsphenoidal selective microadenomectomy in 30 patients with Cushing’s disease. J Clin Endocrinol Metab 64(6):1150–1159

    Article  CAS  PubMed  Google Scholar 

  17. Shimon I, Ram Z, Cohen ZR, Hadani M (2002) Transsphenoidal surgery for Cushing’s disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery 51(1):57–61 discussion 61-2

    Article  PubMed  Google Scholar 

  18. Hammer GD, Tyrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, Rahl R, Lu A, Wilson CB (2004) Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab 89(12):6348–6357

    Article  CAS  PubMed  Google Scholar 

  19. 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 (Oxf) 63(5):549–559

    Article  Google Scholar 

  20. Chen JC, Amar AP, Choi S, Singer P, Couldwell WT, Weiss MH (2003) Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg 98(5):967–973

    Article  PubMed  Google Scholar 

  21. Esposito F, Dusick JR, Cohan P, Moftakhar P, McArthur D, Wang C, Swerdloff RS, Kelly DF (2006) Clinical review: early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 91(1):7–13

    Article  CAS  PubMed  Google Scholar 

  22. Rees DA, Hanna FW, Davies JS, Mills RG, Vafidis J, Scanlon MF (2002) Long-term follow-up results of transsphenoidal surgery for Cushing’s disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf) 56(4):541–551

    Article  CAS  Google Scholar 

  23. Yap LB, Turner HE, Adams CB, Wass JA (2002) Undetectable postoperative cortisol does not always predict long-term remission in Cushing’s disease: a single centre audit. Clin Endocrinol (Oxf) 56(1):25–31

    Article  CAS  Google Scholar 

  24. McCance DR, Besser M, Atkinson AB (1996) Assessment of cure after transsphenoidal surgery for Cushing’s disease. Clin Endocrinol (Oxf) 44(1):1–6

    Article  CAS  Google Scholar 

  25. Trainer PJ, Lawrie HS, Verhelst J, Howlett TA, Lowe DG, Grossman AB, Savage MO, Afshar F, Besser GM (1993) Transsphenoidal resection in Cushing’s disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf) 38(1):73–78

    Article  CAS  Google Scholar 

  26. Pieters GF, Hermus AR, Meijer E, Smals AG, Kloppenborg PW (1989) Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing’s disease. J Clin Endocrinol Metab 69(6):1122–1126

    Article  CAS  PubMed  Google Scholar 

  27. Locatelli M, Vance ML, Laws ER (2005) Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 90(9):5478–5482

    Article  CAS  PubMed  Google Scholar 

  28. Patil CG, Prevedello DM, Lad SP, Vance ML, Thorner MO, Katznelson L, Laws ER (2008) Late recurrences of Cushing’s disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab 93(2):358–362

    Article  CAS  PubMed  Google Scholar 

  29. Alexandraki KI, Kaltsas GA, Isidori AM, Storr HL, Afshar F, Sabin I, Akker SA, Chew SL, Drake WM, Monson JP, Besser GM, Grossman AB (2013) Long-term remission and recurrence rates in Cushing’s disease: predictive factors in a single-centre study. Eur J Endocrinol 168(4):639–648

    Article  CAS  PubMed  Google Scholar 

  30. Hofmann BM, Hlavac M, Martinez R, Buchfelder M, Muller OA, Fahlbusch R (2008) Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg 108(1):9–18

    Article  PubMed  Google Scholar 

  31. Toms GC, McCarthy MI, Nieven MJ, Orteu CH, King TT, Monson JP (1993) Predicting relapse after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 76(2):291–294

    CAS  PubMed  Google Scholar 

  32. Valassi E, Biller BM, Swearingen B, Pecori Giraldi F, Losa M, Mortini P, Hayden D, Cavagnini F, Klibanski A (2010) Delayed remission after transsphenoidal surgery in patients with Cushing’s disease. J Clin Endocrinol Metab 95(2):601–610

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Bochicchio D, Losa M, Buchfelder M (1995) Factors influencing the immediate and late outcome of Cushing’s disease treated by transsphenoidal surgery: a retrospective study by the European Cushing’s Disease Survey Group. J Clin Endocrinol Metab 80(11):3114–3120

    CAS  PubMed  Google Scholar 

  34. Newell-Price J, Trainer P, Besser M, Grossman A (1998) The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 19(5):647–672

    CAS  PubMed  Google Scholar 

  35. Kidambi S, Raff H, Findling JW (2007) Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing’s syndrome. Eur J Endocrinol 157(6):725–731

    Article  CAS  PubMed  Google Scholar 

  36. Raff H, Raff JL, Findling JW (1998) Late-night salivary cortisol as a screening test for Cushing’s syndrome. J Clin Endocrinol Metab 83(8):2681–2686

    CAS  PubMed  Google Scholar 

  37. Putignano P, Toja P, Dubini A, Pecori Giraldi F, Corsello SM, Cavagnini F (2003) Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J Clin Endocrinol Metab 88(9):4153–4157

    Article  CAS  PubMed  Google Scholar 

  38. Hofmann BM, Hlavac M, Kreutzer J, Grabenbauer G, Fahlbusch R (2006) Surgical treatment of recurrent Cushing’s disease. Neurosurgery 58(6):1108–1118 discussion 1108–1118

    Article  PubMed  Google Scholar 

  39. Dickerman RD, Oldfield EH (2002) Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery. J Neurosurg 97(6):1343–1349

    Article  PubMed  Google Scholar 

  40. Nakane T, Kuwayama A, Watanabe M, Takahashi T, Kato T, Ichihara K, Kageyama N (1987) Long term results of transsphenoidal adenomectomy in patients with Cushing’s disease. Neurosurgery 21(2):218–222

    Article  CAS  PubMed  Google Scholar 

  41. Benveniste RJ et al (2005) Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg 102(6):1004–1012

    Article  PubMed  Google Scholar 

  42. Hofmann BM, Fahlbusch R (2006) Treatment of Cushing’s disease: a retrospective clinical study of the latest 100 cases. Front Horm Res 34:158–184

    Article  PubMed  Google Scholar 

  43. Knappe UJ, Lüdecke DK (1996) Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing’s disease. Acta Neurochir Suppl 65:31–34

    CAS  PubMed  Google Scholar 

  44. Friedman RB, Oldfield RB, Nieman LK, Chrousos GP, Doppman JL, Cutler GB, Loriaux DL (1989) Repeat transsphenoidal surgery for Cushing’s disease. J Neurosurg 71(4):520–527

    Article  CAS  PubMed  Google Scholar 

  45. Knappe UJ, Lüdecke DK (1996) Transnasal microsurgery in children and adolescents with Cushing’s disease. Neurosurgery 39(3):484–492 discussion 492–493

    CAS  PubMed  Google Scholar 

  46. Patil CG, Veeravagu A, Prevedello DM, Katznelson L, Vance ML, Laws ER (2008) Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery 63(2):266–270 discussion 270–271

    Article  PubMed  Google Scholar 

  47. Estrada J, Boronat M, Mielgo M, Magallón R, Millan I, Díez S, Lucas T, Barceló B (1997) The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing’s disease. N Engl J Med 336(3):172–177

    Article  CAS  PubMed  Google Scholar 

  48. McLaughlin N, Kassam AB, Prevedello DM, Kelly DF (2011) Management of Cushing’s disease after failed surgery–a review. Can J Neurol Sci 38(1):12–21

    PubMed  Google Scholar 

  49. Sheehan JM, Vance ML, Sheehan JP, Ellegala DB, Laws ER (2000) Radiosurgery for Cushing’s disease after failed transsphenoidal surgery. J Neurosurg 93(5):738–742

    Article  CAS  PubMed  Google Scholar 

  50. Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Steiner L, Vance ML (2007) Gamma Knife surgery for Cushing’s disease. J Neurosurg 106(6):980–987

    Article  PubMed  Google Scholar 

  51. Castinetti F, Nagai M, Dufour H, Kuhn JM, Morange I, Jaquet P, Conte-Devolx B, Regis J, Brue T (2007) Gamma knife radiosurgery is a successful adjunctive treatment in Cushing’s disease. Eur J Endocrinol 156(1):91–98

    Article  CAS  PubMed  Google Scholar 

  52. Aghi MK, Petit J, Chapman P, Loeffler J, Klibanski A, Biller BK, Swearingen B (2008) Management of recurrent and refractory Cushing’s disease with reoperation and/or proton beam radiosurgery. Clin Neurosurg 55:141–144

    PubMed  Google Scholar 

  53. Petit JH, Biller BK, Yock TI, Swearingen B, Coen JJ, Chapman P, Ancukiewicz M, Bussiere M, Klibanski A, Loeffler JS (2008) Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas. J Clin Endocrinol Metab 93(2):393–399

    Article  CAS  PubMed  Google Scholar 

  54. Kelly DF (2007) Transsphenoidal surgery for Cushing’s disease: a review of success rates, remission predictors, management of failed surgery, and Nelson’s Syndrome. Neurosurg Focus 23(3):E5

    Article  PubMed  Google Scholar 

  55. Chow JT, Thompson GB, Grant CS, Farley DR, Richards ML, Young WF (2008) Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing’s syndrome: a review of the Mayo Clinic experience. Clin Endocrinol (Oxf) 68(4):513–519

    Article  Google Scholar 

  56. Thompson SK, Hayman AV, Ludlam WH, Deveney CW, Loriaux DL, Sheppard BC (2007) Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing’s disease: a 10-year experience. Ann Surg 245(5):790–794

    Article  PubMed Central  PubMed  Google Scholar 

  57. Assié G, Bahurel H, Coste J, Silvera S, Kujas M, Dugué MA, Karray F, Dousset B, Bertherat J, Legmann P, Bertagna X (2007) Corticotroph tumor progression after adrenalectomy in Cushing’s Disease: a reappraisal of Nelson’s Syndrome. J Clin Endocrinol Metab 92(1):172–179

    Article  PubMed  Google Scholar 

  58. Brunicardi FC, Rosman PM, Lesser KL, Andersen DK (1985) Current status of adrenalectomy for Cushing’s disease. Surgery 98(6):1127–1134

    CAS  PubMed  Google Scholar 

  59. Sonino N, Zielezney M, Fava GA, Fallo F, Boscaro M (1996) Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab 81(7):2647–2652

    CAS  PubMed  Google Scholar 

  60. Miller JW, Crapo L (1993) The medical treatment of Cushing’s syndrome. Endocr Rev 14(4):443–458

    Article  CAS  PubMed  Google Scholar 

  61. Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T (2008) Ketoconazole revisited: a preoperative or postoperative treatment in Cushing’s disease. Eur J Endocrinol 158(1):91–99

    Article  CAS  PubMed  Google Scholar 

  62. Sonino N, Boscaro M (1999) Medical therapy for Cushing’s disease. Endocrinol Metab Clin North Am 28(1):211–222

    Article  CAS  PubMed  Google Scholar 

  63. Sonino N, Boscaro M, Fallo F (2005) Pharmacologic management of Cushing syndrome: new targets for therapy. Treat Endocrinol 4(2):87–94

    Article  CAS  PubMed  Google Scholar 

  64. Fleseriu M, Petersenn S (2012) Medical management of Cushing’s disease: what is the future? Pituitary 15(3):330–341

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Hale AC, Coates PJ, Doniach I, Howlett TA, Grossman A, Rees LH, Besser GM (1988) A bromocriptine-responsive corticotroph adenoma secreting alpha-MSH in a patient with Cushing’s disease. Clin Endocrinol (Oxf) 28(2):215–223

    Article  CAS  Google Scholar 

  66. Koppeschaar HP, Croughs RJ, Thijssen JH, Schwarz F (1986) Response to neurotransmitter modulating drugs in patients with Cushing’s disease. Clin Endocrinol (Oxf) 25(6):661–667

    Article  CAS  Google Scholar 

  67. Pivonello R, Ferone D, de Herder WW, Kros JM, De Caro MLDB, Arvigo M, Annunziato L, Lombardi G, Colao A, Hofland LJ, Lamberts SWJ (2004) Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab 89(5):2452–2462

    Article  CAS  PubMed  Google Scholar 

  68. Pivonello R, De Martino MC, Cappabianca P, De Leo M, Faggiano A, Lombardi G, Hofland LJ, Lamberts SWJ, Colao A (2009) The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 94(1):223–230

    Article  CAS  PubMed  Google Scholar 

  69. Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A (2010) Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol 163(5):709–716

    Article  CAS  PubMed  Google Scholar 

  70. Colao A, Petersenn S, Newell-Price J (2011) Pasireotide (SOM230) demonstrates efficacy in patients with Cushing disease: results from a large, randomized-dose, double-blind, phase III study. in ENDO 2011. Boston

  71. Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM, Pasireotide B2305 Study Group (2012) A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366(10):914–924

    Article  CAS  PubMed  Google Scholar 

  72. Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C, SEISMIC Study Investigators (2012) Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab 97(6):2039–2049

    Article  CAS  PubMed  Google Scholar 

  73. Blevins LS, Christy JH, Khajavi M, Tindall GT (1998) Outcomes of therapy for Cushing’s disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab 83(1):63–67

    CAS  PubMed  Google Scholar 

  74. Barbetta L, Dall’Asta C, Tomei G, Locatelli M, Giovanelli M, Ambrosi B (2001) Assessment of cure and recurrence after pituitary surgery for Cushing’s disease. Acta Neurochir (Wein) 143(5):477–481 discussion 481-482

    Article  CAS  Google Scholar 

  75. Rollin GA, Ferreira NP, Junges M, Gross JL, Czepielewski MA (2004) Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing’s disease. J Clin Endocrinol Metab 89(3):1131–1139

    Article  CAS  PubMed  Google Scholar 

  76. Boggan JE, Tyrrell JB, Wilson CB (1983) Transsphenoidal microsurgical management of Cushing’s disease. Report of 100 cases. J Neurosurg 59(2):195–200

    Article  CAS  PubMed  Google Scholar 

  77. Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F (1999) Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 84(2):440–448

    CAS  PubMed  Google Scholar 

  78. Castinetti F, Martinie M, Morange I, Dufour H, Sturm N, Passagia JG, Conte-Devolx B, Chabre O, Brue T (2009) A combined dexamethasone desmopressin test as an early marker of postsurgical recurrence in Cushing’s disease. J Clin Endocrinol Metab 94(6):1897–1903

    Article  CAS  PubMed  Google Scholar 

  79. Valassi E, Crespo I, Santos A, Webb SM (2012) Clinical consequences of Cushing’s syndrome. Pituitary 15(3):319–329

    Article  PubMed  Google Scholar 

  80. Leong GM, Abad V, Charmandari E, Reynolds JC, Hill S, Chrousos GP, Nieman LK (2007) Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study into young adulthood. J Bone Miner Res 22:110–118

    Article  PubMed  Google Scholar 

  81. Barahona MJ, Sucunza N, Resmini E, Fernández-Real JM, Ricart W, Moreno-Navarrete JM, Puig T, Farrerons J, Webb SM (2009) Persistent body fat mass and inflammatory marker increases after long-term cure of Cushing’s syndrome. J Clin Endocrinol Metab 94(9):3365–3371

    Article  CAS  PubMed  Google Scholar 

  82. Krsek M, Silha JV, Jezková J, Hána V, Marek J, Weiss V, Stepán JJ, Murphy LJ (2004) Adipokine levels in Cushing’s syndrome; elevated resistin levels in female patients with Cushing’s syndrome. Clin Endocrinol (Oxf) 60(3):350–357

    Article  CAS  Google Scholar 

  83. Colao A, Pivonello R, Spiezia S, Faggiano A, Ferone D, Filippella M, Marzullo P, Cerbone G, Siciliani M, Lombardi G (1999) Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J Clin Endocrinol Metab 84(8):2664–2672

    CAS  PubMed  Google Scholar 

  84. Tiemensma J, Kokshoorn NE, Biermasz NR, Keijser BJSA, Wassenaar MJ, Middelkoop HAM, Pereira AM, Romijn JA (2010) Subtle cognitive impairments in patients with long-term cure of Cushing’s disease. J Clin Endocrinol Metab 95(6):2699–2714

    Article  CAS  PubMed  Google Scholar 

  85. Hook JN, Giordani B, Schteingart DE, Guire K, Giles J, Ryan K, Gebarski SS, Langenecker SA, Starkman MN (2007) Patterns of cognitive change over time and relationship to age following successful treatment of Cushing’s disease. J Int Neuropsychol Soc 13(1):21–29

    PubMed  Google Scholar 

  86. Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP (1997) The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 82(3):912–919

    CAS  PubMed  Google Scholar 

  87. Tiemensma J, Biermasz NR, Middelkoop HAM, 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(10):E129–E141

    Article  CAS  PubMed  Google Scholar 

  88. van Aken MO, Pereira AM, Biermasz NR, van Thiel SW, Hoftijzer HC, Smit JWA, Roelfsema F, Lamberts SWJ, Romijn JA (2005) Quality of life in patients after long-term biochemical cure of Cushing’s disease. J Clin Endocrinol Metab 90(6):3279–3286

    Article  PubMed  Google Scholar 

  89. Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jørgensen 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(1):117–123

    CAS  PubMed  Google Scholar 

  90. 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(2):447–453

    Article  CAS  PubMed  Google Scholar 

  91. Webb SM, Badia X, Barahona MJ, Colao A, Strasburger CJ, Tabarin A, van Aken MO, Pivonello R, Stalla G, Lamberts SWJ et al (2008) Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur J Endocrinol 158(5):623–630

    Article  CAS  PubMed  Google Scholar 

  92. Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J (2006) Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: a prospective, long-term study. Eur J Endocrinol 154(1):109–118

    Article  CAS  PubMed  Google Scholar 

  93. Barahona MJ, Sucunza N, Resmini E, Fernández-Real JM, Ricart W, Moreno-Navarrete JM, Puig T, Wägner AM, Rodriguez-Espinosa J, Farrerons J, Webb SM (2009) Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing’s syndrome. J Bone Miner Res 24(11):1841–1846

    Article  CAS  PubMed  Google Scholar 

  94. Lambert JK, Goldberg L, Fayngold S, Kostadinov J, Post KD, Geer EB (2013) Predictors of mortality and long-term outcomes in treated Cushing’s disease: a study of 346 patients. J Clin Endocrinol Metab 98(3):1022–1030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grant K23 DK082617.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1055, New York, NY, 10029, USA

    Eliza B. Geer

  2. Division of Endocrinology, Department of Medicine, Mount Sinai Medical Center, New York, NY, 10029, USA

    Nina K. Sundaram

  3. Department of Medicine, Mount Sinai Medical Center, New York, NY, 10029, USA

    Alessia Carluccio

Authors
  1. Nina K. Sundaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessia Carluccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eliza B. Geer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eliza B. Geer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sundaram, N.K., Carluccio, A. & Geer, E.B. Characterization of persistent and recurrent Cushing’s disease. Pituitary 17, 381–391 (2014). https://doi.org/10.1007/s11102-013-0511-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-013-0511-3

Keywords

Search

Navigation