pituitary acth hypersecretion


Summary: A disease of the PITUITARY GLAND characterized by the excess amount of ADRENOCORTICOTROPIC HORMONE secreted. This leads to hypersecretion of cortisol (HYDROCORTISONE) by the ADRENAL GLANDS resulting in CUSHING SYNDROME.

Top Publications

  1. Boscaro M, Ludlam W, Atkinson B, Glusman J, Petersenn S, Reincke M, et al. Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab. 2009;94:115-22 pubmed publisher
    ..These results suggest that pasireotide holds promise as an effective medical treatment for this disorder. ..
  2. Manavela M, Danilowicz K, Bruno O. Macrocorticotropinoma shrinkage and control of hypercortisolism under long-term cabergoline therapy: case report. Pituitary. 2012;15 Suppl 1:33-6 pubmed publisher
    ..We show the effectiveness of cabergoline in maintaining long-term biochemical control of hypercortisolism with significant reduction and stabilization of macroadenoma volume in a patient with Cushing's disease. ..
  3. Liu J, Fleseriu M, Delashaw J, Ciric I, Couldwell W. Treatment options for Cushing disease after unsuccessful transsphenoidal surgery. Neurosurg Focus. 2007;23:E8 pubmed
    ..The indications, current results reported in the literature, and complications of each treatment modality are discussed. ..
  4. Ben Shlomo A, Schmid H, Wawrowsky K, Pichurin O, Hubina E, Chesnokova V, et al. Differential ligand-mediated pituitary somatostatin receptor subtype signaling: implications for corticotroph tumor therapy. J Clin Endocrinol Metab. 2009;94:4342-50 pubmed publisher
    ..The results indicate that SST5 determines short- and long-term enhanced pasireotide action in corticotroph cells, whereas the ligand action on SST2 is negligible. ..
  5. Colao A, Petersenn S, Newell Price J, Findling J, Gu F, Maldonado M, et al. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med. 2012;366:914-24 pubmed publisher
    ..Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.). ..
  6. Ikeda H, Abe T, Watanabe K. Usefulness of composite methionine-positron emission tomography/3.0-tesla magnetic resonance imaging to detect the localization and extent of early-stage Cushing adenoma. J Neurosurg. 2010;112:750-5 pubmed publisher
    ..Composite MET-PET/3.0-T MR imaging is useful for the improvement of the delineation of Cushing microadenoma and offers high-quality detectability for early-stage Cushing adenoma. ..
  7. Tritos N, Biller B, Swearingen B. Management of Cushing disease. Nat Rev Endocrinol. 2011;7:279-89 pubmed publisher
    ..Adrenalectomized patients require lifelong adrenal hormone replacement and are at risk of Nelson syndrome. The development of medical therapies with improved efficacy might influence the management of this challenging condition. ..
  8. Hsu P, Tung Y, Lee C, Lo F, Wu M, Tsai W, et al. Cushing's disease in children: report of three cases. Pediatr neonatol. 2010;51:303-7 pubmed publisher
    ..Careful follow-up of these patients with awareness of the possibilities of relapse and the complications of hypopituitarism is indicated. ..
  9. Wagenmakers M, Netea Maier R, van Lindert E, Timmers H, Grotenhuis J, Hermus A. Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD). Clin Endocrinol (Oxf). 2009;70:274-80 pubmed publisher
    ..Repeated transsphenoidal surgery via the endoscopic technique is a good treatment option for selected patients with recurrent or persistent Cushing's disease following primary pituitary surgery. ..

More Information


  1. Savage M, Storr H, Chan L, Grossman A. Diagnosis and treatment of pediatric Cushing's disease. Pituitary. 2007;10:365-71 pubmed
    ..The management of pediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life. ..
  2. Hofland L. Somatostatin and somatostatin receptors in Cushing's disease. Mol Cell Endocrinol. 2008;286:199-205 pubmed publisher
    ..In this review an overview of the current insights into the role of SS and sst in the regulation of normal and pathological ACTH secretion is provided. ..
  3. Patil C, Prevedello D, Lad S, Vance M, Thorner M, Katznelson L, et al. Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab. 2008;93:358-62 pubmed
    ..This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery. ..
  4. Reznik Y, Bertherat J, Borson Chazot F, Brue T, Chanson P, Cortet Rudelli C, et al. Management of hyperglycaemia in Cushing's disease: experts' proposals on the use of pasireotide. Diabetes Metab. 2013;39:34-41 pubmed publisher
  5. Jagannathan J, Sheehan J, Jane J. Evaluation and management of Cushing syndrome in cases of negative sellar magnetic resonance imaging. Neurosurg Focus. 2007;23:E3 pubmed
    ..Radiosurgery is an effective treatment option in patients with persistent Cushing disease. When a target cannot be found on MR imaging, one can target the entire sellar region with radiosurgery. ..
  6. Lindsay J, Oldfield E, Stratakis C, Nieman L. The postoperative basal cortisol and CRH tests for prediction of long-term remission from Cushing's disease after transsphenoidal surgery. J Clin Endocrinol Metab. 2011;96:2057-64 pubmed publisher
    ..Although an undetectable postoperative serum cortisol (<2 ?g/dl) has been advocated as an index of remission, there is no consensus on predictors of recurrence...
  7. Prevedello D, Pouratian N, Sherman J, Jane J, Vance M, Lopes M, et al. Management of Cushing's disease: outcome in patients with microadenoma detected on pituitary magnetic resonance imaging. J Neurosurg. 2008;109:751-9 pubmed publisher
    ..A multidisciplinary approach is essential to the achievement of satisfactory overall remission rates. ..
  8. Chan L, Storr H, Grossman A, Savage M. Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment. Arq Bras Endocrinol Metabol. 2007;51:1261-71 pubmed
    ..This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS. ..
  9. Obinata D, Yamaguchi K, Hirano D, Yoshida T, Soma M, Takahashi S. Preoperative management of Cushing's syndrome with metyrapone for severe psychiatric disturbances. Int J Urol. 2008;15:361-2 pubmed publisher
    ..Preoperative management of Cushing's syndrome with metyrapone may be useful in cases of severe psychiatric disturbances due to hypercortisolism. ..
  10. Fleseriu M. Medical management of persistent and recurrent cushing disease. Neurosurg Clin N Am. 2012;23:653-68 pubmed publisher
    ..The development of new therapeutic agents has been eagerly anticipated. This article discusses the results of currently available and promising new therapeutic agents used to treat this challenging disease...
  11. Yaneva M, Vandeva S, Zacharieva S, Daly A, Beckers A. Genetics of Cushing's syndrome. Neuroendocrinology. 2010;92 Suppl 1:6-10 pubmed publisher
    ..The cAMP signaling pathway is affected in this setting. In recent times the involvement of genes such as PDE11A, PDE8B and others have expanded the spectrum of the genetic pathophysiology of CS. ..
  12. Rollin G, Ferreira N, Czepielewski M. Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease. Arq Bras Endocrinol Metabol. 2007;51:1355-61 pubmed
    ..The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative. ..
  13. Drouin J, Bilodeau S, Vallette S. Of old and new diseases: genetics of pituitary ACTH excess (Cushing) and deficiency. Clin Genet. 2007;72:175-82 pubmed
    ..These recent advances have provided improved diagnosis and opened new perspectives for patient management and therapies. ..
  14. Castillo V, Theodoropoulou M, Stalla J, Gallelli M, Cabrera Blatter M, Haedo M, et al. Effect of SOM230 (pasireotide) on corticotropic cells: action in dogs with Cushing's disease. Neuroendocrinology. 2011;94:124-36 pubmed publisher
    ..The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease. ..
  15. Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno O, Lacroix A. Cabergoline monotherapy in the long-term treatment of Cushing's disease. Eur J Endocrinol. 2010;163:709-16 pubmed publisher
    ..No long-term response was maintained in four initial partial responders. Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments. ..
  16. Buchfelder M, Schlaffer S. Pituitary surgery for Cushing's disease. Neuroendocrinology. 2010;92 Suppl 1:102-6 pubmed publisher
    ..A close cooperation with the endocrinologist is mandatory for a neurosurgeon operating on patients with Cushing's disease, namely for the pre- and perioperative care and for long-term follow-up...
  17. Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing's disease. Best Pract Res Clin Endocrinol Metab. 2009;23:607-23 pubmed publisher
    ..There is at present no recognised efficient medical treatment towards the corticotroph adenoma -still an orphan disease. ..
  18. Raverot G, Wierinckx A, Jouanneau E, Auger C, Borson Chazot F, Lachuer J, et al. Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing's disease. Eur J Endocrinol. 2010;163:35-43 pubmed publisher
    ..65; P<0.05). Despite the absence of hypercortisolism, SCAs exhibit histological, biochemical and molecular corticotroph differentiation. SCA and MCA show hormonal and molecular similarities differentiating them from mCA. ..
  19. Pivonello R, De Martino M, Cappabianca P, De Leo M, Faggiano A, Lombardi G, et al. 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. 2009;94:223-30 pubmed publisher
    ..If this evidence is confirmed by additional studies, this agent may be considered as a useful treatment option in patients with CD who are unsuccessfully treated by neurosurgery. ..
  20. Pecori Giraldi F, Ambrogio A, Andrioli M, Sanguin F, Karamouzis I, Karamouzis I, et al. Potential role for retinoic acid in patients with Cushing's disease. J Clin Endocrinol Metab. 2012;97:3577-83 pubmed publisher
    ..Long-term treatment with retinoic acid proved beneficial and well tolerated in five of seven patients with Cushing's disease. This represents a novel, promising approach to medical treatment in Cushing's disease. ..
  21. Andrioli M, Pecori Giraldi F, Losa M, Terreni M, Invitti C, Cavagnini F. Cushing's disease due to double pituitary ACTH-secreting adenomas: the first case report. Endocr J. 2010;57:833-7 pubmed
    ..Careful radiological, surgical and pathological examination is necessary to recognize this condition and avoid surgical failure. ..
  22. Pinchot S, Sippel R, Chen H. ACTH-producing carcinoma of the pituitary with refractory Cushing's Disease and hepatic metastases: a case report and review of the literature. World J Surg Oncol. 2009;7:39 pubmed publisher
    ..The latency period between initial presentation of a pituitary adenoma and the development of distal metastases marking carcinoma is extremely variable, and some patients may live well over 10 years with pituitary carcinoma. ..
  23. Thompson S, Hayman A, Ludlam W, Deveney C, Loriaux D, Sheppard B. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing's disease: a 10-year experience. Ann Surg. 2007;245:790-4 pubmed
    ..The majority of patients experience considerable improvement in their Cushing's disease symptoms, and their quality of life equals that of patients initially cured by transsphenoidal pituitary tumor resection. ..
  24. Alexandraki K, Kaltsas G, Isidori A, Akker S, Drake W, Chew S, et al. The prevalence and characteristic features of cyclicity and variability in Cushing's disease. Eur J Endocrinol. 2009;160:1011-8 pubmed publisher
    ..Physicians should be alert since it can lead to frequent problems in diagnosis and management, and no specific features can be used as markers. ..
  25. Clayton R, Raskauskiene D, Reulen R, Jones P. Mortality and morbidity in Cushing's disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab. 2011;96:632-42 pubmed publisher
  26. Mettauer N, Brierley J. A novel use of etomidate for intentional adrenal suppression to control severe hypercortisolemia in childhood. Pediatr Crit Care Med. 2009;10:e37-40 pubmed publisher
    ..The adrenal suppression caused by etomidate, so controversial in the care of the critically ill at present, can be therapeutically used for short-term control of severe hypercortisolemia in children. ..
  27. Tirabassi G, Papa R, Faloia E, Boscaro M, Arnaldi G. Corticotrophin-releasing hormone and desmopressin tests in the differential diagnosis between Cushing's disease and pseudo-Cushing state: a comparative study. Clin Endocrinol (Oxf). 2011;75:666-72 pubmed publisher
    ..Because of these characteristics, the use of both tests offers the physician a valuable tool for those cases of hypercortisolism which are difficult to interpret. ..
  28. Stratakis C. Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am. 2012;41:793-803 pubmed publisher
    ..Barriers to optimal care of a pediatric patient with Cushing syndrome are discussed. ..
  29. Rotondo F, Khatun N, Scheithauer B, Horvath E, Marotta T, Cusimano M, et al. Unusual double pituitary adenoma: a case report. Pathol Int. 2011;61:42-6 pubmed publisher
    ..The two tumors differed not only in Ki-67 labeling indices but in MGMT immunoexpression as well...
  30. Acebes J, Martino J, Masuet C, Montanya E, Soler J. Early post-operative ACTH and cortisol as predictors of remission in Cushing's disease. Acta Neurochir (Wien). 2007;149:471-7; discussion 477-9 pubmed
    ..55 pmol/L, and/or those in which an adenoma is not identified in the histological study, have a high risk of treatment failure. ..
  31. Valassi E, Biller B, Swearingen B, Pecori Giraldi F, Losa M, Mortini P, et al. Delayed remission after transsphenoidal surgery in patients with Cushing's disease. J Clin Endocrinol Metab. 2010;95:601-10 pubmed publisher
    ..Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined. ..
  32. Zemskova M, Nylen E, Patronas N, Oldfield E, Becker K, Nieman L. Diagnostic accuracy of chromogranin A and calcitonin precursors measurements for the discrimination of ectopic ACTH secretion from Cushing's disease. J Clin Endocrinol Metab. 2009;94:2962-5 pubmed publisher
    ..These preliminary results suggest that an abnormal CgA and normal pituitary magnetic resonance imaging favor the diagnosis of EAS, but normal tumor markers do not exclude the diagnosis. ..
  33. Alwani R, de Herder W, van Aken M, van den Berge J, Delwel E, Dallenga A, et al. Biochemical predictors of outcome of pituitary surgery for Cushing's disease. Neuroendocrinology. 2010;91:169-78 pubmed publisher
    ..CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing. ..
  34. Lila A, Gopal R, Acharya S, George J, Sarathi V, Bandgar T, et al. Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr Pract. 2010;16:968-76 pubmed publisher
    ..To evaluate the efficacy of cabergoline therapy in patients with Cushing disease who remained uncured (had persistent or recurrent disease) after a pituitary surgical procedure with or without radiotherapy...
  35. Hwang Y, Chung J, Min Y, Lee M, Lee M, Kim K. Comparisons between macroadenomas and microadenomas in Cushing's disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci. 2009;24:46-51 pubmed publisher
    ..73.3% [11/15] for microadenoma patients, p=0.53). Thus, tumor size is not a major determinant of hormone secretion or clinical outcomes in patients with Cushing's disease. ..
  36. Castinetti F, Morange I, Jaquet P, Conte Devolx B, Brue T. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease. Eur J Endocrinol. 2008;158:91-9 pubmed publisher
    ..Ketoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging. ..
  37. Baudry C, Coste J, Bou Khalil R, Silvera S, Guignat L, Guibourdenche J, et al. Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center. Eur J Endocrinol. 2012;167:473-81 pubmed publisher
    ..Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients. ..
  38. Shah N, Lila A. Childhood Cushing disease: a challenge in diagnosis and management. Horm Res Paediatr. 2011;76 Suppl 1:65-70 pubmed publisher
    ..Even after curative therapy, these children require long-term follow-up into adulthood to assess growth and body composition and routine monitoring for metabolic anomalies and/or recurrence of the disease. ..
  39. Vilar L, Naves L, Azevedo M, Arruda M, Arahata C, Moura e Silva L, et al. Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing's disease. Pituitary. 2010;13:123-9 pubmed publisher
    ..Moreover, the addition of relatively low doses of ketoconazole led to normalization of UFC in about two-thirds of patients not achieving a full response to cabergoline. ..
  40. Smith P, Turza K, Carter C, Vance M, Laws E, Hanks J. Bilateral adrenalectomy for refractory Cushing disease: a safe and definitive therapy. J Am Coll Surg. 2009;208:1059-64 pubmed publisher
    ..Our experience demonstrates excellent survival and clinical results, despite the inherent risk in patients with CD. There are persistent fatigue and QOL deficits that are not ameliorated by laparoscopic compared with open resection. ..
  41. Aghi M. Management of recurrent and refractory Cushing disease. Nat Clin Pract Endocrinol Metab. 2008;4:560-8 pubmed publisher
    ..Here, we review the treatment options and latest surgical, medical, and radiosurgical advances for patients who have persistent or recurrent Cushing disease after transsphenoidal surgery. ..
  42. Hofmann B, Hlavac M, Martinez R, Buchfelder M, Müller O, Fahlbusch R. Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg. 2008;108:9-18 pubmed publisher
    ..Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse. ..
  43. Fukuoka H, Cooper O, Ben Shlomo A, Mamelak A, Ren S, Bruyette D, et al. EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas. J Clin Invest. 2011;121:4712-21 pubmed publisher
    ..These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease. ..
  44. Giordano R, Picu A, Marinazzo E, D Angelo V, Berardelli R, Karamouzis I, et al. Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission. Clin Endocrinol (Oxf). 2011;75:354-60 pubmed publisher
    ..Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. ..
  45. Nieman L. Difficulty in the diagnosis of Cushing disease. Nat Clin Pract Endocrinol Metab. 2006;2:53-7; quiz following 57 pubmed
    ..Cushing disease. The patient underwent trans-sphenoidal resection, assessment of remission and subsequent treatment with hydrocortisone. ..
  46. Netea Maier R, van Lindert E, Den Heijer M, van der Eerden A, Pieters G, Sweep C, et al. Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing's disease. Eur J Endocrinol. 2006;154:675-84 pubmed
    ..A randomized clinical trial, comparing endoscopic and conventional pituitary surgery in patients with Cushings disease, is needed to determine the pros and cons of both techniques. ..
  47. Castillo V, Giacomini D, Paez Pereda M, Stalla J, Labeur M, Theodoropoulou M, et al. Retinoic acid as a novel medical therapy for Cushing's disease in dogs. Endocrinology. 2006;147:4438-44 pubmed
    ..This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease. ..
  48. Ceyhan K, Yagmurlu B, Dogan B, Erdogan N, Bulut S, Erekul S. Cytopathologic features of pituitary carcinoma with cervical vertebral bone metastasis: a case report. Acta Cytol. 2006;50:225-30 pubmed
    ..In the differential diagnosis, metastatic neuroendocrine carcinomas should be kept in mind. In the absence of sufficient clinical data, these 2 entities cannot be distinguished correctly through the cytologic features. ..
  49. Pecori Giraldi F, Scaroni C, Arvat E, Martin M, Giordano R, Albiger N, et al. Effect of protracted treatment with rosiglitazone, a PPARgamma agonist, in patients with Cushing's disease. Clin Endocrinol (Oxf). 2006;64:219-24 pubmed
    ..Further investigations are needed to fully define the therapeutic potential of PPARgamma agonists in this disorder. ..
  50. Devin J, Allen G, Cmelak A, Duggan D, Blevins L. The efficacy of linear accelerator radiosurgery in the management of patients with Cushing's disease. Stereotact Funct Neurosurg. 2004;82:254-62 pubmed
  51. Heaney A. PPAR-gamma in Cushing's disease. Pituitary. 2004;7:265-9 pubmed
  52. Woo Y, Isidori A, Wat W, Kaltsas G, Afshar F, Sabin I, et al. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab. 2005;90:4963-9 pubmed
    ..Few patients with macroadenomas were cured by surgery. Pituitary macroadenomas causing Cushing's disease have biochemical features largely distinct from patients harboring microadenomas but represent one end of a continuum. ..
  53. Tysome J, Gnanalingham K, Chopra I, Mendoza N. Intradural metastatic spinal cord compression from ACTH-secreting pituitary carcinoma. Acta Neurochir (Wien). 2004;146:1251-4 pubmed
    ..Spinal metastases in pituitary carcinoma are uncommon, but aggressive surgical resection of the spinal metastases produces good symptomatic relief. ..