{"id":1114,"date":"2012-09-12T14:42:21","date_gmt":"2012-09-12T14:42:21","guid":{"rendered":"https:\/\/touchendocrinology.com\/2012\/09\/12\/medical-treatment-of-cushings-disease-with-pasireotide\/"},"modified":"2012-09-12T14:42:21","modified_gmt":"2012-09-12T14:42:21","slug":"medical-treatment-of-cushings-disease-with-pasireotide","status":"publish","type":"post","link":"https:\/\/touchendocrinology.com\/pituitary\/journal-articles\/medical-treatment-of-cushings-disease-with-pasireotide\/","title":{"rendered":"Medical Treatment of Cushing\u2019s Disease with Pasireotide"},"content":{"rendered":"

Cushing\u2019s disease is caused by a pituitary adenoma that secretes elevated levels of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce excess cortisol.1<\/sup> The tumours are most frequently microadenomas (\u22641 cm in diameter) while corticotroph macroadenomas are responsible for approximately 10 % of cases.
\n
\nCushing\u2019s disease is caused by a pituitary adenoma that secretes elevated levels of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce excess cortisol.1<\/sup> The tumours are most frequently microadenomas (\u22641 cm in diameter) while corticotroph macroadenomas are responsible for approximately 10 % of cases. Cushing\u2019s disease is the most common form of endogenous Cushing\u2019s syndrome accounting for about 70 % of patients with this condition and has an estimated annual incidence of 0.1\u20132.0 new cases per 100,000 worldwide.2\u20134<\/sup> Chronic stimulation by ACTH produces diffuse bilateral hyperplasia of the adrenal cortex which can sometimes become nodular and enlarged. The primary clinical symptoms of Cushing\u2019s disease are due to hypercortisolism. Symptoms and signs develop gradually and include weight gain (particularly on the trunk and face), fatigue, proximal muscle weakness, oedema, diabetes, hypertension, sleep disturbances, cognitive impairment, depression, osteoporosis, infections, skin atrophy, ecchymosis, hirsutism and menstrual irregularities in women and decreased libido and erectile dysfunction in men. If Cushing\u2019s disease is left untreated or uncontrolled, this can result in severe complications including ischaemic and thromboembolic cardiovascular events.5<\/sup> Individuals with such progression have a mortality rate four to five times higher than an age- and sex-matched population.4,6,7<\/sup> <\/p>\n

Surgical Therapy of Cushing\u2019s Disease <\/b>
The treatment goals in Cushing\u2019s disease include elective removal of corticotroph tumour while preserving pituitary function, reversal of clinical features, normalisation of biochemical changes and long-term control without recurrence. Surgical removal of the tumour is the first-line treatment; however, the risk of initial surgical failure in microadenoma is 10\u201335 % and recurrence of Cushing\u2019s disease may reach 20 % in the subsequent ten years. In the case of macroadenoma, surgery is unsuccessful in achieving remission in >45 % of cases, remission rates are lower (12\u201345 %) and recurrence occurs sooner than in microadenoma (mean 16 versus 49 months).8<\/sup> The reported rates of remission vary as a result of differing criteria of cortisol values and endpoints used to determine remission, and differences in the timeframe of patient monitoring (see Table 1<\/i>). Patil et al. found that although surgical remission was achieved in 85.6 % of 215 patients with Cushing\u2019s disease who underwent first line transsphenoidal surgery for resection of a pituitary microadenoma, disease recurrence was found in a quarter of these (25.5 %) at five-year follow up.9<\/sup> Another study reported a remission rate of 56 % of 63 patients at 9.6 years post-transsphenoidal surgery.10<\/sup> <\/p>\n

To view the full article in PDF or eBook formats, please click on the icons above.<\/b><\/p>\n","protected":false},"excerpt":{"rendered":"

Cushing\u2019s disease is caused by a pituitary adenoma that secretes elevated levels of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce excess cortisol.1 The tumours are most frequently microadenomas (\u22641 cm in diameter) while corticotroph macroadenomas are responsible for approximately 10 % of cases.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","rank_math_lock_modified_date":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1114","post","type-post","status-publish","format-standard","hentry","category-uncategorized","vocabulary_1-pituitary"],"acf":{"wpcf-article_introduction":"","wpcf-article_abstract":"Cushing\u2019s disease is the most common form of endogenous Cushing\u2019s syndrome and results from excess adrenocorticotropic hormone (ACTH) production by a corticotroph pituitary adenoma. Transsphenoidal surgical removal of the corticotroph adenoma is the treatment of choice for patients with Cushing\u2019s disease. However, despite advances in surgery, complete tumour removal is sometimes impossible and eventual disease recurrence occurs later even in patients who achieved an initial remission. Medical therapy is one of the second-line options, which can provide a primary or adjunctive role if the patient cannot safely undergo pituitary surgery, if surgery fails, or if the tumour recurs. However, until recently, few effective therapeutic options existed. Somatostatin receptors in the corticotroph tumours have been identified as potential therapeutic targets for Cushing\u2019s disease. Pasireotide is a novel somatostatin analogue which has high affinity for these receptors. In a recent Phase III clinical trial, pasireotide treatment was demonstrated to significantly reduce elevated cortisol levels in patients with Cushing\u2019s disease achieving normalisation of urinary free cortisol (UFC) levels in subset of patients and close to 50 % mean reduction in UFC levels were seen in the patients. Initial data also suggest that pasireotide could be highly effective as part of combined therapy for Cushing\u2019s disease.","wpcf-article_keywords":"Cushing","wpcf-article_citation_override":"European Endocrinology, <\/i>2012;8(2):99-104 DOI: http:\/\/doi.org\/10.17925\/EE.2012.08.02.99<\/a>","wpcf-compliance-with-ethics":"","wpcf-article_disclosure":"Andr\u00e9 Lacroix is an investigator in clinical trials on pasireotide in Cushing's disease and is a member of advisory boards for Novartis on the therapy of pituitary tumours. Rosario Pivonello has received research funding grants from Novartis and has been an occasional consultant for Novartis.","wpcf-review_process":"","wpcf-authorship":"","wpcf-article_correspondence":"Andr\u00e9 Lacroix, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, (CHUM), 3840 Rue Saint-Urbain, Montr\u00e9al, Qu\u00e9bec, H2W 1T8, Canada. E: andre.lacroix@umontreal.ca","wpcf-article_support":"The publication of this article was funded by Novartis. The views and opinions expressed are those of the authors and not necessarily those of Novartis.","wpcf-open_access":"","wpcf-article_pdf":"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2015\/06\/lacroix.pdf","wpcf-article_pdf-gated":true,"wpcf-article_doi":"","wpcf-old_nid":"","wpcf-article_image":"","wpcf-editor_choice":false,"wpcf-old_author_ids":"","wpcf-article_references":"

    \r\n\r\n\r\n
  1. Tritos NA, Biller BM, Swearingen B, Management of Cushing\r\ndisease, Nat Rev Endocrinol, 2011;7:279\u201389.\r\n
  2. Boscaro M, Barzon L, Fallo F, et al., Cushing\u2019s syndrome,\r\nLancet, 2001;357:783\u201391.\r\n
  3. Etxabe J, Vazquez JA, Morbidity and mortality in Cushing\u2019s\r\ndisease: an epidemiological approach, Clin Endocrinol (Oxf),\r\n1994;40:479\u201384.\r\n
  4. Lindholm J, Juul S, Jorgensen JO, et al., Incidence and late\r\nprognosis of cushing\u2019s syndrome: a population-based study,\r\nJ Clin Endocrinol Metab, 2001;86:117\u201323.\r\n
  5. Pivonello R, De Martino MC, De Leo M, et al., Cushing\u2019s\r\nsyndrome, Endocrinol Metab Clin North Am, 2008;37:135\u201349, ix.\r\n
  6. Mancini T, Kola B, Mantero F, et al., High cardiovascular risk\r\nin patients with Cushing\u2019s syndrome according to 1999\r\nWHO\/ISH guidelines, Clin Endocrinol (Oxf), 2004;61:768\u201377.\r\n
  7. Clayton RN, Raskauskiene D, Reulen RC, et al., Mortality\r\nand morbidity in Cushing\u2019s disease over 50 years in\r\nStoke-on-Trent, UK: audit and meta-analysis of\r\nliterature, J Clin Endocrinol Metab, 2011;96:632\u201342.\r\n
  8. Biller BM, Grossman AB, Stewart PM, et al., Treatment of\r\nadrenocorticotropin-dependent Cushing\u2019s syndrome: a\r\nconsensus statement, J Clin Endocrinol Metab, 2008;93:2454\u201362.\r\n
  9. Patil CG, Prevedello DM, Lad SP, et al., Late recurrences of\r\nCushing\u2019s disease after initial successful transsphenoidal\r\nsurgery, J Clin Endocrinol Metab, 2008;93:358\u201362.\r\n
  10. Atkinson AB, Kennedy A, Wiggam MI, et al., Long-term\r\nremission rates after pituitary surgery for Cushing\u2019s disease:\r\nthe need for long-term surveillance, Clin Endocrinol (Oxf),\r\n2005;63:549\u201359.\r\n
  11. Patil CG, Veeravagu A, Prevedello DM, et al., Outcomes after\r\nrepeat transsphenoidal surgery for recurrent Cushing\u2019s\r\ndisease, Neurosurgery, 2008;63:266\u201370; discussion 70\u20131.\r\n
  12. Mancini T, Porcelli T, Giustina A, Treatment of Cushing\r\ndisease: overview and recent findings, Ther Clin Risk Manag,\r\n2010;6:505\u201316.\r\n\r\n\r\n<\/ol>","wpcf-article_received_date":"2012-10-24T00:00:00","wpcf-article_accepted_date":"2012-11-08T00:00:00","wpcf-article_published_online":null,"wpcf-podcast":"","wpcf-ogg":"","wpcf-article_end_page":"104","wpcf-article_start_page":"99","wpcf-acknowledgements":"","wpcf-errata_pdf":"","wpcf-article_flipper_image":"","wpcf-corrected_online":null,"wpcf-supplementary_information":"","wpcf-article_highlight_pdf":"","data_availability":"","digital_features":""},"_links":{"self":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts\/1114","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/comments?post=1114"}],"version-history":[{"count":0,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts\/1114\/revisions"}],"wp:attachment":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/media?parent=1114"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/categories?post=1114"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/tags?post=1114"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}