Medical Management of Cushing’s Disease

Petersenn, Stephan

doi:10.1007/978-1-4614-0011-0_12

Cited by 3 publications

(6 citation statements)

References 81 publications

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“…В зависимости от ряда факторов нейро-хирургическое лечение позволяет достичь ремиссии болезни в 65-90% случаев при микроаденомах ги-пофиза и в 50-70% -при макроаденомах [16,17]. Вместе с тем в 25% случаев отмечаются рецидивы заболевания, в том числе через 10 лет после опера-тивного вмешательства [18].…”

Section: трансназальная аденомэктомия и лучевая терапияunclassified

Medicamental treatment of Itsenko-Cushing’s disease. The current state-of-the art

Мельниченко¹,

Popovich²,

Рожинская³

et al. 2014

Probl Endokrinol (Mosk)

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Болезнь Иценко-Кушинга (БИК) -тяжелое прогрессирующее нейроэндокринное заболевание с гетерогенной клини-ческой картиной, высоким риском осложнений и смерти. К основным задачам терапии БИК относятся удаление ново-образования гипофиза, либо уменьшение объема опухоли и/или стабилизация ее роста, нормализация уровня и ритма секреции кортизола, достижение обратного развития клинических проявлений при сохранении гормональной функции гипофиза с минимальным риском рецидива. В настоящее время существует потребность как в более совершенных мето-дах ранней диагностики БИК, так и в развитии лекарственной терапии данного заболевания. Для лечения БИК в рутинной практике применяются препараты следующих групп: блокаторы рецепторов к глюкокортикоидам, блокаторы стероидо-генеза, агонисты дофаминовых рецепторов и мультилигандные аналоги соматостатина. Для большинства лекарственных средств, используемых в лечении БИК, доказательная база представлена ретроспективными исследованиями с описани-ем серии случаев, что существенно ограничивает полноценную интерпретацию данных об эффективности и безопасно-сти применения различных средств при данном заболевании. Мультилигандный аналог соматостатина -пасиреотид -единственный препарат, зарегистрированный для лечения взрослых пациентов с БИК, у которых хирургическое лечение неэффективно или невозможно. Основная оценка эффективности и безопасности препарата основывается на данных проспективного рандомизированного двойного слепого клинического исследования, в котором изучались две дозы паси-реотида. К 6-му месяцу терапии пасиреотидом медиана снижения суточного уровня кортизола в моче у пациентов БИК составляла 47,9%. Профиль безопасности пасиреотида оказался схожим с профилем безопасности других аналогов со-матостатина, за исключением более высокой частоты развития гипергликемии. Как и при применении других аналогов соматостатина, наиболее часто отмечались нарушения со стороны желудочно-кишечного тракта. Снижая уровень АКТГ, пасиреотид обеспечивает стойкое снижение уровня кортизола, что приводит к уменьшению основных проявлений ги-перкортицизма, клинико-гормональной ремиссии и улучшению качества жизни пациентов с БИК.

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Section: трансназальная аденомэктомия и лучевая терапияunclassified

Medicamental treatment of Itsenko-Cushing’s disease. The current state-of-the art

Мельниченко¹,

Popovich²,

Рожинская³

et al. 2014

Probl Endokrinol (Mosk)

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“…Table 1 [ 10 ] summarizes several studies investigating the expression of the 5 somatostatin receptor subtypes in corticotropic pituitary adenomas [ 15 – 21 ]. Although sst1 , sst2 , and sst5 are widely expressed, the expression levels are low, except for sst5 [ 18 ].…”

Section: Pituitary-targeted Therapymentioning

confidence: 99%

“… 13/13 (high) Hofland [ 18 ] Realtime RT-PCR 1/6 (low) 6/6 (low) 2/6 (low) 2/6 (low) 6/6 (high) Author’s data (SP) Realtime RT-PCR 7/10 (low–high) 8/10 (low–high) 3/10 (med) 4/10 (high) 7/10 (low–high) Total (%) 25/39 (64 %) 29/39 (74 %) 8/38 (21 %) 12/37 (32 %) 31/37 (84 %) Ref. [ 10 ] (adapted from Petersenn S, Endocrine Updates, 2011 with kind permission from Springer Science+Business Media B.V.) …”

Section: Pituitary-targeted Therapymentioning

confidence: 99%

“…Whereas octreotide and lanreotide have high affinity for sst 2 and modest affinity for sst 5 , pasireotide demonstrates high binding affinity for sst 1,2,3 and sst 5 , and has a 40-fold higher affinity for sst 5 than octreotide (Fig. 2 , [ 10 , 29 , 30 ]). Pasireotide was highly effective in lowering ACTH secretion in a mouse cell model.…”

Section: Pituitary-targeted Therapymentioning

confidence: 99%

“…The most physiological approach targets ACTH secretion at the level of the pituitary, with possible inhibition of corticotrope proliferation (Fig. 1 , [ 10 ]). Pasireotide, a new multiligand somatostatin analog has recently been studied in this regard.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Medical management of Cushing’s disease: what is the future?

Fleseriu

Petersenn²

2012

Pituitary

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Cushing’s disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)—secreting pituitary adenoma resulting in significant morbidity and mortality. Transsphenoidal surgery is the initial treatment of choice in almost all cases. Remission rates for microadenomas are good at 65–90 % (with an experienced neurosurgeon) but remission rates are much lower for macroadenomas. However, even after postoperative remission, recurrence rates are high and can be seen up to decades after an initial diagnosis. Repeat surgery or radiation can be useful in these cases, although both have clear limitations with respect to efficacy and/or side effects. Hence, there is a clear unmet need for an effective medical treatment. Currently, most drugs act by inhibiting steroidogenesis in the adrenal glands. Most is known about the effects of ketoconazole and metyrapone. While effective, access to ketoconazole and metyrapone is limited in many countries, experience with long-term use is limited, and side effects can be significant. Recent studies have suggested a role for a pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide, recently approved in Europe for treatment of CD), second-generation dopamine agonists, or a combination of both. Mifepristone (a glucocorticoid receptor antagonist) is another promising drug, recently approved by the FDA for treatment of hyperglycemia associated with Cushing’s syndrome. We review available medical treatments for CD with a focus on the two most recent compounds referenced above. Our aim is to expand awareness of current research, and the possibilities afforded by available medical treatments for this mesmerizing, but often frightful disease.

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New avenues in the medical treatment of Cushing’s disease: corticotroph tumor targeted therapy

Fleseriu

Petersenn²

2013

J Neurooncol

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Cushing’s disease (CD) is a condition of chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. First-line transsphenoidal surgery is not always curative and disease sometimes recurs. Radiotherapy often requires months or years to be effective, and is also not curative in many cases. Consequently, effective medical therapies for patients with CD are needed. Corticotroph adenomas frequently express both dopamine (D2) and somatostatin receptors (predominantly sstr5). Pasireotide, a somatostatin analog with high sstr5 binding affinity, has shown urinary free cortisol (UFC) reductions in most patients with CD in a large phase 3 trial, with UFC normalization and tumor shrinkage in a subset of patients. Adverse events were similar to other somatostatin analogs, with the exception of the degree and severity of hyperglycemia. Two small trials (one prospective and one retrospective) have suggested that cabergoline, a D2 receptor agonist, could be effective in normalizing UFC, but current long-term data results are conflicting. Combination treatment with pasireotide plus cabergoline and the adrenal steroidogenesis inhibitor ketoconazole has been successful, but further investigation in larger trials is necessary. Retinoic acid also showed interesting results in a recent very small prospective study. Glucocorticoid receptor blockade with mifepristone has recently demonstrated improvement in signs and symptoms of Cushing’s and glycemic control; however, this modality does not address the etiology of the disease and has inherent adverse events related to its mechanism of action. Pituitary-targeted medical therapies will soon play a more prominent role in treating CD, and may potentially become first-line medical therapy when surgery fails or is contraindicated.

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Medical Management of Cushing’s Disease

Cited by 3 publications

References 81 publications

Medicamental treatment of Itsenko-Cushing’s disease. The current state-of-the art

Medicamental treatment of Itsenko-Cushing’s disease. The current state-of-the art

Medical management of Cushing’s disease: what is the future?

New avenues in the medical treatment of Cushing’s disease: corticotroph tumor targeted therapy

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