Cushing’s syndrome: an update on current pharmacotherapy and future directions

Creemers, Sara G; Hofland, Leo J.; Lamberts, Steven W. J.; Feelders, Richard A

doi:10.1517/14656566.2015.1061995

Cited by 26 publications

(11 citation statements)

References 139 publications

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“…Agents that block adrenal steroidogenesis at various enzymatic steps have been available for many years, including metyrapone (11β-hydroxylase), ketoconazole (side chain cleavage, 17-hydroxylase and 17,20-lyase, 11β-hydroxylase and aldosterone synthase), and mitotane (11β-hydroxylase and cholesterol side chain cleavage; with additional cytotoxic effects at high doses). As monotherapy, their use and recommendations have been reviewed recently; they are effective in about 50% of patients [ 27 ]. There are few data on combined therapy, although this is commonly used, especially in patients with severe hypercortisolism (see below).…”

Section: Recent Changes In the Management Of Cushing's Syndromementioning

confidence: 99%

Recent Updates on the Diagnosis and Management of Cushing's Syndrome

Nieman

2018

Endocrinol Metab

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Cushing's syndrome, a potentially lethal disorder characterized by endogenous hypercortisolism, may be difficult to recognize, especially when it is mild and the presenting features are common in the general population. However, there is a need to identify the condition at an early stage, as it tends to progress, accruing additional morbidity and increasing mortality rates. Once a clinical suspicion is raised, screening tests involve timed measurement of urine, serum or salivary cortisol at baseline or after administration of dexamethasone, 1 mg. Each test has caveats, so that the choice of tests must be individualized for each patient. Once the diagnosis is established, and the cause is determined, surgical resection of abnormal tumor/tissue is the optimal treatment. When this cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used to normalize cortisol production. Recent updates in screening for and treating Cushing's syndrome are reviewed here.

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Section: Recent Changes In the Management Of Cushing's Syndromementioning

confidence: 99%

Recent Updates on the Diagnosis and Management of Cushing's Syndrome

Nieman

2018

Endocrinol Metab

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“…Until relatively recently the treatment of the EAS involved the use of bilateral adrenalectomy(preferably after period of control of the EAS), and medical treatment of the hypercortisolemia using mitotane, metapyrone and ketoconazole[131, •132, 133, 134]. Recently other classes of drugs have been used and reported to be helpful including glucocorticoid receptor antagonists(mifepristone[•135], etc.…”

Section: Summary Of Recent Advances/controversies In Management Ofmentioning

confidence: 99%

“…); adrenal specific therapy(etomidate, osilodrostat and fluconazole=11B-hydroxylase inhibitors); somatostatin analogues including pasireotide; and dopamine receptor agonists(cabergoline, etc. )[ 131, •132, 133, 134]. In addition PRRT has been reported to be helpful in controlling the hypercortisolism with EAS and will be discussed under the specific syndromes in a later section.…”

Section: Summary Of Recent Advances/controversies In Management Ofmentioning

confidence: 99%

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Ito¹,

Lee²,

Jensen³

2016

Expert Opinion on Pharmacotherapy

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Introduction Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there are many advances, well-covered in reviews/consensus papers on imaging-NETs;new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed. Areas covered Advances in the last 5-years are concentrated on, but a review up to 10-years was performed. PubMed and other databases(Cochrane, etc) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies[serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies(octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib), cytoreductive surgery, liver-directed therapies(embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and 131I-MIBG, ablation of primary F-NETs. Expert Opinion Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas, such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large, controlled studies.

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“…By different mechanisms, mitotane treatment can already result in some control of hormone levels (see the 'Adjuvant treatment' section). Adrenal steroidogenesis inhibitors like ketoconazole or metyrapone (alone or in combination; Corcuff et al 2015) can also be used, or more rarely aminoglutethimide or etomidate (Creemers et al 2015). Mifepristone, a glucocorticoid receptor antagonist, is another treatment modality for excess cortisol levels (Fleseriu et al 2012).…”

Section: Current Therapeutic Strategiesmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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Cushing’s syndrome: an update on current pharmacotherapy and future directions

Cited by 26 publications

References 139 publications

Recent Updates on the Diagnosis and Management of Cushing's Syndrome

Recent Updates on the Diagnosis and Management of Cushing's Syndrome

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

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