Short and long‐term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome

Verhelst, Johan; Trainer, Peter; Howlett, Trevor A.; Perry, Les; Rees, Linford; Grossman, Ashley; Wass, John; Besser, G. M.

doi:10.1111/j.1365-2265.1991.tb03517.x

Cited by 282 publications

(214 citation statements)

References 24 publications

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“…Medical treatment may also be used in preparation for surgery or when surgery is not feasible, as adjunctive treatment in patients who have failed surgery, or as a bridge for radiotherapy until remission of hypercortisolism occurs (7,13,14). Such medical treatments, including ketoconazole, cabergoline, metyrapone, and mitotane, have been widely used in clinical practice (15)(16)(17)(18)(19)(20)(21), but none of these are licensed for use to treat patients with endogenous CS. Centrally acting agents that target excessive pituitary adrenocorticotropic hormone (ACTH) secretion, inhibitors of See accompanying article, p. 1175. steroidogenesis, or glucocorticoid receptor antagonists have been utilized depending on the underlying cause of CS.…”

Section: Introductionmentioning

confidence: 99%

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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Section: Introductionmentioning

confidence: 99%

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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“…Its main site of action is 11b-hydroxylase, as Verhelst et al (1991) found a concomitant decrease in cortisol concentrations and increase in 11-deoxycortisol levels in 91 CS patients treated with metyrapone. Side effects that occur during metyrapone therapy include dizziness, rash, and gastrointestinal complaints (Tritos et al 2011).…”

Section: Inhibitors Of Adrenocortical Steroidogenesismentioning

confidence: 89%

“…In addition, concentrations of mineralocorticoid precursors and adrenal androgens can increase due to R van der Pas et al: Developments in the medical treatment of CS www.endocrinology-journals.org the 11b-hydroxylase block and the subsequent increase in ACTH production, which stimulates steroidogenesis (Nieman 2002, Tritos et al 2011. As a result, metyrapone administration might be accompanied by worsening of hypertension, acne, and hirsutism (Verhelst et al 1991, Nieman 2002, Feelders et al 2010c. In contrast to ketoconazole, metyrapone does not cause gynecomastia.…”

Section: Inhibitors Of Adrenocortical Steroidogenesismentioning

confidence: 99%

New developments in the medical treatment of Cushing's syndrome

Pas¹,

Herder²,

Hofland³

et al. 2012

Endocrine-Related Cancer

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Cushing's syndrome (CS) is a severe endocrine disorder characterized by chronic cortisol excess due to an ACTH-secreting pituitary adenoma, ectopic ACTH production, or a cortisol-producing adrenal neoplasia. Regardless of the underlying cause, untreated CS is associated with considerable morbidity and mortality. Surgery is the primary therapy for all causes of CS, but surgical failure and ineligibility of the patient to undergo surgery necessitate alternative treatment modalities. The role of medical therapy in CS has been limited because of lack of efficacy or intolerability. In recent years, however, new targets for medical therapy have been identified, both at the level of the pituitary gland (e.g. somatostatin, dopamine, and epidermal growth factor receptors) and the adrenal gland (ectopically expressed receptors in ACTH-independent macronodular adrenal hyperplasia). In this review, results of preclinical and clinical studies with drugs that exert their action through these molecular targets, as well as already established medical treatment options, will be discussed.

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“…The major limitation of metyrapone is in women as the accumulation of cortisol precursors results in elevated androgens, which frequently is manifest as hirsutism and acne. Although mineralocorticoid precursors levels are elevated, hypokalaemia, hypertension and oedema are not problems, presumably because of the benefits of lower circulating cortisol levels (5,6). In patients with pituitary-dependent Cushing's disease, ACTH levels rise but there is no evidence that this results in tachyphylaxis (5,7).…”

Section: Metyraponementioning

confidence: 99%

Pharmacological management of Cushing's syndrome: an update

Dang

Trainer

2007

Arq Bras Endocrinol Metab

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The treatment of choice for Cushing's syndrome remains surgical. The role for medical therapy is twofold. Firstly it is used to control hypercortisolaemia prior to surgery to optimize patient's preoperative state and secondly, it is used where surgery has failed and radiotherapy has not taken effect. The main drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and mitotane. RESUMOManejo Farmacológico da Síndrome de Cushing: Uma Atualização. O tratamento de escolha para a síndrome de Cushing ainda é a cirurgia. O papel da terapia medicamentosa é duplo: ele é usado para controlar o hipercortisolismo antes da cirurgia e otimizar o estado pré-operatório do paciente e, adicionalmente, quando ocorre falha cirúrgica e a radioterapia ainda não se mostrou efetiva. Os principais medicamentos são empregados para inibir a esteroidogênese e incluem: metirapona, cetoconazol e mitotano. Medicamentos visando o eixo hipotálamo-hipofisário têm sido investigados, mas seu papel na prática clínica permanece limitado, embora o agonista PPAR-γ e análogo de somatostatina, som-230 (pasireotídeo), requeira estudos adicionais. A única droga que age perifericamente no receptor glicocorticóide é a mifepristona (RU486). O manejo da síndrome de Cushing deve envolver uma combinação terapêutica atuando em diferentes vias da hipercortisolemia, mas o monitoramento dessa terapia ainda permanece um desafio. (Arq Bras Endocrinol Metab

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Short and long‐term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome

Abstract: In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.

Cited by 282 publications

References 24 publications

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

New developments in the medical treatment of Cushing's syndrome

Pharmacological management of Cushing's syndrome: an update

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