Use of Intravenous Etomidate to Control Acute Psychosis Induced by the Hypercortisolaemia in Severe Paediatric Cushing’s Disease

Chan, Li F.; Vaidya, Mamta; Westphal, Birgit; Allgrove, Jeremy; Martin, Lee; Afshar, F.; Hindmarsh, Peter C.; Savage, M O; Grossman, Ashley; Storr, Helen L

doi:10.1159/000324419

Cited by 28 publications

(22 citation statements)

References 96 publications

(76 reference statements)

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“…Several publications that followed report sub-hypnotic i.v. 2.5-3.5 mg/h doses of etomidate completely inhibiting endogenous cortisol production (21,23,24). In the case reports where patients were rendered hypoadrenal, this was demonstrated by serum cortisol levels !100 nmol/l and glucocorticoid replacement therapy was provided by a continuous i.v.…”

Section: Clinical Experiencementioning

confidence: 99%

THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review

Preda

Sen

Karavitaki

et al. 2012

European Journal of Endocrinology

132

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This review addresses the practical usage of intravenous etomidate as a medical therapy in Cushing's syndrome. We reviewed the relevant literature, using search terms 'etomidate', 'Cushing's syndrome', 'adrenocortical hyperfunction', 'drug therapy' and 'hypercortisolaemia' in a series of public databases. There is a paucity of large randomised controlled trials, and data on its use rely only on small series, case study reports and international consensus guideline recommendations. Based on these, etomidate is an effective parenteral medication for the management of endogenous hypercortisolaemia, particularly in cases with significant biochemical disturbance, sepsis and other serious complications such as severe psychosis, as well as in preoperative instability. We suggest treatment protocols for the safe and effective use of etomidate in Cushing's syndrome.

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Section: Clinical Experiencementioning

confidence: 99%

THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review

Preda

Sen

Karavitaki

et al. 2012

European Journal of Endocrinology

132

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“…Because of these peculiar pharmacokinetic properties, etomidate can be particularly useful in patients with acute and/or lifethreatening complications of CS, such as serious psychosis and severe hypertension (549 -553). Generally, patients with such a severe disease have an ectopic source of CS, but patients with CD treated with etomidate have also been reported (549,(552)(553)(554)(555)(556). Etomidate has been shown to rapidly normalize cortisol levels in almost all patients with CD (549, 552-556).…”

Section: Etomidatementioning

confidence: 99%

The Treatment of Cushing's Disease

et al. 2015

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Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.

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“…Etomidate is the only parenteral active steroidogenesis inhibitor and should be used in cases where rapid control of hypercortisolaemia is vital and an oral agent is contraindicated (9,102,116,117,118). In addition, it can be very useful in situations where sedation is a desired effect, such as patients requiring intubation for respiratory support or patients with acute psychosis.…”

Section: Choice Of Agentmentioning

confidence: 99%

“…Psychotic symptoms improve, usually within days (116,118). Sedative doses are not essential for the rapid control of hypercortisolaemia; they can be used if short-term sedation is felt to be beneficial.…”

Section: Psychosismentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

Daniel

Newell‐Price

2015

European Journal of Endocrinology

111

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Steroidogenesis enzyme inhibitors are the mainstay of medical therapy in Cushing's syndrome (CS). Ketoconazole (KTZ) and metyrapone are the most commonly used agents. Although there is considerable experience of their use in individual specialist centres, these drugs have not been rigorously tested in prospective clinical trials. Clinicians face uncertainties and concerns with respect to the safety profile of these agents, and best means to monitor effect. We review steroidogenesis inhibitors in the management of CS, including older agents (KTZ, metyrapone, etomidate and mitotane) and those currently under development (LCI699, non-racemic KTZ), and offer a practical approach for their use in clinical practice.

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Use of Intravenous Etomidate to Control Acute Psychosis Induced by the Hypercortisolaemia in Severe Paediatric Cushing’s Disease

Cited by 28 publications

References 96 publications

THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review

THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review

The Treatment of Cushing's Disease

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

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