Etomidate in the Treatment Of Cushing Syndrome

Posted on September 25, 2023 by MaryO

Cushing syndrome is a metabolic disease caused by chronic exposure to high levels of glucocorticoids. It can present as an endocrine emergency due to a rapid increase in circulating cortisol leading to increased risk of cardiovascular disease and infection. Etomidate rapidly reduces plasma cortisol levels by inhibiting the action of 11β-hidroxilase. We report the case of a patient with severe hypercortisolaemia accompanied by metabolic and psychiatric disorders in whom administration of etomidate reduced preoperative levels of cortisol.

Introduction

Cushing’s syndrome is a metabolic disease caused by chronic exposure to high levels of glucocorticoids. The main causes are ectopic ACTH secretion, adrenal tumours (adenomas or carcinomas), adrenal hyperplasia, and administration of exognous glucocorticoids—the latter being the most common aetiology.1

In most cases, Cushing’s syndrome presents an indolent course for years before diagnosis is made, although it can sometime present as an endocrine emergency due to a rapid increase in circulating cortisol levels.2 In these cases, treatment to control hypercortisolaemia must be started quickly due to the high morbidity and mortality associated with the potentially life-threatening metabolic, infectious, and neuropsychiatric alterations that occur in this syndrome.1, 2, 3, 4

The options for treating Cushing’s syndrome include surgery, radiotherapy, and pharmacological treatment. The most commonly used drugs are adrenal steroidogenesis inhibitors (ketoconazole, metyrapone),3 but this treatment is not always well tolerated and its efficacy is limited.2 Etomidate is a drug from the imidazole family that inhibits the enzyme 11β-hydroxylase, and can reduce cortisol secretion within 48−72 h.2

Section snippets

Case report

Our patient was a 27-year-old woman with no known drug allergies or personal history of interest. She was studied in April 2021 for anxious-depressive symptoms with rapidly evolving paranoid ideation and hirsutism. A Nugent test was performed, which was positive (46.1 mcg/dl), and cortisol in urine was measured (2715 mcg/24 h), leading to a diagnosis of Cushing’s syndrome.

A CT scan showed a large mass on the right adrenal gland, compatible with a primary adrenal gland tumour (Fig. 1).

Discussion

Endogenous Cushing’s syndrome is characterized by over-production of cortisol. In patients such as ours, the syndrome presents in its most serious form, with very high hypercortisolaemia and metabolic, cardiovascular, and neuropsychiatric disorders. Cushing’s syndrome is a medical emergency due to its association with several comorbidities and its high rate of mortality.5 The first therapeutic option is surgical resection of the underlying tumour; however, the accompanying hypercortisolaemia

Conclusion

In its severe form, Cushing’s syndrome is a medical emergency that must be rapidly controlled.

Etomidate is both safe and effective, and has shown promising results in the treatment of severe hypercortisolaemia.

We believe that these patients should be admitted to the Anaesthesia Intensive Care Unit during etomidate therapy in order to monitor their level of consciousness, lung function, and haemodynamics, and to closely monitor cortisol and electrolyte levels.

Ethical considerations

Informed consent was obtained for the use of patient information for teaching and research purposes in accordance with our hospital protocol.

Conflict of interests

None.

Funding

The authors have not received any funding for this manuscript.

References (8)

  • A. Ferriere et al.

    Cushing’s syndrome: Treatment and new therapeutic approaches

    Best Pract Res Clin Endocrinol Metab

    (2020)
  • Juszczak A, Morris D, Grossman A. Cushing’s Syndrome [Internet]. South Dartmouth (MA): MDText.com, Inc; 2000 [revised…
  • T.B. Carroll et al.

    Continuous Etomidate Infusion for the Management of Severe Cushing Syndrome: Validation of a Standard Protocol

    J Endocr Soc

    (2018)
  • V.A. Preda et al.

    Etomidate in the management of hypercortisolaemia in Cushing’s syndrome: a review

    Eur J Endocrinol

    (2012)
There are more references available in the full text version of this article.

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© 2023 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España, S.L.U. All rights reserved.

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The Cushings Disease Treatment Market To Be Consistent In The Next 10 Years

Posted on August 26, 2021 by MaryO

Cushing disease is caused by tumour in the pituitary gland which leads to excessive secretion of a hormone called adrenocorticotrophic (ACTH), which in turn leads to increasing levels of cortisol in the body. Cortisol is a steroid hormone released by the adrenal glands and helps the body to deal with injury or infection.

Increasing levels of cortisol increases the blood sugar and can even cause diabetes mellitus. However the disease is also caused due to excess production of hypothalamus corticotropin releasing hormone (CRH) which stimulates the synthesis of cortisol by the adrenal glands. The condition is named after Harvey Cushing, the doctor who first identified the disease in 1912. Cushing disease results in Cushing syndrome.

Cushing syndrome is a group of signs and symptoms developed due to prolonged exposure to cortisol. Signs and symptoms of Cushing syndrome includes hypertension, abdominal obesity, muscle weakness, headache, fragile skin, acne, thin arms and legs, red stretch marks on stomach, fluid retention or swelling, excess body and facial hair, weight gain, acne, buffalo hump, tiredness, fatigue, brittle bones, low back pain, moon shaped face etc. Symptoms vary from individual to individual depending upon the disease duration, age and gender of the patient.

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Disease diagnosis is done by measuring levels of cortisol in patient’s urine, saliva or blood. For confirming the diagnosis, a blood test for ACTH is performed. The first-line treatment of the disease is through surgical resection of ACTH-secreting pituitary adenoma, however disease management is also done through medications, Cushing disease treatment market comprises of the drugs designed for lowering the level of cortisol in the body. Thus patients suffering from Cushing disease are prescribed medications such as ketoconazole, mitotane, aminoglutethimide metyrapone, mifepristone, etomidate and pasireotide.

Cushing’s disease treatment market revenue is growing with a stable growth rate, this is attributed to increasing number of pipeline drugs. Also increasing interest of pharmaceutical companies to develop Cushing disease drugs is a major factor contributing to the revenue growth of Cushing disease treatment market over the forecast period.

Current and emerging players’ focuses on physician education and awareness regarding availability of different drugs for curing Cushing disease, thus increasing the referral speeds, time to diagnosis and volume of diagnosed Cushing disease individuals.

Growing healthcare expenditure and increasing awareness regarding Cushing syndrome aids in the revenue growth of Cushing’s disease treatment market. Increasing number of new product launches also drives the market for Cushing’s disease Treatment devices. However availability of alternative therapies for curing Cushing syndrome is expected to hamper the growth of the Cushing’s disease treatment market over the forecast period.

For entire list of market players, request for Table of content here @ https://www.persistencemarketresearch.com/toc/14155

The Cushing’s disease Treatment market is segment based on the product type, technology type and end user

Cushing’s disease Treatment market is segmented into following types:

By Drug Type
  • Ketoconazole
  • Mitotane
  • Aminoglutethimide
  • Metyrapone
  • Mifepristone
  • Etomidate
  • Pasireotide
By End User
  • Hospital Pharmacies
  • Retail Pharmacies
  • Drug Stores
  • Clinics
  • e-Commerce/Online Pharmacies

Cushing’s disease treatment market revenue is expected to grow at a good growth rate, over the forecast period. The market is anticipated to perform well in the near future due to increasing awareness regarding the condition. Also the market is anticipated to grow with a fastest CAGR over the forecast period, attributed to increasing investment in R&D and increasing number of new product launches which is estimated to drive the revenue growth of Cushing’s disease treatment market over the forecast period.

Depending on geographic region, the Cushing’s disease treatment market is segmented into five key regions: North America, Latin America, Europe, Asia Pacific (APAC) and Middle East & Africa (MEA).

North America is occupying the largest regional market share in the global Cushing’s disease treatment market owing to the presence of more number of market players, high awareness levels regarding Cushing syndrome. Healthcare expenditure and relatively larger number of R&D exercises pertaining to drug manufacturing and marketing activities in the region. Also Europe is expected to perform well in the near future due to increasing prevalence of the condition in the region.

Asia Pacific is expected to grow at the fastest CAGR because of increase in the number of people showing the symptoms of Cushing syndrome, thus boosting the market growth of Cushing’s disease treatment market throughout the forecast period.

Some players of Cushing’s disease Treatment market includes CORCEPT THERAPEUTICS, HRA Pharma, Strongbridge Biopharma plc, Novartis AG, etc. However there are numerous companies producing branded generics for Cushing disease. The companies in Cushing’s disease treatment market are increasingly engaged in strategic partnerships, collaborations and promotional activities to capture a greater pie of market share.

The research report presents a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, and statistically supported and industry-validated market data. It also contains projections using a suitable set of assumptions and methodologies. The research report provides analysis and information according to categories such as market segments, geographies, types, technology and applications.

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Etomidate Found Effective in Severe Cushing’s Syndrome

Posted on May 18, 2018 by MaryO

Etomidate — a steroid synthesis blocker — is an effective treatment for patients with severe Cushing’s syndrome who do not respond to ketoconazole, according to a new case report from Mexico.

The report, “Etomidate in the control of severe Cushing’s syndrome by neuroendocrine carcinoma,” appeared in the journal Clinical Case Reports.

The investigators reported the case of a 51-year-old woman with ectopic Cushing’s syndrome caused by a pancreatic tumor. Ectopic Cushing’s refers to cases of excess secretion of adrenocorticotropin hormone (ACTH) outside the pituitary or adrenal glands.

The patient underwent distal pancreatectomy — the surgical removal of the bottom half of the pancreas — in 2015 due to an ACTH-secreting tumor. Although she had a good initial response, liver metastasis was evident by 2016.

Compared to measurements in 2016, morning blood cortisol, 24-hour urinary-free cortisol, and ACTH levels significantly increased in 2017. The patient also showed low levels of the luteinizing and follicle-stimulating hormones, which the scientists attributed to her severe hypercortisolism (excess cortisol levels).

The woman was being treated with ketoconazole to lower her cortisol values and later received chemoembolization — a method to reduce blood supply and deliver chemotherapy directly to a tumor — for her liver metastasis.

Although ketoconazole is generally the treatment of choice for the control of hormone production in the adrenal glands, its effectiveness is often limited and is associated with side effects, clinicians noted.

In April 2017, the patient arrived at the emergency room with sepsis — a potentially life-threatening complication of an infection — that originated in the gut.

Because ketoconazole had failed to lower cortisol levels, the patient started receiving infused etomidate, an inhibitor of the enzyme 11‐beta‐hydroxylase that prevents cortisol synthesis.

This treatment was stopped one day before the bilateral removal of the adrenal glands as a definitive treatment for the elevated production of cortisol.

While the patient experienced decreased levels of potassium, calcium, and magnesium with an initial dose of 0.04 mg per kg body weight an hour of etomidate, a gradual decrease of etomidate — depending on her cortisol levels — corrected these alterations.

After surgery, the patient showed a significant improvement in her general health, including control of her sepsis. She is currently taking hydrocortisone and fludrocortisone, with treatment for liver metastasis pending.

“Etomidate is a very effective drug in severe Cushing’s syndrome that is refractory to ketoconazole,” the researchers wrote.

“Control of the serum cortisol levels in ectopic Cushing’s syndrome can be obtained with infusion rates much lower than those used in anesthesia, without respiratory side effects,” they added.

The authors recommend an initial dose of etomidate of 0.04 mg/kg per hour, daily monitoring of 24-hour urinary cortisol and cortisol levels, and a gradual decrease of the etomidate dose according to daily measurements of metabolites.

From https://cushingsdiseasenews.com/2018/05/17/severe-cushings-syndrome-case-study-finds-etomidate-effective-therapy/

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Cushing’s Disease Treatment Market to Witness an Outstanding Growth by 2017 – 2025

Posted on March 2, 2017 by MaryO

Cushing disease is caused by tumour in the pituitary gland which leads to excessive secretion of a hormone called adrenocorticotrophic (ACTH), which in turn leads to increasing levels of cortisol in the body. Cortisol is a steroid hormone released by the adrenal glands and helps the body to deal with injury or infection. Increasing levels of cortisol increases the blood sugar and can even cause diabetes mellitus. However the disease is also caused due to excess production of hypothalamus corticotropin releasing hormone (CRH) which stimulates the synthesis of cortisol by the adrenal glands.

The condition is named after Harvey Cushing, the doctor who first identified the disease in 1912. Cushing disease results in Cushing syndrome. Cushing syndrome is a group of signs and symptoms developed due to prolonged exposure to cortisol.

Signs and symptoms of Cushing syndrome includes hypertension, abdominal obesity, muscle weakness, headache, fragile skin, acne, thin arms and legs, red stretch marks on stomach, fluid retention or swelling, excess body and facial hair, weight gain, acne, buffalo hump, tiredness, fatigue, brittle bones, low back pain, moon shaped face etc.

Symptoms vary from individual to individual depending upon the disease duration, age and gender of the patient.  Disease diagnosis is done by measuring levels of cortisol in patient’s urine, saliva or blood. For confirming the diagnosis, a blood test for ACTH is performed. The first-line treatment of the disease is through surgical resection of ACTH-secreting pituitary adenoma, however disease management is also done through medications, Cushing disease treatment market comprises of the drugs designed for lowering the level of cortisol in the body. Thus patients suffering from Cushing disease are prescribed medications such as ketoconazole, mitotane, aminoglutethimide metyrapone, mifepristone, etomidate and pasireotide.

Request to View Tables of Content @ http://www.persistencemarketresearch.com/toc/14155

Cushing’s disease treatment market revenue is growing with a stable growth rate, this is attributed to increasing number of pipeline drugs. Also increasing interest of pharmaceutical companies to develop Cushing disease drugs is a major factor contributing to the revenue growth of Cushing disease treatment market over the forecast period. Current and emerging players’ focuses on physician education and awareness regarding availability of different drugs for curing Cushing disease, thus increasing the referral speeds, time to diagnosis and volume of diagnosed Cushing disease individuals. Growing healthcare expenditure and increasing awareness regarding Cushing syndrome aids in the revenue growth of Cushing’s disease treatment market. Increasing number of new product launches also drives the market for Cushing’s disease Treatment devices. However availability of alternative therapies for curing Cushing syndrome is expected to hamper the growth of the Cushing’s disease treatment market over the forecast period.

The Cushing’s disease Treatment market is segment based on the product type, technology type and end user

Cushing’s disease Treatment market is segmented into following types:

By Drug Type

  • Ketoconazole
  • Mitotane
  • Aminoglutethimide
  • Metyrapone
  • Mifepristone
  • Etomidate
  • Pasireotide

By End User

  • Hospital Pharmacies
  • Retail Pharmacies
  • Drug Stores
  • Clinics
  • e-Commerce/Online Pharmacies

Cushing’s disease treatment market revenue is expected to grow at a good growth rate, over the forecast period. The market is anticipated to perform well in the near future due to increasing awareness regarding the condition. Also the market is anticipated to grow with a fastest CAGR over the forecast period, attributed to increasing investment in R&D and increasing number of new product launches which is estimated to drive the revenue growth of Cushing’s disease treatment market over the forecast period.

Depending on geographic region, the Cushing’s disease treatment market is segmented into five key regions: North America, Latin America, Europe, Asia Pacific (APAC) and Middle East & Africa (MEA).

North America is occupying the largest regional market share in the global Cushing’s disease treatment market owing to the presence of more number of market players, high awareness levels regarding Cushing syndrome. Healthcare expenditure and relatively larger number of R&D exercises pertaining to drug manufacturing and marketing activities in the region. Also Europe is expected to perform well in the near future due to increasing prevalence of the condition in the region.

Asia Pacific is expected to grow at the fastest CAGR because of increase in the number of people showing the symptoms of Cushing syndrome, thus boosting the market growth of Cushing’s disease treatment market throughout the forecast period.

Some players of Cushing’s disease Treatment market includes CORCEPT THERAPEUTICS, HRA Pharma, Strongbridge Biopharma plc, Novartis AG, etc. However there are numerous companies producing branded generics for Cushing disease. The companies in Cushing’s disease treatment market are increasingly engaged in strategic partnerships, collaborations and promotional activities to capture a greater pie of market share.

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From http://www.medgadget.com/2017/03/cushings-disease-treatment-market-to-witness-an-outstanding-growth-by-2017-2025-persistence-market-research.html 

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Medical Therapies in Cushing’s Syndrome

Posted on December 4, 2016 by MaryO
Chapter

The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

pp 165-179

Date: 03 December 2016

Medical Therapies in Cushing’s Syndrome

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

Keywords

Cabergoline, Etomidate, Ketoconazole, Levoketoconazole, Metyrapone, Mifepristone, Mitotane, Osilodrostat, Pasireotide, Pituitary adenoma

From http://link.springer.com/chapter/10.1007/978-3-319-45950-9_9

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