Abstract
Cushings syndrome is a rare disease with significant morbidity and mortality. Surgical intervention represents the most effective treatment option in both adrenocorticotropin-dependent and – independent forms of hypercortisolism. It is not uncommon, however, that surgery fails to cure or control the disease. Pharmacotherapy with drugs inhibiting steroid biosynthesis can be effectively used in these cases in order to alleviate symptoms or even to induce chemical adrenalectomy. A few drugs inhibiting single or multiple steps in adrenal steroid biosynthesis can be used in clinical practice. Drugs predominantly inhibiting single enzymatic steps include the 11β-hydroxylase inhibitor metyrapone and the 3β- hydroxysteroid dehydrogenase inhibitor trilostane, whereas mitotane, aminoglutethimide, ketoconazole and etomidate block multiple enzymatic reactions. Etomidate is the only agent available for parenteral administration that renders it as a treatment of choice in critically ill patients requiring a rapid control of hypercortisolemia. Ketoconazole, metyrapone and aminoglutethimide can be used alone or in combination for the treatment of hypercortisolism caused by benign adrenocorticotropin- or cortisol-secreting tumors. The clinical utility of trilostane is variable. Besides blocking multiple steps in adrenal steroid biosynthesis, the DDT (insecticide) analogue mitotane also has adrenolytic properties by inducing mitochondrial degeneration that renders it superior to other drugs in the treatment of adrenocortical cancer. Severe side effects may develop during therapy with each aforementioned drug that include hepatic, endocrine and neurological toxicity. After summarizing the chemical and biological properties of steroid biosynthetic inhibitors, the authors describe their possible clinical applications and limitations.
Keywords: Cushing's syndrome, steroid biosynthesis, cytochrome, inhibition, adrenolytic, toxicity
Current Medicinal Chemistry
Title: Steroid Biosynthesis Inhibitors in the Therapy of Hypercortisolism: Theory and Practice
Volume: 15 Issue: 26
Author(s): P. Igaz, Z. Tombol, P. M. Szabo, I. Liko and K. Racz
Affiliation:
Keywords: Cushing's syndrome, steroid biosynthesis, cytochrome, inhibition, adrenolytic, toxicity
Abstract: Cushings syndrome is a rare disease with significant morbidity and mortality. Surgical intervention represents the most effective treatment option in both adrenocorticotropin-dependent and – independent forms of hypercortisolism. It is not uncommon, however, that surgery fails to cure or control the disease. Pharmacotherapy with drugs inhibiting steroid biosynthesis can be effectively used in these cases in order to alleviate symptoms or even to induce chemical adrenalectomy. A few drugs inhibiting single or multiple steps in adrenal steroid biosynthesis can be used in clinical practice. Drugs predominantly inhibiting single enzymatic steps include the 11β-hydroxylase inhibitor metyrapone and the 3β- hydroxysteroid dehydrogenase inhibitor trilostane, whereas mitotane, aminoglutethimide, ketoconazole and etomidate block multiple enzymatic reactions. Etomidate is the only agent available for parenteral administration that renders it as a treatment of choice in critically ill patients requiring a rapid control of hypercortisolemia. Ketoconazole, metyrapone and aminoglutethimide can be used alone or in combination for the treatment of hypercortisolism caused by benign adrenocorticotropin- or cortisol-secreting tumors. The clinical utility of trilostane is variable. Besides blocking multiple steps in adrenal steroid biosynthesis, the DDT (insecticide) analogue mitotane also has adrenolytic properties by inducing mitochondrial degeneration that renders it superior to other drugs in the treatment of adrenocortical cancer. Severe side effects may develop during therapy with each aforementioned drug that include hepatic, endocrine and neurological toxicity. After summarizing the chemical and biological properties of steroid biosynthetic inhibitors, the authors describe their possible clinical applications and limitations.
Export Options
About this article
Cite this article as:
Igaz P., Tombol Z., Szabo M. P., Liko I. and Racz K., Steroid Biosynthesis Inhibitors in the Therapy of Hypercortisolism: Theory and Practice, Current Medicinal Chemistry 2008; 15 (26) . https://dx.doi.org/10.2174/092986708786242921
DOI https://dx.doi.org/10.2174/092986708786242921 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Treatment of Metastases to the Vertebrae with Radiofrequency Ablation: Determination of Effectiveness by Evaluation of Tumor Necrosis – A Preliminary Result
Current Radiopharmaceuticals Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives
Current Pharmaceutical Design Effects of Aging on Thyroidal Function and Proliferation
Current Aging Science “Letting the Air In” Can Set the Stage for Tumor Recurrences
Current Cancer Therapy Reviews Editorial
Recent Patents on Anti-Cancer Drug Discovery Advances in Targeting Insulin-like Growth Factor Signaling Pathway in Cancer Treatment
Current Pharmaceutical Design Immunomodulatory Roles of VIP and PACAP in Models of Multiple Sclerosis
Current Pharmaceutical Design 12-Lipoxygenase: A Potential Target for Novel Anti-Platelet Therapeutics
Cardiovascular & Hematological Agents in Medicinal Chemistry How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?
Current Women`s Health Reviews Beyond the Reproductive Effect of Sex Steroids: Their Role During Immunity to Helminth Parasite Infections
Mini-Reviews in Medicinal Chemistry Retraction Notice: Clinical Strategies for Preventing Postoperative Nausea and Vomiting After Middle Ear Surgery in Adult Patients
Current Drug Safety Identification of Drug Candidates for Breast Cancer Therapy Through Scaffold Repurposing: A Brief Review
Current Drug Research Reviews Peptidergic Regulation of Pheochromocytoma
Current Pharmacogenomics Thyroid Hormone Modulation of Immunity: Its Participation in Chronic Stress-Induced Immune Alterations
Current Immunology Reviews (Discontinued) Glucocorticoids and Vascular Reactivity
Current Vascular Pharmacology Promotion of Insulin-Like Growth Factor-I Production by Sensory Neuron Stimulation; Molecular Mechanism(s) and Therapeutic Implications
Current Medicinal Chemistry Key Epigenetic Events Involved in the Maintenance of Breast Cancer Stem Cells
Current Stem Cell Research & Therapy Approach to the Patient with Subclinical Cushing’s Syndrome
Current Pharmaceutical Design Anti-Aging Property of G2013 Molecule as a Novel Immunosuppressive Agent on Enzymatic and Non-Enzymatic Oxidative Stress Determinants in Rat Model
Current Drug Discovery Technologies