Advances in the medical treatment of Cushing's syndrome.

Abstract

Cushing's syndrome is associated with multisystem morbidity and, when suboptimally treated, increased mortality. Medical therapy is an option for patients if surgery is not successful and can be classified into pituitary-directed drugs, steroid synthesis inhibitors, and glucocorticoid receptor antagonists. In the last decade there have been new developments in each drug category. Targeting dopamine and somatostatin receptors on corticotroph adenomas with cabergoline or pasireotide, or both, controls cortisol production in up to 40% of patients. Potential new targets in corticotroph adenomas include the epidermal growth factor receptor, cyclin-dependent kinases, and heat shock protein 90. Osilodrostat and levoketoconazole are new inhibitors of steroidogenesis and are currently being evaluated in multicentre trials. CORT125134 is a new selective glucocorticoid receptor antagonist under investigation. We summarise the drug therapies for various forms of Cushing's syndrome and focus on emerging drugs and drug targets that have the potential for new and effective tailor-made pharmacotherapy for patients with Cushing's syndrome.

• Authors: Richard A Feelders, John Newell-Price, Rosario Pivonello, Lynnette K Nieman, Leo J Hofland, Andre Lacroix
• Journal: The lancet. Diabetes & endocrinology (Lancet Diabetes Endocrinol) Vol. 7 Issue 4 Pg. 300-312 (04 2019) ISSN: 2213-8595 [Electronic] England
• PMID: 30033041 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• ALD1613 monoclonal antibody
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Antineoplastic Agents, Alkylating
• Dopamine Agonists
• Hormones
• Imidazoles
• Isoquinolines
• Pyrazoles
• Pyridines
• Receptors, Glucocorticoid
• Roscovitine
• relacorilant
• Somatostatin
• Tretinoin
• Osilodrostat
• pasireotide
• ErbB Receptors
• Cabergoline
• Gefitinib
• Temozolomide

Topics

• ACTH Syndrome, Ectopic (complications, drug therapy)
• ACTH-Secreting Pituitary Adenoma (complications, drug therapy)
• Adenoma (complications, drug therapy)
• Adrenal Gland Neoplasms (complications, drug therapy)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Agents, Alkylating (therapeutic use)
• Cabergoline (therapeutic use)
• Cushing Syndrome (drug therapy, etiology)
• Dopamine Agonists (therapeutic use)
• ErbB Receptors (antagonists & inhibitors)
• Gefitinib (therapeutic use)
• Hormones (therapeutic use)
• Humans
• Imidazoles (therapeutic use)
• Isoquinolines (therapeutic use)
• Molecular Targeted Therapy
• Pituitary ACTH Hypersecretion (complications, drug therapy)
• Pyrazoles (therapeutic use)
• Pyridines (therapeutic use)
• Receptors, Glucocorticoid (antagonists & inhibitors)
• Roscovitine (therapeutic use)
• Somatostatin (analogs & derivatives, therapeutic use)
• Temozolomide (therapeutic use)
• Tretinoin (therapeutic use)