Advances in the medical treatment of Cushing's syndrome

Richard A Feelders; John Newell-Price; Rosario Pivonello; Lynnette K Nieman; Leo J Hofland; Andre Lacroix

doi:10.1016/S2213-8587(18)30155-4

Advances in the medical treatment of Cushing's syndrome

Lancet Diabetes Endocrinol. 2019 Apr;7(4):300-312. doi: 10.1016/S2213-8587(18)30155-4. Epub 2018 Jul 20.

Authors

Richard A Feelders¹, John Newell-Price², Rosario Pivonello³, Lynnette K Nieman⁴, Leo J Hofland⁵, Andre Lacroix⁶

Affiliations

¹ Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Centre, Rotterdam, Netherlands. Electronic address: r.feelders@erasmusmc.nl.
² Academic Unit of Endocrinology, University of Sheffield, Sheffield, UK.
³ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
⁴ Eunice Kennedy Shriver National Institute of Diabetes and Kidney Disease, National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Centre, Rotterdam, Netherlands.
⁶ Division of Endocrinology, Department of Medicine and Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada.

PMID: 30033041
DOI: 10.1016/S2213-8587(18)30155-4

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.

Publication types

Review

MeSH terms

ACTH Syndrome, Ectopic / complications
ACTH Syndrome, Ectopic / drug therapy
ACTH-Secreting Pituitary Adenoma / complications
ACTH-Secreting Pituitary Adenoma / drug therapy
Adenoma / complications
Adenoma / drug therapy
Adrenal Gland Neoplasms / complications
Adrenal Gland Neoplasms / drug therapy
Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Agents / therapeutic use*
Antineoplastic Agents, Alkylating / therapeutic use
Cabergoline / therapeutic use
Cushing Syndrome / drug therapy*
Cushing Syndrome / 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
Pituitary ACTH Hypersecretion / drug therapy
Pyrazoles / therapeutic use
Pyridines / therapeutic use
Receptors, Glucocorticoid / antagonists & inhibitors*
Roscovitine / therapeutic use
Somatostatin / analogs & derivatives
Somatostatin / therapeutic use
Temozolomide / therapeutic use
Tretinoin / therapeutic use

Substances

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