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Review
. 2020 Oct 29;6(1):18.
doi: 10.1186/s40842-020-00105-4.

Clinical management of patients with Cushing syndrome treated with mifepristone: consensus recommendations

David R Brown  1 , Honey E East  2 , Bradley S Eilerman  3 , Murray B Gordon  4 , Elizabeth E King  5 , Laura A Knecht  6 , Brandon Salke  7 , Susan L Samson  8 , Kevin C J Yuen  9 , Hanford Yau  10
Affiliations
Review

Clinical management of patients with Cushing syndrome treated with mifepristone: consensus recommendations

David R Brown et al. Clin Diabetes Endocrinol. .

Abstract

Background: While surgery is the first-line treatment for patients with endogenous hypercortisolism (Cushing syndrome [CS]), mifepristone has been shown to be a beneficial medical treatment option, as demonstrated in the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial. Mifepristone is a competitive glucocorticoid receptor antagonist and progesterone receptor antagonist that is associated with several treatment effects and adverse events that clinicians need to be aware of when considering its use. The objective of this review was to provide updated clinical management recommendations for patients with CS treated with mifepristone.

Methods: A panel of endocrinologists from the US with extensive experience in treating patients with CS, including with mifepristone, convened as part of a clinical advisory board to develop a consensus on the practical, real-world clinical management of patients on mifepristone.

Results: Comprehensive considerations and recommendations are provided for managing mifepristone-associated effects, including symptoms of cortisol withdrawal, hypokalemia, and change in thyroid function; effects related to its antiprogesterone activity; and rash. Additional management strategies to address concomitant medications and special clinical situations, such as surgery and use in specific populations, are also provided.

Conclusion: Safe and effective use of mifepristone requires clinical judgment and close patient monitoring to ensure optimal clinical outcomes. These consensus recommendations provide useful, practical guidance to clinicians using mifepristone.

Keywords: Cushing syndrome; Drug effects; Education.

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Conflict of interest statement

D.R.B has been a consultant/advisor for Corcept and a speaker for Corcept, Merck, and Novo Nordisk.

H.E.E. has been a consultant/advisor for Amgen and Corcept, a speaker for Amgen, BI/Lilly, and Corcept, and has received research support from Acasti and Corcept.

B.S.E. has been a consultant/advisor for Corcept.

M.B.G. has been a consultant/advisor for Corcept and Novo Nordisk, and has received research support from Camurus, Corcept, Crinetics, Ionis, Ipsen, Novartis, Novo Nordisk, Opko, Teva, and Strongbridge.

E.E.K. has been a consultant/advisor and speaker for Corcept.

L.A.K. has been a consultant/advisor for Corcept and a speaker for Corcept, Ipsen, and Strongbridge.

B.S. reports that Optime Care, Inc. is the limited distribution contracted pharmacy for Corcept Therapeutics to dispense mifepristone.

S.L.S. has received research support from Corcept and Novartis.

K.C.J.Y. has been a consultant/advisor for Corcept, Novartis, and Strongbridge, and has received research support from Corcept, Crinetics, Millendo, and Novartis.

H.Y. has been a consultant/advisor and a speaker for Corcept.

All authors, except Dr. Salke, received a consulting fee from Corcept for participating in the Consensus Advisory Board in May 2019. Discussion during this event contributed to these consensus recommendations.

Figures

Fig. 1
Fig. 1
Signs and symptoms associated with excess GR antagonism, cortisol withdrawal, and adrenal insufficiency [8, 15, 16]. aThe presence of these signs and symptoms may not always be indicative of excess GR antagonism due to mifepristone and should also be considered in the context of the patient. bIncidence and magnitude may depend on concomitant medications being taken with mifepristone. cOccurs with primary adrenal insufficiency. Abbreviations: GR glucocorticoid receptor, MR mineralocorticoid receptor
Fig. 2
Fig. 2
Suggested potassium monitoring and spironolactone dosing algorithm for potassium. aNote that all patients may not need proactive spironolactone. For instance, some patients, particularly those with adrenal disease may not experience substantial increases in cortisol (and associated MR activation) during mifepristone treatment. bMR activation with mifepristone may take several days to occur. Direct patient to call clinician’s office to report when the MR antagonist is started to facilitate appropriate follow-up. If spironolactone is not tolerated, consider an alternative MR antagonist, such as eplerenone. cCheck for signs of excess MR activation (e.g., edema, elevated blood pressure). Abbreviations: eGFR estimated glomerular filtration rate, MR mineralocorticoid receptor
Fig. 3
Fig. 3
Thyroid assessment recommendations during mifepristone treatment [34, 35]. Abbreviations: AACE American Association of Clinical Endocrinologists, ATA American Thyroid Association, BMJ British Medical Journal, MAGIC MAGIC (Making Grade the Irresistible Choice) Foundation, T3 tri-iodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone
See this image and copyright information in PMC

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