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Table 1 Summary of recommendations for the management of some common signs and symptoms of cortisol withdrawal

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

Arthralgia

Rheumatologic arthralgia

 •May be unmasked during mifepristone treatment

 •Consult with Rheumatology. Consider treatment with nonsteroidal therapies (e.g., biologics/targeted immune modulators)

Non-rheumatologic arthralgias

 •Recommend treatment with acetaminophen or transdermal preparations (e.g., lidocaine). Avoid systemic/targeted injectable steroids and NSAIDs

 •Nonpharmacological treatments may also be considered, including acupuncture, physical therapy, yoga, weight loss, and TENS

Nausea and vomiting

Mild nausea and vomiting (i.e., non-emergency setting)

 •5-HT3 receptor antagonists are the first-line treatment. Do not exceed 8 mg of oral ondansetron in order to minimize the potential for drug-drug interactions and side effects (e.g., fatigue)

 •Alternative agents include promethazine or scopolamine patch

 •Consult with pharmacy for potential drug-drug interactions

Intractable nausea/vomiting

 •If patient is showing signs of volume depletion or is seeking emergency help, temporarily hold mifepristone and give dexamethasone

Fatigue

Mild fatigue

 •Reassure patients that this is a sign of therapeutic effect and may resolve over time

Moderate-severe fatigue

 •For fatigue that interferes with the patient’s activities of daily life, recommend additional laboratory assessments, such as thyroid function tests, complete blood count, iron panel, 25-hydroxy vitamin D level, and B12 level

 •Address other comorbidities (e.g., obstructive sleep apnea)

  1. Note: For intolerable symptoms of cortisol withdrawal, we recommend temporary holding of mifepristone and rechallenge later, restarting at a lower dose
  2. Abbreviations: 5-HT3 5-hyroxytryptamine 3, NSAIDs nonsteroidal anti-inflammatory drugs, TENS transcutaneous electrical nerve stimulation