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

Brown, David R.; East, Honey E.; Eilerman, Bradley S.; Gordon, Murray B.; King, Elizabeth E.; Knecht, Laura A.; Salke, Brandon; Samson, Susan L.; Yuen, Kevin C.J.; Yau, Hanford

doi:10.1186/s40842-020-00105-4

Cited by 25 publications

(25 citation statements)

References 47 publications

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“…Different hypotheses have been proposed to explain the effects of mifepristone on thyroid function, but they are not yet fully elucidated. The increased TSH secretion can be explained by the hypothalamic and pituitary GR inhibition [ 74 ]. Furthermore, an underlying thyroid disorder (autoimmune thyroid disease) can be masked by hypercortisolism and then can appear after the correction of hypercortisolism, as reported after successful surgery [ 36 ].…”

Section: Drugs Used For Cushing’s Syndrome and Their Effects On Thmentioning

confidence: 99%

“…Furthermore, an underlying thyroid disorder (autoimmune thyroid disease) can be masked by hypercortisolism and then can appear after the correction of hypercortisolism, as reported after successful surgery [ 36 ]. Recent consensus recommendations suggest that all patients should undergo a baseline thyroid function test before starting mifepristone treatment as well as to check thyroid function every 3 months or in the presence of any signs or symptoms consistent with abnormal thyroid function [ 74 ]. A case series of five patients affected by CD and central hypothyroidism showed that mifepristone treatment increased the levothyroxine requirement (median 1.83 times the initial dose of levothyroxine to achieve normal FT3 and FT4 levels).…”

Section: Drugs Used For Cushing’s Syndrome and Their Effects On Thmentioning

confidence: 99%

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Cushing’s Syndrome Effects on the Thyroid

Paragliola

Corsello

Papi

et al. 2021

IJMS

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The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.

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Section: Drugs Used For Cushing’s Syndrome and Their Effects On Thmentioning

confidence: 99%

Section: Drugs Used For Cushing’s Syndrome and Their Effects On Thmentioning

confidence: 99%

Cushing’s Syndrome Effects on the Thyroid

Paragliola

Corsello

Papi

et al. 2021

IJMS

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“… 24 A similar proactive approach to mitigating the risk of hypokalemia has been suggested based on consensus recommendations for the management of patients treated with mifepristone from clinical practice. 42 These recommendations included consideration of potassium supplementation and concomitant spironolactone for patients with baseline potassium levels less than 4 mEq/L followed by monitoring during and after mifepristone titration. 42 The patient in Case 6 also had a history of central hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

“… 42 These recommendations included consideration of potassium supplementation and concomitant spironolactone for patients with baseline potassium levels less than 4 mEq/L followed by monitoring during and after mifepristone titration. 42 The patient in Case 6 also had a history of central hypothyroidism. Substantial increases in thyroid hormone requirement (median levothyroxine dose increase 1.83 times initial dose) have been documented during mifepristone treatment in patients with CD and central hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

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Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases

Chang

Mirfakhraee

King

et al. 2021

Clin Med Insights Endocrinol Diabetes

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Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

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Glucocorticoid receptor blockers

Molitch

2022

Pituitary

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

Cited by 25 publications

References 47 publications

Cushing’s Syndrome Effects on the Thyroid

Cushing’s Syndrome Effects on the Thyroid

Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases

Glucocorticoid receptor blockers

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