Mifepristone Treatment in Four Cases of Primary Bilateral Macronodular Adrenal Hyperplasia (BMAH)

Cohan, Pejman; East, Honey E.; Galati, Sandi-Jo; Mercado, Jennifer; Lim, Precious J; Lamerson, Michele; Smith, James J.; Peters, Anne L.; Yuen, Kevin C.J.

doi:10.1210/jc.2018-02638

Cited by 24 publications

(11 citation statements)

References 49 publications

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“…In line with our case series, there have been other reports of symptom management benefits with the use of mifepristone in patients with hypercortisolism prior to surgery. 13 , 35 - 37 Additionally, in Case 3, the pituitary tumor became visible during the interval period of medical therapy, allowing more targeted surgery, which may increase the likelihood of long-term remission. Mifepristone has been shown to increase ACTH levels.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Unilateral adrenalectomy has recently been proposed as an alternative in selected patients, with some advocating for the removal of the larger gland, especially in older patients [ 23 ]. Recently the use of mifepristone has also been proposed [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

ARMC5 Primary Bilateral Macronodular Adrenal Hyperplasia Associated with a Meningioma: A Family Report

Ferreira

Pedro

Salazar

et al. 2020

Case Reports in Endocrinology

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Primary bilateral adrenal macronodular hyperplasia is characterized by functioning adrenal macronodules and variable cortisol secretion. Familial clustering suggests a genetic cause that has been confirmed with the identification of some genetic mutations, including inactivating germline mutations, in armadillo repeat containing 5 (ARMC5) gene. The identification of the pathogenic variant enables the physician to identify and treat these patients earlier and more effectively. It has also been noticed that patients with germline causative variants show a different clinical spectrum, presenting specific clinical characteristics, as the association with the presence of meningiomas.

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“…Mifepristone, administered 300 mg daily over 6 months, led to a significant reduction in insulin resistance as measured and an improvement in Beck’s Depression Inventory scores and Cushing’s Quality of Life scores in most patients [ 107 ]. In the same year, other authors showed that mifepristone was able to induce an improvement in cardiometabolic parameters as early as 2 weeks after treatment initiation in 4 patients with BMAH, who also experienced an amelioration of glycemic control and hypertension as well as weight loss [ 108 ]. Overall, the possible use of mifepristone as a treatment of adrenal mHC for patients with impaired glucose metabolism is hindered by its adverse events (abnormal vaginal bleeding, edema and potential hypocortisolism).…”

Section: Medical Therapy Of Mild Hypercortisolismmentioning

confidence: 99%

Management and Medical Therapy of Mild Hypercortisolism

Favero

Cremaschi

Falchetti

et al. 2021

IJMS

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Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing’s syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the—nowadays—rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-βhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.

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Mifepristone Treatment in Four Cases of Primary Bilateral Macronodular Adrenal Hyperplasia (BMAH)

Cited by 24 publications

References 49 publications

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

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

ARMC5 Primary Bilateral Macronodular Adrenal Hyperplasia Associated with a Meningioma: A Family Report

Management and Medical Therapy of Mild Hypercortisolism

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