4.7 Review

Management and Medical Therapy of Mild Hypercortisolism

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Letter Endocrinology & Metabolism

Osilodrostat in Cushing's disease: The risk of delayed adrenal insufficiency should be carefully monitored

Frederic Castinetti et al.

Summary: This short manuscript reports three cases of atypical adrenal insufficiency with osilodrostat, which is highly effective in blocking cortisol secretion but also carries the risk of adrenal insufficiency.

CLINICAL ENDOCRINOLOGY (2023)

Article Endocrinology & Metabolism

Mental Health in Patients With Adrenal Incidentalomas: Is There a Relation With Different Degrees of Cortisol Secretion?

Valentina Morelli et al.

Summary: Subclinical hypercortisolism may influence patients' mental health and cognitive performances, requiring an integrated treatment.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

Article Endocrinology & Metabolism

Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing's Syndrome Treatment

Sara G. Creemers et al.

Summary: This study compared the effects of Levoketoconazole and RK on adrenocortical and pituitary adenoma cells, with Levoketoconazole showing more potent inhibition of cortisol production and a more significant effect on steroid profiles. Levoketoconazole also demonstrated potential in inhibiting ACTH secretion and growth of pituitary adenoma cells, suggesting it as a promising novel pharmacotherapy for Cushing's syndrome.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

Article Endocrinology & Metabolism

Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing's syndrome

Eliza B. Geer et al.

Summary: The study demonstrated significant improvements in skin symptoms and patient-reported quality of life and depression symptoms in patients with CS treated with levoketoconazole during the maintenance phase.

PITUITARY (2021)

Review Endocrinology & Metabolism

Hidden hypercortisolism: a too frequently neglected clinical condition

L. Giovanelli et al.

Summary: Research shows that HidHyCo can present as a hidden hypercortisolism in patients with bone fragility, hypertension, and diabetes, where bone fragility, hypertension, diabetes, or a combination of hypertension and diabetes are the main manifestations. Screening for HidHyCo is recommended in patients with resistant or suddenly worsening hypertension, diabetes, or unexplainable bone fragility.

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION (2021)

Article Endocrinology & Metabolism

Cardiovascular complications of mild autonomous cortisol secretion

Carmen Aresta et al.

Summary: Adrenal incidentalomas (AI) may be associated with mild autonomous cortisol secretion (MACS), with MACS patients having an increased risk of cardiovascular disease. Adrenalectomy seems to have beneficial effects in MACS patients, and some studies suggest that so-called non-functioning AI may actually have increased cardiovascular risk. The degree of cortisol secretion remains a key predictor of cardiovascular risk in AI patients, although the reliability of the current cortisol level cut-off for ruling out hypercortisolism is unclear.

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Risk of Bone Fractures after the Diagnosis of Adrenal Adenomas: A Population-based Cohort Study

Dingfeng Li et al.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2021)

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Osilodrostat for the treatment of Cushing's disease

Syeda Rasool et al.

Summary: Osilodrostat has shown clinical efficacy and tolerability in phase 2 and 3 trials with Cushing's disease patients who had inadequate response to transsphenoidal surgery (TSS) and conventional first-line treatment. In the phase 3 trial (LINC3), 86% of the treatment group achieved normal urinary free cortisol (UFC) levels compared to 29% in the placebo group (p < 0.001). Considered well-tolerated in all current pivotal trials, oral osilodrostat offers a noninvasive option for patients unable to undergo surgery or experiencing recurring hypercortisolemia.

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Article Endocrinology & Metabolism

Levoketoconazole in the Treatment of Patients With Cushing's Syndrome and Diabetes Mellitus: Results From the SONICS Phase 3 Study

Rosario Pivonello et al.

Summary: Treatment with levoketoconazole resulted in sustained normalization of mUFC levels and improvement in glycemic control, with more pronounced effects in patients with diabetes mellitus.

FRONTIERS IN ENDOCRINOLOGY (2021)

Article Medicine, General & Internal

Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas A Cohort Study

Albin Kjellbom et al.

Summary: Autonomous cortisol secretion in patients with adrenal incidentalomas is positively correlated with mortality. The association between mortality and cortisol(DST) increases linearly until reaching 200 nmol/L. Further studies are recommended, and some clinicians may take these findings into consideration when determining which patients to recommend for surgery.

ANNALS OF INTERNAL MEDICINE (2021)

Article Endocrinology & Metabolism

When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis

Carmen Aresta et al.

Summary: The meta-analysis revealed that patients with advanced type 2 diabetes are more likely to have hidden hypercortisolism. Studies also showed that patients with hypertension, insulin treatment, and dyslipidemia are more likely to have hidden hypercortisolism.

ENDOCRINE PRACTICE (2021)

Article Endocrinology & Metabolism

An Open-label Phase I/IIa Clinical Trial of 11β-HSD1 Inhibitor for Cushing's Syndrome and Autonomous Cortisol Secretion

Satoko Oda et al.

Summary: S-707106 demonstrates significant hypoglycemic and antisarcopenic effects in patients with CS and ACS, particularly in participants with a high body mass index.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

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Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

Iacopo Chiodini et al.

FRONTIERS IN ENDOCRINOLOGY (2021)

Article Endocrinology & Metabolism

Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study

Rosario Pivonello et al.

Summary: The study evaluated the efficacy and safety of the SGRM relacorilant in patients with endogenous Cushing syndrome, showing clinical benefit for hypertension and/or hyperglycemia. In the low-dose group, about 41.7% of hypertensive patients and 15.4% of hyperglycemic patients achieved clinical response, while in the high-dose group, approximately 63.6% of hypertensive patients and 50% of hyperglycemic patients achieved response.

FRONTIERS IN ENDOCRINOLOGY (2021)

Review Endocrinology & Metabolism

Adrenally Directed Medical Therapies for Cushing Syndrome

Nicholas A. Tritos

Summary: Endogenous Cushing syndrome, characterized by excess cortisol secretion, may require adrenally directed medical therapies when surgery is not feasible or ineffective. Different drugs are available for the treatment of CS, each with varying mechanisms of action and considerations for dosage titration and patient monitoring. Proper use of these medications is crucial for the management of persistent or recurrent hypercortisolism in CS patients.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

Article Endocrinology & Metabolism

Tumor Shrinkage by Metyrapone in Cushing Disease Exhibiting Glucocorticoid-Induced Positive Feedback

Yasutaka Tsujimoto et al.

Summary: This study reported a case of CD patient with paradoxical increases in cortisol, ACTH suppression, and tumor shrinkage during DST and metyrapone treatment. The findings suggest the existence of a new subtype of CD characterized by glucocorticoid-driven positive feedback, for which further investigation is needed for the mechanisms and therapeutic approaches.

JOURNAL OF THE ENDOCRINE SOCIETY (2021)

Review Pharmacology & Pharmacy

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease

John A. Dougherty et al.

Summary: Osilodrostat was effective and safe in treating Cushing's disease in middle-aged Caucasian women, with a significant reduction in cortisol levels. However, precautions should be taken for QT interval prolongation, hypocortisolism, edema, and hypertension risks. Careful monitoring and management are needed in clinical practice.

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Amandine Ferriere et al.

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Advances in the Medical Treatment of Cushing Disease

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ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA (2020)

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Dimitra A. Vassiliadi et al.

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Evaluation and Treatment of Patients With Hypercortisolism A Review

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Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials

Rosario Pivonello et al.

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Advances in the medical treatment of Cushing's syndrome

Richard A. Feelders et al.

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MIFEPRISTONE TREATMENT FOR MILD AUTONOMOUS CORTISOL SECRETION DUE TO ADRENAL ADENOMAS: A PILOT STUDY

Regina Belokovskay et al.

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Pejman Cohan et al.

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Cortisol Secretion, Sensitivity, and Activity Are Associated With Hypertension in Postmenopausal Eucortisolemic Women

Iacopo Chiodini et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2019)

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Modern Management of Mild Autonomous Cortisol Secretion

Danae A. Delivanis et al.

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Toward a Diagnostic Score in Cushing's Syndrome

Leah T. Braun et al.

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Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities

Iacopo Chiodini et al.

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Recent Advances on Subclinical Hypercortisolism

Guido Zavatta et al.

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Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis

Leonie H. A. Broersen et al.

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Andre Lacroix et al.

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