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Sonino, Nicoletta; Fava, Giovanni A.; Fallo, Francesco; Franceschetto, Antonella; Belluardo, Piera; Boscaro, Marco

doi:10.1023/a:1009986822146

Cited by 41 publications

(4 citation statements)

References 33 publications

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“…Despite the beneficial effects of cyproheptadine in some cases [79][80][81][82][83], its efficacy was not consistently reproduced [29,55,56,84] and its use have been abandoned. Similar results were reported for ketanserin, another serotonin antagonist, which was ineffective in the suppression of ACTH levels in patients with NS [85,86].…”

Section: Serotonin Antagonistssupporting

confidence: 84%

Management of Nelson’s Syndrome

Fountas

Karavitaki

2022

Medicina

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Nelson’s syndrome is a potentially severe condition that may develop in patients with Cushing’s disease treated with bilateral adrenalectomy. Its management can be challenging. Pituitary surgery followed or not by radiotherapy offers the most optimal tumour control, whilst pituitary irradiation alone needs to be considered in cases requiring intervention and are poor surgical candidates. Observation is an option for patients with small lesions, not causing mass effects to vital adjacent structures but close follow-up is required for a timely detection of corticotroph tumour progression and for further treatment if required. To date, no medical therapy has been consistently proven to be effective in Nelson’s syndrome. Pharmacotherapy, however, should be considered when other management approaches have failed. A subset of patients with Nelson’s syndrome may develop further tumour growth after primary treatment, and, in some cases, a truly aggressive tumour behaviour can be demonstrated. In the absence of evidence-based guidance, the management of these cases is individualized and tailored to previously offered treatments. Temozolomide has been used in patients with aggressive Nelson’s with no consistent results. Development of tumour-targeted therapeutic agents are an unmet need for the management of aggressive cases of Nelson’s syndrome.

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Section: Serotonin Antagonistssupporting

confidence: 84%

Management of Nelson’s Syndrome

Fountas

Karavitaki

2022

Medicina

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“…Antipsychotics are known to increase the incidence of immune-related adverse events because they decrease cortisol levels. Sonino et al reported a significant decrease in cortisol levels after the administration of ritanserin [ 45 ]. Another study indicated that a healthy population receiving olanzapine resulted in a reduction of cortisol levels [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Approaches for Assessing Risk Factors of Adrenal Insufficiency in Patients Undergoing Immune Checkpoint Inhibitor Therapy

et al. 2023

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Adrenal insufficiency is a rare, yet life-threatening immune-related adverse event of immune checkpoint inhibitors (ICIs). This study aimed to establish a risk scoring system for adrenal insufficiency in patients receiving anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. Moreover, several machine learning methods were utilized to predict such complications. This study included 209 ICI-treated patients from July 2015 to February 2021, excluding those with prior adrenal insufficiency, previous steroid therapy, or incomplete data to ensure data integrity. Patients were continuously followed up at Gyeongsang National University Hospital, with morning blood samples taken for basal cortisol level measurements, facilitating a comprehensive analysis of their adrenal insufficiency risk. Using a chi-squared test and logistic regression model, we derived the odds ratio and adjusted odds ratio (AOR) through univariate and multivariable analyses. This study utilized machine learning algorithms, such as decision trees, random forests, support vector machines (SVM), and logistic regression to predict adrenal insufficiency in patients treated with ICIs. The performance of each algorithm was evaluated using metrics like accuracy, sensitivity, specificity, precision, and the area under the receiver operating characteristic curve (AUROC), ensuring rigorous assessment and reproducibility. A risk scoring system was developed from the multivariable and machine learning analyses. In a multivariable analysis, proton pump inhibitors (PPIs) (AOR 4.5), and α-blockers (AOR 6.0) were significant risk factors for adrenal insufficiency after adjusting for confounders. Among the machine learning models, logistic regression and elastic net showed good predictions, with AUROC values of 0.75 (0.61–0.90) and 0.76 (0.64–0.89), respectively. Based on multivariable and machine learning analyses, females (1 point), age ≥ 65 (1 point), PPIs (1 point), α-blockers (2 points), and antipsychotics (3 points) were integrated into the risk scoring system. From the logistic regression curve, patients with 0, 1, 2, 4, 5, and 6 points showed approximately 1.1%, 2.8%, 7.3%, 17.6%, 36.8%, 61.3%, and 81.2% risk for adrenal insufficiency, respectively. The application of our scoring system could prove beneficial in patient assessment and clinical decision-making while administering PD-1/PD-L1 inhibitors.

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“…Serotonin antagonists and gamma-amino butyric acid (GABA) agonists are neuromodulatory drugs that have previously been studied in CD, but shown to have limited efficacy, and serious adverse effects [4, 77, 78]. Results from studies analyzing the nuclear receptor ligand, peroxisome proliferator-activated receptor gamma (PPAR-gamma) have also been inconsistent, mainly demonstrating short-term disease control, high rates of treatment escape and minimal clinical improvement [79–81].…”

Section: Medical Treatments Currently Used In Cushing’s Diseasementioning

confidence: 99%

Update on medical treatment for Cushing’s disease

Cuevas‐Ramos

Lim

Fleseriu

2016

Clin Diabetes Endocrinol

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Cushing’s disease (CD) is the most common cause of endogenous Cushing’s syndrome (CS). The goal of treatment is to rapidly control cortisol excess and achieve long-term remission, to reverse the clinical features and reduce long-term complications associated with increased mortality.While pituitary surgery remains first line therapy, pituitary radiotherapy and bilateral adrenalectomy have traditionally been seen as second-line therapies for persistent hypercortisolism. Medical therapy is now recognized to play a key role in the control of cortisol excess. In this review, all currently available medical therapies are summarized, and novel medical therapies in phase 3 clinical trials, such as osilodrostat and levoketoconazole are discussed, with an emphasis on indications, efficacy and safety. Emerging data suggests increased efficacy and better tolerability with these novel therapies and combination treatment strategies, and potentially increases the therapeutic options for treatment of CD. New insights into the pathophysiology of CD are highlighted, along with potential therapeutic applications. Future treatments on the horizon such as R-roscovitine, retinoic acid, epidermal growth factor receptor inhibitors and somatostatin-dopamine chimeric compounds are also described, with a focus on potential clinical utility.

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Cited by 41 publications

References 33 publications

Management of Nelson’s Syndrome

Management of Nelson’s Syndrome

Machine Learning Approaches for Assessing Risk Factors of Adrenal Insufficiency in Patients Undergoing Immune Checkpoint Inhibitor Therapy

Update on medical treatment for Cushing’s disease

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