Alternative Management of Cushing's Syndrome During Covid-19 Pandemic

Cushing's syndrome results from prolonged exposure to glucocorticoids. Surgery is often the first-line treatment for this condition, regardless of etiology. However, the COVID-19 pandemic caused a decrease in surgical procedures due to the risk of infection transmission. There are still emergency cases of Cushing's syndrome that are admitted to the hospital and require urgent management. The current treatment should be focused on medical management and endovascular embolization in selective cases. Embolization can be performed in facilities where there aretrained personnel with experience in adrenal embolization. Surgery, which traditionally is a first-line therapy, can increase the risk of infection, therefore, it should be avoided. The current review provides a brief description of the possible options for the management of adrenal Cushing's syndrome during the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Pituitary and SARS CoV-2: An unremitting conundrum.

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies.

Epidemiology, course, and outcomes of Sars-CoV-2 infection in patients with acromegaly and Cushing's disease: a monocentric experience in Southern Italy.

PURPOSE: Acromegaly (AC) and Cushing's disease (CD) increase morbidity and mortality due to cardio-metabolic alterations, and overall cause frailty in the affected patients, potentially making them more susceptible to infective diseases. However, up to now, very few studies evaluated the course of COVID-19 disease in this setting. METHODS: We investigated epidemiology, course, and outcomes of COVID-19 disease in patients with AC or CD, managed in the Endocrine Unit of a Sicilian University Hospital during 2 years of pandemic outbreak. RESULTS: We enrolled 136 patients with AC or CD (74 and 62 cases, respectively, 39 males) from Sicily and Calabria regions. Incidence of Sars-CoV-2 infection in these subjects was lower than in the general population, becoming quite similar after vaccines introduction (11%). No difference was observed concerning prevalence. Mean age of infected patients (IPs) was significantly lower than the unaffected ones (p < 0.02). No differences were found for sex, BMI, disease control, occurrence of diabetes mellitus, OSAS, cardiomyopathy, and hypopituitarism. The rate of IPs was similar in AC and CD patients' groups. None of them died. CONCLUSIONS: In conclusion, we did not find a significantly different incidence of Sars-CoV-2 infection in AC or CD patients compared to the general population. IPs were younger than the unaffected patients, but sex, BMI, or diabetes mellitus were not risk factors for infection/worse outcomes. Nevertheless, these results could have been biased by a safer behavior probably adopted by older and more complicated patients.

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess.

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.

Treatment of Cushing's syndrome with osilodrostat: practical applications of recent studies with case examples.

Endogenous Cushing's syndrome (CS) is a rare endocrine condition frequently caused by a tumor resulting in elevated cortisol levels. Cushing's disease (CD) caused by an adrenocorticotropic hormone-secreting pituitary adenoma is the most common form of endogenous CS. Medical therapy for CD is mostly used as second-line treatment after failed surgery or recurrence and comprises several pituitary-directed drugs, adrenal steroidogenesis inhibitors, and a glucocorticoid receptor blocker, some of which are US Food and Drug Administration (FDA)-approved for this condition. The recent Pituitary Society consensus guidelines for diagnosis and management of CD described osilodrostat, an oral inhibitor of 11ß-hydroxylase, as an effective, FDA-approved medical therapy for CD. Because clinical experience outside clinical trials is limited, we provide here a review of published data about osilodrostat and offer example case studies demonstrating practical considerations on the use of this medication. Recommendations regarding osilodrostat are provided for the following situations: specific assessments needed before treatment initiation; monitoring for adrenal insufficiency, hypokalemia, and changes in QTc; the potential value of a slow up-titration in patients with mild disease; managing temporary treatment cessation for patients with CD who have acquired coronavirus disease 2019; monitoring for increased testosterone levels in women; exercising caution with concomitant medication use; considering whether a higher dose at nighttime might be beneficial; and managing cortisol excess in ectopic and adrenal CS. This review highlights key clinical situations that physicians may encounter when using osilodrostat and provides practical recommendations for optimal patient care when treating CS, with a focus on CD.

Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing's Syndrome: A Case Report and Review of Literature.

Introduction: Patients with Cushing's syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient's condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient's condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients.

Analysis of Deaths in Patients with Cushing's Syndrome in the Republic of Uzbekistan According to the Register

Objective: Purpose of the study is to analysis of deaths in patients with Cushing's syndrome (CK) in the Republic of Uzbekistan ( RUz ) according to the register. Methods: According to the etiologic classification of the Republic of Uzbekistan from the period 2002 to 2021 established 317 patients with the following clinical forms of Cushing's syndrome: AСTН-dependent CS - 258 (81.3% ) of patients are women -174 (54.8%), men-84 (26.4%), ectopic CS -8 patients (2.5%) women-5 (1.5%), men-3 (0.94%);ACTH independent Cushing's syndrome - 51 patients (16.08%) women - 41 (12.9%), men - 10 (3.15%). Depending on the stage of the disease, patients with ACTH dependent CS : women in the stage of relapse - 19 (5.9%), active phase - 30, without radical treatment (9.4%), remission - 109 (34.3%);men in the stage of relapse -6 (1.8%), active phase - 14 (4.4%), remission - 46 (14.5%). ACTH independent CS in remission: 36 women (11.3%), 8 men (2.52%). ACTH ectopic CS in the stage of remission: women - 2 (0.6%), in the active phase - 2 (0.6%);men in remission-1 (0.01%). Performed methods of therapy: Transsphenoidal adenomectomy of the pituitary gland (TPAEG) was performed in 92 (35.6%) patients with ACTH dependent CS, in the form of monotherapy, 11 patients (4.26%) underwent repeated TPAEG;29 patients (11.2%) received combined treatment;Radiation therapy - 4 patients (1.5%), bilateral adrenalectomy was performed in 12 patients with ACTH dependent CS and one patient with ACTH ectopic CS (3.7%), 85 patients ( 32.9%) are on drug therapy, Unilateral adrenalectomy - in 60 patients (18.9 %) embolization and electrocoagulation vessel adrenal - 3 (0.9%) patients refusing treatment - 9 (2.8%);removing ectopic focus - 3 ACTH ectopic CS patients (37.5%), chemotherapy surround formation performed 2 patients (25%). Results: It was found that among these groups 41 (12.9%) deaths were registered over the 19 year period, of which 36 (11.3%) were with ACTH dependent CS -19 women (5.9%), 17 men (5.3%);ACTH independent CS -2 (0.6%) 1 woman (0.3%), 1 man- (0.3%);ACTH ectopic CS -3 patients (0.9%) of them women - 1 (0.3%), men - 2 (0.6%). Discussion/Conclusion: The causes of death in patients with CS were mainly cardiovascular accidents, of which myocardial infarction was established in 11 (3.4%), acute cerebrovascular accident-10 (3.15%), pulmonary embolism(PE)-10 (3.15%), the consequences of purulent complications of diabetes mellitus - 9 ( 2.8%), Covid 19-1 (0.31%).

Ectopic ACTH by Carcinoid Tumor Mimicking Nelson Syndrome in a Patient with Bilateral Adrenalectomy

Introduction: Nelson syndrome has been reported in up to 25% of adults after bilateral adrenalectomy (BLA) for Cushing’s disease (CD). It usually manifests as an expanding pituitary mass, rising adrenocorticotropic (ACTH) hormone levels and, in many patients, the development of hyperpigmentation. We review the clinical course of a patient with rising ACTH levels after BLA for presumed CD. Although the diagnosis of Nelson syndrome was considered, he was found 9 years after BLA to have an ectopic ACTH secreting bronchial carcinoid tumor as a cause for the elevated ACTH levels. Case Description: A 35 year old male was evaluated at another institution in 2010 after he presented with weight gain, new onset hypertension, muscle weakness with multiple falls, depression, irritability and emotional lability. He was diagnosed with CD and was referred to a university center where he underwent trans-sphenoidal pituitary surgery in May 2011. An adenoma was seen on frozen section but not on the final pathology. He developed transient symptoms of adrenal insufficiency on the second post-operative day. Because of persistent hypercortisolism he underwent BLA in November 2011. We started following him in 2012 and signs of hypercortisolism gradually resolved. He appeared euadrenal on hydrocortisone 10 mg am, 5 mg 12 noon and 5 mg 6 pm and fludrocortisone 0.05 mg daily. ACTH levels increased from 54 pg/ml (6-50) in 2012 to 1024 pg/ml in 2019. He had no hyperpigmentation and MRI of the pituitary from 2014-20 did not show a pituitary mass. During an evaluation for COVID-19 infection in May 2020, a chest x ray revealed a right lower lobe lung mass measuring 3.3 x 2.0 cm. He underwent right lower lobe lung lobectomy in July 2020 and pathology revealed a carcinoid tumor-spindle cell pattern which stained strongly positive for ACTH and weakly positive for chromogranin. ACTH levels after the surgery decreased to 16.3 pg/ml. Discussion: Some authors have suggested that Nelson syndrome be considered in patients with BLA who have one of the following: an expanding pituitary mass or ACTH levels >500 p/ml at 3 different time points after surgery. This case highlights the need to consider ectopic ACTH syndrome as another cause for rising ACTH levels after BLA for CD especially in those patients who are not found to have a discreet adenoma after pituitary surgery.

Steroid Stewardship.

Steroid stewardship is the systematic effort to prescribe and monitor glucocorticoids in a rational manner, while balancing benefit and potential risk, in patients who require this therapy. Steroid stewardship includes pre-prescription screening, rational prescription, medical care during corticosteroid use, and appropriate monitoring after corticosteroid use has been discontinued. The current usage of this class of drugs has highlighted the need to focus on this collective responsibility, and ensure effective prescription, while minimizing adverse events.

[Practical recommendations for screening and management of functional disorders of the adrenal cortex in cases of SARS-CoV-2 infections]. / Praktische Empfehlungen zum Screening und Management von Funktionsstörungen der Nebennierenrinde bei einer akuten SARS-CoV-2-Infektion.

Diseases of the adrenal cortex require particular attention during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Firstly, SARS-CoV­2 infections can give rise to extrapulmonary manifestations and cause endocrine disorders, particularly in the adrenal cortex. Furthermore, patients with pre-existing insufficiency of the adrenal cortex or hypercortisonism are particularly at risk from a severe infection such as SARS-CoV­2, to suffer from additional complications or a more severe course of a SARS-CoV­2 infection with a higher mortality. Especially in hemodynamically unstable patients with a SARS-CoV­2 infection, diseases of the adrenal glands should also be considered in the differential diagnostics and if necessary clarified, if this is not already known. Prolonged treatment of patients with a SARS-CoV­2 infection with regimens containing high doses of glucocorticoids can also result in a secondary adrenal insufficiency. In order to address these special aspects, some practical recommendations for the diagnostic and therapeutic management of functional disorders of the adrenal glands in patients with a SARS-CoV­2 infection are therefore presented.

Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses.

BACKGROUND: Diagnosis of pituitary pars intermedia dysfunction (PPID) using the thyrotropin-releasing hormone (TRH) stimulation test requires blood collection 10 minutes after TRH injection; it is unknown if small differences in timing affect test results. OBJECTIVE: To determine whether early or late sampling results in a significant (≥10%) difference in plasma adrenocorticotropic hormone (ACTH) concentration compared to standard 10-minute sampling. ANIMALS: Twenty-four healthy adult horses with unknown PPID status. METHODS: In this prospective study, subjects underwent a single TRH stimulation test, with blood collected exactly 9 minutes (early), 10 minutes (standard), and 11 minutes (late) after injection. ACTH was measured by chemiluminescent immunoassay. Two aliquots of the 10-minute plasma sample were analyzed separately to assess intra-assay variability. Data were reported descriptively and bias was calculated using Bland-Altman plots. Significance was set at P = .05. RESULTS: Minor variability was observed between the paired 10-minute sample aliquots (range, 0%-6%; median 3%). Overall variability of early or late samples compared to the corresponding paired (average) 10-minute standard concentration ranged from 0% to 92% (median 10%). Seventy-five percent of horses (18/24) tested had at least 1 early or late reading that differed by ≥10% from its corresponding 10-minute standard concentration, and 21% of horses (5/24) would have a different interpretation of testing result with either early or late sampling. Incidence of ≥10% variability was independent of PPID status (P = .59). CONCLUSIONS AND CLINICAL IMPORTANCE: Precise timing of sample collection is critical to ensure accurate assessment of PPID status given the observation of significant variability associated with minor alterations in timing of sample collection.

A Young Man Suspicious for Cushing's Syndrome With Coronavirus Disease-19 (COVID-19): A Case Report

The 2019 global Coronavirus syndrome pandemic (COVID-19) has entered more than two hundred countries around the world, involving <82 million persons and >1,800,000 deaths (until January, 1st 2021). We report on COVID-19 infection in the context of a Cushing's syndrome (CS) from Iran. A 36-year-old man with proximal myopathy, plethora, and striae with central obesity was evaluated for Cushing's syndrome. During the high dose dexamethasone test, the patient developed symptoms of cough, low-grade fever, and weakness then was admitted to the ICU with a diagnosis of COVID-19. Despite treatment according to national protocols for COVID-19, the patient unfortunately died. In this report, we intend to discuss the various aspects of Cushing's syndrome and severe COVID-19 infection.

Prescribing intranasal steroids in HIV-positive patients: systematic review of the literature.

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

The etiology of preeclampsia.

Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention.

Vasospasm due to eosinophilic coronary periarteritis treated with an anti-IL-5

Background: Vasospasm due to eosinophilic coronary periarteritis (VECP) can cause not only vasospastic angina but also myocardial infarction and sudden cardiac death. It is usually resistant to conventional treatment of coronary disease and responds to systemic corticosteroids. The role that may have the monoclonal antibodies reducers eosinophils is unknown. Method: A 52-year-old female with chronic rhinosinusitis with nasal polyposis, moderate persistent bronchial asthma and Aspirinexacerbated respiratory disease(AERD), without atopy, had been treated with inhaled and intranasal fluticasone, oral montelukast and inhaled formoterol. In July 2019, she arrived at the emergency room with an acute coronary syndrome. Results: The procedures performed revealed high levels of troponin 16717ng/L(0- 47ng/L), and abnormal electrocardiogram (alteration of repolarization in II, III and aVF). Marked eosinophilia of 750cells/ mm3 was noticed. She was treated with oral vasodilators and aspirin, which due to her AERD required rapid desensitization, being effective. However, she continued with recurrent chest pain and electrocardiographic abnormalities. Diagnostic coronary angiography revealed vasospasm in the right coronary artery without atheromatous lesions. Type 2 myocardial infarction secondary to VECP was suspected and prednisone 30mg/day was started with complete resolution of chest pain. She developed a Cushing syndrome and prednisone dose was reduced, but chest pain and eosinophilia(1000/mm3) reappeared, and prednisone 20mg/day was reintroduced. It was decided to discontinue corticosteroids and treatment was begun with anti-IL-5(benralizumab) in May 2020, reducing eosinophilia( 0/mm3) from the first dose. At 6 months we suspended prednisone without new episodes of pain. In August 2020, she was visited due to SARS-CoV-2 infection without symptoms of bronchospasm or pneumonia and received the 4th dose of benralizumab without complications. Conclusion: An acute coronary syndrome refractory to conventional medications with normal coronary arteries and eosinophilia, with a history of chronic rhinosinusitis/polyposis, asthma and/or AERD, VECP should be considered and early treatment with corticosteroids could save lives. This is the first case to our knowledge in which anti IL 5 has been used for VECP to control of the eosinophilic disorder. Likewise, it was administrated during the SARS-CoV-2 infection without complications.

Old Problem, New Concerns: Hypercortisolemia in the Time of COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic forced a change in the way we provide medical treatment. Endocrinology in the era of COVID-19 had to transform and reduce its vast potential to the absolute necessities. Medical professionals needed to update their clinical practice to provide their patients as much support and as little harm as possible in these increasingly difficult times. International expert statements were published to offer guidance regarding proper care. It was suggested to simplify the diagnostic scheme of hypercortisolemia and to modify the approach to treatment. Hypercortisolemic patients with COVID-19 and iatrogenic hypercortisolemia due to glucocorticoid use are important clinical scenarios - we aimed to provide a cohesive summary of issues to consider.

Management of Patients With Glucocorticoid-Related Diseases and COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health crisis affecting millions of people worldwide. SARS-CoV-2 enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2) after being cleaved by the transmembrane protease serine 2 (TMPRSS2). In addition to the lung, gastrointestinal tract and kidney, ACE2 is also extensively expressed in endocrine tissues, including the pituitary and adrenal glands. Although glucocorticoids could play a central role as immunosuppressants during the cytokine storm, they can have both stimulating and inhibitory effects on immune response, depending on the timing of their administration and their circulating levels. Patients with adrenal insufficiency (AI) or Cushing's syndrome (CS) are therefore vulnerable groups in relation to COVID-19. Additionally, patients with adrenocortical carcinoma (ACC) could also be more vulnerable to COVID-19 due to the immunosuppressive state caused by the cancer itself, by secreted glucocorticoids, and by anticancer treatments. This review comprehensively summarizes the current literature on susceptibility to and outcome of COVID-19 in AI, CS and ACC patients and emphasizes potential pathophysiological mechanisms of susceptibility to COVID-19 as well as the management of these patients in case of SARS-CoV-2. Finally, by performing an in silico analysis, we describe the mRNA expression of ACE2, TMPRSS2 and the genes encoding their co-receptors CTSB, CTSL and FURIN in normal adrenal and adrenocortical tumors (both adenomas and carcinomas).

Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease.

OBJECTIVE: Cushing disease (CD) is characterized by chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. Surgery remains the first-line treatment option; however, medical therapy is essential if surgery is contraindicated or fails to achieve remission or when recurrence occurs after surgical remission. Osilodrostat (Isturisa), a novel steroidogenic inhibitor, is now approved for the treatment of CD in the United States and Cushing syndrome in Europe. Herein, we review pharmacology and data on the efficacy, safety, and clinical use of osilodrostat and provide guidance on its use in treating patients with CD. METHODS: We reviewed the literature and published clinical trial data of osilodrostat use in patients with Cushing syndrome. Detailed information related to the clinical assessment of osilodrostat use, potential drug-to-drug interactions, drug initiation, dose titration, and the monitoring of drug tolerability were discussed. RESULTS: Clinical trial data demonstrated that osilodrostat, by virtue of inhibiting 11-ß hydroxylase, potently and rapidly decreased the 24-hour urinary free cortisol levels and sustained these reductions, with improved glycemia, blood pressure, body weight, and quality of life as well as lessened depression. Osilodrostat may interact with certain drugs, resulting in QT prolongation, which requires careful assessment of concomitant medications and periodic monitoring using electrocardiogram, respectively. The common adverse effects include adrenal insufficiency, hypokalemia, edema, and hyperandrogenic symptoms, which can be minimized using a slower up-titration dosing regimen. CONCLUSION: Osilodrostat is an effective, new treatment option for CD, with positive effects on cardiovascular and quality of life parameters as well as tolerable adverse effects. This article provides a review of the pharmacology of osilodrostat and offers practical recommendations on the use of osilodrostat to treat CD.