Ketoconazole as second-line treatment for Cushing’s disease after transsphenoidal surgery: systematic review and meta-analysis

Viecceli, Camila; Mattos, Ana Carolina Viana; Hirakata, Vânia Naomi; Garcia, Sheila Piccoli; Rodrigues, Ticiana da Costa; Czepielewski, Mauro Antônio

doi:10.3389/fendo.2023.1145775

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…Oral 200-1200 mg/day 45-93 % [5,6,8,54,55] Hirsutism (36 %), hepatotoxicity (11-19 %), adrenal insufficiency (5-19 %), gastrointestinal problems (4-19 %), skin rash (4-6 %), and gynecomastia (new onset or worsening) (17-25 %) [5,6,8,54,55] Levoketoconazole Oral 300-1200 mg/day 31-81 % [9,10] Nausea (29-32 %), headache (23-28 %), hypokalemia (11-26 %), hypertension (17-24 %), and QT prolongation (5-11 %) [9,10] Metyrapone Oral 250-6000 mg/day 45-100 % [3,8,11,12,14,47] Hirsutism (5-71 %), nausea (5-33 %), dizziness (10-44 %), edema (6-20 %), decreased appetite (18 %), -fatigue (14 %), headache (10 %), hypokalemia (6 %), and hypertension (6-48 %) [3,8,11,12,14,47] Osilodrostat Oral 4-60 mg/day 66-100 % [4,[14][15][16]39] Fatigue (29-58 %), nausea (32-42 %), headache (25-34 %), diarrhea (25-32 %), adrenal insufficiency (28-32 %), QT prolongation (4-13 %), and hypertension (12 %) [4,[14][15][16]39] Mitotane Oral Mean drug dose 2500-3300 g/day (according to blood concentration)…”

Section: Ketoconazolementioning

confidence: 99%

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Detomas,

Deutschbein,

Altieri

2024

Exp Clin Endocrinol Diabetes

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Endogenous Cushing’s syndrome (CS) is a rare disease characterized by a glucocorticoid excess. If inadequately treated, the latter can lead to increased morbidity and mortality. Surgical removal of the underlying tumor is the first line treatment but is sometimes not feasible or even contraindicated. Additionally, in cases with severe CS, rapid control of hypercortisolism may be required. In these scenarios steroidogenesis inhibitors represent a therapeutic alternative to surgery. Over the last years, the knowledge on the broad therapeutic effects of steroidogenesis inhibitors and the number of available drugs have increased. However, large comparative studies are still lacking. Accordingly, the decision on which drug to be used in a certain patient or clinical setting may be difficult. The aim of this review is to summarize the main characteristics of steroidogenesis inhibitors.

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Section: Ketoconazolementioning

confidence: 99%

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Detomas,

Deutschbein,

Altieri

2024

Exp Clin Endocrinol Diabetes

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Budget impact analysis of cabergoline for medical treatment of Cushing’s disease in Brazil

Silva,

Galendi,

Martins

et al. 2024

Archives of Endocrinology and Metabolism

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Objective The aim of this study was to estimate the budget impact of adding cabergoline to the Brazilian Unified Health System (SUS) formulary for the treatment of patients with Cushing’s disease (CD) who do not achieve disease control after transsphenoidal surgery. Materials and methods We conducted a budget impact analysis (BIA) from the perspective of the Brazilian SUS over a 5-year time horizon. We compared two scenarios: ketoconazole (Scenario 1) versus including cabergoline as a treatment option (Scenario 2). All analyses were conducted using Microsoft Excel. Uncertainty was explored in univariate sensitivity analyses. Results The total costs were BRL $25,596,729 for Scenario 1 and BRL $32,469,169 for Scenario 2. The budget impact of adding cabergoline to the formulary for CD treatment within the SUS would be BRL $6,091,036 over 5 years. On univariate analyses, variations in the rates of surgical failure and CD recurrence had the greatest potential to affect the final costs associated with cabergoline. Conclusions The estimated budget impact of adding cabergoline to the formulary for CD treatment within the Brazilian SUS would be about BRL $6 million. While cost savings cannot be expected, the budget impact of adding cabergoline would be lower than that of adding other treatment options for CD.

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Current and Emerging Pharmacological Therapies for Cushing's Disease

Divaris,

Kostopoulos,

Efstathiadou

2024

CPD

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Cushing’s Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm), is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing’s disease are discussed.

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Ketoconazole as second-line treatment for Cushing’s disease after transsphenoidal surgery: systematic review and meta-analysis

Cited by 3 publications

References 35 publications

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Budget impact analysis of cabergoline for medical treatment of Cushing’s disease in Brazil

Current and Emerging Pharmacological Therapies for Cushing's Disease

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