Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha

Huguet, Isabel; Aguirre, Miguel; Vicente, Almudena; Alramadan, Mubarak; Quiroga, Ivan; Silva, Júlia; Lamas, Cristina

doi:10.1016/j.endoen.2015.05.005

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Our cohort's response rate was lower than that of Sonino et al (89%) (20) but higher than that of a multicenter cohort by Castinetti et al (approximately 50%) (14). Regarding other smaller series (35)(36)(37) our results reinforce some findings that demonstrate a percentage of control greater than 50% of the cases.…”

Section: Discussionsupporting

confidence: 71%

Evaluation of ketoconazole as a treatment for Cushing’s disease in a retrospective cohort

Viecceli

Mattos²,

Costa³

et al. 2022

Front. Endocrinol.

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ObjectiveThe first-line treatment for Cushing’s disease is transsphenoidal surgery, after which the rates of remission are 60 to 80%, with long-term recurrence of 20 to 30%, even in those with real initial remission. Drug therapies are indicated for patients without initial remission or with surgical contraindications or recurrence, and ketoconazole is one of the main available therapies. The objective of this study was to evaluate the safety profile of and the treatment response to ketoconazole in Cushing’s disease patients followed up at the endocrinology outpatient clinic of a Brazilian university hospital.Patients and methodsThis was a retrospective cohort of Cushing’s disease patients with active hypercortisolism who used ketoconazole at any stage of follow-up. Patients who were followed up for less than 7 days, who did not adhere to treatment, or who were lost to follow-up were excluded.ResultsOf the 172 Cushing’s disease patients who were followed up between 2004 and 2020, 38 received ketoconazole. However, complete data was only available for 33 of these patients. Of these, 26 (78%) underwent transsphenoidal surgery prior to using ketoconazole, five of whom (15%) had also undergone radiotherapy; seven used ketoconazole as a primary treatment. Ketoconazole use ranged from 14 days to 14.5 years. A total of 22 patients had a complete response (66%), three patients had a partial response (9%), and eight patients had no response to treatment (24%), including those who underwent radiotherapy while using ketoconazole. Patients whose hypercortisolism was controlled or partially controlled with ketoconazole had lower baseline 24-h urinary free cortisol levels than the uncontrolled group [times above the upper limit of normal: 0.62 (SD, 0.41) vs. 5.3 (SD, 8.21); p < 0.005, respectively] in addition to more frequent previous transsphenoidal surgery (p < 0.04). The prevalence of uncontrolled patients remained stable over time (approximately 30%) despite ketoconazole dose adjustments or association with other drugs, which had no significant effect. One patient received adjuvant cabergoline from the beginning of the follow-up, and it was prescribed to nine others due to clinical non-response to ketoconazole alone. Ten patients (30%) reported mild adverse effects, such as nausea, vomiting, dizziness, and loss of appetite. Only four patients had serious adverse effects that warranted discontinuation. There were 20 confirmed episodes of hypokalemia among 10/33 patients (30%).ConclusionKetoconazole effectively controlled hypercortisolism in 66% of Cushing’s disease patients, being a relatively safe drug for those without remission after transsphenoidal surgery or whose symptoms must be controlled until a new definitive therapy is carried out. Hypokalemia is a frequent metabolic effect not yet described in other series, which should be monitored during treatment.

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Section: Discussionsupporting

confidence: 71%

Evaluation of ketoconazole as a treatment for Cushing’s disease in a retrospective cohort

Viecceli

Mattos²,

Costa³

et al. 2022

Front. Endocrinol.

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“…6,7 Obesity and metabolic alterations, hypertension and cardiovascular/ cerebrovascular complications, neuropsychiatric, muscle/ skeletal, hypercoagulability/thromboembolism, and immune consequences remain the most challenging. 8 Although there is no solid evidence indicating that inappropriate replacement therapy with a nonphysiological circadian cortisol profile is a significant cause of poor outcomes in AD, it is reasonable to strive for the most physiologically relevant replacement therapy to avoid the inevitable consequences of long-term glucocorticoid overdosing. 9…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Monitoring of Hair Cortisol Using Liquid Chromatography–Mass Spectrometry to Prevent Hypercortisolism in Patients Undergoing Glucocorticoid Replacement Therapy

Kostolanská

Šiprová

Bartečků

et al. 2022

Therapeutic Drug Monitoring

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Objective:Currently available methods for endogenous cortisol monitoring in patients with hormonal insufficiency rely on measurements of plasma levels only at a single time point; thus, any kind of chronic exposure to cortisol is challenging to evaluate because it requires collecting samples at different time points. Hair cortisol levels acquired longitudinally better reflected chronic exposure (both cortisol synthesis and deposition) and may significantly contribute to better outcomes in glucocorticoid replacement therapies.Design:Twenty-two patients on cortisol substitution therapy were monitored for plasma, urinary, and hair cortisol levels for 18 months to determine whether hair cortisol may serve as a monitoring option for therapy setting and adjustment.Methods:Plasma and urinary cortisol levels were measured using standardized immunoassay methods, and segmented (∼1 cm) hair cortisol levels were monitored by liquid chromatography coupled to mass spectrometry. A log-normal model of the changes over time was proposed, and Bayesian statistics were used to compare plasma, urinary, and hair cortisol levels over 18 months.Results and conclusions:Hair cortisol levels decreased over time in patients undergoing substitutional therapy. The residual variance of hair cortisol in comparison to plasma or urinary cortisol levels was much lower. Thus, longitudinal monitoring of hair cortisol levels could prove beneficial as a noninvasive tool to reduce the risk of overdosing and improve the overall patient health.

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Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis

Galendi

Neto

Demetres³

et al. 2021

Front. Endocrinol.

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ObjectiveThe objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing’s disease (CD).MethodsThe primary outcomes were the proportion of CD control, adverse events (AE), and reduction of urinary free cortisol. Search strategies were applied to Embase, Medline, and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Standardized mean difference was calculated with 95% confidence interval (CI) for continuous data (i.e., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.ResultsTwenty-nine controlled and non-controlled studies were included. No study with temozolomide and levoketoconazole and one study with osilodrostat fulfilled the inclusion criteria. The meta-analyses of proportion of CD control was 35% for cabergoline (95% CI: 27–43%, six studies, 141 participants), 44% for pasireotide (95% CI: 25–35%, eight studies, 522 participants), 41% for ketoconazole (95% CI: 36–46%, six studies, 450 participants), 66% for metyrapone (95% CI: 46–87%, four studies, 66 participants), and of 66.4% for osilodrostat (95% CI: 57.9, 74.3, 97 participants, one study). One study compared two different treatments (cabergoline vs. ketoconazole), and no statistical difference was observed in CD control (RR: 0.53, 95% CI: 0.15 to 1.87, 14 participants, very low certainty of evidence). The most frequent AE associated with pasireotide was hyperglycemia, dizziness and nausea with cabergoline and metyrapone, and elevated transaminases with ketoconazole.ConclusionThe superiority of one drug over another could not be determined due to lack of controlled studies, but the proportion of disease control identified in our meta-analysis may support clinical decision. New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing’s disease.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.

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Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha

Cited by 4 publications

References 17 publications

Evaluation of ketoconazole as a treatment for Cushing’s disease in a retrospective cohort

Evaluation of ketoconazole as a treatment for Cushing’s disease in a retrospective cohort

Longitudinal Monitoring of Hair Cortisol Using Liquid Chromatography–Mass Spectrometry to Prevent Hypercortisolism in Patients Undergoing Glucocorticoid Replacement Therapy

Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis

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