The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients
Open accessAbstract
BACKGROUND: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. OBJECTIVE: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. DESIGN: This was designed as a retrospective, multicenter study. SETTING: Thirteen University hospitals were studied. PATIENTS: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). MEASUREMENTS: Measurements included biochemical parameters of activity of CS: mean serum cortisol "day-curve" (CDC) (target 150-300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). RESULTS: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 μg/dL] vs 348.6 nmol/L [12.6 μg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 μg/dL] vs 491.1 nmol/L [17.8 μg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 μg/24 h] vs 452.6 nmol/24 h [164 μg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. CONCLUSIONS: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mean UFC is routinely used in clinical practice and research to monitor disease control and treatment response in patients with CS treated with medical therapy (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [131]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In clinical trials, the efficacy of steroidogenesis inhibitors and pituitary-directed therapies in patients with CS was primarily evaluated by the normalization of cortisol secretion per UFC (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [131]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The restoration of cortisol circadian rhythm following medical therapy has not been investigated or established for most medications used to treat CS, and it is not routinely measured to determine treatment response (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [131]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lacroix, A., Feelders, R. A., Stratakis, C. A., & Nieman, L. K. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61375-1 · Cited by 1,777
Newell-Price, J. D. C., BERTAGNA, X. Y., Grossman, A. B., & Nieman, L. K. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68699-6 · Cited by 1,258 · cited 1×
“ing effective biochemical control (1).”
Self-citationCANDIA, S. D. (1951) · PubMed · Cited by 365
Verhelst, J. A., Trainer, P. J., Howlett, T. A., Perry, L., Rees, L. H., Grossman, A. B., Wass, J. A. H., & Sesser, G. M. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb03517.x · Cited by 308 · cited 13×
“The main indication for metyrapone therapy was the control of severe symptoms of CS (CD 58%, EAS 77%, benign adrenal disease 44% and ACC 80%).”
BackgroundInfluentialSelf-citationKetoconazole in Cushing's disease: is it worth a try?
Castinetti, F., Guignat, L., Giraud, P., Muller, M., Kamenicky, P., Drui, D., Caron, P., Luca, F., Donadille, B., Vantyghem, M. C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3628 · Cited by 285 · cited 3×
“The modern use of ketoconazole has recently been reported in a multicenter French Study (4), although its availability in the United States has been restricted after an Food and Drug Administration safety warning for hepatotoxicity in 2013 (5, 6), but it is widely available in Europe in 2015 (7).”
BackgroundInfluentialPasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease
Feelders, R. A., de Bruin, C., Pereira, A. M., Romijn, J. A., Netea-Maier, R. T., Hermus, A. R., ZELISSEN, P. M. J., van Heerebeek, R., de Jong, F. H., van der Lely, A. J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmc1000094 · Cited by 262 · cited 2×
“Nine out of 17 patients normalized with pasireotide/cabergoline and ketoconazole induced biochemical control in 6/8 remaining patients (75%) within 20 days of treatment (23).”
BackgroundMethodLiddle, G. W., Island, D. P., Lance, E. M., & Harris, A. P. (1958) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-18-8-906 · Cited by 249 · cited 2×
“The cortisol-lowering effect of metyrapone was described as early as 1958 by Liddle et al (8), with later reports confirming metyrapone as a potent inhibitor of the steroidogenesis enzyme 11 -hydroxylase (8, 9).”
BackgroundKamenický, P., Droumaguet, C., Salenave, S., Blanchard, A., Jublanc, C., Gautier, J., Brailly‐Tabard, S., Leboulleux, S., Schlumberger, M. J., Baudin, É., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0536 · Cited by 218 · cited 3×
“Kamenický et al (21) used a triplemedication protocol with simultaneous administration of ketoconazole, metyrapone and mitotane in 11 patients with hypercortisolism and life-threatening complications as an alternative to bilateral adrenalectomy; all patients showed rapid clinical and biochemical improvement.”
BackgroundMethodMedical Therapy of Cushing's Disease
Nieman, L. K. (2002) · Pituitary · doi:10.1023/a:1022308429992 · Cited by 184 · cited 1×
“glucocorticoid receptor antagonist, mifepristone (2, 3).”
Metyrapone in long-term management of Cushing's disease.
Jeffcoate, W. J., REES, L. H., Tomlin, S., Jones, A. E., Edwards, C., & BESSER, G. M. (1977) · BMJ · doi:10.1136/bmj.2.6081.215 · Cited by 164 · cited 2×
“reported the efficacy of metyrapone in patients with CD undergoing radiotherapy (13-15) and EAS (17).”
Background
Cited by
Sorted by citations
Diagnosis and Treatment of Pituitary Adenomas: A Review
Molitch, M. E. (2017) · JAMA · doi:10.1001/jama.2016.19699 · Cited by 933
Consensus on diagnosis and management of Cushing's disease: a guideline update
Fleseriu, M., Auchus, R., Bancos, I., Ben-Shlomo, A., Bertherat, J., Biermasz, N. R., Boguszewski, C. L., Bronstein, M. D., Buchfelder, M., Carmichael, J. D., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00235-7 · Cited by 953
Self-citationThe Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids
Oster, H., Challet, E., Ott, V., Arvat, E., de Kloet, E. R., Dijk, D.-J., Lightman, S., Vgontzas, A., & Van Cauter, E. (2017) · Endocrine Reviews · doi:10.1210/er.2015-1080 · Cited by 548
Diagnosis and Management of Pituitary Adenomas: A Review
Tritos, N. A., & Miller, K. K. (2023) · JAMA · doi:10.1001/jama.2023.5444 · Cited by 331
Pivonello, R., Fleseriu, M., Newell-Price, J., Bertagna, X., Findling, J., Shimatsu, A., Gu, F., Auchus, R., Leelawattana, R., Lee, E. J., et al. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30240-0 · Cited by 222
Self-citationManagement of hormone-secreting pituitary adenomas
Mehta, G. U., & Lonser, R. R. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now130 · Cited by 174
Advances in the medical treatment of Cushing's syndrome
Feelders, R. A., Newell-Price, J. D. C., Pivonello, R., Nieman, L. K., Hofland, L. J., & Lacroix, A. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30155-4 · Cited by 160
Self-citationFleseriu, M., Pivonello, R., Young, J., Hamrahian, A. H., Molitch, M. E., Shimizu, C., Tanaka, T., Shimatsu, A., White, T. A., Hilliard, A., et al. (2015) · Pituitary · doi:10.1007/s11102-015-0692-z · Cited by 155
Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management
Scaroni, C., Zilio, M., Foti, M., & Boscaro, M. (2017) · Endocrine Reviews · doi:10.1210/er.2016-1105 · Cited by 140
Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials
Pivonello, R., Ferrigno, R., Martino, M. C. D., Simeoli, C., Paola, N. D., Pivonello, C., Barba, L., Negri, M., de Angelis, C., & Colao, A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00648 · Cited by 130
“available reports are heterogeneous for the definition of disease control, with variable treatment response criteria among studies (4, 62, 63).”
BackgroundInfluentialRandomized trial of osilodrostat for the treatment of Cushing disease
Gadelha, M., Bex, M., Feelders, R. A., Heaney, A. P., Auchus, R. J., Gilis-Januszewska, A., Witek, P., Belaya, Z., Yu, Y., Liao, Z., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac178 · Cited by 114
“6 years; dose schedule: 2–4 doses/day) in patients with Cushing’s syndrome (n=115/164 had Cushing’s disease), 43% of 37 patients with mUFC measurements available had normalized mUFC (17).”
BackgroundCabergoline for Cushing’s disease: a large retrospective multicenter study
Ferrière, A., Cortet, C., Chanson, P., Delemer, B., Caron, P. J., Chabre, O., Reznik, Y., Bertherat, J. Y., Rohmer, V., Briet, C., et al. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0662 · Cited by 114
Stereotactic Radiosurgery for Cushing Disease: Results of an International, Multicenter Study
Mehta, G. U., Ding, D., Patibandla, M. R., Kano, H., Sisterson, N. D., Su, Y.-H., Kršek, M., Nabeel, A. M., El-Shehaby, A. M. N., Abdelkarim, K., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01385 · Cited by 103
“New endocrinopathy after treatment 70 (25) Thyroid 46 (17) Testosterone/estrogen 28 (10) Growth hormone 29 (10) Diabetes insipidus 6 (2) New cranial neuropathy 7 (3) CN II 4 (1) CN III 2 (0.”
BackgroundEffectiveness of medical treatment for Cushing’s syndrome: a systematic review and meta-analysis
Broersen, L. H. A., Jha, M., Biermasz, N. R., Pereira, A. M., & Dekkers, O. M. (2018) · Pituitary · doi:10.1007/s11102-018-0897-z · Cited by 101
Fleseriu, M., & Castinetti, F. (2016) · Pituitary · doi:10.1007/s11102-016-0742-1 · Cited by 87
“Combination therapy with ketoconazole and metyrapone is relatively common, but is generally only considered for patients with more severe disease or for those who have failed to respond to monotherapy with either agent [10, 30].”
BackgroundInfluentialBertherat, J. Y., Bourdeau, I., Bouys, L., Chasseloup, F., Kamenický, P., & Lacroix, A. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac034 · Cited by 92
Functioning Pituitary Adenomas – Current Treatment Options and Emerging Medical Therapies
Varlamov, E. V., McCartney, S., & Fleseriu, M. (2019) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2019.15.1.30 · Cited by 87
“Nausea and headache were most common side effects and liver function test elevation of >3 ULN in 11% of patients is relatively similar to the ketoconazole data from retrospective and observational data, although the studies are not comparable.(139) Levoketoconazole is currently being assessed in a phase III, double-bl…”
BackgroundResultDiabetes Mellitus Secondary to Cushing’s Disease
Barbot, M., Ceccato, F., & Scaroni, C. M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00284 · Cited by 80
“The agent’s effects on glucose metabolism were not analyzed by the study, but hypoglycemia was reported in three patients taking antidiabetic drugs following an improvement in hypercortisolism (95).”
BackgroundCushing's syndrome: Treatment and new therapeutic approaches
Ferrière, A., & Tabarin, A. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101381 · Cited by 76
Approach to the Patient Treated with Steroidogenesis Inhibitors
Castinetti, F., Nieman, L. K., Reincke, M., & Newell-Price, J. D. C. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab122 · Cited by 79
Self-citationCreemers, S. G., Feelders, R. A., de Jong, F. H., Franssen, G. J. H., de Rijke, Y. B., van Koetsveld, P. M., & Hofland, L. J. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00217 · Cited by 73
Dormoy, A., Haissaguerre, M., Vitellius, G., Cao, C. D., Geslot, A., Drui, D., Lasolle, H., Vieira-Pinto, O., Salenave, S., François, M., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac691 · Cited by 75
An individualized approach to the management of Cushing disease
Fleseriu, M., Varlamov, E., Hinojosa-Amaya, J. M., Langlois, F., & Melmed, S. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00868-7 · Cited by 59
Metyrapone treatment in Cushing’s syndrome: a real-life study
Ceccato, F., Zilio, M., Barbot, M., Albiger, N. M. E., Antonelli, G., Plebani, M., Watutantrige‐Fernando, S., Sabbadin, C., Boscaro, M., & Scaroni, C. M. (2018) · Endocrine · doi:10.1007/s12020-018-1675-4 · Cited by 69
Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension
Fleseriu, M., Newell-Price, J. D. C., Pivonello, R., Shimatsu, A., Auchus, R. J., Scaroni, C. M., Belaya, Z. E., Feelders, R. A., Vila, G., Houde, G., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-22-0317 · Cited by 69
Self-citationBilateral adrenalectomy in the 21st century: when to use it for hypercortisolism?
Guérin, C., Taïeb, D., Treglia, G., Brue, T. C., Lacroix, A., Sebag, F. A., & Castinetti, F. (2016) · Endocrine Related Cancer · doi:10.1530/erc-15-0541 · Cited by 69
“%) were the most frequent side effects (Daniel et al. 2015).”
BackgroundNishioka, H., & Yamada, S. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8111951 · Cited by 65
“reported side effect was diffuse gastrointestinal discomfort [232].”
BackgroundInfluentialThe diagnosis and management of Cushing's syndrome in pregnancy
Hamblin, R., Coulden, A., Fountas, A., & Karavitaki, N. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13118 · Cited by 61
“Even with the application of strict definition criteria (mean serum cortisol level between 150– 300 nmol L 1 assessed serially on a cortisol day curve), over 50% of patients with CS achieve target cortisol levels with metyrapone monotherapy.(94) The evidence for use during pregnancy is limited to a small number of cas…”
MethodSelf-citationPetersenn, S., Salgado, L. R., Schopohl, J., Portocarrero-Ortiz, L. A., Arnaldi, G., Lacroix, A., Scaroni, C. M., Ravichandran, S., Kandra, A., & Biller, B. M. K. (2017) · Endocrine · doi:10.1007/s12020-017-1316-3 · Cited by 58
“In a retrospective series of 195 patients with Cushing’s syndrome, 38 patients were treated with metyrapone for a mean duration of 18 months; ≥64% achieved normalisation of cortisol secretion [23].”
BackgroundValassi, E., Franz, H., Brue, T. C., Feelders, R. A., Netea-Maier, R. T., Tsagarakis, S., Webb, S. M., Yaneva, M., Reincke, M., Droste, M., et al. (2018) · European Journal of Endocrinology · doi:10.1530/eje-17-0997 · Cited by 56
Self-citationUpdates in adrenal steroidogenesis inhibitors for Cushing’s syndrome – A practical guide
Varlamov, E. V., Han, A. J., & Fleseriu, M. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101490 · Cited by 57
Current management of Cushing's disease
Tritos, N. A., & Biller, B. M. K. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12975 · Cited by 56
Fleseriu, M., & Biller, B. M. K. (2022) · Pituitary · doi:10.1007/s11102-022-01268-2 · Cited by 53
“Obtaining potassium and magnesium levels and ECG measurements are critical both before initiating treatment, as a baseline, and during treatment with osilodrostat; this is also true with other adrenal steroidogenesis inhibitors, such as metyrapone [10, 16] and levoketoconazole [12, 17] or with the glucocorticoid recep…”
BackgroundTherapeutic Strategies for the Treatment of Severe Cushing’s Syndrome
Alexandraki, K., & Grossman, A. B. (2016) · Drugs · doi:10.1007/s40265-016-0539-6 · Cited by 52
Self-citationCushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.
Buliman, A., Tătăranu, L. G., Păun, D. L., Mirică, A., & Dumitrache, C. (2016) · PubMed Central · Cited by 51
Adrenocortical Carcinoma with Hypercortisolism
Puglisi, S., Perotti, P., Pia, A. R., Reimondo, G., & Terzolo, M. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.02.003 · Cited by 50
“Metyrapone per se does not have antineoplastic activity 48,53 .”
Adrenally Directed Medical Therapies for Cushing Syndrome
Tritos, N. A. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa778 · Cited by 51
Fallo, F., Dalmazi, G. D., Beuschlein, F., Biermasz, N. R., Castinetti, F., Elenkova, A. P., Faßnacht, M., Isidori, A. M., Kaštelan, D., Korbonits, M., et al. (2022) · Journal of Hypertension · doi:10.1097/hjh.0000000000003252 · Cited by 48
“Drugs targeting the adrenals are more effective than those targeting the pituitary gland and usually control cortisol secretion in 50–80% of the cases [166,168,169].”
BackgroundSelf-citationCushing’s disease: adrenal steroidogenesis inhibitors
Pivonello, R., Simeoli, C., Paola, N. D., & Colao, A. (2022) · Pituitary · doi:10.1007/s11102-022-01262-8 · Cited by 48
“In a subsequent and largest retrospective study, conducted in 164 CS patients, metyrapone at a median dosage of 1375 mg/day in CD patients, for a median follow-up of 8 months, induced remission in 43% of patients [15].”
ResultModern management of mild autonomous cortisol secretion
Delivanis, D. A., Athimulam, S., & Bancos, I. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1551 · Cited by 46
“Another agent used in patients with overt CS is the adrenal steroidogenesis blocker metyrapone, an 11β-hydroxylase inhibitor.(55,56) Metyrapone was studied in a proofof-concept study that demonstrated that when administered in the evening to patients with MACS, a correction of the abnormal circadian rhythm of cortisol…”
BackgroundTanaka, T., Satoh, F., Ujihara, M., Midorikawa, S., Kaneko, T., Takeda, T., Suzuki, A., Sato, M., & Shimatsu, A. (2020) · Endocrine Journal · doi:10.1507/endocrj.ej19-0617 · Cited by 44
“Endocrine Journal Advance Publication Endocrine Journal Advance Publication efficacy in some patients, and around 43% of patients have mean urinary free cortisol (mUFC) levels < upper limit of normal (ULN) with metyrapone monotherapy [8].”
BackgroundUpdate on medical treatment for Cushing’s disease
Cuevas-Ramos, D., Lim, D., & Fleseriu, M. (2016) · Clinical Diabetes and Endocrinology · doi:10.1186/s40842-016-0033-9 · Cited by 40
“Longer-term data (mean 18 months) available for 38 patients showed biochemical eucortisolism in 72 % [32].”
BackgroundFleseriu, M., Petersenn, S., Biller, B. M. K., Kadıoğlu, P., Block, C. E. M. D., T'Sjoen, G. G., Vantyghem, M., Tauchmanovà, L., Wojna, J., Roughton, M., et al. (2019) · Clinical Endocrinology · doi:10.1111/cen.14081 · Cited by 41
Self-citationCristante, J., Lefournier, V., Stürm, N., Passagia, J. G., Gauchez, A. S., Tahon, F., Cantin, S., Chabre, O., & Gay, E. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00333 · Cited by 39
Fiorentini, C., Fragni, M., Perego, P., Vezzoli, S., Bonini, S. A., Tortoreto, M., Galli, D., Claps, M., Tiberio, G. A. M., Terzolo, M., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2414 · Cited by 41
“…steroid synthesis inhibitors currently used in the treatment of Cushing’s syndrome, AA is less hepatotoxic than ketoconazole, and the concomitant inhibitory effect of cortisol and androgen synthesis is a potential advantage of AA over metyrapone [14], since ACC often co-secretes both hormones.”
Management and Medical Therapy of Mild Hypercortisolism
Favero, V., Cremaschi, A., Falchetti, A., Gaudio, A., Gennari, L., Scillitani, A., Vescini, F., Morelli, V., Aresta, C., & Chiodini, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111521 · Cited by 38
“The metyrapone immediate-release capsule, which contains a 250 mg dose with a maximum daily dose of 6 g/day, is suggested [42,66].”
BackgroundDetomas, M., Altieri, B., Deutschbein, T., Faßnacht, M., & Dischinger, U. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.903545 · Cited by 38
Fleseriu, M., Auchus, R., Greenman, Y., Zacharieva, S., Geer, E., Salvatori, R., Pivonello, R., Feldt-Rasmussen, U., Kennedy, L., Buchfelder, M., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-22-0506 · Cited by 23
“In contrast, cortisol synthesis inhibitors with a different mechanism of action, such as osilodrostat and metyrapone, tend to have opposite effects to increase testosterone, and in some women worsen acne and hirsutism (26, 27, 28, 29).”
Therapeutic options after surgical failure in Cushing's disease: A critical review
Rubinstein, G., Oßwald, A., Zopp, S., Ritzel, K., Theodoropoulou, M., Beuschlein, F., & Reincke, M. (2019) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2019.04.004 · Cited by 36
Surgery and perioperative management of patients with Cushing's disease
Honegger, J. B., & Nasi‐Kordhishti, I. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13177 · Cited by 34
“Whether pretreatment is used prior to TSS in CD and which drugs are preferred differs substantially between centres and countries.(4,5) Data from the European registry ERCUSYN showed that 20% of patients had received preoperative medical treatment.”
BackgroundIatrogenic adrenal insufficiency in adults
Martin‐Grace, J., Tomkins, M., O’Reilly, M., & Sherlock, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00929-x · Cited by 35
“These medications include metyrapone 203,204 , ketoconazole and levoketoconazole 205,206 , osilodrostat (LCI699) 207,208 , and etomidate 209,210 .”
Updates in the Medical Treatment of Pituitary Adenomas
Gheorghiu, M. L., Negreanu, F. A., & Fleseriu, M. (2019) · Hormone and Metabolic Research · doi:10.1055/a-1066-4592 · Cited by 36
“The effect is usually long-lasting, with escapes described in 9–19 % of cases [144, 145].”
BackgroundIndividualized medical treatment options in Cushing disease
Gilis‐Januszewska, A., Bogusławska, A., Rzepka, E., Ziaja, W., & Hubalewska–Dydejczyk, A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1060884 · Cited by 36
“Furthermore, elevated 11-deoxycortisol may also cross-react with cortisol immunoassays causing false increase of serum cortisol by approximately 20% (12).”
BackgroundTumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?
Georgantzoglou, N., Kokkali, S., Tsourouflis, G. S., & Theocharis, S. E. (2021) · Cancers · doi:10.3390/cancers13081798 · Cited by 33
“Metyrapone is a steroidogenesis enzyme blocker that can be used concomitantly to chemotherapy and mitotane during the first weeks of treatment until mitotane therapeutic levels are obtained, leading to the rapid resolution of symptoms [50].”
BackgroundEffectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis
Galendi, J. S. C., Neto, A. N. S. C., Demetres, M. R., Boguszewski, C. L., & Nogueira, V. D. S. N. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.732240 · Cited by 33
“considered MNSC and LDSC, while four studies considered the morning serum cortisol (66, 67, 74, 76).”
BackgroundMethodMRI–Negative Cushing's Disease: A Review on Therapeutic Management
Sabahi, M., Shahbazi, T., Maroufi, S. F., Vidal, K., Recinos, P. F., Kshettry, V. R., Röser, F., Adada, B., & Borghei-Razavi, H. (2022) · World Neurosurgery · doi:10.1016/j.wneu.2022.03.076 · Cited by 33
The Treatment of Refractory Pituitary Adenomas
Dai, C., Liu, X.-H., Ma, W., & Wang, R. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00334 · Cited by 32
“However, metyrapone use also results in adverse events includingmild gastrointestinal upset and dizziness in 25% of patients (63).”
BackgroundHidden hypercortisolism: a too frequently neglected clinical condition
Giovanelli, L., Aresta, C., Favero, V., Bonomi, M., Cangiano, B., Eller-Vainicher, C., Grassi, G., Morelli, V., Pugliese, F., Falchetti, A., et al. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01484-2 · Cited by 32
Endocrine Hypertension: A Practical Approach
Pappachan, J. M., & Buch, H. (2016) · Advances in experimental medicine and biology · doi:10.1007/5584_2016_26 · Cited by 32
Claps, M., Cerri, S., Grisanti, S., Lazzari, B., Ferrari, V. D., Roca, E., Perotti, P., Terzolo, M., Sigala, S., & Berruti, A. (2017) · Endocrine · doi:10.1007/s12020-017-1428-9 · Cited by 31
“The drug has been also employed in the management Cushing's syndrome associated with ACC either administered alone or in association with other inhibitors of steroidogenesis [8], or chemotherapy [13;14].”
BackgroundMethodInfluentialMedical therapy in severe hypercortisolism
Marques, J. V. O., & Boguszewski, C. L. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101487 · Cited by 31
Bonnet-Serrano, F., Poirier, J., Vaczlavik, A., Laguillier, C., Blanchet, B., Baron, S., Guignat, L., Bessiène, L., Bricaire, L., Groussin, L., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-22-0208 · Cited by 30
Recent Progress in the Medical Therapy of Pituitary Tumors
Langlois, F., McCartney, S., & Fleseriu, M. (2017) · Endocrinology and Metabolism · doi:10.3803/enm.2017.32.2.162 · Cited by 29
Paraneoplastic Cushing syndrome, case-series and review of the literature
Deldycke, A., Haenebalcke, C., & Taes, Y. (2018) · Acta Clinica Belgica · doi:10.1080/17843286.2017.1373927 · Cited by 24
An Individualized Approach to the Evaluation of Cushing Syndrome
Sharma, S. T. (2017) · Endocrine Practice · doi:10.4158/ep161721.ra · Cited by 28
Medical management of Cushing's disease: When and how?
Castinetti, F. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13120 · Cited by 27
“The most recent phase 3 studies on cortisol-lowering drugs have used this parameter as a surrogate to define the antisecretory efficacy of a given drug.(7,16,17) Although UFC does not take into account the nycthemeral rhythm of cortisol, a pattern that is abolished in patients with CD, it also has several limitations,…”
BackgroundPharmacological Treatment of Cushing's Syndrome
Castinetti, F. (2023) · Archives of Medical Research · doi:10.1016/j.arcmed.2023.102908 · Cited by 27
Lacroix, A., Gu, F., Schopohl, J., Kandra, A., Pedroncelli, A. M., Jin, L., & Pivonello, R. (2019) · Pituitary · doi:10.1007/s11102-019-01021-2 · Cited by 27
Radiotherapy as a tool for the treatment of Cushing’s disease
Castinetti, F., Brue, T. C., & Ragnarsson, Ó. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0092 · Cited by 30
Currently used and investigational drugs for Cushing´s disease
Ciato, D., Mumbach, A. G., Páez-Pereda, M., & Stalla, G. K. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1266338 · Cited by 27
“reversed when the treatment is interrupted [40].”
BackgroundSynergistic cortisol suppression by ketoconazole–osilodrostat combination therapy
Amodru, V., Brue, T. C., & Castinetti, F. (2021) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-21-0071 · Cited by 26
The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)
Wu, W., Chen, J., Bai, C., Chi, Y., Du, Y., Feng, S., Huo, L., Jiang, Y., Li, J., Lou, W., et al. (2021) · Journal of Pancreatology · doi:10.1097/jp9.0000000000000064 · Cited by 26
Glucocorticoids are active players and therapeutic targets in atherosclerotic cardiovascular disease
van der Sluis, R. J., & Hoekstra, M. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110728 · Cited by 27
Advances in the Medical Treatment of Cushing Disease
Tritos, N. A., & Biller, B. M. K. (2020) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2020.05.003 · Cited by 25
Medical Therapy for Cushing’s Syndrome in the Twenty-first Century
Tritos, N. A., & Biller, B. M. K. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.01.006 · Cited by 24
Yoshida, K., Fukuoka, H., Odake, Y., Nakajima, S., Tachibana, M., Ito, J., Hosokawa, Y., Yamada, T., Miura, H., Suematsu, N., et al. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00375 · Cited by 23
Alba, E. L., Japp, E., Fernandez-Ranvier, G. G., Badani, K. K., Wilck, E. J., Ghesani, M. V., Wolf, A., Wolin, E. M., Corbett, V., Steinmetz, D., et al. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac073 · Cited by 23
“Its efficacy has been reported for decades and confirmed in recent studies [42].”
ResultMANAGEMENT OF ENDOCRINE DISEASE: Can we cure Cushing’s disease? A personal view
BERTAGNA, X. Y. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0062 · Cited by 22
Puglisi, S., Perotti, P., Barbot, M., Cosio, P., Scaroni, C. M., Stigliano, A., Lardo, P., Morelli, V., Polledri, E., Chiodini, I., et al. (2018) · Endocrine Connections · doi:10.1530/ec-18-0400 · Cited by 22
What is the role of medical therapy in adrenal-dependent Cushing’s syndrome?
Braun, L. T., & Reincke, M. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101376 · Cited by 21
Factors Affecting Dexamethasone Suppression Test Results
Berlińska, A., Świątkowska-Stodulska, R., & Sworczak, K. (2019) · Experimental and clinical endocrinology & diabetes · doi:10.1055/a-1017-3217 · Cited by 14
Valassi, E., Aulinas, A., Glad, C. A. M., Johannsson, G., Ragnarsson, Ó., & Webb, S. M. (2017) · Clinical Endocrinology · doi:10.1111/cen.13414 · Cited by 21
Current and Emerging Medical Therapies in Pituitary Tumors
Sahakian, N., Castinetti, F., Brue, T. C., & Cuny, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11040955 · Cited by 20
“One retrospective study, including 164 patients with CS, showed that a mean dose of 1040–1465 mg per day of metyrapone resulted in normalization of UFC in 43% of patients over a mean period of 8 months [97].”
BackgroundDrug repurposing approach against chikungunya virus: an in vitro and in silico study
Kasabe, B., Ahire, G., Patil, P., Punekar, M., Davuluri, K. S., Kakade, M. B., Alagarasu, K., Parashar, D., & Cherian, S. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1132538 · Cited by 20
“Metyrapone is an inhibitor of glucocorticoid synthesis and has a positive effect against Cushing’s syndrome (Daniel et al., 2015).”
BackgroundSevere Cushing’s syndrome due to small cell prostate carcinoma: a case and review of literature
Elston, M. S., Crawford, V., Swarbrick, M. J., Dray, M. S., Head, M., & Conaglen, J. V. (2017) · Endocrine Connections · doi:10.1530/ec-17-0081 · Cited by 20
Yuno, A., Kenmotsu, Y., Takahashi, Y., Nomoto, H., Kameda, H., Cho, K. Y., Nakamura, A., Yamashita, Y., Nakamura, J., Nakakubo, S., et al. (2020) · Endocrine Journal · doi:10.1507/endocrj.ej20-0613 · Cited by 19
“A retrospective study reported the outcomes of 195 patients with hypercortisolism (including 115 patients with Cushing’s disease) who were treated with metyrapone [17]; metyrapone mono‐ therapy administered before surgery for an average of 4.”
BackgroundFerrière, A., & Tabarin, A. (2021) · La Presse Médicale · doi:10.1016/j.lpm.2021.104091 · Cited by 20
Inoue, M., Okamura, K., Kitaoka, C., Kinoshita, F., Namitome, R., Nakamura, U., Shiota, M., Gotō, K., Ohtsubo, T., Matsumura, K., et al. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0025 · Cited by 18
“The decrease in cortisol is rapid, with trough levels at 2 hours post dose [41-43].”
BackgroundFleseriu, M., Auchus, R. J., Bancos, I., & Biller, B. M. K. (2025) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaf027 · Cited by 20
“[74], and in a retrospective study, the main reasons for metyrapone discontinuation were gastrointestinal upset and dizziness [75].”
Levoketoconazole: a novel treatment for endogenous Cushing's syndrome
Fleseriu, M., Auchus, R. J., Pivonello, R., Salvatori, R., Zacharieva, S., & Biller, B. M. K. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2021.1945440 · Cited by 18
“Multiple measurements of salivary cortisol throughout the day, similar to the serum cortisol day curve used for metyrapone in some countries [59], may provide a better marker for visualizing the change in diurnal cortisol rhythm; however, this information was not collected in the SONICS study.”
MethodFleseriu, M., Iweha, C., Salgado, L. R., Mazzuco, T. L., Campigotto, F., Maamari, R., & Limumpornpetch, P. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00436 · Cited by 16
Medical Management of Cushing Disease
Tritos, N. A., & Biller, B. M. K. (2019) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2019.05.007 · Cited by 16
Punekar, M., Kasabe, B., Patil, P., Kakade, M. B., Parashar, D., Alagarasu, K., & Cherian, S. (2022) · Viruses · doi:10.3390/v14102150 · Cited by 18
“11β-hydroxylase enzyme inhibitor [49] 2.”
Update and Practical Recommendations for the Use of Medical Treatment of Cushing Syndrome
Araujo-Castro, M., Lamas, C., Nowak, E., Newell-Price, J. D. C., Reincke, M., & Castinetti, F. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf042 · Cited by 19
Self-citationRegulation of the EGFR Pathway by HSP90 Is Involved in the Pathogenesis of Cushing’s Disease
Shen, Y., Ji, C., Jian, X., Zhou, J., Zhang, Q., Qiao, N., Zhang, Y., Shou, X., Zhou, X., & Ma, Z. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601984 · Cited by 15
“, ketoconazole, metoprolol, metyrapone (5, 8, 9)], or cortisol receptors in peripheral tissues [e.”
BackgroundMehta, G. U., Ding, D., Gupta, A., Kano, H., Sisterson, N. D., Martínez-Moreno, N., Kršek, M., Yang, H.-C., Lee, C.-C., Liščák, R., et al. (2018) · Journal of Neuro-Oncology · doi:10.1007/s11060-018-2817-5 · Cited by 12
Current strategies for the treatment of severe Cushing’s syndrome
Alexandraki, K., & Grossman, A. B. (2015) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.2016.1123615 · Cited by 14
Self-citationBostan, H., Düğer, H., Akhanlı, P., Çalapkulu, M., Türkmenoğlu, T. T., Erdöl, A. K., Duru, S. A., Sencar, M. E., Kızılgül, M., Uçan, B., et al. (2021) · HORMONES · doi:10.1007/s42000-021-00316-z · Cited by 13
Advanced Adrenocortical Carcinoma: From Symptoms Control to Palliative Care
Ruggiero, E., Tizianel, I., Caccese, M., Lombardi, G., Pambuku, A., Zagonel, V., Scaroni, C. M., Formaglio, F., & Ceccato, F. (2022) · Cancers · doi:10.3390/cancers14235901 · Cited by 13
“It acts by inhibiting CYP11B1 and CYP11B2, which has the consequence of reducing aldosterone and cortisol secretion [25].”
BackgroundMedical treatment of Cushing’s disease with concurrent diabetes mellitus
Mehlich, A., Bolanowski, M., Mehlich, D., & Witek, P. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1174119 · Cited by 13
Metadata
- Authors
- Daniel, E., Aylwin, S., Mustafa, O., Ball, S., Munir, A., Boelaert, K., Chortis, V., Cuthbertson, D. J., Daousi, C., Rajeev, S. P., Davis, J., Cheer, K., Drake, W., Gunganah, K., Grossman, A., Gurnell, M., Powlson, A. S., Karavitaki, N., Huguet, I., Kearney, T., Mohit, K., Meeran, K., Hill, N., Rees, A., Lansdown, A. J., Trainer, P. J., Minder, A.-E. H., & Newell-Price, J.
- Affiliations
- University of Liverpool (GB)
- St Bartholomew's Hospital (GB)
- Corresponding author
- Newell-Price, John
- ORCID
- Daniel, Eleni
- Aylwin, Simon
- Mustafa, Omar
- Boelaert, Kristien
- Chortis, Vasileios
- Cuthbertson, Daniel J.
- Davis, Julian
- Drake, William
- Grossman, Ashley
- Gurnell, Mark
- Powlson, Andrew S.
- Karavitaki, Niki
- Huguet, Isabel
- Kearney, Tara
- Meeran, Karim
- Hill, Neil
- Rees, Aled
- Lansdown, Andrew J.
- Trainer, Peter J.
- Minder, Anna-Elisabeth H.
- Newell-Price, John
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-11
- Volume
- 100
- Issue
- 11
- Pages
- 4146-4154
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5393433
- OpenAlex
- W2145652401
- Semantic Scholar
- be0aef20802f4f370e4b64b56cf53c0bf9ace992
- Cited by
- 231
- References
- 31
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 19 · 2023: 17 · 2022: 36 · 2021: 24 · 2020: 14 · 2019: 24 · 2018: 21 · 2017: 19 · 2016: 18 · 2015: 2
- FWCI
- 17.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institute for Health and Care Research (ACF-2011-04-005)
- Society for Endocrinology
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- metyrapone, Cushing's syndrome, hypercortisolism, Cushing's disease, ectopic ACTH syndrome, adrenocortical carcinoma, steroidogenesis inhibition, urinary free cortisol, treatment effectiveness, adverse effects, drug discontinuation, adrenal insufficiency
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cushing Syndrome, Dose-Response Relationship, Drug, Drug Therapy, Combination, Enzyme Inhibitors, Humans, Hydrocortisone, Infant, Male, Metyrapone, Middle Aged, Pituitary Neoplasms, Retrospective Studies, Treatment Outcome, ACTH-Secreting Pituitary Adenoma, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
