{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:35:53Z","timestamp":1790422553484,"version":"4.1.0"},"reference-count":90,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Endogenous Cushing syndrome (CS) is characterized by excess cortisol secretion, which is driven by tumorous secretion of corticotropin in the majority of patients. Untreated, CS results in substantial morbidity and mortality. Tumor-directed surgery is generally the first-line therapy for CS. However, hypercortisolism may persist or recur postoperatively; in other cases, the underlying tumor may not be resectable or its location may not be known. Yet other patients may be acutely ill and require stabilization before definitive surgery. In all these cases, additional interventions are needed, including adrenally directed medical therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Evidence Acquisition<\/jats:title>\n                  <jats:p>Electronic literature searches were performed to identify studies pertaining to adrenally acting agents used for CS. Data were abstracted and used to compile this review article.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Evidence Synthesis<\/jats:title>\n                  <jats:p>Adrenally directed medical therapies inhibit one or several enzymes involved in adrenal steroidogenesis. Several adrenally acting medical therapies for CS are currently available, including ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate. Additional agents are under investigation. Drugs differ with regards to details of their mechanism of action, time course of pharmacologic effect, safety and tolerability, potential for drug-drug interactions, and route of administration. All agents require careful dose titration and patient monitoring to ensure safety and effectiveness, while avoiding hypoadrenalism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These medications have an important role in the management of CS, particularly among patients with persistent or recurrent hypercortisolism postoperatively or those who cannot undergo tumor-directed surgery. Use of these drugs mandates adequate patient instruction and close monitoring to ensure treatment goals are being met while untoward adverse effects are minimized.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa778","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T01:30:51Z","timestamp":1603935051000},"page":"16-25","source":"Crossref","is-referenced-by-count":48,"title":["Adrenally Directed Medical Therapies for Cushing Syndrome"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-607X","authenticated-orcid":false,"given":"Nicholas A","family":"Tritos","sequence":"first","affiliation":[{"name":"Neuroendocrine Unit and Neuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, 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