{ "schemaVersion": 2, "eyebrow": "Endocrinology", "title": "Cushing Syndrome", "summary": "Confirm autonomous hypercortisolism before localization, then use ACTH to separate adrenal from pituitary or ectopic disease. Surgical cure is preferred, but urgent cortisol control, source-directed imaging, petrosal sampling, and medical bridging are essential when disease is severe or surgery is not curative.", "seoDescription": "Physician guide to diagnosing and managing Cushing syndrome: biochemical confirmation, ACTH-based localization, imaging, surgery, and cortisol-lowering therapy.", "clinicalQuestion": "How should physicians confirm, localize, stabilize, and treat endogenous hypercortisolism?", "specialty": "Endocrinology", "audience": "U.S. physicians and medical trainees", "tags": [ "Cushing syndrome", "hypercortisolism", "Cushing disease", "ACTH-dependent Cushing syndrome", "inferior petrosal sinus sampling", "osilodrostat" ], "keyTakeaways": [ "Exclude exogenous glucocorticoid exposure before biochemical testing; then confirm endogenous hypercortisolism with late-night salivary cortisol, 1-mg overnight dexamethasone suppression testing, and/or 24-hour urinary free cortisol. [3][7]", "Do not localize before confirming hypercortisolism. Once confirmed, measure plasma ACTH: suppression redirects evaluation to an adrenal source, whereas nonsuppression requires discrimination between pituitary and ectopic ACTH secretion. [3][15]", "A post-1-mg dexamethasone serum cortisol below 1.8 micrograms/dL is normal suppression; persistent cortisol at or above this threshold supports autonomous cortisol excess in the appropriate clinical setting. [15][16]", "For ACTH-dependent disease with negative or equivocal pituitary MRI, particularly a lesion smaller than 6 mm, bilateral inferior petrosal sinus sampling with CRH or desmopressin is the key localization procedure before pituitary surgery. [12][14]", "Resect the causative pituitary, adrenal, or ectopic neuroendocrine tumor when feasible. Use cortisol-lowering therapy for severe disease, surgical delay, persistent or recurrent disease, or while awaiting radiotherapy effect. [3][6][20][21]", "During steroidogenesis-inhibitor treatment, monitor for hypocortisolism and treatment-related hypertension, edema, hypokalemia, hepatic toxicity, and QT prolongation according to agent-specific risk. [18][19]" ], "sections": [ { "id": "triage-and-first-actions", "eyebrow": "Immediate priorities", "heading": "Identify patients needing urgent cortisol control", "intro": "Severe hypercortisolism can require treatment before definitive source control.", "paragraphs": [ "Urgently assess patients with florid or rapidly progressive hypercortisolism for complications that alter immediate management: severe hypertension, hypokalemia, edema, hyperglycemia, infection, thrombotic risk, neuropsychiatric deterioration, and cardiovascular symptoms. Obtain blood pressure, electrolytes, glucose, renal function, liver tests, and a resting ECG; pursue additional cardiovascular testing or imaging when symptoms or examination suggest cardiac disease. [18]", "When hypercortisolism is life-threatening, surgery is delayed, or surgery is not feasible, begin a rapid cortisol-lowering strategy rather than waiting for definitive treatment. For UFC greater than 5 but less than 10 times the upper limit of normal without life-threatening complications, higher-dose, relatively rapid-acting steroidogenesis-inhibitor monotherapy with osilodrostat, metyrapone, or ketoconazole and serum cortisol and/or UFC reassessment every 5-7 days is one recommended approach; block-and-replace therapy is an alternative. [20]", "Correct clinically consequential hypokalemia, edema, and hypertension concurrently. Mineralocorticoid-receptor blockade can be effective for these manifestations, including during mifepristone, metyrapone, or osilodrostat therapy; avoid eplerenone with mifepristone because mifepristone increases eplerenone exposure. [18]" ], "bullets": [ "Use preoperative medical therapy selectively rather than routinely: consider it for severe or life-threatening hypercortisolism, contraindication to surgery, or a prolonged wait to surgery. [21]", "Treat a patient receiving cortisol-lowering therapy who develops symptoms compatible with adrenal insufficiency as potentially overblocked; reassess cortisol promptly and adjust therapy. [19]" ], "subsections": [], "table": { "caption": "Immediate management triggers in severe endogenous hypercortisolism. [18][20][21]", "columns": [ "Clinical situation", "Immediate action", "Monitoring focus" ], "rows": [ [ "Life-threatening hypercortisolism or delayed definitive surgery", "Initiate rapid cortisol-lowering therapy while arranging definitive source treatment. [20][21]", "Clinical status, serum cortisol and/or UFC, electrolytes, blood pressure, and glucose. [18][20]" ], [ "UFC >5 to <10 times ULN without life-threatening complication", "Use higher-dose osilodrostat, metyrapone, or ketoconazole with relatively rapid titration; block-and-replace is an alternative. [20]", "Recheck serum cortisol and/or 24-hour UFC every 5-7 days during dose adaptation. [20]" ], [ "Hypokalemia, edema, or hypertension during cortisol excess or therapy", "Treat the mineralocorticoid phenotype; consider mineralocorticoid-receptor blockade when appropriate. [18]", "Potassium, blood pressure, volume status, and drug interactions. [18]" ] ] } }, { "id": "confirm-endogenous-hypercortisolism", "eyebrow": "Biochemical confirmation", "heading": "Confirm hypercortisolism before imaging", "intro": "Testing is most useful when clinical probability justifies evaluation.", "paragraphs": [ "First exclude exogenous corticosteroid exposure, the most common cause of Cushing syndrome. In patients with persistent clinical suspicion after that review, confirm endogenous hypercortisolism using late-night salivary cortisol, a 1-mg overnight dexamethasone suppression test, and/or 24-hour urinary free cortisol. [3][7]", "For the overnight dexamethasone suppression test, administer dexamethasone 1 mg orally between 11 PM and midnight and measure serum cortisol between 8 AM and 9 AM the next morning. A morning cortisol below 1.8 micrograms/dL indicates normal suppression; failure to suppress requires confirmatory assessment in the clinical context. [15][16]", "Use tests of cortisol excess—not pituitary or adrenal imaging—as the first localization gate. Hypercortisolemia must be established before attempting etiologic differentiation, because incidental pituitary and adrenal lesions can misdirect management. [15]" ], "bullets": [ "For 24-hour urinary free cortisol, obtain repeated collections; three normal collections are listed as a normal reference approach in florid Cushing syndrome evaluation. [15]", "Prefer liquid chromatography-tandem mass spectrometry for UFC when available because it improves measurement accuracy. [15]", "Mild biochemical abnormalities merit particular caution in patients with central obesity, insulin resistance, and hypertension, in whom metabolic syndrome can resemble mild Cushing syndrome clinically. [3]" ], "subsections": [ { "heading": "Pseudo-Cushing states and discordant tests", "paragraphs": [ "When clinical findings and first-line testing remain equivocal, do not proceed directly to source-directed surgery. Dynamic CRH and desmopressin testing with combined ACTH and cortisol interpretation has been studied to distinguish Cushing disease from pseudo-Cushing states, but should be used as a specialized adjudication tool rather than a replacement for initial biochemical confirmation. [8]" ], "bullets": [] } ], "table": { "caption": "Tests used to establish hypercortisolism and their actionable interpretation. [3][15][16]", "columns": [ "Test", "How to perform", "Decision point" ], "rows": [ [ "1-mg overnight dexamethasone suppression test", "Give dexamethasone 1 mg at 11 PM-midnight; measure cortisol at 8-9 AM. [16]", "Cortisol <1.8 micrograms/dL indicates normal suppression. [15]" ], [ "24-hour urinary free cortisol", "Obtain repeated 24-hour collections; LC-MS/MS improves accuracy when available. [15]", "Use biochemical elevation to support hypercortisolism; three normal collections are a normal reference approach. [15]" ], [ "Late-night salivary cortisol", "Collect at late night or around 11 PM according to local assay protocol. [3][15]", "Loss of late-night cortisol nadir supports endogenous hypercortisolism after exogenous steroid exclusion. [3][15]" ] ] } }, { "id": "acth-based-localization", "eyebrow": "Etiologic branching", "heading": "Use ACTH to direct adrenal versus pituitary or ectopic evaluation", "intro": "ACTH is the pivotal branch point after biochemical confirmation.", "paragraphs": [ "Measure plasma ACTH after endogenous hypercortisolism is confirmed. Suppressed ACTH indicates ACTH-independent cortisol excess and should redirect imaging and management to the adrenal glands; nonsuppressed ACTH indicates ACTH-dependent disease requiring pituitary-versus-ectopic source assessment. [3][15]", "An ACTH concentration above 20 ng/L establishes ACTH dependence in the Endotext diagnostic framework. Intermediate values are a gray zone because pituitary Cushing disease and adrenal pathology can overlap; repeat assessment and integrate the biochemical pattern rather than assigning etiology from a single indeterminate ACTH value. [15]", "In ACTH-dependent Cushing syndrome, obtain gadolinium-enhanced pituitary MRI before invasive sampling. MRI detects only approximately 40%-52% of corticotroph tumors, so a negative study does not exclude Cushing disease. [9]" ], "bullets": [ "Pituitary ACTH-secreting tumors account for about 65%-70% of endogenous Cushing syndrome; adrenal disease accounts for about 30% in one contemporary synthesis, while ectopic ACTH secretion is less common. [10][20]", "Do not use a pituitary lesion alone as proof of Cushing disease when biochemical and radiologic findings are discordant. MRI sensitivity is limited, and source confirmation may change the surgical target. [9][12]" ], "subsections": [ { "heading": "When to perform inferior petrosal sinus sampling", "paragraphs": [ "Perform bilateral inferior petrosal sinus sampling (BIPSS) in confirmed ACTH-dependent hypercortisolism when pituitary MRI is negative or inconclusive, especially with a lesion smaller than 6 mm, or when noninvasive tests do not reliably distinguish pituitary from ectopic ACTH secretion. BIPSS is the reference invasive discriminator for central versus nonpituitary ACTH secretion. [12][14]", "During BIPSS, obtain bilateral petrosal and peripheral ACTH samples before and after CRH or desmopressin stimulation. A central-to-peripheral ACTH ratio greater than 2 before stimulation or greater than 3 after stimulation supports Cushing disease; prolactin measurement can help verify adequate catheter placement. [12]" ], "bullets": [ "Use BIPSS to establish a pituitary ACTH source, not to determine intrapituitary tumor laterality for surgical planning. [14]", "In a patient with convincing biochemical Cushing disease and concordant noninvasive findings, BIPSS may not be necessary; reserve it for unresolved pituitary-versus-ectopic localization. [9][12]" ] } ], "table": { "caption": "ACTH-directed localization pathway after confirmed endogenous hypercortisolism. [3][9][12][15]", "columns": [ "Biochemical or imaging pattern", "Most likely branch", "Next action" ], "rows": [ [ "Suppressed plasma ACTH", "ACTH-independent cortisol excess. [3]", "Evaluate the adrenal glands for an autonomous cortisol-secreting lesion. [3]" ], [ "ACTH >20 ng/L", "ACTH-dependent Cushing syndrome. [15]", "Perform pituitary MRI with gadolinium and evaluate for pituitary versus ectopic ACTH source. [9][15]" ], [ "ACTH-dependent disease with negative/equivocal MRI or lesion <6 mm", "Pituitary versus ectopic source remains unresolved. [12]", "Perform BIPSS with CRH or desmopressin stimulation. [12][14]" ], [ "BIPSS central:peripheral ACTH ratio >2 baseline or >3 after stimulation", "Central ACTH production consistent with Cushing disease. [12]", "Proceed with pituitary-directed management in an experienced multidisciplinary setting. [12]" ] ] } }, { "id": "definitive-treatment", "eyebrow": "Source control", "heading": "Prioritize resection, then select salvage therapy by source and urgency", "intro": "Definitive treatment is removal of the cortisol- or ACTH-producing lesion whenever feasible.", "paragraphs": [ "Surgical resection of the causative pituitary, adrenal, or ectopic neuroendocrine tumor is primary treatment for endogenous Cushing syndrome. For Cushing disease, transsphenoidal pituitary surgery is first-line; reported initial remission is approximately 70%-90% for microadenomas and 50%-65% for macroadenomas. [1][3][24]", "After persistent or recurrent Cushing disease, choose among repeat pituitary surgery, pituitary radiotherapy, medical therapy, and bilateral adrenalectomy according to localization, resectability, urgency of cortisol control, and patient preference. Medical therapy is also appropriate when surgery or radiotherapy is not feasible, in metastatic disease, or as a bridge when severe hypercortisolism requires immediate control. [1][6][20]", "For adrenal cortisol excess, manage as an ACTH-independent source with adrenal-directed definitive treatment when an operable lesion is identified. For ectopic ACTH secretion, pursue resection of the ACTH-secreting tumor when feasible; steroidogenesis inhibitors can control cortisol excess regardless of source while localization, surgery, or oncologic treatment proceeds. [3][23]" ], "bullets": [ "Use pituitary-directed agents selectively in Cushing disease when surgery is not an option or has not been curative: U.S. indications include pasireotide and osilodrostat in this setting. [19]", "Steroidogenesis inhibitors that can be used across etiologies include ketoconazole, levoketoconazole, metyrapone, osilodrostat, mitotane, and etomidate; mifepristone blocks peripheral glucocorticoid receptors rather than cortisol synthesis. [20][23]", "Mitotane has a specific role in hypercortisolism caused by adrenocortical carcinoma. [23]" ], "subsections": [ { "heading": "Selecting and monitoring medical therapy", "paragraphs": [ "Select a cortisol-lowering drug according to desired speed of control, disease severity, comorbidity, and adverse-effect profile. Metyrapone lowers cortisol rapidly, with trough cortisol levels reported approximately 2 hours after a dose; maintenance therapy is usually 750-6000 mg/day in 3-4 divided doses. Patients with adrenal tumors may be sensitive to lower doses, whereas Cushing disease often requires higher doses. [23]", "Monitor ketoconazole and levoketoconazole for gastrointestinal adverse effects, hepatotoxicity, and QT-interval prolongation, particularly when coadministered with another QT-prolonging medication. Monitor metyrapone and osilodrostat for hypokalemia, edema, and hypertension; monitor all effective cortisol-lowering regimens for biochemical and clinical hypocortisolism. [18][19]", "Mifepristone requires clinical rather than cortisol-based assessment of glucocorticoid receptor blockade and carries a boxed warning for antiprogestational effects that can terminate pregnancy. Do not combine mifepristone with eplerenone. [18][19]" ], "bullets": [ "Consider a block-and-replace regimen when rapid, complete suppression is needed but variable endogenous cortisol production makes titration difficult. [20]", "While awaiting pituitary radiotherapy effect, use medical therapy to control hypercortisolism. [20]", "Avoid assuming that preoperative therapy improves surgical cortisol normalization; available meta-analysis found no difference in cortisol normalization by timing of preoperative versus later adjuvant treatment. [21]" ] } ], "table": { "caption": "Medical treatment choices and key safety signals for persistent, recurrent, or urgently uncontrolled Cushing syndrome. [18][19][20][23]", "columns": [ "Therapy class or agent", "Clinical role", "Key monitoring or constraint" ], "rows": [ [ "Metyrapone", "Rapid steroidogenesis inhibition; used in adrenal tumors, ectopic ACTH syndrome, and Cushing disease. [23]", "Monitor cortisol response, hypokalemia, edema, and hypertension; usual maintenance range 750-6000 mg/day in 3-4 divided doses. [18][23]" ], [ "Ketoconazole or levoketoconazole", "Steroidogenesis inhibition when cortisol reduction is needed. [20]", "Monitor liver toxicity and QT interval; consider interactions with QT-prolonging drugs. [18][19]" ], [ "Osilodrostat", "Steroidogenesis inhibitor; U.S. indication includes adults with Cushing disease when pituitary surgery is not an option or has not been curative. [19]", "Monitor for hypocortisolism, QT prolongation, hypokalemia, edema, and hypertension. [18][19]" ], [ "Pasireotide", "Pituitary-directed option for Cushing disease when pituitary surgery is not possible or noncurative. [19]", "Use as a Cushing disease-specific medical option rather than for an unlocalized ACTH-dependent syndrome. [19]" ], [ "Mifepristone", "Peripheral glucocorticoid-receptor blockade. [20]", "Boxed warning for pregnancy termination risk; avoid eplerenone interaction and monitor clinical response. [18][19]" ], [ "Etomidate", "Steroidogenesis inhibitor used in selected circumstances requiring cortisol control. [20][23]", "Use in a setting able to monitor cortisol and treatment complications closely. [23]" ] ] } }, { "id": "post-treatment-surveillance", "eyebrow": "Follow-up", "heading": "Monitor for remission, recurrence, and treatment-related adrenal insufficiency", "intro": "Biochemical response and complications require longitudinal reassessment after source-directed treatment.", "paragraphs": [ "After pituitary surgery, interpret follow-up in the context of postoperative adrenal function and recurrent hypercortisolism risk. Initial surgery does not cure every patient, particularly macroadenomas, so persistent signs or biochemical evidence of cortisol excess should prompt reassessment for residual pituitary disease, ectopic ACTH secretion, or an incorrect initial localization. [1]", "Patients receiving medical therapy require serial assessment of cortisol control and drug toxicity. During rapid dose adjustment for substantial cortisol excess, repeat serum cortisol and/or UFC every 5-7 days; evaluate blood pressure, potassium, edema, liver tests, ECG/QT risk, and symptoms of hypocortisolism according to the selected agent. [18][20]", "If bilateral adrenalectomy is chosen after failure of pituitary-directed approaches, it provides definitive adrenal cortisol control but does not treat the pituitary ACTH source; plan long-term endocrine follow-up and surveillance for progressive corticotroph tumor behavior. [1][6]" ], "bullets": [ "Reassess disease activity with the same biochemical modalities used for diagnosis when recurrence is clinically suspected, rather than relying on phenotype alone. [3][7]", "Escalate persistent ACTH-dependent disease to a multidisciplinary pituitary and endocrine team before repeat surgery, radiotherapy, BIPSS, or adrenalectomy. [1][12][21]" ], "subsections": [], "table": { "caption": "Follow-up priorities after treatment of endogenous Cushing syndrome. [1][18][20]", "columns": [ "Treatment phase", "Primary question", "Action" ], "rows": [ [ "After pituitary surgery", "Is hypercortisolism persistent or recurrent?", "Reassess clinically and biochemically; reconsider localization and salvage options when cortisol excess persists. [1]" ], [ "During rapid medical titration", "Is cortisol controlled without overblock?", "Measure serum cortisol and/or UFC every 5-7 days during adaptation and monitor for hypocortisolism. [20]" ], [ "During steroidogenesis-inhibitor therapy", "Are agent-specific toxicities developing?", "Check potassium, blood pressure, edema, liver toxicity, and QT-related risk as applicable. [18][19]" ] ] } } ], "faq": [ { "question": "When is inferior petrosal sinus sampling unnecessary in ACTH-dependent Cushing syndrome?", "answer": "BIPSS may be omitted when pituitary MRI and noninvasive testing convincingly support Cushing disease. Use it when MRI is negative or equivocal, particularly with a lesion smaller than 6 mm, or when pituitary versus ectopic ACTH secretion remains uncertain. [9][12]" }, { "question": "Can steroidogenesis inhibitors be used before the source is fully localized?", "answer": "Yes. Adrenal steroidogenesis inhibitors reduce cortisol production regardless of cause and are useful when severe hypercortisolism requires prompt control during localization, before surgery, after surgical failure, or while awaiting radiotherapy effect. 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Endotext - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/books/NBK279088", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov" }, { "number": 24, "title": "Treatment options for Cushing disease after unsuccessful ...", "detail": "pubmed.ncbi.nlm.nih.gov", "url": "https://pubmed.ncbi.nlm.nih.gov/17961031", "authors": "pubmed.ncbi.nlm.nih.gov", "host": "pubmed.ncbi.nlm.nih.gov" } ], "editorialNote": "Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.", "citations": [ { "number": 1, "title": "202107Orig1s000 - accessdata.fda.gov", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000CrossR.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov", "snippet": "a significant proportion of patients is not cured by surgery. For instance, remission rates following initial surgery for Cushing’s disease due to microadenomas of the pituitary are between 70-90% and smaller (50-65%) if due to macroadenomas3. Patients who fail surgery have several therapeutic optio", "score": 0.5971152 }, { "number": 2, "title": "Consensus on diagnosis and management of Cushing's ...", "detail": "www.thelancet.com", "url": "https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00235-7/abstract", "authors": "www.thelancet.com", "host": "www.thelancet.com", "snippet": "by M Fleseriu · 2021 · Cited by 1105 — Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and", "score": 0.4804549 }, { "number": 3, "title": "Cushing syndrome - Symptoms, diagnosis and treatment | BMJ Best Practice US", "detail": "bestpractice.bmj.com", "url": "https://bestpractice.bmj.com/topics/en-us/205?locale=ja", "authors": "bestpractice.bmj.com", "host": "bestpractice.bmj.com", "snippet": "It may be difficult to distinguish patients with mild Cushing syndrome from those with metabolic syndrome (central obesity with insulin resistance and hypertension).\n\nAfter excluding exogenous corticosteroid use, patients with suspected Cushing syndrome should undergo biochemical testing (late-night", "score": 0.79958355 }, { "number": 4, "title": "Approach to the Patient: Diagnosis of Cushing Syndrome", "detail": "academic.oup.com", "url": "https://academic.oup.com/jcem/article/107/11/3162/6678587", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "by M Savas · 2022 · Cited by 106 — The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline . Consensus on diagnosis and management of Cushing's disease: a guideline", "score": 0.77589405 }, { "number": 5, "title": "The Diagnosis of Cushing's Syndrome: An Endocrine ...", "detail": "academic.oup.com", "url": "https://academic.oup.com/jcem/article-pdf/93/5/1526/20288083/jcem1526.pdf", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "by LK Nieman · 2008 · Cited by 3677 — The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. Consensus was guided by", "score": 0.7116118 }, { "number": 6, "title": "Treatment of Cushing's Syndrome: An Endocrine Society ...", "detail": "academic.oup.com", "url": "https://academic.oup.com/jcem/article-abstract/100/8/2807/2836065", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "by LK Nieman · 2015 · Cited by 1606 — The objective is to formulate clinical practice guidelines for treating Cushing's syndrome. Participants: Participants include an Endocrine Society", "score": 0.7050753 }, { "number": 7, "title": "Diagnosis of Cushing's Syndrome: An Endocrine Society ...", "detail": "academic.oup.com", "url": "https://academic.oup.com/jcem/article/93/5/1526/2598096", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "by LK Nieman · 2008 · Cited by 3684 — The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. we recommend testing for Cushing's syndrome in", "score": 0.65597594 }, { "number": 8, "title": "Corticotrophin‐releasing hormone and desmopressin tests in the differential diagnosis between Cushing’s disease and pseudo‐Cushing state: a comparative study - Tirabassi - 2011 - Clinical Endocrinology - Wiley Online Library", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2265.2011.04096.x", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "# Corticotrophin-releasing hormone and desmopressin tests in the differential diagnosis between Cushing’s disease and pseudo-Cushing state: a comparative study. **Background** We recently proposed a new and effective way of interpreting human corticotrophin-releasing hormone (hCRH) and desmopressin ", "score": 0.81770587 }, { "number": 9, "title": "Evaluation and treatment of Cushing’s syndrome - ScienceDirect", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/science/article/pii/S0002934305001609", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Cushing’s syndrome results from sustained pathologic hypercortisolism caused by excessive corticotropin (ACTH) secretion by tumors in the pituitary gland (Cushing’s disease, 70%) or elsewhere (15%), or by ACTH-independent cortisol secretion from adrenal tumors (15%). Plasma ACTH levels overlap signi", "score": 0.783542 }, { "number": 10, "title": "Cushing's syndrome: Overview of clinical presentation, diagnostic tools and complications - ScienceDirect", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/science/article/pii/S1521690X20300075", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Cushing's syndrome (CS) is a severe condition that results from chronic exposure to elevated circulating cortisol levels; it is a rare but potentially life-threating condition, especially when not timely diagnosed and treated. Cushing's syndrome (CS) is a rare condition due to prolonged exposure to ", "score": 0.77731717 }, { "number": 11, "title": "Petrosal Sinus Sampling - an overview | ScienceDirect Topics", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/immunology-and-microbiology/petrosal-sinus-sampling", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "In patients with elevated cortisol and suspected Cushing's syndrome, a 24-hour urinary free cortisol of more than 400 μg/day in a patient is diagnostic 8; these patients will also have an elevated midnight plasma cortisol, which under normal physiological conditions is at low levels.9 The low-dose d", "score": 0.7715858 }, { "number": 12, "title": "Positive predictive value and trends of inferior petrosal sinus sampling (IPSS) in diagnosing cushing disease and ectopic ACTH secretion: A systematic review and meta-analysis", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0303846722002311", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Dexamethasone suppression testing in addition to pituitary MRI are common techniques utilized in diagnosis of CD and EAS . However, per Pituitary Society consensus, IPSS is typically indicated after failure of 2–3 standard screening tools (late-night salivary cortisol, dexamethasone suppression test", "score": 0.7522497 }, { "number": 13, "title": "Diagnosis of Cushing’s syndrome with generalized linear... : Medicine", "detail": "journals.lww.com", "url": "https://journals.lww.com/md-journal/fulltext/2025/06200/diagnosis_of_cushing_s_syndrome_with_generalized.80.aspx", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "Title: Diagnosis of Cushing’s syndrome with generalized linear... : Medicine\nTraditional diagnostic approaches rely on statistical methods and different cutoff points for sensitivity and specificity, leading to varying evaluations of test results.[21] ML offers a promising solution to overcome these", "score": 0.7190094 }, { "number": 14, "title": "Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH‐dependent Cushing's syndrome: A reappraisal - Valizadeh - 2024 - Journal of Internal Medicine - Wiley Online Library", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/10.1111/joim.13789", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. It has long been establis", "score": 0.6554468 }, { "number": 15, "title": "Florid Cushing’s Syndrome - Endotext - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/books/NBK279044", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov", "snippet": "### Table 6 Tests Used For The Establishment Of Hypercortisolemia\n\nView in own window\n\n| | | |\n --- \n| | | Normal |\n| 24-hr UFC | free cortisol/ creatinine measurement | 3 normal collections |\n| ODST | 1mg dexamethasone midnight | <50nmol/L(<1.8μg/dL) 9:00 next morning |\n| LDDST | 0.5mg dexame", "score": 0.7371019 }, { "number": 16, "title": "Investigations | Diagnosis | Cushing's syndrome - CKS - NICE", "detail": "cks.nice.org.uk", "url": "https://cks.nice.org.uk/topics/cushings-syndrome/diagnosis/investigations", "authors": "cks.nice.org.uk", "host": "cks.nice.org.uk", "snippet": "1 mg oral dexamethasone is given between 11 pm and midnight, and a blood sample for cortisol level is taken between 8 am and 9 am the next morning.", "score": 0.7065353 }, { "number": 17, "title": "Case Presentations", "detail": "journal.chestnet.org", "url": "http://journal.chestnet.org/article/S0882-5963(08)00129-2/pdf", "authors": "journal.chestnet.org", "host": "journal.chestnet.org", "snippet": "by ML Castaneda · 2008 — late-night salivary cortisol levels, and a 2-day low-dose dexamethasone suppression test. The diagnosis of Cushing syndrome and Carney complex was made. pone", "score": 0.65597594 }, { "number": 18, "title": "Perioperative Management of a Patient With Cushing Disease", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8845122", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "Medical therapy is frequently associated with various other side effects. Ketoconazole and levoketoconazole may cause gastrointestinal distress, hepatotoxicity, and QT interval prolongation, especially if coadministered with other QT-prolonging drugs . Metyrapone and osilodrostat, but also mifeprist", "score": 0.8674071 }, { "number": 19, "title": "Osilodrostat Treatment for Adrenal and Ectopic Cushing Syndrome: Integration of Clinical Studies With Case Presentations", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11915091", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "## , approximately one-third of patients present with ectopic or adrenal causes. Surgery is the first-line treatment for most patients with Cushing syndrome; however, medical therapy is an important management option for those who are not eligible for, refuse, or do not respond to surgery. Clinical ", "score": 0.78532547 }, { "number": 20, "title": "Update and Practical Recommendations for the Use of Medical Treatment of Cushing Syndrome", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13167195", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "## , including those who are not candidates for curative surgery. It may also be used in the presurgical period when hypercortisolism is severe, as long-term treatment following surgical failure or recurrence after surgery, or while waiting for the effects of pituitary radiation in Cushing disease. ", "score": 0.77913743 }, { "number": 21, "title": "Consensus on Diagnosis and Management of Cushing’s Disease: A Guideline Update", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8743006", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "As in adults, surgical resection of the ACTH-secreting tumor is the first-line treatment. However, unlike in adults, thromboprophylaxis should not be routinely used due to bleeding risk, but reserved for selected pediatric patients. With successful treatment, adrenal function typically recovers with", "score": 0.76152116 }, { "number": 22, "title": "Medical treatment of Cushing's syndrome: adrenal- ...", "detail": "pubmed.ncbi.nlm.nih.gov", "url": "https://pubmed.ncbi.nlm.nih.gov/20829630", "authors": "pubmed.ncbi.nlm.nih.gov", "host": "pubmed.ncbi.nlm.nih.gov", "snippet": "Cushing's syndrome is primarily treated surgically. Ketoconazole and metyrapone are most frequently used for this purpose, low-dose ketoconazole seems a", "score": 0.7206637 }, { "number": 23, "title": "Cushing’s Syndrome - Endotext - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/books/NBK279088", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov", "snippet": "These agents are primarily used as inhibitors of steroid biosynthesis in the adrenal cortex (Figure 5), and thus can be utilized in all cases of hypercortisolemia regardless of cause, but most commonly in ACTH-dependent forms, often with rapid improvement in the clinical features of Cushing's syndro", "score": 0.6793707 }, { "number": 24, "title": "Treatment options for Cushing disease after unsuccessful ...", "detail": "pubmed.ncbi.nlm.nih.gov", "url": "https://pubmed.ncbi.nlm.nih.gov/17961031", "authors": "pubmed.ncbi.nlm.nih.gov", "host": "pubmed.ncbi.nlm.nih.gov", "snippet": "by JK Liu · 2007 · Cited by 61 — Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates", "score": 0.59880555 } ], "publishedAt": "2026-08-21T02:29:06.418157+00:00", "updatedAt": "2026-08-21T02:29:06.418157+00:00", "readingMinutes": 7, "slug": "cushing-syndrome" }