INTRODUCTION

Cushing’s disease (CD) is a serious endocrine disorder characterized by chronic hypercortisolism due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor [1]. In Korea, a nationwide epidemiological study using the Health Insurance Review and Assessment Service database has provided important insights into the burden and demographic features of CD. Between January 2013 and December 2017, 584 new CD cases were identified, with an annual incidence of 2.3 cases per million and a prevalence of 9.3 cases per million population [2]. Despite advances in diagnosis and treatment, CD continues to present clinical challenge [3]. Even after achieving remission, patients remain at elevated risk for cardiovascular events, bone fractures, and persistent reductions in quality of life, and their mortality rates remain high [4]. Therefore, early diagnosis and therapeutic intervention are crucial to improve outcomes. However, CD is often overlooked in daily clinical practice because of its rareness, leading to delays in diagnosis [5]. It is thus essential to establish clear guidelines outlining when to suspect and how to diagnose CD. Several factors contribute to the diagnostic difficulty of CD, including its complex and variable clinical presentation and the challenges associated with localizing small pituitary tumors. Addressing these issues through standardized diagnosis criteria is critical to improving the clinical management and outcomes of patients with CD. Traditionally, hypercortisolism has been categorized into ACTH-dependent and ACTH-independent forms [6,7], and standardized diagnostic guidelines have been developed by various endocrine societies [8,9], including the Korean Endocrine Society (KES) [10] and the Japan Endocrine Society (JES) (Supplemental Data S1) [11].

Despite shared pathophysiological principles, the KES and JES guidelines have notable differences, particularly in the selection of diagnostic tests, that reflect differences in healthcare systems, clinical practice patterns, and population-specific considerations. Therefore, a collaborative group from the KES and JES reviewed the current evidence and national guidelines to propose regionally relevant suggestions for the diagnosis of CD.

METHODS

A joint task force was assembled by the KES and JES in 2024, comprising endocrinologists and pituitary-adrenal specialists from both countries. Given the scarcity of high-quality comparative trials and meta-analytic evidence in the diagnostic evaluation of CD, particularly in original articles from both countries that demonstrate East Asian characteristics, and the substantial methodological heterogeneity between Korean and Japanese studies, applying a formal evidence-grading framework was not methodologically appropriate. Accordingly, the recommendations were formulated through multiple rounds of structured expert-consensus discussions involving specialists from both countries, consistent with international standards for harmonizing diagnostic guidelines. The task force conducted structured reviews of the existing the KES and JES guidelines, examined relevant literature, and engaged in multiple rounds of structured virtual and in-person discussions. Although the group did not apply formal evidence-grading tools, the recommendations reflect expert consensus and a synthesis of clinical experience across the two healthcare systems. This final document presents a narrative-based consensus intended to offer regionally relevant guidance for clinicians in East Asia.

Each diagnostic topic is organized into a ‘Consensus statement,’ which summarizes the agreement reached by the KES–JES task force, and a ‘Clinical context,’ which outlines the supporting evidence, rationale, and country-specific considerations. This format aims to provide clear, practical guidance alongside necessary background information for clinical decision-making.

CONSENSUS ON CLINICAL FEATURES OF CD

Consensus statement

The task force agrees that several clinical features are consistently observed in patients with CD and should raise clinical suspicion. Core manifestations commonly recognized across both the KES and JES guidelines include central obesity, moon face, proximal muscle weakness, purple striae, easy bruising, hypertension, glucose intolerance, menstrual irregularities, osteoporosis, and neuropsychiatric symptoms such as mood changes and cognitive impairment.

Clinical context

Symptoms listed only in the JES guidelines include thin skin, dorsocervical fat pads (buffalo hump), acne, peripheral edema, hyperpigmentation, and reduced growth velocity with obesity in children. Certain features such as facial plethora, dyslipidemia, delayed puberty, venous thromboembolism, immune dysfunction, and hypokalemia, are also noted as potentially relevant findings, particularly in East Asian populations. In contrast, the KES highlights symptoms such as facial plethora, weight gain, dyslipidemia, hypokalemia, delayed puberty, venous thromboembolism, cognitive dysfunction, and abnormalities in immune function. The JES categorizes clinical findings into specific and non-specific features and suggests that the presence of at least one from each category can support further diagnostic testing. The task force supports this approach in principle but emphasizes the need for clinician awareness that some patients might not spontaneously report even classic features [12]. Thus, thorough clinical questioning and physical examination remain essential. The panel agrees that reddish-purple striae wider than 1 cm and disproportionate central adiposity—regardless of body mass index— are highly suggestive of CD. Although hyperpigmentation is typically associated with ACTH-dependent forms, it should not be confused with acanthosis nigricans related to insulin resistance, which may appear even in ACTH-independent adrenal disease [13].

CONSENSUS ON DIAGNOSTIC EVALUATIONS FOR CD

General diagnostic principles

The task force agrees that no single diagnostic test provides definitive confirmation of CD. Therefore, a multimodal diagnostic strategy is essential to maximize diagnostic accuracy. Both the KES and JES recommend the use of at least two complementary screening tests to confirm hypercortisolism and reduce the risk of misdiagnosis. Test selection will depend on clinical presentation, institutional resources, and patient-specific factors.

Biochemical diagnostic test

Recommended initial tests

The following tests are considered core first-line screening tools to evaluate endogenous hypercortisolism:

• • 24-hour urinary free cortisol (UFC)

• • Overnight dexamethasone suppression test (ODST)

• • Late-night salivary cortisol (LNSC) or midnight serum cortisol

The initial step in CD diagnosis is to confirm cortisol excess through biochemical screening tests. KES recommends 24-UFC, LNSC, and 1-mg ODST as primary screening tests for suspected Cushing’s syndrome (CS). JES recommends measurements of early morning plasma ACTH and serum cortisol levels and the 24-UFC as the initial tests.

An essential aspect of screening is identifying conditions that can lead to false-positive results in each test, including medications that increase corticosteroid-binding globulin (CBG) or enhance CYP3A4 activity and pseudo-CS, also known as non-neoplastic hypercortisolemia due to depression, severe weight loss or severe obesity, or excessive alcohol consumption. Conversely, cyclic CS can produce false-negative findings, further complicating the diagnostic process.

Plasma ACTH and serum cortisol levels

Consensus statement: Although morning ACTH levels are useful in differentiating ACTH-dependent CS from ACTH-independent CS, the task force notes that overlapping ACTH levels between CD and adrenal CS limit diagnostic specificity.

• • The KES guidelines place greater emphasis on suppression tests and diurnal variation rather than ACTH, as a primary screening tool, due to inconsistent findings in Korean studies.

• • The JES guidelines support the use of early morning plasma ACTH and serum cortisol as part of the initial evaluation, particularly when levels are normal or elevated in the presence of clinical suspicion.

A flexible approach is endorsed, with ACTH levels interpreted alongside other biochemical and imaging data.

1. Clinical context

In both Korea and Japan, serum cortisol is predominantly measured using automated immunoassay platforms, although the specific analyzers and reagents may vary among institutions, leading to modest inter-assay variability. However, these minor methodological differences do not sufficiently explain the discrepancies in cutoff values between the two national guidelines, which primarily reflect distinct diagnostic strategies rather than assay methodology. It should also be noted that mass spectrometry- based cortisol measurements have not yet been widely adopted in either country. Cortisol secretion follows a pulsatile pattern that is regulated by the circadian rhythm of ACTH. In healthy individuals, this diurnal variation is well established, with peak cortisol levels in the early morning and the lowest levels around midnight [14]. The measurement of basal ACTH concentrations is particularly useful in distinguishing between pituitary-dependent (CD) and ACTH-independent CS [15]. Because plasma ACTH is highly unstable, appropriate pre-analytical handling, including use of pre-chilled tubes, immediate placement on ice, and prompt centrifugation, is essential to prevent degradation and avoid falsely low values that may lead to diagnostic misclassification. In clinical practice, morning ACTH levels <10 pg/mL (2 pmol/L) with normal or high cortisol levels strongly suggest ACTH-independent CS, and ACTH levels >20 pg/mL (4 pmol/L) indicate ACTH-dependent CS [16]. However, the KES guidelines do not explicitly include morning ACTH measurements as a required screening test for CS. Instead, the KES emphasizes biochemical suppression tests and diurnal cortisol variation for initial hypercortisolism detection. A Korean study found that plasma ACTH levels have significant overlap between CD and adrenal CS, which limits their diagnostic utility [17]. That study reported that although low ACTH levels traditionally indicate adrenal CS, a considerable proportion of adrenal CS patients still had detectable ACTH levels (3.5 to 15.6 pmol/L), making differentiation unreliable. Another study conducted at a tertiary center in Korea analyzed baseline ACTH levels and diagnostic markers in patients with CD [18]. That study found that preoperative ACTH levels did not differ significantly between macro-tumors (101.5±23.2 pg/mL) and microtumors (83.6±11.1 pg/mL, P=0.44), demonstrating a lack of correlation between ACTH levels and tumor size. Additionally, the ACTH-to-cortisol ratio did not predict remission after transsphenoidal surgery, further limiting its clinical utility in decision-making. Given those limitations, the KES guidelines deemphasize morning ACTH levels as a core screening parameter due to inconsistent results between CD and adrenal CS. In contrast, the JES guidelines pose early morning plasma ACTH and serum cortisol levels as reference indicators for proceeding to other screening tests. Specifically, the presence of normal to high ACTH and cortisol levels in the context of clinical features suggestive of ACTH-dependent CS supports proceeding with further diagnostic evaluation. In contrast, clearly low levels of both ACTH and cortisol suggest that endogenous CS is unlikely, and in such cases, an additional workup is generally not recommended. It should be noted, however, that the guidelines do not define a precise lower limit for ACTH and cortisol, and further studies are needed to clarify those thresholds.

Midnight cortisol levels

Consensus statement: Both societies agree that late-night serum or salivary cortisol provides valuable diagnostic information. The JES defines cortisol >5 μg/dL at 11:00 PM (with repeated measures and a failed ODST) as indicative of ACTH-dependent CS. The KES suggests that an ‘awake’ midnight serum cortisol >7.5 μg/dL is highly suggestive of CS, and a midnight serum cortisol of <1.8 μg/dL during sleep excludes the diagnosis.

1. Clinical context

In physiological conditions, serum cortisol levels exhibit a circadian rhythm, reaching a nadir around midnight. Measuring cortisol levels during the late-night nadir provides information that is valuable for diagnosing CS and differentiating it from other causes of hypercortisolism.

UFC levels

Consensus statement: Both societies recommend at least two abnormal UFC values with proper 24-hour collection protocols for diagnostic reliability. Ethnicity-specific thresholds might be appropriate due to higher baseline UFC levels in Asian patients than in other populations.

1. Clinical context

UFC has classically been the CD screening test most used in Korea. In contrast, UFC is regarded as a supportive laboratory finding for the diagnosis in Japan. It is of note that the method for measuring UFC in Japan changed in 2022 from a radioimmunoassay (RIA) to a chemiluminescent immunoassay (CLIA), which is known to yield lower values than the RIA. Because the cortisol excreted in urine is collected for a full 24 hours, the UFC avoids the confounding effects of diurnal cortisol fluctuations and is not affected by changes in CBG levels [19,20]. A positive UFC result is typically defined as >90 μg/day when measured by RIA or >50 μg/day using high-performance liquid chromatography or CLIA in at least 2–3 repeated tests and concurrent 24-hour urinary creatinine/volume measurement to ensure accuracy [10]. On the other hand, UFC testing has several limitations. UFC values can fluctuate due to renal function, hydration status, and inter-assay variability [19,21]. Additionally, in cases of mild or cyclic CD, cortisol secretion can intermittently fall within normal ranges, leading to potential false-negative results [22]. Obesity, depression, and alcoholism can all cause mild elevations in UFC, leading to false positives [23]. The Cowork of Adrenal Research project in Korea, a large prospective multicenter study, found that UFC levels showed notably poor diagnostic performance. That study highlighted that UFC might not reliably detect subtle cortisol alterations and those technical challenges, such as assay variability and collection inconsistencies, can limit its accuracy [24]. Interestingly, emerging data suggest that Asian patients, including Koreans, can present with inherently higher baseline UFC levels and more severe disease manifestations than non-Asians. A pooled analysis indicated that 39.3% of Asian patients had severe disease (UFC >5× upper limit of normal) versus 20.1% in non-Asians [25]. This disparity can be attributed to a higher prevalence of macro-tumors, which lead to increased cortisol production in Asian populations [26–28]. Given those variations, ethnicity-specific UFC thresholds and further validation of cutoff values in Asian cohorts are needed to improve diagnostic accuracy.

LNSC

Consensus statement: The task force supports the clinical utility of LNSC and encourages its broad implementation in East Asia. However, neither society has established standardized cutoffs. Validation studies are needed to define population-specific reference ranges.

1. Clinical context

LNSC measurement is a non-invasive and reliable method for assessing free cortisol levels, which are in equilibrium with the unbound, biologically active form of cortisol in serum [29,30]. This equilibrium exists because free cortisol diffuses through the acinar cells of the salivary glands into the oral cavity, with only a small fraction (approximately 15%) bound to CBG [31]. Because LNSC reflects only the free fraction, its levels are unaffected by binding proteins and accurately follow the physiological circadian rhythm, including the early morning peak and late-night nadir [32]. Moreover, saliva sampling is simple and non-invasive, which minimizes stress-induced cortisol elevations. LNSC is considered to be a practical and patient-friendly tool for repeated assessment and longitudinal monitoring of hypothalamic–pituitary–adrenal axis function. Despite international acceptance of LNSC as a screening tool, its clinical application remains limited in Korea, partly due to the lack of standardized cutoff values. A systemic literature review reported that the optimal cutoff values for LNSC vary widely (range 0.13 μg/dL [3.6 nmol/L] to 0.55 μg/dL [15.2 nmol/L]), with a pooled sensitivity of 92% (95% confidence interval [CI], 88% to 94%) and specificity of 96% (95% CI, 94% to 97%) [33]. A study from Taiwan showed that a cutoff for LNSC level of 0.17 μg/dL (4.69 nmol/L) was associated with a sensitivity of 98% and specificity of 100% [34]. In a Japanese study, LNSC was measured using three different assays—RIA, electro-chemiluminescence, and enzyme-linked immunosorbent assay—across four facilities. With an absolute cutoff value of 0.4 μg/dL (11.04 nmol/L), the sensitivity and specificity were 86% and 100%, respectively. To address variability across assays and enable standardization, those investigators evaluated a ratio-based cutoff set at 1.5 times the mean value in healthy controls, and it yielded a sensitivity of 96% and specificity of 88%. Those findings highlight the need for assay standardization in the interpretation of LNSC measurements [35]. It is important to note that LNSC is not recommended for individuals with an altered circadian rhythm, such as night-shift workers [9]. The KES guidelines currently do not specify a definitive LNSC cutoff, reflecting the ongoing need for large-scale validation studies. However, efforts to establish reference values and promote the clinical application of LNSC testing in Korea are ongoing. Although the JES diagnostic guidelines acknowledge the usefulness of LNSC in Japan, the measurement method has not been standardized, and reference values have yet to be established. In addition, salivary cortisol testing is not currently covered by insurance.

1-mg ODST or 0.5-mg ODST

Consensus statement: The task force acknowledges the utility of both the 1-mg ODST and 0.5-mg ODST, noting that national practices reflect different clinical and population-based priorities. Whereas the KES adheres to internationally accepted standards to ensure comparability, JES’s modified approach is designed to improve early detection in milder or subclinical cases, which is especially relevant in a population with pharmacogenetic responses that potentially differ from those in other places.

1. Clinical context

The 1-mg ODST is used most widely when screening for CS [36]. In this test, 1-mg of dexamethasone is administered orally at 11 PM, and serum cortisol levels are measured between 8:00 AM and 9:00 AM the following morning. A serum cortisol level >1.8 μg/dL (50 nmol/L) suggests the failure of suppression, indicating possible hypercortisolism [8,9,37]. The KES guidelines align with global recommendations, adopting the 1.8 μg/dL cutoff due to its high sensitivity (~95%). This threshold was established based on studies demonstrating that post-dexamethasone cortisol levels above 1.8 μg/dL are associated with increased morbidity and mortality, even in patients without overt CS [38]. Additionally, using a higher cutoff (5 μg/dL) risks underestimating the clinical significance of mild autonomous cortisol secretion, which has been linked to cardiovascular disease, osteoporosis, and metabolic abnormalities [39]. In Korea, most clinical studies evaluating the ODST have also used the 1.8 μg/dL cutoff as the primary reference value, reflecting its established diagnostic accuracy and clinical applicability [18,24,27,40]. Despite its high sensitivity, the ODST has limitations due to the potential for false positives in patients with obesity, alcoholism, or psychiatric disorders [16]. Therefore, it is recommended that the ODST be interpreted alongside additional screening tests to improve diagnostic specificity.

In Japan, a dose of 0.5-mg of dexamethasone has been used for the ODST. Japanese prior data indicate that a 0.5-mg ODST is more sensitive than the 1-mg ODST in the Japanese. This higher sensitivity has been attributed to population-specific factors such as leaner body habitus and greater cortisol suppressibility in response to dexamethasone, leading to adoption of the 0.5 mg dose with a higher cutoff for screening [41]. A cortisol cutoff value of 5 μg/dL for diagnosing ACTH-dependent CS showed a sensitivity of 94.2% with a 1-mg dose and 99.1% with a 0.5-mg dose [42]. Furthermore, to enable the early detection of mild hypercortisolism, the JES uses a cutoff value of 3 μg/dL for screening subclinical CD. Thus, the 0.5‑mg ODST is characterized by higher sensitivity for mild or subclinical disease, at the expense of a potential reduction in specificity and an increased need for confirmatory testing.

Overall, the differing preferences of the KES and JES reflect variations in historical validation studies, population-specific responses to dexamethasone, and diagnostic priorities rather than differences in assay methodology. The 1-mg ODST offers broad international comparability and robust sensitivity, whereas the 0.5-mg ODST provides increased sensitivity for mild disease at the potential cost of specificity, necessitating careful clinical correlation.

Recommended confirmatory tests

The following tests can be used as core second-line tools to differentiate CD from other ACTH-dependent CS:

• • Desmopressin test

• • Corticotropin-releasing hormone (CRH) test

• • High-dose dexamethasone suppression test (HDDST) or 8-mg ODST

Desmopressin test

Consensus statement: The desmopressin test can be used as a diagnostic tool for differentiating CD, especially in institutions where the CRH test is not readily available. In Japan, the desmopressin test is listed in the guidelines for screening for CD [40,41], but it is not routinely performed because it is not covered by insurance. The test is also gaining utility in postoperative monitoring for disease recurrence.

1. Clinical context

The desmopressin test is emerging as a valuable tool in the diagnostic evaluation of CS, particularly in distinguishing CD from non-neoplastic hypercortisolism (NNH) [43] and ectopic ACTH syndrome (EAS). Desmopressin acts on arginine vasopressin (AVP) receptor 1b, which is highly expressed in corticotrophic tumors, or ectopically expressed AVP receptor 2, which stimulates ACTH and cortisol release, making it a useful functional test in the differential diagnosis of ACTH-dependent CS [44,45]. A positive response (ACTH increase >50% and cortisol increase >20%) strongly suggests CD, and a lack of response suggests NNH or EAS. A recent systematic review and meta-analysis, which included an Asian cohort, assessed the accuracy of intravenous desmopressin testing in differentiating CD from NNH and EAS. The combined criteria of ΔACTH >35% and Δ cortisol >20% showed a sensitivity of 85% and specificity of 64% [46]. Beyond diagnosis, the desmopressin stimulation test is increasingly used for postoperative monitoring in CD patients [47,48], and the KES guidelines note that an exaggerated ACTH and cortisol response to desmopressin post-surgery can indicate residual tumor tissue and predict disease recurrence. This approach aligns with international trends, in which desmopressin used as an alternative to the CRH test, which is becoming less available globally [49]. The desmopressin test protocols of both the KES and JES use a 4-μg dose of desmopressin, in contrast to the 10-μg dose commonly used in Western countries. This lower-dose protocol in East Asia is based on early Japanese clinical studies demonstrating that 4 to 5 μg produced a clear stimulatory response in most patients with CD [41]. These data were subsequently incorporated into the early JES recommendations and later into the 2015 KES guideline, which specifies a 4-μg dose. Although no head-to-head comparison between 4–5 μg and 10 μg dosing has been conducted, accumulated regional experience indicates that the lower dose provides adequate diagnostic stimulation while minimizing vasopressin-related adverse effects. In contrast, the 10-μg dose became standard in Western centers largely because early desmopressin stimulation protocols adopted this dose to maximize ACTH responsiveness [50].

CRH test

Consensus statement: The task force acknowledges the utility of the CRH test as a supportive diagnostic tool for confirming the pituitary origin of ACTH hypersecretion. When available, it should be considered in the differential diagnosis of ACTH-dependent CS, particularly when imaging and other biochemical tests yield inconclusive results.

1. Clinical context

The CRH test is a dynamic function test that assesses the pituitary response to CRH [46]. In most cases of CD, CRH stimulates ACTH secretion, leading to a subsequent rise in cortisol levels. This response is less pronounced in EAS, making the test useful in differentiating CD from other ACTH-dependent causes of hypercortisolism [51]. The KES and JES both incorporate the CRH test into their diagnostic frameworks. The test involves the intravenous administration of 100-μg of CRH after an overnight fast, followed by the measurement of plasma ACTH and serum cortisol levels at 15-, 30-, and 60-minutes post-injection [8,9,52]. A ≥50% increase in ACTH and ≥20% increase in cortisol within 30 minutes of CRH administration is suggestive of CD.

The differential response to CRH between CD and EAS reflects their underlying pathophysiology. Corticotroph tumors in CD overexpress CRH receptor 1 (CRHR1) and retain sensitivity to hypothalamic stimulation, leading to a marked rise in ACTH and cortisol after CRH administration [53]. In contrast, most EAS demonstrate minimal or absent CRHR1 expression and synthesize ACTH autonomously, independent of hypothalamic regulation [54]. Because EAS do not rely on CRH-mediated signaling, they exhibit little or no biochemical response to CRH administration. These differences in CRH-receptor expression and regulatory dependence on the hypothalamic–pituitary axis form the principal mechanistic basis for the diagnostic utility of the CRH stimulation test in distinguishing CD from EAS. Furthermore, this test is contingent on the presence of hypercortisolism, a state in which normal corticotrophs no longer synthesize ACTH in a CRH-dependent manner.

However, false-negative results can occur in cases of macro-tumors, and false-positive results can be seen in EAS, particularly in bronchial carcinoids. Therefore, caution is warranted, and clinical decisions should not be based on this test alone. In Japan, the CRH test is a routine diagnostic tool, but in Korea, it is rarely performed due to cost constraints.

HDDST and 8-mg ODST

Consensus statement: The task force supports the use of the 8-mg dexamethasone suppression test as a valuable tool for differentiating CD from EAS in the context of ACTH-dependent hypercortisolism. Given the potential for incomplete suppression in patients with severe hypercortisolism or those harboring large pituitary macroadenomas, test results should be interpreted with caution.

1. Clinical context

Currently, both the low-dose dexamethasone suppression test (LDDST) and HDDST are still widely used for the diagnosis and differential diagnosis of CS. The LDDST typically involves oral administration of 0.5-mg of dexamethasone every 6 hours for 2 days, followed by the measurement of serum cortisol [1]. However, its diagnostic performance of is comparable to that of the 1-mg ODST, so its clinical utility is gradually declining [55]. The HDDST has been a traditional tool for distinguishing CD from adrenal CS or EAS. It requires administration of dexamethasone over 2 days, commonly 2 mg every 6 hours for 2 consecutive days (total 16 mg). Serum cortisol and 24-UFC is measured before and after dexamethasone administration. Compared with the HDDST, the 8-mg ODST is more convenient due to its single-dose administration and lack of requirement for 24- hour urine collection [56]. The 8-mg ODST has been reported to have a sensitivity of approximately 95%, making it more effective than the traditional HDDST in distinguishing between CD and EAS [57,58]. Although the 8-mg ODST is increasingly being adopted as a convenient and efficient alternative for diagnosing CD, the HDDST continues to be commonly used in clinical practice in Korea. The KES recommends that the HDDST be interpreted based on an absolute post-suppression cortisol level <5 μg/dL, which is considered indicative of CD. The JES recommends >50% suppression from the baseline cortisol level after the 8-mg ODST as the diagnostic threshold for CD.

Given current differences in diagnostic practice and population characteristics, additional studies in Asian populations are warranted to validate the diagnostic performance of the 8-mg ODST and further clarify its role relative to the HDDST. Caution is required in cases of ectopic ACTH-secreting pheochromocytoma because high-dose dexamethasone can trigger a hypertensive crisis in those patients.

Pituitary magnetic resonance imaging

Consensus statement

Sella magnetic resonance imaging (MRI) is recommended as the first-line imaging modality for all patients with confirmed ACTH-dependent CS. Dynamic contrast-enhanced MRI with high spatial resolution (e.g., spoiled gradient recalled imaging or equivalent sequences) should be used to improve the detection of microadenomas.

1. Clinical context

The KES guideline’s recommendation to used sella MRI as the primary imaging modality for diagnosing CD is well-supported by both international and Korean studies. Sella MRI provides high anatomical resolution for detecting pituitary tumors and assessing structural abnormalities before surgery. A Korean study demonstrated that MRI had a positive predictive value of 86% for tumor localization, with intraoperative findings confirming tumors in 77.8% of cases [59]. However, approximately 18% of CD cases have microtumors that are too small to be detected by standard MRI [60]. To improve detection, dynamic contrast-enhanced MRI is recommended over conventional T1- and T2-weighted imaging [61]. That method increases the likelihood of identifying tumors in the far anterior or posterior of the pituitary gland. Further refinements in imaging techniques, such as using half-dose contrast MRI and spoiled gradient recalled echo with 1-mm sections, have also been proposed to enhance the detection of microtumors [62]. Low doses of gadolinium contrast improve differentiation between normal pituitary tissue and tumors, making MRI a crucial tool for surgical planning. Recent studies, including a Korean study using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) have explored alternative imaging modalities for pituitary tumor localization [63]. However, a recent study found that dexamethasone suppression did not significantly improve the localization of ACTH-secreting pituitary tumors using ¹⁸F-FDG PET/CT. Therefore, PET/CT is primarily used to evaluate patients with suspected EAS when biochemical evidence of ACTH-dependent hypercortisolism exists but no pituitary tumor is identified on MRI. In that context, PET/CT helps localize the ectopic source of ACTH production.

Inferior petrosal sinus sampling using desmopressin or CRH

Consensus statement

Inferior petrosal sinus sampling (IPSS) is recommended for patients with biochemically confirmed ACTH-dependent CS when a pituitary tumor is not definitively identified on MRI or when clinical and biochemical findings are equivocal. A baseline central-to-peripheral ACTH ratio >2, or a post-stimulation ratio >3, indicates a pituitary source. The task force affirms IPSS as an indispensable tool in cases of ambiguous imaging or discordant biochemical findings. However, limitations in lateralization accuracy should be acknowledged, and decision-making should not rely solely on IPSS side-dominance. The group supports broader application of prolactin-adjusted metrics to improve procedural reliability and suggests further collaborative research into optimization strategies.

1. Clinical context

IPSS is a critical diagnostic tool for differentiating CD from EAS [64]. In Korean studies, IPSS has shown high diagnostic accuracy, with a 100% positive detection rate for CD in a cohort of Korean patients [59]. This supports the continued reliance on IPSS as a gold standard test, particularly when MRI fails to localize a tumor. The procedure involves comparing ACTH levels in blood collected from the bilateral IPSS and a peripheral vein before and after stimulation with either desmopressin or CRH. Desmopressin (administered 10-μg intravenously [IV] over 15 seconds) is an alternative to CRH (100-μg IV), with studies showing comparable efficacy [65].

A baseline IPS/peripheral ACTH ratio >2 is indicative of CD. A post-stimulation IPS/peripheral ACTH ratio >3 strongly suggests CD. Lateralization (a post-stimulation ACTH ratio >1.4 between the two sinuses) suggests the tumor’s location, though this finding correlates with surgical biopsy results in only 38.9% of Korean cases [59]. False negatives can occur due to anatomical variations in venous drainage or procedural technicalities [66]. To ensure catheterization accuracy, prolactin measurement is recommended [67]; an IPS-to-peripheral prolactin ratio >1.8 confirms successful sampling. Additionally, a normalized prolactin-adjusted ACTH ratio >1.3 supports a CD diagnosis, whereas a ratio <0.8 suggests EAS. The KES guidelines recommend checking IPS-to-peripheral prolactin ratios to confirm catheterization. Reports from Japan have demonstrated the usefulness of IPSS in patients with MRI-negative tumors, and prolactin adjustment has been shown to aid in distinguishing between CD and EAS [68]. Although IPSS plays a key role in differentiating between CD and EAS, both countries acknowledge that its accuracy in determining tumor lateralization is limited.

Pathological findings

According to the JES guidelines, pathological confirmation of a neuroendocrine tumor is essential in all cases treated with pituitary surgery. When the diagnosis is uncertain, the use of neuroendocrine markers such as chromogranin A, synaptophysin, and insulinoma-associated protein 1 (INSM1) is recommended to confirm endocrine differentiation. If distinction from non-neoplastic anterior pituitary tissue is difficult, reticulin staining can also aid in diagnosis.

Furthermore, immunohistochemical staining for ACTH and the lineage-specific transcription factor, T-box pituitary transcription factor (TPIT) is recommended to verify that the resected tumor is indeed a corticotroph pituitary neuroendocrine tumor (PitNET) responsible for ACTH production. This step is particularly important in patients with inconclusive biochemical or imaging findings, in whom a non-ACTH-producing PitNET or the removal of an unrelated lesion remains a possibility

DIFFERENCES BETWEEN THE TWO COUNTRIES AND FUTURE PROSPECTS

The 1-mg ODST is used most widely when the two societies lie in the dose of dexamethasone used for the LDDST: the JES adopts a 0.5-mg dose with a higher cutoff value, and the KES follows international guidelines to use 1 mg (Table 1). Although the JES suggests that this difference might reflect a characteristic specific to East Asian populations, further validation will be necessary. The appropriate cutoff value of ACTH for distinguishing ACTH-dependent from ACTH-independent CS is also a point of discussion and requires further validation. Additionally, although both the KES and JES acknowledge the usefulness of LNSC, neither has established a standardized cutoff value. In Japan, debate is ongoing about which method for measuring salivary cortisol levels should be adopted, and an additional unresolved issue is that the test is not currently covered by insurance. Both the KES and JES primarily recommend the use of MRI to localize pituitary tumors; however, the JES recognizes that some tumors might not be visible on MRI. As a result, the JES recommends performing IPSS when the tumor is smaller than 6 mm. Both guidelines support the use of IPSS for differential diagnosis, but the KES incorporates prolactin-adjusted

ACTH ratios to enhance the accuracy of catheterization, and the JES is currently evaluating the clinical utility of prolactin adjustment. Despite the detailed comparison above, several diagnostic discrepancies remain unresolved. Because these differences arise from variations in available evidence, assay use, and practice environments, the task force could not propose a fully harmonized diagnostic pathway at this stage. Until comparative data become available, clinicians are encouraged to select among the divergent approaches based on institutional test availability, assay performance characteristics, and individual patient risk profiles.

CONCLUSIONS

This consensus highlights the key differences and similarities between the KES and the JES guidelines in diagnosing CD. While both guidelines share a multifaceted approach integrating biochemical, functional, and imaging-based evaluations, regional variations in diagnostic emphasis and methodology exist.

By integrating the strengths of both guidelines, this consensus provides a foundation for developing evidence-based, region-specific recommendations. It also highlights the value of the future task based on the collaborative multicenter studies in Asian populations to validate diagnostic tools, to evaluate their clinical utility, and to refine algorithms. Ultimately, this consensus contributes to the development of a more unified and optimized diagnostic strategy that may improve clinical outcomes of patients with CD in East Asia.

Supplementary Material

Article information

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

ACKNOWLEDGMENTS

This review was conducted through the collaborative efforts of the Committee of Clinical Practice Guidelines of the Korean Endocrine Society and Japan Endocrine Society, with additional contributions from the Korean Neuroendocrine Study Group. We sincerely appreciate the dedication of all the researchers who contributed to this work. This consensus statement has been simultaneously published with permission in Endocrinology and Metabolism and Endocrine Journal.

References

• 1. Nieman LK. Molecular derangements and the diagnosis of ACTH-dependent Cushing’s syndrome. Endocr Rev 2022;43:852–77.ArticlePubMedPMCPDF
• 2. Park JS, Yun SJ, Lee JK, Park SY, Chin SO. Descriptive epidemiology and survival analysis of prolactinomas and Cushing’s disease in Korea. Endocrinol Metab (Seoul) 2021;36:688–96.PubMedPMC
• 3. Chin SO. For the forthcoming winning shot in the battle against Cushing disease. Endocrinol Metab (Seoul) 2024;39:573–5.ArticlePubMedPMCPDF
• 4. Limumpornpetch P, Morgan AW, Tiganescu A, Baxter PD, Nyawira Nyaga V, Pujades-Rodriguez M, et al. The effect of endogenous Cushing syndrome on all-cause and cause-specific mortality. J Clin Endocrinol Metab 2022;107:2377–88.ArticlePubMedPMCPDF
• 5. Valassi E, Santos A, Yaneva M, Toth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol 2011;165:383–92.ArticlePubMed
• 6. Sharma ST, Nieman LK, Feelders RA. Comorbidities in Cushing’s disease. Pituitary 2015;18:188–94.ArticlePubMedPMCPDF
• 7. Reincke M, Fleseriu M. Cushing syndrome: a review. JAMA 2023;330:170–81.ArticlePubMed
• 8. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93:1526–40.ArticlePubMedPMC
• 9. Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR, et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 2021;9:847–75.PubMedPMC
• 10. Hur KY, Kim JH, Kim BJ, Kim MS, Lee EJ, Kim SW. Clinical guidelines for the diagnosis and treatment of Cushing’s disease in Korea. Endocrinol Metab (Seoul) 2015;30:7–18.ArticlePubMedPMC
• 11. Takahashi Y, Tahara S, Nishiyama M, Makita N, Mizuno H, Yamada M, et al. Clinical practice guidelines for the diagnosis and management of hypothalamic-pituitary dysfunction, congenital arginine vasopressin resistance, and related disorders: 2023 edition by the Japan Endocrine Society. Nihon Naibunpi Gakkai Zasshi 2023 99(S. July):1–171. (Japanese).
• 12. Motomura Y, Urai S, Bando H, Yamamoto M, Suzuki M, Yamamoto N, et al. Diagnostic dilemma in Cushing’s syndrome: discrepancy between patient-reported and physician-assessed manifestations. Endocrine 2024;86:417–27.ArticlePubMedPMCPDF
• 13. Stratakis CA. Skin manifestations of Cushing’s syndrome. Rev Endocr Metab Disord 2016;17:283–6.ArticlePubMedPMCPDF
• 14. Lightman SL, Birnie MT, Conway-Campbell BL. Dynamics of ACTH and cortisol secretion and implications for disease. Endocr Rev 2020;41:bnaa002..ArticlePubMedPMCPDF
• 15. Wright K, van Rossum EFC, Zan E, Werner N, Harris A, Feelders RA, et al. Emerging diagnostic methods and imaging modalities in Cushing’s syndrome. Front Endocrinol (Lausanne) 2023;14:1230447.ArticlePubMedPMC
• 16. Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing’s disease. Best Pract Res Clin Endocrinol Metab 2009;23:607–23.ArticlePubMed
• 17. Hong AR, Kim JH, Hong ES, Kim IK, Park KS, Ahn CH, et al. Limited diagnostic utility of plasma adrenocorticotropic hormone for differentiation between adrenal Cushing syndrome and Cushing disease. Endocrinol Metab (Seoul) 2015;30:297–304.ArticlePubMedPMC
• 18. Hwang YC, Chung JH, Min YK, Lee MS, Lee MK, Kim KW. Comparisons between macroadenomas and microadenomas in Cushing’s disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci 2009;24:46–51.ArticlePubMedPMC
• 19. Casals G, Hanzu FA. Cortisol measurements in Cushing’s syndrome: immunoassay or mass spectrometry? Ann Lab Med 2020;40:285–96.ArticlePubMedPMCPDF
• 20. Clarke SA, Eng PC, Comninos AN, Lazarus K, Choudhury S, Tsang C, et al. Current challenges and future directions in the assessment of glucocorticoid status. Endocr Rev 2024;45:795–817.ArticlePubMedPMCPDF
• 21. Guarnotta V, Amato MC, Pivonello R, Arnaldi G, Ciresi A, Trementino L, et al. The degree of urinary hypercortisolism is not correlated with the severity of Cushing’s syndrome. Endocrine 2017;55:564–72.ArticlePubMedPDF
• 22. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017;376:1451–9.ArticlePubMed
• 23. Flowers KC, Shipman KE. Pitfalls in the diagnosis and management of hypercortisolism (Cushing syndrome) in humans; a review of the laboratory medicine perspective. Diagnostics (Basel) 2023;13:1415.ArticlePubMedPMC
• 24. Ahn SH, Kim JH, Baek SH, Kim H, Cho YY, Suh S, et al. Characteristics of adrenal incidentalomas in a large, prospective computed tomography-based multicenter study: the COAR Study in Korea. Yonsei Med J 2018;59:501–10.ArticlePubMedPMCPDF
• 25. Shimatsu A, Biller BM, Fleseriu M, Pivonello R, Lee EJ, Leelawattana R, et al. Osilodrostat treatment in patients with Cushing’s disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4). Endocr J 2024;71:1103–23.ArticlePubMedPMC
• 26. Nakane T, Kuwayama A, Watanabe M, Takahashi T, Kato T, Ichihara K, et al. Long term results of transsphenoidal adenomectomy in patients with Cushing’s disease. Neurosurgery 1987;21:218–22.ArticlePubMed
• 27. Kim JH, Shin CS, Paek SH, Jung HW, Kim SW, Kim SY. Recurrence of Cushing’s disease after primary transsphenoidal surgery in a university hospital in Korea. Endocr J 2012;59:881–8.ArticlePubMed
• 28. Parksook WW, Laichuthai N, Sunthornyothin S. Clinical characteristics and treatment outcomes in endogenous Cushing’s syndrome: a 15-year experience from Thailand. Case Rep Endocrinol 2020;2020:2946868.ArticlePubMedPMCPDF
• 29. Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem 1983;20(Pt 6):329–35.ArticlePubMedPDF
• 30. Gatti R, Antonelli G, Prearo M, Spinella P, Cappellin E, De Palo EF. Cortisol assays and diagnostic laboratory procedures in human biological fluids. Clin Biochem 2009;42:1205–17.ArticlePubMed
• 31. Choi MH. Clinical and technical aspects in free cortisol measurement. Endocrinol Metab (Seoul) 2022;37:599–607.ArticlePubMedPMCPDF
• 32. Vining RF, McGinley RA. The measurement of hormones in saliva: possibilities and pitfalls. J Steroid Biochem 1987;27:81–94.ArticlePubMed
• 33. Carroll T, Raff H, Findling JW. Late-night salivary cortisol for the diagnosis of Cushing syndrome: a meta-analysis. Endocr Pract 2009;15:335–42.ArticlePubMed
• 34. Lin DC, Tsai PS, Lin YC. Midnight salivary cortisol for the diagnosis of Cushing’s syndrome in a Chinese population. Singapore Med J 2019;60:359–63.ArticlePubMedPMC
• 35. Sakihara S, Kageyama K, Oki Y, Doi M, Iwasaki Y, Takayasu S, et al. Evaluation of plasma, salivary, and urinary cortisol levels for diagnosis of Cushing’s syndrome. Endocr J 2010;57:331–7.ArticlePubMed
• 36. Yorke E, Atiase Y, Akpalu J, Sarfo-Kantanka O. Screening for Cushing syndrome at the primary care level: what every general practitioner must know. Int J Endocrinol 2017;2017:1547358.ArticlePubMedPMCPDF
• 37. Martinerie L, Bouligand J, North MO, Bertherat J, Assie G, Espiard S. Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) for the diagnosis of Cushing’s syndrome: genetics of Cushing’s syndrome. Ann Endocrinol (Paris) 2024;85:284–93.ArticlePubMed
• 38. Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab 2014;99:4462–70.ArticlePubMedPMC
• 39. Mansour N, Bruedgam D, Heinrich D, Dischinger U, Reisch N, Volter F, et al. Mild autonomous cortisol secretion leads to reduced volumetric BMD at lumbar spine in patients with primary aldosteronism. Front Endocrinol (Lausanne) 2024;15:1521680.ArticlePubMedPMC
• 40. Hong AR, Kim JH, Park KS, Kim KY, Lee JH, Kong SH, et al. Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice. Eur J Endocrinol 2017;177:475–83.ArticlePubMed
• 41. Kageyama K, Oki Y, Sakihara S, Nigawara T, Terui K, Suda T. Evaluation of the diagnostic criteria for Cushing’s disease in Japan. Endocr J 2013;60:127–35.ArticlePubMed
• 42. Oki Y, Hashimoto K, Hirata Y, Iwasaki Y, Nigawara T, Doi M, et al. Development and validation of a 0.5 mg dexamethasone suppression test as an initial screening test for the diagnosis of ACTH-dependent Cushing’s syndrome. Endocr J 2009;56:897–904.ArticlePubMed
• 43. Mondin A, Barbot M, Voltan G, Tizianel I, Vedolin CK, Mazzeo P, et al. Second-line tests in the differential diagnosis of neoplastic and non-neoplastic hypercortisolism: a systematic review and meta-analysis. J Endocrinol Invest 2023;46:1947–59.ArticlePubMedPMCPDF
• 44. Moro M, Putignano P, Losa M, Invitti C, Maraschini C, Cavagnini F. The desmopressin test in the differential diagnosis between Cushing’s disease and pseudo-Cushing states. J Clin Endocrinol Metab 2000;85:3569–74.ArticlePubMedPDF
• 45. Shichi H, Fukuoka H, Kanzawa M, Yamamoto M, Yamamoto N, Suzuki M, et al. Responsiveness to DDAVP in Cushing’s disease is associated with USP8 mutations through enhancing AVPR1B promoter activity. Pituitary 2022;25:496–507.ArticlePubMedPDF
• 46. Giampietro RR, Cabral MV, Pereira EG, Machado MC, Vilar L, Nunes-Nogueira VD. Accuracy of the 10 μg desmopressin test for differential diagnosis of Cushing syndrome: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024;15:1332120.ArticlePubMedPMC
• 47. Losa M, Mortini P, Dylgjeri S, Barzaghi R, Franzin A, Mandelli C, et al. Desmopressin stimulation test before and after pituitary surgery in patients with Cushing’s disease. Clin Endocrinol (Oxf) 2001;55:61–8.ArticlePubMedPDF
• 48. Pinelli S, Barbot M, Scaroni C, Ceccato F. Second-line tests in the diagnosis of adrenocorticotropic hormone-dependent hypercortisolism. Ann Lab Med 2021;41:521–31.ArticlePubMedPMC
• 49. Ceccato F, Di Dalmazi G. Shortage of hCRH for the diagnosis of endogenous CS: the end of an era or the beginning of a new journey? J Endocrinol Invest 2023;46:2189–91.ArticlePubMedPDF
• 50. Detomas M, Ritzel K, Nasi-Kordhishti I, Wolfsberger S, Quinkler M, Losa M, et al. Outcome of CRH stimulation test and overnight 8 mg dexamethasone suppression test in 469 patients with ACTH-dependent Cushing’s syndrome. Front Endocrinol (Lausanne) 2022;13:955945.ArticlePubMedPMC
• 51. Savas M, Mehta S, Agrawal N, van Rossum EF, Feelders RA. Approach to the patient: diagnosis of Cushing syndrome. J Clin Endocrinol Metab 2022;107:3162–74.ArticlePubMedPMCPDF
• 52. Nieman LK, Castinetti F, Newell-Price J, Valassi E, Drouin J, Takahashi Y, et al. Cushing syndrome. Nat Rev Dis Primers 2025;11:4.ArticlePubMedPDF
• 53. Elamin MB, Murad MH, Mullan R, Erickson D, Harris K, Nadeem S, et al. Accuracy of diagnostic tests for Cushing’s syndrome: a systematic review and metaanalyses. J Clin Endocrinol Metab 2008;93:1553–62.ArticlePubMedPDF
• 54. Bertherat J. CRH-receptor molecular imaging reveals the intimacy of corticotroph adenomas. J Clin Endocrinol Metab 2021;106:e1902–4.ArticlePubMedPDF
• 55. Carton T, Mathieu E, Wolff F, Bouziotis J, Corvilain B, Driessens N. Two-day low-dose dexamethasone suppression test more accurate than overnight 1-mg in women taking oral contraceptives. Endocrinol Diabetes Metab 2021;4:e00255.ArticlePubMedPMCPDF
• 56. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet 2015;386:913–27.ArticlePubMedPMC
• 57. Barbot M, Trementino L, Zilio M, Ceccato F, Albiger N, Daniele A, et al. Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Pituitary 2016;19:488–95.ArticlePubMedPDF
• 58. Aytug S, Laws ER, Vance ML. Assessment of the utility of the high-dose dexamethasone suppression test in confirming the diagnosis of Cushing disease. Endocr Pract 2012;18:152–7.ArticlePubMed
• 59. Lim JS, Lee SK, Kim SH, Lee EJ, Kim SH. Intraoperative multiple-staged resection and tumor tissue identification using frozen sections provide the best result for the accurate localization and complete resection of tumors in Cushing’s disease. Endocrine 2011;40:452–61.ArticlePubMedPDF
• 60. Fukuhara N, Inoshita N, Yamaguchi-Okada M, Tatsushima K, Takeshita A, Ito J, et al. Outcomes of three-Tesla magnetic resonance imaging for the identification of pituitary adenoma in patients with Cushing’s disease. Endocr J 2019;66:259–64.ArticlePubMed
• 61. Grober Y, Grober H, Wintermark M, Jane JA, Oldfield EH. Comparison of MRI techniques for detecting microadenomas in Cushing’s disease. J Neurosurg 2018;128:1051–7.ArticlePubMed
• 62. Castle-Kirszbaum M, Amukotuwa S, Fuller P, Goldschlager T, Gonzalvo A, Kam J, et al. MRI for Cushing disease: a systematic review. AJNR Am J Neuroradiol 2023;44:311–6.ArticlePubMedPMC
• 63. Kim K, Kim DK, Moon JH, Kim EH, Kim SH, Ku CR, et al. Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors. Cancer Imaging 2023;23:85.ArticlePubMedPMCPDF
• 64. Valizadeh M, Rahmani F, Nikoohemmat M, Ramezani Ahmadi A, Hosseinpanah F, Niroomand M, et al. Diagnostic accuracy of the desmopressin stimulation test in the comprehensive assessment of ACTH-dependent Cushing’s syndrome: a comparative analysis with BIPSS and TSS. Endocr Res 2024;49:232–42.ArticlePubMed
• 65. Zampetti B, Grossrubatscher E, Dalino Ciaramella P, Boccardi E, Loli P. Bilateral inferior petrosal sinus sampling. Endocr Connect 2016;5:R12–25.ArticlePubMedPMC
• 66. Valizadeh M, Abiri B, Hosseinpanah F, Grossman A. Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing’s syndrome: a reappraisal. J Intern Med 2024;296:2–23.ArticlePubMed
• 67. Mulligan GB, Faiman C, Gupta M, Kennedy L, Hatipoglu B, Hui F, et al. Prolactin measurement during inferior petrosal sinus sampling improves the localization of pituitary adenomas in Cushing’s disease. Clin Endocrinol (Oxf) 2012;77:268–74.ArticlePubMed
• 68. Ishida A, Asakuno K, Shiramizu H, Yoshimoto H, Nakase K, Kato M, et al. Revalidation of inferior petrosal sinus sampling: the latest results from a single-center experience. Endocr J 2021;68:1217–23.ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by