Cushing's syndrome: A review of diagnostic tests

Crapo, Lawrence M.

doi:10.1016/0026-0495(79)90097-0

Cited by 399 publications

(189 citation statements)

References 191 publications

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“…It is considered that the accuracy of this test is lower than the pre-test probability of Cushing's disease in the population (45). Some controversies regarding the HDDST are due to the different suppression criteria utilized (16,46). Considering the criterion of 50% suppression, in our series, 5 out of 20 (25%) cases had a positive response to HDDST.…”

Section: Discussionmentioning

confidence: 64%

“…In corticotropic pituitary adenomas, plasma ACTH concentrations are at the upper limit of normality or slightly elevated (50-210 pg/ml), whereas in EAS, these are usually higher (O200 pg/ml), although in some cases they overlap those found in Cushing's disease (16). In our series, 6 out of 24 (25%) cases exhibited normal plasma ACTH levels, 4 of them harboring pheocromocytomas and those with high plasma ACTH levels ranged from 87 to 1453 pg/ml.…”

Section: Discussionmentioning

confidence: 99%

“…For ACTH-dependent differential diagnosis, patients underwent HDDST (8 mg) (14)(15)(16), desmopressin test (17,18), corticotropin-releasing hormone (CRH) test (19)(20)(21)(22)(23), growth hormone releasing peptide (GHRP)-6 test (24,25), and IPSS (26)(27)(28) with desmopressin stimulus indicated when magnetic resonance imaging (MRI) was negative for a pituitary lesion. IPSS was performed by collecting blood samples simultaneously from the inferior petrosal sinuses and a peripheral vein before and 3, 5, and 10 min after 10 mg of IV desmopressin (DDAVP, Ferring Pharmaceuticals, Limhamn, Sweden) (29 (31)(32)(33).…”

Section: Diagnosis Of Ectopic Acth Syndromementioning

confidence: 99%

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Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

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Objective: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111 In-pentetreotide scintigraphy were revised. Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH-and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases.111 In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.European Journal of Endocrinology 155 725-733

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Diagnosis Of Ectopic Acth Syndromementioning

confidence: 99%

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Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

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“…In recent years, assessment of late-night salivary cortisol (LNSC) is increasingly being used as a first-line screening test (1,5,6). However, first-line screening tests are not always able to differentiate accurately between CD and PCS (2,7,8). The substantial overlap in test results has resulted in the development of several second-line tests.…”

Section: Introductionmentioning

confidence: 99%

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Alwani

Jongbloed

Jong

et al. 2014

European Journal of Endocrinology

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Objective: To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS). Methods: In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone-CRH (Dex-CRH) test was performed in 54 patients. Results: Fifty-three patients were diagnosed with CD and subsequently treated. Twenty patients were classified as having PSC. Serum cortisol circadian rhythm: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of O0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration O243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level O9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex-CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level O87 nmol/l (TZ15 min) resulted in a PPV of 100% and an NPV of 90%. Conclusion: The Dex-CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

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“…Additionally, DST has a significant false positive rate, especially in chronically ill (23%) or obese patients (13%) and in patients with major depression (43%) or other psychiatric disorders (8-41%). A false-positive rate of up to 30% has been reported in other admitted patients and healthy individuals (27)(28)(29). Therefore, because of many interfering conditions and the significant variability of the biological behavior of corticotroph adenomas, neither the overnight nor 2-day DST test appears to be able to reliably rule out Cushing's syndrome using standard cut-offs for serum cortisol (12).…”

Section: Low-dose Dexamethasone Suppression Tests (Dst)mentioning

confidence: 99%

Screening and diagnosis of Cushing's syndrome

Castro

Moreira

2007

Arq Bras Endocrinol Metab

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Cushing's syndrome (CS) results from sustained pathologic hypercortisolism. The clinical features are variable and the most specific features for CS include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Clinical presentation of CS can be florid and in this case the diagnosis is usually straightforward. However, the diagnosis can be difficult particularly in states of mild or cyclical or periodical hypercortisolism. Several tests based on the understanding of the physiologic characteristics of the hypothalamic-pituitary-adrenal axis have been used extensively to confirm the diagnosis of Cushing's syndrome, but none has proven fully capable of distinguishing all cases of CS from normal and/or pseudo-Cushing individuals. Three first-line diagnostic tests are currently used to screen for CS: measurement of free cortisol in 24-hour urine (UFC), cortisol suppressibility by low doses of dexamethasone (DST), and assessment of cortisol circadian rhythm using late-night serum and/or salivary cortisol. This paper discusses the effectiveness regarding best cut-off values, the sensitivity and the specificity of these tests to screen for CS. Late-night salivary cortisol appears to be the most useful screening test. UFC and DST should be performed to provide further confirmation of the diagnosis. RESUMO Rastreamento e Diagnóstico da Síndrome de Cushing.A síndrome de Cushing (SC) resulta de um hipercortisolismo patológico mantido. As manifestações clínicas são variáveis e os achados mais específicos para a SC incluem distribuição anormal de gordura, particularmente nas fossas supraclaviculares e temporais, fraqueza muscular proximal, estrias purpúreas largas e interrupção do crescimento linear com ganho contínuo de peso na criança. A apresentação clínica da SC pode ser florida e, neste caso, o diagnósti-co é usualmente direto. Entretanto, o diagnóstico pode ser dificultado particularmente em estados de hipercortisolismo leve ou cíclico/periódico. Vários testes baseados na compreensão das características fisiológicas do eixo hipotálamo-hipófise-adrenal têm sido usados extensivamente para confirmar o diagnóstico da SC, mas nenhum deles mostrou-se totalmente capaz de distinguir todos os casos de SC dos indivíduos normais e/ou portadores de pseudo-Cushing. Três testes diagnósticos de primeira linha são atualmente empregados para rastrear SC: a medida do cortisol livre em urina de 24-horas (CLU), a supressão do cortisol por doses baixas de dexametasona (TSD) e a avaliação do ritmo circadiano do cortisol usando a dosagem do cortisol sérico ou salivar às 23-24 hs. Este artigo discute a efetividade com relação aos melhores valores de corte e a sensibilidade e especificidade destes testes no rastreamento da SC. O cortisol salivar às 23-24 hs parece ser o teste mais útil de rastreamento. O CLU e o TSD devem ser realizados na tentativa de fornecer confirmação adicional ao diagnósti...

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Cushing's syndrome: A review of diagnostic tests

Cited by 399 publications

References 191 publications

Ectopic ACTH syndrome: our experience with 25 cases

Ectopic ACTH syndrome: our experience with 25 cases

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Screening and diagnosis of Cushing's syndrome

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