The Desmopressin Test in the Differential Diagnosis between Cushing’s Disease and Pseudo-Cushing States

M, Moro Serrano; Putignano, Pietro; Losa, Marco; Invitti, Cecilia; Maraschini, C.; Cavagnini, Francesco

doi:10.1210/jcem.85.10.6862

Cited by 57 publications

(66 citation statements)

References 27 publications

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“…A potential limitation of the use of this test is represented by the existence of false negative responses in patients with Cushing's disease; these were found in 10 -20% of patients (27,28,30). Furthermore, we obviously cannot rule out that some of the patients currently classified as in remission will experience a later recurrence, resulting in an underestimation of the positive predictive value of the test and overestimation of its negative predictive value.…”

Section: Discussionmentioning

confidence: 98%

The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

Valéro

Vallette-Kasic²,

Conte-Devolx³

et al. 2004

European Journal of Endocrinology

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Objective: Taking advantage of the over-expression of V3 receptors in adenomatous corticotroph cells, we evaluated the response to the vasopressin agonist desmopressin in 22 patients operated on for Cushing's disease, with a mean follow-up of 4.5 years. Subjects and methods: Twenty-two patients (17 women) operated on for Cushing's disease with a follow-up . 2 years (median, 48; range, 24 -141 months) underwent one desmopressin test (10 mg i.v. bolus) 3-6 months postoperatively. Twelve were in remission (R group), five had immediate failure (IF) after surgery and five had late recurrence (LR). Results: Both ACTH and cortisol peaks after desmopressin were significantly lower in the R group than in the LR group (P ¼ 0.003 and P ¼ 0.013 respectively). The receiver operator characteristic curve method defined an ACTH peak threshold $22 pg/ml or ACTH rise $ 35%; cortisol peak $350 nmol/l or cortisol rise $14%. None of twelve patients in remission had ACTH or cortisol peaks above these thresholds vs three of five patients from the LR group and five of five in the IF group. Discussion: On the basis of ACTH or cortisol peaks respectively, the desmopressin test was predictive of a later recurrence with a positive predictive value of 100% or 80% respectively, and a negative predictive value of 92%. Sensitivity and specificity were 80% and 100% respectively based on ACTH peak, and 80% and 92% respectively based on cortisol peak. Conclusion: In this first long-term study, a marked response of ACTH or cortisol to desmopressin was predictive of a later recurrence with good specificity and sensitivity.European Journal of Endocrinology 151 727-733

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Section: Discussionmentioning

confidence: 98%

The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

Valéro

Vallette-Kasic²,

Conte-Devolx³

et al. 2004

European Journal of Endocrinology

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“…Although the method requires confirmation and does suffer from some limitations -in particular, like the DDAVP test (4,22) and, theoretically, the DEX/CRH test (3)(4)(5), it cannot be applied in patients with ACTH-independent CS -we suggest its adoption as a second-level test in subjects with normal/high plasma ACTH, who need a differential diagnosis between CD and PC.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting SE and SP, despite the broad CI, exceeded even those of diagnostic tools such as the DDAVP test and the DEX/CRH test, which are considered as the most appropriate second-line tools to differentiate CD from PC (3)(4)(5)(6)(7)22). Table 3 Human CRH (hCRH) test: diagnostic performance of the parameters (peak and basal ACTH and cortisol), alone and combined, in subjects with and without ACTH-dependent Cushing's syndrome (CS).…”

Section: Discussionmentioning

confidence: 99%

Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis

Arnaldi¹,

Tirabassi²,

Papa³

et al. 2009

European Journal of Endocrinology

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Objective: Corticotropin releasing hormone (CRH) test does not reliably distinguish Cushing's disease (CD) from normality or pseudo-Cushing state (PC). We assessed whether this could be achieved with a novel approach while preserving the ability of the test to distinguish CD from ectopic ACTH syndrome (EAS). Design: Retrospective/prospective study. Subjects and methods: We studied 51 subjects with CD, 7 with EAS, 26 with PC, and 31 controls (CT). Human CRH (hCRH) test was performed at 0830 h by measuring plasma ACTH and serum cortisol at K15, 0, 15, 30, 45, 60, 90, and 120 min. Results: The area under the curve-ACTH exhibited a significant negative correlation with baseline serum cortisol in CT and PC, but not in CD or EAS patients. ACTH response to hCRH was blunted in PC compared with CT, whereas peak serum cortisol was higher in PC than in CT subjects. These findings suggested that ACTH-dependent Cushing's syndrome can be diagnosed by the presence of two hCRH test parameters and excluded if either or both are absent. Application of i) basal serum cortisol O12 mg/dl and peak plasma ACTH O54 pg/ml, or ii) peak serum cortisol O21 mg/dl and peak plasma ACTH O45 pg/ml, had 91.3% (95% confidence intervals (CI) 81-97.1) and 94.8% (CI 85.6-98.9) sensitivity and 98.2% (CI 90.6-99.9) and 91.2% (CI 80.7-97) specificity respectively, in diagnosing ACTH-dependent Cushing's syndrome. The O14% serum cortisol increase from mean baseline values to the mean of 15 and 30 min values in patients who were positive for the test completely discriminated between CD and EAS. Conclusions: Simultaneous plasma ACTH and serum cortisol analysis enables the hCRH test to distinguish CD from PC and from normality, while preserving its ability to discriminate CD from EAS.

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“…Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CS but not in the majority of normal, obese, and depressed subjects, it has been used to investigated its ability to discriminate CS from pseudo-Cushing states (54,55). In these studies, a plasma peak ACTH increase equal to or greater than 6 pmol/L (27 pg/mL), indicated by ROC analysis, allowed the best discrimination between patients with CS and the other groups, with a sensitivity of 86.8%, a specificity of 90.7%, and a diagnostic accuracy of 89%.…”

Section: Other Second-line Diagnostic Tests To Screen For Csmentioning

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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The Desmopressin Test in the Differential Diagnosis between Cushing’s Disease and Pseudo-Cushing States

Cited by 57 publications

References 27 publications

The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis

Screening and diagnosis of Cushing's syndrome

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