Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome

Heppner, Christina; Becker, Kenneth L.; Saeger, Wolfgang; Günther, R.; Allolio, Bruno; Krone, W; Winkelmann, W.

doi:10.1530/eje.0.1370074

Cited by 17 publications

(6 citation statements)

References 18 publications

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“…With broadened experience with BIPSS, it clearly appears that the actual accuracy of BIPSS in clinical practice is lower than expected; both false-negative (19, 60, 61, 62, 63, 64, 65, 66, 67) and, less commonly, false-positive results have been reported (68, 69, 70). …”

Section: Diagnostic Accuracy Of Bipssmentioning

confidence: 95%

Bilateral inferior petrosal sinus sampling

Zampetti

Grossrubatscher

Ciaramella

et al. 2016

Endocrine Connections

106

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Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing’s syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88–100% and 67–100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50–70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres.

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Section: Diagnostic Accuracy Of Bipssmentioning

confidence: 95%

Bilateral inferior petrosal sinus sampling

Zampetti

Grossrubatscher

Ciaramella

et al. 2016

Endocrine Connections

106

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“…Administration of CRH to induce stimulation of ACTH secretion during BIPSS is being routinely used to elicit diagnostic gradients in patients with Cushing's disease (CD) and to improve the sensitivity of the procedure. Nevertheless, with the exception of the study of Oldfield et al (1), which quoted an accuracy approaching 100%, in subsequent series a false-negative rate of 4 -15% has been reported (2,(5)(6)(7)(8)(9). This illustrates that in many centers a significant proportion of patients with CD will undergo further unnecessary tests and sustain considerable delay of curative transsphenoidal surgery, based on such false-negative results.…”

Section: B Ilateral Inferior Petrosal Sinus Sampling (Bi-mentioning

confidence: 91%

The Application of the Combined Corticotropin-Releasing Hormone plus Desmopressin Stimulation during Petrosal Sinus Sampling Is Both Sensitive and Specific in Differentiating Patients with Cushing’s Disease from Patients with the Occult Ectopic Adrenocorticotropin Syndrome

Tsagarakis

Vassiliadi

Kaskarelis

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:Although bilateral inferior petrosal sinus sampling (BI-PSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), 4 -15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study. Objective:We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation. Design and Setting:A retrospective analysis was conducted at a single tertiary care center. Participants:Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients. Intervention(s):All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging. Main Outcome Measures:Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin. Results:The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%. Conclusions:The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity. (J Clin Endocrinol Metab

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“…Although BIPSS is a highly accurate test, its sensitivity in the various studies ranges from 88 to 100%, owing to a low but still considerable rate of false-negative results (71,72,73). One reason for a false-negative gradient is poor responsiveness of some corticotroph adenomas to CRH, which involves around 10-20% of patients with CD (74,75).…”

Section: Bilateral Inferior Petrosal Sinus Sampling (Bipss)mentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: The role of the desmopressin test in the diagnosis and follow-up of Cushing’s syndrome

Vassiliadi

Tsagarakis

2018

European Journal of Endocrinology

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Desmopressin is a vasopressin analogue selective for type 2 vasopressin receptors that mediate renal water retention. In contrast to the native hormone arginine vasopressin, a well-known ACTH secretagogue, desmopressin, exerts minimal or no activity on ACTH excretion. However, in a substantial proportion of patients with ACTH-dependent Cushing's syndrome (CS), desmopressin elicits an ACTH and cortisol response, which contrasts with the minimal responses obtained in healthy subjects. The mechanism underlying this paradoxical response involves upregulation of vasopressin type 3 and/or the aberrant expression of type 2 receptors by neoplastic ACTH-producing cells. This makes desmopressin administration a suitable test enabling the distinction between neoplastic from functional (formerly termed 'pseudo-Cushing syndrome') ACTH-dependent cortisol excess. Several studies have now established an adjunctive role of desmopressin in the initial diagnostic workup of CS. Despite some early data indicating that this test may also have a role in distinguishing between Cushing's disease (CD) and ectopic ACTH secretion, subsequent studies failed to confirm this observation. The ability of the paradoxical response to desmopressin to depict the presence of neoplastic ACTH-secreting cells was also exploited in the follow-up of patients with CD undergoing surgery. Loss of the desmopressin response, performed in the early postoperative period, was a good predictor for a favorable long-term outcome. Moreover, during follow-up, reappearance of desmopressin paradoxical response was an early indicator for recurrence. In conclusion, the desmopressin test is a valid tool in both the diagnosis and follow-up of patients with CD and should be more widely applied in the workup of these patients.

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Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome

Cited by 17 publications

References 18 publications

Bilateral inferior petrosal sinus sampling

Bilateral inferior petrosal sinus sampling

The Application of the Combined Corticotropin-Releasing Hormone plus Desmopressin Stimulation during Petrosal Sinus Sampling Is Both Sensitive and Specific in Differentiating Patients with Cushing’s Disease from Patients with the Occult Ectopic Adrenocorticotropin Syndrome

DIAGNOSIS OF ENDOCRINE DISEASE: The role of the desmopressin test in the diagnosis and follow-up of Cushing’s syndrome

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