Postoperative follow‐up of Cushing's disease using cortisol, desmopressin and coupled dexamethasone‐desmopressin tests: a head‐to‐head comparison

Marc'hadour, Pauline Le; Müller, Marie; Albarel, F.; Coulon, A.L.; Morange, Isabelle; Martinie, M.; Gay, Emmanuel; Graillon, Thomas; Dufour, H.; Conte-Devolx, B.; Chabre, Olivier; Brue, Thierry; Castinetti, Frédéric

doi:10.1111/cen.12739

Cited by 22 publications

(25 citation statements)

References 37 publications

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“…In the present study, we applied the criterion developed to diagnose patients with Cushing’s disease prior to surgery ( 8 ) to identify a response to desmopressin after surgery. This strategy is in line with other studies ( 20 , 38 ) and proved rational as patients in long-term remission presented a modest – if any – increase in ACTH upon desmopressin stimulation, well within the range observed in normal subjects. Indeed, ROC curve analysis and Youden’s index confirmed its good diagnostic effectiveness and superiority to percent ACTH increase.…”

Section: Discussionsupporting

confidence: 88%

“…Moreover, no specific cut-off could be identified; indeed, criteria for response varied from absolute cortisol increase over 7 µg/dL ( 23 ) to percentage ACTH and cortisol increase over 30% and 20%, respectively ( 20 ). Variants of desmopressin testing, i.e., dexamethasone-suppressed desmopressin stimulation, have also been proposed but again results proved promising though not fully predictive of surgical outcomes ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

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Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

Ambrogio

Andrioli

Martin

et al. 2017

Endocrine Connections

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Recurrence of Cushing’s disease after successful transsphenoidal surgery occurs in some 30% of the patients and the response to desmopressin shortly after surgery has been proposed as a marker for disease recurrence. The aim of the present study was to evaluate the response to desmopressin over time after surgery. We tested 56 patients with Cushing’s disease in remission after transsphenoidal surgery with desmopressin for up to 20 years after surgery. The ACTH and cortisol response to desmopressin over time was evaluated in patients on long-term remission or undergoing relapse; an increase by at least 27 pg/mL in ACTH levels identified responders. The vast majority of patients who underwent successful adenomectomy failed to respond to desmopressin after surgery and this response pattern was maintained over time in patients on long-term remission. Conversely, a response to desmopressin reappeared in patients who subsequently developed a recurrence of Cushing’s disease, even years prior to frank hypercortisolism. It appears therefore that a change in the response pattern to desmopressin proves predictive of recurrence of Cushing’s disease and may indicate which patients require close monitoring.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

Ambrogio

Andrioli

Martin

et al. 2017

Endocrine Connections

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“…In this study, the loss of circadian rhythm (no clear definition is given) followed the positivity of CDDT in most patients. A subsequent study by the same group (94) reported similar performance of the DT and CDDT in the early postoperative period; during follow-up, however, the CDDT was more accurate in predicting the lack of recurrence (100% NPV), albeit with a worse positive predictive value, when performed in the first 3 years after surgery. Most importantly, as with DT, the positivity of CDDT was observed earlier than other markers of recurrence.…”

Section: Coupled Dexamethasone-desmopressin Test (Cddt)mentioning

confidence: 81%

“…The existing studies that assessed the usefulness of the DT in this regard are presented in Table 3. In these studies (92,93,94,95,96,97,98,99), the reported negative predictive value of the test ranges from 76 to 100%, being above 90% in the vast majority of the studies, whereas the sensitivity and specificity to detect recurrence vary greatly from 20 to 100% and from 57 to 100%, respectively. There is considerable disparity, however, among the studies with regards to the definition of response, the applied criteria for remission and recurrence and, the postoperative timing that the DT was performed.…”

Section: The Desmopressin Test In the Immediate Postoperative Period mentioning

confidence: 99%

“…There is considerable disparity, however, among the studies with regards to the definition of response, the applied criteria for remission and recurrence and, the postoperative timing that the DT was performed. Moreover, a few studies do not report on the preoperative response to desmopressin (92,94,97), and it is likely that inclusion of desmopressin non-responders compromised the predicting ability of the test. Caution is also needed on the applied criteria of what constitutes a positive desmopressin response.…”

Section: The Desmopressin Test In the Immediate Postoperative Period mentioning

confidence: 99%

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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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Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment

et al. 2020

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Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

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Postoperative follow‐up of Cushing's disease using cortisol, desmopressin and coupled dexamethasone‐desmopressin tests: a head‐to‐head comparison

Abstract: Adding the CDDT the first 3 years after surgery to immediate postsurgical cortisol evaluation should allow obtaining an optimal follow-up management of patients operated for Cushing's disease.

Cited by 22 publications

References 37 publications

Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

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

Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment

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