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A case series of bilateral inferior petrosal sinus sampling with desmopressin in evaluation of ACTH-dependent Cushing’s syndrome in Iran



Differentiating the etiology of ACTH-dependent Cushing’s syndrome (CS) has remained challenging due to the limited accuracy of noninvasive assays. Nowadays, bilateral inferior petrosal sinus sampling (BIPSS) with corticotropin-releasing hormone (CRH) is the gold standard method in the diagnostic work-up of complex CS. However, this method is as yet far from being widespread. The limited utility of this method could be due to many factors such as limited availability of an experienced interventionist, limited availability of CRH, and cost of the procedure. So far, very few studies have been conducted using desmopressin instead of CRH. In this study, we report the use of BIPSS with desmopressin as a diagnostic tool in a series of patients with suspected Cushing’s disease (CD) and equivocal imaging in a tertiary referral center in Iran.


A total of 13 patients with ACTH-dependent CS and no significant lesions in their pituitary MRI participated in this retrospective case series. All patients underwent BIPSS with desmopressin, and, following centralization of CS, transsphenoidal surgery (TSS) was carried out and diagnosis of CD was confirmed using standard methods.


Of the 13 patients with confirmed CD (by pathology or biochemical response after surgery), eight (61.5%) were female, with a median age of 32 years (IQR: 26–41). The median duration of disease was 24 months (IQR: 11–48). During BIPSS, all patients had a central-to-peripheral gradient greater than 2 under basal conditions. This central-to-peripheral gradient did not increase to > 3 after desmopressin administration in two of these patients. Based on the gradient after BIPSS, the sensitivity of this modality in the diagnosis of CD was 100%. Eight of the 13 patients had right lateralization in both BIPSS and TSS; therefore, the accuracy rate of lateralization by BIPSS was 61.5%. No complications occurred after BIPSS, the exception being the development of groin hematoma in one patient.


No significant benefits of adding desmopressin to BIPSS were observed. The sensitivity of BIPSS in the diagnosis of CD was high, whereas it has moderate accuracy in tumor lateralization.

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Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available due to the privacy statement in the patients’ informed consent form. However, they are available from the corresponding author on reasonable request.


CS :

Cushing’s syndrome


Cushing’s disease


bilateral inferior petrosal sinus sampling


corticotropin-releasing hormone


transsphenoidal surgery


magnetic resonance imaging


low-dose dexamethasone suppression test


high-dose dexamethasone suppression test


immunohistochemical staining


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The authors wish to acknowledge Prof. Farzad Hadaegh and Dr. Zahra Piri for their assistance in the preparation of the article and Mrs. Niloofar Shiva for critical editing of the English grammar and syntax of the manuscript.

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Authors and Affiliations



FR, MV, and KE conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted. FR and MM carried out the analysis, reviewed, and revised the manuscript, and approved the final manuscript as submitted. KE and MV designed the case series, coordinated and supervised the data collection, critically reviewed the manuscript, and approved the final manuscript as submitted. Finally, all authors have read and approved the manuscript as presented.

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Correspondence to Majid Valizadeh.

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The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

The research and ethics committee of Shahid Beheshti University of Medical Sciences provided us with ethical clearance to publish this case series. Written informed consent was obtained from the patients for publication of this case series. For those who were under 16 years old, informed consent was provided by their parents or guardians. Documentation of the written consent will be provided to the journal upon request.

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Rahmani, F., Mahdavi, M., Edraki, K. et al. A case series of bilateral inferior petrosal sinus sampling with desmopressin in evaluation of ACTH-dependent Cushing’s syndrome in Iran. Hormones 20, 299–304 (2021).

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  • ACTH-dependent Cushing’s syndrome
  • Cushing’s disease
  • Bilateral inferior petrosal sinus sampling