Skip to main content

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

Hormones volume 20, pages 299–304 (2021)Cite this article

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

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.

Abbreviations

CS :

Cushing’s syndrome

CD:

Cushing’s disease

BIPSS:

bilateral inferior petrosal sinus sampling

CRH:

corticotropin-releasing hormone

TSS:

transsphenoidal surgery

MRI:

magnetic resonance imaging

LDDST:

low-dose dexamethasone suppression test

HDDST:

high-dose dexamethasone suppression test

IHC:

immunohistochemical staining

References

  1. Giraldi FP, Cavallo LM, Tortora F, Pivonello R, Colao A, Cappabianca P, Mantero F (2015) The role of inferior petrosal sinus sampling in ACTH-dependent Cushing’s syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology. Neurosurg Focus 38(2):E5

    Article  Google Scholar 

  2. Boscaro M, Arnaldi G (2009) Approach to the patient with possible Cushing’s syndrome. J Clin Endocrinol Metab 94(9):3121–3131

    CAS  Article  Google Scholar 

  3. Machado MC, De Sa SV, Domenice S, Fragoso MCBV, Puglia P Jr, Pereira MAA, De Mendonça BB, Salgado LR (2007) The role of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-dependent Cushing's syndrome. Clin Endocrinol 66(1):136–142

    CAS  Google Scholar 

  4. Corrigan DF, Schaaf M, Whaley RA, Czerwinski CL, Earll JM (1977) Selective venous sampling to differentiate ectopic ACTH secretion from pituitary Cushing's syndrome. N Engl J Med 296(15):861–862

    CAS  Article  Google Scholar 

  5. Landolt A, Valavanis A, Girard J, Eberle A (1986) Corticotrophin-releasing factor-test used with bilateral, simultaneous inferior petrosal sinus blood-sampling for the diagonosis of pituitary-dependent Cushing’s disease. Clin Endocrinol 25(6):687–696

    CAS  Article  Google Scholar 

  6. Deipolyi A, Oklu R (2015) Bilateral inferior petrosal sinus sampling in the diagnosis of Cushing disease. J Vasc Diagn 3:1–7

    Google Scholar 

  7. Malerbi DA, Mendonça BB, Liberman B, Toledo SP, Corradini MCM, Cunha-Neto MB, Fragoso MCB, Leo Wajchenberg B (1993) The desmopressin stimulation test in the differential diagnosis of Cushing’s syndrome. Clin Endocrinol 38(5):463–472

    CAS  Article  Google Scholar 

  8. Castinetti F, Morange I, Dufour H, Jaquet P, Conte-Devolx B, Girard N, Brue T (2007) Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing’s syndrome. Eur J Endocrinol 157(3):271–277

    CAS  Article  Google Scholar 

  9. Belli S, Oneto A, Mendaro E (2007) Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Rev Med Chil 135(9):1095–1102

    CAS  Article  Google Scholar 

  10. Deipolyi AR, Alexander B, Rho J, Hirsch JA, Oklu R (2015) Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience. J Neurointervent Surg 7(9):690–693

    Article  Google Scholar 

  11. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 93(5):1526–1540

    CAS  Article  Google Scholar 

  12. Flack MR, Oldfield EH, Cutler GB, Zweig MH, Malley JD, Chrousos GP, Loriaux DL, Nieman LK (1992) Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Ann Intern Med 116(3):211–217

    CAS  Article  Google Scholar 

  13. Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB Jr, Loriaux DL (1991) Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med 325(13):897–905

    CAS  Article  Google Scholar 

  14. Czepielewski MA, Rollin GA, Casagrande A, Ferreira NP (2007) Criteria of cure and remission in Cushing’s disease: an update. Arq Bras Endocrinol Metabol 51(8):1362–1372

    Article  Google Scholar 

  15. Jehle S, Walsh JE, Freda PU, Post KD (2008) Selective use of bilateral inferior petrosal sinus sampling in patients with adrenocorticotropin-dependent Cushing’s syndrome prior to transsphenoidal surgery. J Clin Endocrinol Metab 93(12):4624–4632

    CAS  Article  Google Scholar 

  16. Tsagarakis S, Kaskarelis I, Kokkoris P, Malagari C, Thalassinos N (2000) The application of a combined stimulation with CRH and desmopressin during bilateral inferior petrosal sinus sampling in patients with Cushing’s syndrome. Clin Endocrinol 52(3):355–361

    CAS  Article  Google Scholar 

  17. De Keyzer Y, Rene P, Beldjord C, Lenne F, Bertagna X (1998) Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours. Clin Endocrinol 49(4):475–482

    Article  Google Scholar 

  18. Antoni FA (1984) Novel ligand specificity of pituitary vasopressin receptors in the rat. Neuroendocrinology 39(2):186–188

    CAS  Article  Google Scholar 

  19. Wind JJ, Lonser RR, Nieman LK, DeVroom HL, Chang R, Oldfield EH (2013) The lateralization accuracy of inferior petrosal sinus sampling in 501 patients with Cushing’s disease. J Clin Endocrinol Metab 98(6):2285–2293

    CAS  Article  Google Scholar 

  20. Kaltsas G, Giannulis M, Newell-Price J, Dacie J, Thakkar C, Afshar F, Monson J, Grossman A, Besser G, Trainer P (1999) A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 84(2):487–492

    CAS  PubMed  Google Scholar 

  21. Gazioglu N, Ulu MO, Ozlen F, Albayram S, Islak C, Kocer N, Oz B, Tanriover N, Yetkin DO, Gundogdu S (2008) Management of Cushing’s disease using cavernous sinus sampling: effectiveness in tumor lateralization. Clin Neurol Neurosurg 110(4):333–338

    Article  Google Scholar 

  22. Flitsch J, Lüdecke D, Knappe U, Grzyska U (2002) Cavernous sinus sampling in selected cases of Cushing’s disease. Exp Clin Endocrinol Diabetes 110(07):329–335

    CAS  Article  Google Scholar 

  23. Teramoto A, Yoshida Y, Sanno N, Nemoto S (1998) Cavernous sinus sampling in patients with adrenocorticotrophic hormone—dependent Cushing’s syndrome with emphasis on inter-and intracavernous adrenocorticotrophic hormone gradients. J Neurosurg 89(5):762–768

    CAS  Article  Google Scholar 

  24. Fujimura M, Ikeda H, Takahashi A, Ezura M, Yoshimoto T, Tominaga T (2005) Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma. Neurol Res 27(1):11–15

    Article  Google Scholar 

  25. Chen S, Chen K, Lu L, Zhang X, Tong A, Pan H, Zhu H, Lu Z (2019) The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing’s disease. Endocrine 63(3):582–591

    CAS  Article  Google Scholar 

  26. Batista D, Gennari M, Riar J, Chang R, Keil MF, Oldfield EH, Stratakis CA (2006) An assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing disease. J Clin Endocrinol Metab 91(1):221–224

    CAS  Article  Google Scholar 

  27. Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr, Nieman LK, Chrousos GP (1994) Cushing’s syndrome in children and adolescents--presentation, diagnosis, and therapy. N Engl J Med 331(10):629–636

    CAS  Article  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fatemeh Rahmani

  2. Obesity Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Iran

    Maryam Mahdavi & Majid Valizadeh

  3. Neurosurgery Department of Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Keyvan Edraki

Authors
  1. Fatemeh Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maryam Mahdavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keyvan Edraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Majid Valizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Majid Valizadeh.

Ethics declarations

Conflict of interest

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.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s42000-020-00240-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-020-00240-8

Keywords

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