Skip to main content
SpringerLink
Log in

Biochemical testing to differentiate Cushing’s disease from ectopic ACTH syndrome

  • Review
  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

The differential diagnosis of ACTH-dependent Cushing’s syndrome is often a diagnostic challenge that has been debated in numerous studies. In this short article, we will discuss the performance and main drawbacks of the biochemical tests used for this diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR et al (2021) Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 9(12):847–875

    Article  Google Scholar 

  2. Young J, Haissaguerre M, Viera-Pinto O, Chabre O, Baudin E, Tabarin A (2020) Management of endocrine disease: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol 182(4):R29–R58

    Article  CAS  Google Scholar 

  3. Messager M, Carriere C, Bertagna X, De Keyzer Y (2006) RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumors in the ectopic ACTH-syndrome. Eur J Endocrinol 154:159–166

    Article  CAS  Google Scholar 

  4. Dahia PL, Grossman AB (1999) The molecular pathogenesis of corticotroph tumors. Endocr Rev 20(2):136–155

    Article  CAS  Google Scholar 

  5. Tsagarakis S, Tsigos C, Vasiliou V, Tsiotra P, Kaskarelis J, Sotiropoulou C et al (2002) The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion. J Clin Endocrinol Metab 87(4):1646–1653

    CAS  PubMed  Google Scholar 

  6. Aron DC, Raff H, Findling JW (1997) Effectiveness versus efficacy: the limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 82(6):1780–1785

    CAS  PubMed  Google Scholar 

  7. Reimondo G, Paccotti P, Minetto M, Termine A, Stura G, Bergui M et al (2003) The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing’s syndrome. Clin Endocrinol (Oxf) 58(6):718–724

    Article  CAS  Google Scholar 

  8. Isidori AM, Kaltsas GA, Mohammed S, Morris DG, Jenkins P, Chew SL et al (2003) Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 88(11):5299–5306

    Article  CAS  Google Scholar 

  9. Dichek HL, Nieman LK, Oldfield EH, Pass HI, Malley JD, Cutler GB Jr (1994) A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 78(2):418–422

    Article  CAS  Google Scholar 

  10. Ritzel K, Beuschlein F, Berr C, Osswald A, Reisch N, Bidlingmaier M et al (2015) ACTH after 15 min distinguishes between Cushing’s disease and ectopic Cushing’s syndrome: a proposal for a short and simple CRH test. Eur J Endocrinol 173(2):197–204

    Article  CAS  Google Scholar 

  11. Barbot M, Trementino L, Zilio M, Ceccato F, Albiger N, Daniele A et al (2016) Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Pituitary 19(5):488–495

    Article  CAS  Google Scholar 

  12. Frete C, Corcuff JB, Kuhn E, Salenave S, Gaye D, Young J et al (2020) Non-invasive diagnostic strategy in ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 105(10):3273–3284

    Article  Google Scholar 

  13. Nieman LK, Oldfield EH, Wesley R, Chrousos GP, Loriaux DL, Cutler GB Jr (1993) A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 77(5):1308–1312

    CAS  PubMed  Google Scholar 

  14. Newell-Price J, Morris DG, Drake WM, Korbonits M, Monson JP, Besser GM et al (2002) Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 87(4):1640–1645

    CAS  PubMed  Google Scholar 

  15. Vassiliadi DA, Tsagarakis S (2018) DIAGNOSIS of endocrine disease: the role of the desmopressin test in the diagnosis and follow-up of Cushing’s syndrome. Eur J Endocrinol 178(5):R201–R214

    Article  CAS  Google Scholar 

  16. PecoriGiraldi F, Cavallo LM, Tortora F, Pivonello R, Colao A, Cappabianca P et al (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 

  17. Findling JW, Kehoe ME, Shaker JL, Raff H (1991) Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing’s syndrome: early recognition of the occult ectopic ACTH syndrome. J Clin Endocrinol Metab 73(2):408–413

    Article  CAS  Google Scholar 

  18. Sheth SA, Mian MK, Neal J, Tritos NA, Nachtigall L, Klibanski A et al (2012) Transsphenoidal surgery for Cushing disease after nondiagnostic inferior petrosal sinus sampling. Neurosurgery 71(1):14–22

    Article  Google Scholar 

  19. Sharma ST, Raff H, Nieman LK (2011) Prolactin as a marker of successful catheterization during IPSS in patients with ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 96(12):3687–3694

    Article  CAS  Google Scholar 

  20. De Sousa SMC, McCormack AI, McGrath S, Torpy DJ (2017) Prolactin correction for adequacy of petrosal sinus cannulation may diminish diagnostic accuracy in Cushing’s disease. Clin Endocrinol (Oxf) 87(5):515–522

    Article  Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

Download references

Funding

No funding was received to assist with the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Nutrition, CHU of Bordeaux and University of Bordeaux, 33604, Pessac, France

    Amandine Ferriere & Antoine Tabarin

Authors
  1. Amandine Ferriere
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antoine Tabarin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AT and AF: wrote the text.

Corresponding author

Correspondence to Antoine Tabarin.

Ethics declarations

Conflict of interest

The authors have no competing interests to declare that are relevant to the content of this article.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferriere, A., Tabarin, A. Biochemical testing to differentiate Cushing’s disease from ectopic ACTH syndrome. Pituitary 25, 705–708 (2022). https://doi.org/10.1007/s11102-022-01241-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-022-01241-z

Keywords

Search

Navigation