Experience in the use of combined cavernous and inferior petrosal sinus sampling in the differential diagnostic of acth-dependent cushing’s syndrome

Though inferior petrosal sinus sampling (IPSS) is considered the gold standard test for the differential diagnosis of ACTH-dependent Cushing’s syndrome, false-negative results have been reported in 1-10 % cases. Cavernous sinus sampling (CSS) was suggested as a diagnostic tool in a complex ACTH-dependent Cushing’s syndrome cases. Objective. To study the role of cavernous and inferior petrosal sinus sampling in differential diagnosis of ACTH-dependent Cushing’s syndrome. Materials and methods. Five patients with ACTH-dependent Cushing’s syndrome were included. All patients underwent transsphenoidal endoscopic surgery. During the surgery pituitary microadenomas were found in all patients, ACTH secretion was approved by immunohistochemistry in four patients, the fifth patient became eucortisolemic after the operation. In all patients CSS and IPSS were performed before operation and ACTH and prolactin levels were measured in plasma samples. Results. ACTH CS/P ratio was more than 2 suggesting the pituitary source in 100 %. As for the IPSS, in three cases ACTH IPS/P ratio was more than 2, supporting the data of CS. But in two cases ACTH IPS/P ratio was less than 2, indicating the ectopic ACTH syndrome, these data contradicted CSS results. Conclusion. According to our experience, catheterization of CS may improve results and increase the accuracy of the method.

АКТГ-зависимый гиперкортицизм, болезнь Кушинга, катетеризация пещеристых и нижних каменистых синусов, транссфеноидальная эндоскопическая аденомэктомия, ACTH-dependent Cushing’s syndrome, Cushing’s basophilism, cavernous and inferior petrosal sinus sampling, transsphenoidal endoscopic adenomectomy

1. Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing‘s syndrome and pseudo-Cushing‘s state. Endocrine Review. 1998;19(5):647-672.

2. Aron DC, Tyrrell JB, Fitzgerald PA, Findling JW, Forsham PH. Cushing‘s syndrome: problems in diagnosis. Medicine. 1981;60(1):25-35.

3. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005;90(8):4955-4962.

4. Findling JW, Raff H. Cushing’s syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91(10):3746-3753.

5. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367 (9522):1605-1617.

6. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120(10):817-820.

7. Buchfelder M, Nistor R, Fahlbusch R, Huk WJ. The accuracy of CT and MR evaluation of the sellaturcica for detection of adrenocorticotropic hormone-secreting adenomas in Cushing disease. AJNR Am J Neuroradiol. 1993;14(5):1183-1190.

8. Tyrrell JB, Findling JW, Aron DC, Fitzgerald PA, Forsham PH. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing’s. Ann Intern Med. 1986;104(2):180-186.

9. Suda T1, Kageyama K, Nigawara T, Sakihara S. Evaluation of diagnostic tests for ACTH-dependent Cushing’s syndrome. Endocr J. 2009;56(3):469-476.

10. Tsagarakis S, Tsigos C, Vasiliou V, Tsiotra P, Kaskarelis J, Sotiropoulou C et al. 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. 2002;87(4):1646-1653.

11. Chrousos GP, Schulte HM, Oldfield EH, Gold PW, Cutler GB Jr, Loriaux DL. The corticotropin-releasing factor stimulation test in the evaluation of patients with Cushing‘s syndrome. N Engl J Med. 1984;310(10):622-626.

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

13. Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA et al. Petrosal sinus sampling with and without corticotrophin-releasing hormone for the differential diagnosis of Cushing‘s syndrome. N Engl J Med. 1991;325 (13): 897-905.

14. Findling JW, Kehoe ME, Shaker JL, Raff H. Routine inferior petrosal sinus sampling in the differential diagnosis of aderenocorticotropin (ACTH)-dependent Cushing‘s syndrome. J Clin Endocrinol Metab. 1991;73(2):408-413.

15. Colao A, Faggiano A, Pivonello R, Pecori Giraldi F, Cavagnini F, Lombardi G. Inferior petrosal sinus sampling in the differential diagnosis of Cushing’s syndrome: results of an Italian multicenter study. Eur J Endocrinol. 2001;144 (5):499-507.

16. Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and Management of Cushing‘s syndrome: Results of an Italian Multicentre Study. J ClinEndocrinolMetab. 1999;84(2):440-448.

17. Kaltsas GA, Giannulis MG, Newell-Price JD, Dacie JE, Thakkar C, Afshar F et al. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing disease and the occult ectopic adrenocorticotropi syndrome. J Clin Endocrinol Metab. 1999;84(2):487-492.

18. Bonelli FS, Huston J 3rd, Carpenter PC, Erickson D, Young WF Jr, Meyer FB. Adrenocorticotropic hormone-dependent Cushing‘s syndrome: sensitivity and specificity of inferior petrosal sinus sampling. AJNR Am J Neuroradiol. 2000;21(4):690-696.

19. Kaskarelis IS, Tsatalou EG, Benakis SV, Malagari K, Komninos I, Vassiliadi D et al. Bilateral inferior petrosal sinuses sampling in the routine investigation of Cushing’s syndrome: a comparison with MRI. AJR Am J Rentgenol. 2006;187(2):562-570.

20. Wiggam MI, Heaney AP, McIlrath EM, McCance DR, Sheridan B, Hadden DR, Atkinson AB. Bilateral inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome: a comparison with other diagnostic tests. J Clin Endocrinol Metab. 2000;85(4):1525-1532.

21. Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman A, Dorer DJ et al. Diagnostic errors after inferior petrosal sinus sampling. J Clin Endocrinol Metab. 2004;89 (8):3752-3763.

22. Doppman JL, Chang R, Oldfield EH, Chrousos G, Stratakis CA, Nieman LK. The hypoplastic inferior petrosal sinus: a potential source of false-negative results in petrosal sampling for Cushing‘s disease. J Clin Endocrinol Metab. 1999;84(2):533-540.

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

24. Teramoto A, Nemoto S, Takakura K, Sasaki Y, Machida T. Selective venous sampling directly from cavernous sinus in Gushing’s syndrome. J Clin Endocrinol Metab. 1993;76(3):637-641.

25. O’Neill OR, Barnwell SL et al. Superselective cavernous sinus catheterization for adrenocorticotropic hormone assay in Cushing’s disease: value in diagnosis and lateralization. Proc of the Congr of Neurological Surgeons. 1994:150.

26. Graham KE, Samuels MH, Nesbit GM, Cook DM, O‘Neill OR, Barnwell SL et al. Cavernous sinus sampling is highly accurate indistinguishing Cushing‘s disease from the ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location. J Clin Endocrinol Metab. 1999;84(5):1602-1610.

27. Potts MB, Shah JK, Molinaro AM, Blevins LS, Tyrrell JB, Kunwar S et al. Cavernous and inferior petrosal sinus sampling and dynamic magnetic resonance imaging in the preoperative evaluation of Cushing‘s disease. J Neurooncol. 2014;116(3):593-600.

28. Hayashi N, Kurimoto M, Kubo M, Kuwayama N, Kurosaki K, Nagai S et al. The impact of cavernous sinus drainage pattern on the results of venous sampling in patients with suspected cushing syndrome. AJNR Am J Neuroradiol. 2008;29(1):69-72.

29. Oldfield EH, Chrousos GP, Schulte HM, Schaaf M, McKeever PE, Krudy AG et al. Preoperative lateralization of ACTH-secreting pituitary microadenomas by bilateral and simultaneous inferior petrosal venous sinus sampling. N Engl J Med. 1985;312(2):100-103.

30. Oldfield EH, Chrousos GP, Neiman L et al. Bilateral inferior petrosal sinus sampling in Cushing syndrome. Adv Biosci. 1988;69:361-362.

31. Sharma T, Raff H, Nieman LK. Prolactin as a marker of successful catheterization during IPSS in Patients with ACTH-dependent Cushing‘s syndrome. J Clin Endocrinol Metab. 2011;96(12):3687-3694.

32. Mulligan GB, Eray E, Faiman C, Gupta M, Pineyro MM, Makdissi A et al. Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotrophin measurement. Endocr Pract. 2011;17(1):33-40. doi: 10.4158/EP10067.OR.