Mahmut Çamlar, Burak Kınalı, Necmettin Tanrıöver, Pınar Kadıoğlu, Seçil Erden, Civan Islak, Naci Koçer, Osman Kızılkılıç, Meryem Merve Ören, Nurperi Gazioğlu

Reliability of cavernous sinus sampling in management of Cushing’s disease

Objectives: The purpose of this study is to find out the accuracy of bilateral cavernous sinus sampling (CSS) for preoperative tumor lateralization within the pituitary in Cushing’s disease (CD). Methods: Sixty-five patients who had undergone transsphenoidal surgery (TSS) following CSS for CD between 2000-2016 at our institution were analyzed retrospectively. All patients underwent bilaterally CSS with corticotropin-releasing hormone (CRH) stimulation. Radiological, preoperative, and pathological findings with remission status were correlated with CSS data. The accuracy of CSS is decided according to compliance with the magnetic resonance imaging (MRI), pathology or remission after surgery of the normal MRI cases. Results: CSS indicated the correct lateralization in 52 (80%) patients. There was the same level elevation of both sides in 3 patients who had central adenoma. Remission rate in the final follow-up was 83.87% for 65 patients. We found out the contralateral pathological side in 13 (20%) of the patients showing false lateralization. Twenty-four patients with normal MRI had a positive accuracy rate of 83%. Of those patients, with a positive accuracy of CSS sampling, 18 (90%) had a positive remission. As a result of the Kappa analysis, statistically significance and relation was found between the final diagnosis and lateralization test (κ=0,63 p < 0.001). Conclusions: Our results showed that CSS is a safe and reliable method for microadenomas which has high diagnostic accuracy (80%) in indicating the correct lateralization in CD, providing us higher remission rates in a challenging pathology.

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1. Etxabe J, Vazquez. Morbidity and mortality in Cushing's disease: an epidemiological approach. JA Clin Endocrinol (Oxf) 1994;40:479-84.
2. Valassi E, Santos A, Yaneva M, Tóth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics. ERCUSYN Study Group. Eur J Endocrinol 2011;165:383-92.
3. Sasaki Y, Katabami T, Asai S, Fukuda H, Tanaka Y. In the overnight dexamethasone suppression test, 1.0 mg loading is superior to 0.5 mg loading for diagnosing subclinical adrenal Cushing's syndrome based on plasma dexamethasone levels determined using liquid chromatography-tandem mass spectrometry. Endocr J 2017;30:833-42.
4. Daniel E, Aylwin S, Mustafa O, Ball S, Munir A, Boelaert K, et al. Effectiveness of metyrapone in treating Cushing's syndrome: a retrospective multicenter study in 195 patients. J Clin Endocrinol Metab 2015;100:4146-54.
5. Nieman LK, Oldfield EH, Wesley R, Chrousos GP, Loriaux DL, Cutler GB. A simplified morning ovine corticotropin releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 1993;77:1308-12.
6. Grober Y, Grober H, Wintermark M, Jane JA Jr, Oldfield EH. Comparison of MRI techniques for detecting microadenomas in Cushing's disease. J Neurosurg 2018;128:1051-7.
7. Bansal V, El Asmar N, Selman WR, Arafah BM. Pitfalls in the diagnosis and management of Cushing’s syndrome. Neurosurg Focus 2015;38:E4.
8. Burkhardt T, Flitsch J, van Leyen P, Sauer N, Aberle J, Grzyska U, et al. Cavernous sinus sampling in patients with Cushing's disease. Neurosurg Focus. 2015;38:E6.
9. Kai Y, Hamada J, Nishi T, Morioka M, Mizuno T, Ushio Y. Usefulness of multiple site venous sampling inthe treatment of adrenocorticotropic hormone producing pituitary adenomas. Surg Neurol 2003;59:292-98.
10. Flitsch J, Lüdecke DK, Knappe UJ, Grzyska U. Cavernous sinus sampling in selected cases of Cushing's disease. Exp Clin Endocrinol Diabetes 2002;110:329-35.
11. Gazioglu N, Ulu MO, Ozlen F, Albayram S, Islak C, Kocer N, et al. Management of Cushing's disease using cavernous sinus sampling: effectiveness in tumor lateralization. Clin Neurol Neurosurg 2008;110:333-8.
12. Doppman JL, Nieman LK, Chang R, Yanovski J, Cutler GB Jr, Chrousos GP, et al. Selective venous sampling from the cavernous sinuses is not a more reliable technique than sampling from the inferior petrosal sinuses in Cushing’s syndrome. J Clin Endocrinol Metab 1995;80:2485-9.
13. 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;312:100-3.
14. Teramoto A, Nemoto S, Takakura K, Sasaki Y, Machida T. Selective venous sampling directly from cavernous sinüs in Cushing’s syndrome. J Clin Endocrinol Metab 1993;76:637-41.
15. Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. New Eng J Med 1991;325:897-905.
16. Booth GL, Redelmeier DA, Grosman H, Kovacs K, Smyth HS, Ezzat S. Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for localizing pituitary pathology in patients with Cushing’s disease. J Clin Endocrinol Metab 1998;83:2291-5.
17. Teramoto A, Yoshida Y, Sanno N, Nemoto S. Cavernous sinus sampling in patients with adrenocorticotrophic hormone-dependent Cushing’s syndrome with emphasis on inter- and intracavernous adrenocorticotrophic hormone gradients. J Neurosurg 1998;89:762-8.
18. Fahlbusch R, Buchfelder M, Müller OA.Transsphenoidal surgery for Cushing's disease. J R Soc Med1986;79:262-9.
19. Liu C, Lo JC, Dowd CF, Wilson CB, Kunwar S, Aron DC, et al. Cavernous and inferior petrosal sinus sampling in the evaluation of ACTH-dependent Cushing's syndrome. Clin Endocrinol (Oxf) 2004;61:478-86.
20. Mamelak AN, Dowd CF, Tyrrell JB, McDonald JF, Wilson CB. Venous angiography is needed to interpret inferior petrosal sinus and cavernous sinus sampling data for lateralizing adrenocorticotropin-secreting adenomas. J Clin Endocrinol Metab 1996;81:475-81.
21. Graham KE, Samuels MH, Nesbit GM, Cook DM, O'Neill OR, Barnwell SL, et al. Cavernous sinus sampling is highly accurate in distinguishing Cushing's disease from the ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location. J Clin Endocrinol Metab 1999;84:1602-10.