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Original Article Diagnosis of Cushing's Disease by Inferior Petrosal Sinus Sampling (IPSS): Evidence of False Negative Results.
Seon Hwa Lee, Hyeon Jeong Jeon, Sun Hee Park, Sun Wook Kim, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee
Endocrinology and Metabolism 1999;14(3):483-492

Published online: January 1, 2001
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Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

BACKGROUND
While inferior petrosal sinus sampling (IPSS) correctly diagnoses pituitary dependent Cushings syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushings disease (e.g. false negative result). We evaluated the results of IPSS with Cushings disease, and compared them with imaging findings through transsphenoidal surgery. METHODS: 29 patients with Cushings disease underwent transsphenoidal examination of the pituitary gland from 1989 to 1998 at Seoul National University Hospital were evaluated. We compared the results of IPSS and imaging findings with sellar CT or dynamic MRI. The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio) and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated before and after CRH infusion. RESULTS: With IPSS the diagnosis of Cushings disease was possible in 90% (26/29), and 3 cases in whom IPSS did not show significant IPS:P ACTH ratio were confirmed to be Cushings disease through hemihypophysectomy of lesion suspected by sellar dynamic MRI and achieved remission after operation (e.g. false negative result of diagnosis for Cushings disease by IPSS). However, accurate localization of microadenoma was achieved in only 59% (17/29). Imaging study detected microadenoma in 76% (22/29) and correctly localized in 66% (19/29). Both IPSS and imaging study precisely localized the pituitary microadenoma in 10 (34.5%) cases of 29 cases and a discrepancy between two studies existed in 7 (24.1%) cases in which the imaging study correctly localized microadenoma in 6 cases and IPSS in 1 case. CONCLUSION: Only when a significant IPS:P ACTH ratio is present can Cushings disease be established by IPSS. The absence of a significant IPS:P ACTH ratio does not necessarily imply ectopic secretion of ACfH, nor does it exclude Cushings disease. The results of lateralization by IPSS do not remove the need for transsphenoidal examination of the sella turcica because false negative result can be. IPSS and radiologic study should be complementary used in diagnosis of Cushings disease and localization of microadenoma, as IPSS can be used when sellar imaging study failed to visualize the lesion and hemihypophysectomy of suspected lesion by imaging study can be considered when IPSS did not show significant ratio of ACTH.

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