In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.

OBJECTIVE Accurate presurgical localization of microadenomas in Cushing's disease (CD) leads to improved remission rates and decreased adverse events. Volumetric gradient recalled echo (3D-GRE) MRI detects pituitary microadenomas in CD in up to 50%-80% cases as a focus of hypointensity due to delayed contrast wash-in. The authors have previously reported that postcontrast FLAIR imaging may be useful in detecting otherwise MRI-negative pituitary microadenomas as foci of hyperintensity. This reflects theoretically complementary imaging of microadenomas due to delayed contrast washout. The authors report on the diagnostic accuracy and clinical utility of FLAIR imaging in the detection of microadenomas in patients with CD. METHODS The authors prospectively analyzed imaging findings in 23 patients (24 tumors) with biochemically proven CD who underwent transsphenoidal surgery for CD. Preoperatively, the patients underwent pituitary MRI with postcontrast FLAIR and postcontrast 3D-GRE sequences. RESULTS Postcontrast FLAIR hyperintensity was detected in macroadenomas, and in 3D-GRE-positive or -negative microadenomas. Overall, 3D-GRE was superior in detecting surgically and histopathologically confirmed, location-concordant microadenomas. Of 24 pituitary adenomas, 18 (75%; sensitivity 82%, positive predictive value 95%) were found on 3D-GRE, and 13 (50% [1 was false positive]; sensitivity 55%, positive predictive value 92%) were correctly identified on FLAIR. The stand-alone specificity of 3D-GRE and FLAIR was similar (50%). These results confirm the superiority of 3D-GRE as a stand-alone imaging modality. The authors then tested the utility of FLAIR as a complementary tool to 3D-GRE imaging. All 5 patients with negative 3D-GRE MRI displayed a distinct focus of FLAIR enhancement. Four of those 5 cases (80%) had location-concordant positive histopathological results and achieved postsurgical biochemical remission. The remaining patient was not cured, because resection did not include the region of FLAIR hyperintensity. CONCLUSIONS This study suggests that delayed microadenoma contrast washout may be detected as FLAIR hyperintensity in otherwise MRI-negative CD cases. The authors propose adding postcontrast FLAIR sequences to complement 3D-GRE for surgical planning in patients with CD. Clinical trial registration no.: NIH protocol 03-N-0164, NCT00060541 (clinicaltrials.gov).

Design: Cell viability, ACTH secretion (enzyme-linked immunosorbent assay), apoptosis, and gene expression profile were investigated on AtT-20 cells. In vivo efficacy was examined in an athymic nude mouse AtT-20 xenograft model. SAHA efficacy against human-derived corticotroph tumor (hCtT) (n = 8) was tested in vitro.Setting: National Institutes of Health.Intervention: SAHA (0.5 to 8 mM). Main Outcome Measures:AtT-20 and hCtT cell survival, in vitro/in vivo ACTH measurements.Results: SAHA (1 mM) reduced AtT-20 viability to 75% at 24 hours, 43% at 48 hours (analysis of variance; P = 0.002). Apoptosis was confirmed with elevated BAX/Bcl2 ratio and FACS. Intriguingly, early (3-hour) significant decline (70%; P , 0.0001) of secreted ACTH and diminished POMC transcription was observed with SAHA (1 mM). Microarray analysis revealed a direct association between liver X receptor alpha (LXRa) and POMC expression. Accordingly, SAHA reduced LXRa in AtT-20 cells but not in normal murine corticotrophs. Xenografted nude-mice tumor involution (126 6 33/160 6 35 vs 337 6 49 mm 3 ; P = 0.0005) was observed with 5-day intraperitoneal SAHA, with reversal of elevated ACTH (P , 0.0001). SAHA did not affect serum ACTH in nontumor mice. Lastly, we confirmed that SAHA (1 mM/24 h) decreased hCtT survival (78.92%; P = 0.0007) and ACTH secretion (83.64%; P = 0.03).Conclusion: Our findings demonstrate SAHA's efficacy in reducing survival and ACTH secretion in AtT-20 and hCtT cells, providing a potential intervention for recurrent/unremitting CD. (J Clin

NEPVs for cortisol and ACTH predicted nonremission after TSS for CD.

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