Potential utility of FLAIR in MRI-negative Cushing's disease

Abstract

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).

Keywords: 3D-GRE; 3D-GRE = volumetric gradient recalled echo; ACTH = adrenocorticotropic hormone; CD = Cushing’s disease; CRH = corticotropin-releasing hormone; Cushing’s disease; FLAIR; HDDST = high-dose dexamethasone suppression test; IPSS = inferior petrosal sinus sampling; MRI; NIH = National Institutes of Health; NINDS = National Institute of Neurological Disorders and Stroke; PPV = positive predictive value; TSS = transsphenoidal surgery; UFC = urinary free cortisol; contrast; fluid attenuated inversion recovery; hypercortisolism; pituitary adenoma; pituitary surgery; transsphenoidal surgery; volumetric gradient recalled echo; washout.

FIG. 1.

Noncontrast T1-weighted (A and E) and T2-weighted images (B and F) were useful in detecting pituitary (B, white arrowhead) and intratumoral (F, white arrowhead) cysts. Corresponding regions were hyperintense on postcontrast FLAIR images (white arrowheads in D and H), whereas they were isointense on precontrast FLAIR images (C and G).

FIG. 2.

Volumetric spoiled gradient–recalled acquisition in the steady state, a 3D gradient echo technique, fails to demonstrate a pituitary microadenoma (A). The T2-weighted sequence is also negative and rules out any cystic or necrotic areas of the pituitary gland (B). Postcontrast FLAIR image reveals marked contrast enhancement in the ACTH-positive adenoma in the far-right lateral aspect of the gland (C, white arrowhead).

FIG. 3.

Postcontrast 3D-GRE image fails to demonstrate a pituitary adenoma (A). Delayed postcontrast FLAIR image reveals marked contrast enhancement in the left aspect of the gland (B, white arrowhead). Resection did not include the hyperintense area on the FLAIR image, as shown by the delineation of the subtotal hypophysectomy (dotted line). The surgical specimen did not contain pituitary adenoma, and the patient did not achieve remission from CD.

FIG. 4.

Graphs showing comparisons of FLAIR-positive versus FLAIR-negative images for tumor volume (A), time to acquisition of FLAIR images following intravenous contrast injection (B), midnight cortisol (C), and midnight ACTH (D). Horizontal bars represent the mean ± SD. *p ≤ 0.05. Figure is available in color online only.

FIG. 5.

Flow chart showing potential pituitary imaging protocol for CD. Patients with biochemical workup suggestive of CD first undergo pituitary MRI with precontrast T2-weighted (T2W) and postcontrast 3D-GRE sequences. We propose adding a postcontrast FLAIR sequence (gray box) for patients who were screened with T2-weighted and postcontrast 3D-GRE sequences, and in whom no adenomas were identified. The T2-weighted sequences assist in detecting cysts that may also appear hyperintense on postcontrast FLAIR imaging.