Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol. The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function. Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. We recently reviewed the current pathophysiological principles, diagnostic methods, and management of CD. While it is known that up to 20% or so of patients with CD recur after apparently successful transsphenoidal tumor resection, little is known about what factors may predict recurrence. Perioperative increases in adrenocorticotropic hormone (ACTH) and cortisol mimic corticotropin releasing hormone (CRH) stimulation testing. This phenomenon may help identify patients with residual adenoma after transsphenoidal surgery (TSS) for Cushing's disease (CD). We retrospectively evaluated whether early post-operative measurements of ACTH and cortisol would be helpful in this regard. This was a case control study of 291 consecutive patients treated at NIH from December 2003 till July 2016. Early and medium-term remission were assessed at 10 days and 11 months. 257 patients had biochemical evidence of CD. Normalized early post-operative values (NEPV) for cortisol and ACTH were calculated as immediate post-operative cortisol or ACTH minus preoperative post-CRH stimulation test levels. The NEPV for cortisol and ACTH predicted early non-remission (adjusted OR 1.1, 95% CI 1.0 - 1.1, P = 0.016; and adjusted OR 1.0, 95% CI 1.0 - 1.0, P = 0.048 respectively). ROC for NEPV cortisol was 0.78, 95% CI 0.61 - 0.95; and for NEPV ACTH was 0.80, 95% CI 0.61 - 0.98. NEPV for both cortisol and ACTH predicted medium-term non-remission (hazard ratios (HR) 1.1, 95% CI 1.0 - 1.1, P = 0.023; and HR 1.0, 95% CI 1.0 - 1.0, P = 0.025 respectively). Thus, NEPV for cortisol and ACTH may help predict non-remission after TSS for CD. 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. We evaluated the diagnostic accuracy and clinical utility of FLAIR imaging in the detection of microadenomas in 23 patients with CD who underwent transsphenoidal surgery. Preoperatively, the patients underwent pituitary MRI with postcontrast FLAIR and postcontrast 3D-GRE sequences. 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. 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. We conclude that delayed microadenoma contrast washout may be detected as FLAIR hyperintensity in otherwise MRI-negative CD cases. These findings suggest that addition of postcontrast FLAIR sequences would complement data from 3D-GRE for surgical planning in patients with CD.
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| Nieman, Lynnette Kaye (2018) Diagnosis of Cushing's Syndrome in the Modern Era. Endocrinol Metab Clin North Am 47:259-273 |
| Chatain, Grégoire P; Patronas, Nicholas; Smirniotopoulos, James G et al. (2018) Potential utility of FLAIR in MRI-negative Cushing's disease. J Neurosurg 129:620-628 |
| Ironside, Natasha; Chatain, Gregoire; Asuzu, David et al. (2018) Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease. Eur J Endocrinol 178:255-263 |
| Nieman, Lynnette K (2018) Recent Updates on the Diagnosis and Management of Cushing's Syndrome. Endocrinol Metab (Seoul) 33:139-146 |
| Asuzu, David; Chatain, Grégoire P; Hayes, Christina et al. (2017) Normalized Early Postoperative Cortisol and ACTH Values Predict Nonremission After Surgery for Cushing Disease. J Clin Endocrinol Metab 102:2179-2187 |
| Del Rivero, Jaydira; Kim, Chul; Eid, Mary et al. (2017) Thymic Hyperplasia after Treatment of ACTH-Dependent Cushing's Syndrome Can Be Mistaken for a Thymic Epithelial Tumor. J Thorac Oncol 12:e29-e32 |
| Lonser, Russell R; Nieman, Lynnette; Oldfield, Edward H (2016) Cushing's disease: pathobiology, diagnosis, and management. J Neurosurg :1-14 |
| Sharma, S T; Nieman, L K; Feelders, R A (2015) Comorbidities in Cushing's disease. Pituitary 18:188-94 |
| Nieman, Lynnette K; Biller, Beverly M K; Findling, James W et al. (2015) Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100:2807-31 |
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