Natasha Ironside1,2, Gregoire Chatain3, David Asuzu1,4, Sarah Benzo1, Maya Lodish5, Susmeeta Sharma6, Lynnette Nieman7, Constantine A Stratakis5, Russell R Lonser8, Prashant Chittiboina9,3. 1. Surgical Neurology BranchNational Institute of Neurological Diseases and Stroke, Bethesda, Maryland, USA. 2. Department of NeurosurgeryAuckland City Hospital, Auckland, New Zealand. 3. Neurosurgery Unit for Pituitary and Inheritable DiseasesNational Institute of Neurological Diseases and Stroke, Bethesda, Maryland, USA. 4. Yale School of MedicineNew Haven, Connecticut, USA. 5. Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA. 6. Pituitary Endocrinology SectionMedStar Washington Hospital Center, Washington, District of Columbia, USA. 7. National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of Health, Bethesda, Maryland, USA. 8. Department of Neurological SurgeryWexner Medical Center, The Ohio State University, Columbus, Ohio, USA. 9. Surgical Neurology BranchNational Institute of Neurological Diseases and Stroke, Bethesda, Maryland, USA prashant.chittiboina@nih.gov.
Abstract
CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing's disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE: We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS: A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. CONCLUSIONS: 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.
CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing's disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE: We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS: A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. CONCLUSIONS: 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.
Authors: E H Oldfield; J L Doppman; L K Nieman; G P Chrousos; D L Miller; D A Katz; G B Cutler; D L Loriaux Journal: N Engl J Med Date: 1991-09-26 Impact factor: 91.245
Authors: M Grino; F Boudouresque; B Conte-Devolx; G Gunz; F Grisoli; C Oliver; P Jaquet Journal: J Clin Endocrinol Metab Date: 1988-04 Impact factor: 5.958
Authors: Sayoa Eulate-Beramendi; Ainhoa Casajús; Lola Ollero; Lynnette K Niemann; Juan Carlos Fernández-Miranda; Michaël Bruneau; Moncef Berhouma; Luigi Maria Cavallo; Jan Frederick Cornelius; Roy T Daniel; Sebastien Froelich; Emmanuel Jouanneau; Ekkehard Kasper; Diego Mazzatenta; Torstein R Meling; Mahmoud Messerer; Henry W S Schroeder; Marcos Tatagiba; Massimiliano Visocchi; Eduard H Voormolen; Idoya Zazpe Journal: Brain Spine Date: 2022-08-07