Outcomes of endoscopic transsphenoidal surgery for Cushing's disease

Abstract

Background Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing’s disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD. Methods A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012–February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission. Results A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4–79) months. Conclusion Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.

Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease

“…Recent studies have reported remission rates of 74–82% after first operations [ 12 , 34 ]. The recurrence rates reported previously varied between 3% and 66% [ 5 , 12 , 34 ]. However, the duration of follow-up differed among the studies.…”

Unmet needs on the current medical management of Cushing’s syndrome: results from a Delphi panel of Italian endocrinologists

“…Literature evidence suggests that pituitary surgery is widely considered the first-line treatment in CD management, even considering that an optimal success rate is reported especially among centers of excellence and may vary according to different factors, including patients’ characteristics, and preoperative visualization, size, and location of the pituitary tumor, as well as the surgeon experience [ 10 , 16 , 22 , 23 ]. Consistent with this evidence, Delphi panel outcomes highlighted that the CD surgical management has some limitations (81% of agreement), mainly related to patients’ characteristics (refusal of surgery, comorbidities increasing the anesthesiologic/surgical risk, non-accessibility to all patients [ 15 ]), and to surgery issues, such as invisible or small size tumors, as well as unfavorable location or extrasellar expansion of the pituitary tumor.…”

Endoscopic Transsphenoidal Surgery with a Layered Peel Strategy for Cushing’s Disease Treatment: A Case Series

“…In addition to different study designs (sample size and follow-up time), tumor characteristics (invasiveness, tumor size, and localization), surgical experience, and adjuvant therapies, this may be due to the lack of a uniform consensus for the definition of remission, including immediate and delayed remission [ 12 , 13 ]. For example, a low (<50 nmol/L, 100 nmol/L, or 138 nmol/L) or normal morning serum cortisol level within 3, 4, or 7 days after surgery, clinical symptom disappearance, normal or decreased UFC levels over the past 24 h, the success of a low-dose dexamethasone test, or a combination of two or more aforementioned criteria was used to define tumor remission [ 4 , 11 , 14 , 15 , 16 , 17 ]. The criteria for CD recurrence seemed to be relatively consistent, including an increase in serum cortisol level, an increase in night salivary cortisol level, and/or an increase in 24 h UFC level, with clinical hallmarks reviewed by Qiao [ 3 ].…”

“…Random cortisol level evaluations were performed, and cortisol replacement treatment was initiated until the HPA axis was restored when patients exhibited signs or symptoms of hypocortisolemia. Immediate remission was defined as a morning serum cortisol level of <138 nmol/L (5 µg/dL) or UFC level of <28–56 nmol/day (10–20 μg/dL) within 7 days after surgery [ 4 , 5 ]. Because a progressive decline in cortisol level to a normal or low level within three months after surgery has been identified in previous studies [ 6 , 7 , 8 ], patients without any additional therapy had a delayed remission with a low or normal morning serum cortisol level with a resolution of clinical features during the first three months of the follow-up period after resection.…”