Repeat Transsphenoidal Surgery Effective in Patients with Recurrent Cushing’s, Study Reports

Repeat transsphenoidal surgery (TSS) in patients experiencing recurrence of Cushing’s disease after the initial procedure is effective and associated with high rates of sustained remission, according to a new study.

The research, “Outcomes After Repeat Transsphenoidal Surgery for Recurrent Cushing Disease: Updated,” appeared in the journal Neurosurgery.

Though considered the first-line treatment for Cushing’s disease, TSS has been associated with high recurrence rates. A second surgery is one of the treatment options for patients with recurrent disease, but few studies have assessed the success of long-term remission after repeat TSS.

Aiming to address this gap, the scientists combined results from surgical procedures conducted at Kentucky’s University of Louisville School of Medicine and Boston’s Brigham and Women’s Hospital.

From a total of 120 patients who underwent TSS between 2008 and 2018, the analysis included the 15 patients (12 women, average age at repeat TSS 45.1 years) who underwent repeat surgery, had a follow-up period of at least 12 months (average 34.7 months), and an initial period of remission longer than three months.

Following the initial TSS, 13 of these patients (86.7%) had evidence of adrenocorticotropic hormone (ACTH) adenoma. The average time from initial surgery to recurrence of Cushing’s symptoms was 77.7 months (about 6.5 years). Before repeat TSS, nine patients revealed a pituitary tumor on magnetic resonance imaging; four of those were macroadenomas (maximum diameter larger than 1 cm). After repeat surgery, nine patients had ACTH adenoma.

These data were then combined with those of 36 patients who had undergone repeat TSS between 1992 and 2006, performed by the same surgeon. Across both groups, 38 patients (74.5%) were women and the average age at repeat TSS was 41.7 years. Forty-four patients (86.3%) had ACTH adenoma at the initial operation. The average period between initial TSS and recurrent disease was 60.3 months.

Before repeat TSS, 35 patients (63.6%) patients had evidence of tumor, 28 of which were microadenomas (maximum diameter under 1 cm). In turn, 33 (64.7%) had ACTH adenoma following repeat TSS.

As for outcomes, 13 of the 15 patients who underwent repeat TSS more recently achieved immediate postoperative remission. All but one were in remission for at least 12 months and 11 (73.3%) had continued biochemical and clinical remission at the latest follow-up — average duration 34.8 months.

Two patients initially in remission experienced subsequent recurrence at months 7 and 24 after TSS. Also, the two patients who did not achieve postoperative remission achieved biochemical remission — defined as normal 24-hour urinary free cortisol (UFC) and/or the need for glucocorticoid replacement therapy — after radiation therapy with or without medical therapy.

Among the 13 patients in remission immediately after repeat surgery, nine (69.2%) had evidence of tumor before surgery and nine of ACTH adenoma after the repeat surgery.

As for the combined group, 35 of the 51 patients (68.6%) achieved biochemical remission immediately after surgery and 31 (60.8%) had continued remission at the most recent follow-up. Four patients initially in remission had recurrence, confirmed throughout 24 months. Twenty-two (62.9%) of the patients in remission after repeat TSSa had evidence of tumor before surgery and 21 (60%) of ACTH adenoma after repeat TSS.

All 15 patients with more recent surgery underwent TSS with endoscopy, unlike the 36 in the initial group. Although a trend was observed, use of endoscopy was not associated with significant differences in the rates of immediate post-surgery remission or recurrence, which researchers attributed to the small number of patients analyzed.

Complications found in the combined group included four cases of transient diabetes insipidus (DI), five of permanent DI, and one of nose bleeding. Fifteen (29.4%) patients had panhypopituitarism, which refers to inadequate or no production of pituitary hormones. No major complications were observed.

“This study helps to validate the concept that repeat surgery for recurrent [Cushing’s disease] is effective and should be strongly considered for appropriate patients,” the scientists stated.