Study Describes 6 Common Surgical Failures in Cushing’s Disease Treatment

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by Alice Melao |

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Isturisa, LINC-3 trial in Cushing's

To help improve the effectiveness of surgical treatment of Cushing’s disease, researchers conducted a study to determine common failures. They classified these failures into six different categories.

Results were reported in the study, “Root cause analysis of diagnostic and surgical failures in the treatment of suspected Cushing’s disease,” published in the Journal of Clinical Neuroscience.

The surgical removal of lesions that secrete excess adrenocorticotropic hormone (ACTH) is the first line of treatment for patients with Cushing’s disease. But while this approach is effective in reducing cortisol levels, up to 31 percent of patients fail to achieve remission.

When initial surgery is ineffective, additional surgical procedures may help to improve patient outcomes. Medications also are used for those who do not see results from surgery.

Recognizing the factors that contribute to the failure of surgical treatment is crucial to avoiding a deterioration of patient health and to improving long-term outcomes.

Researchers at Harvard Medical School examined the clinical records of 51 patients suspected of having Cushing’s disease. These patients were followed and surgically treated at the Brigham and Women’s Hospital in Boston, from April 2008 to July 2017.

In more than 82 percent of the cases, tissue removed during surgery confirmed that the patients had excess ACTH caused by benign tumors in the adrenal gland. Among the remaining patients, two had additional ACTH-secreting tumors, four had no obvious tumor or abnormal tissue, one had a pituitary mass without ACTH secretion, and one had no evidence of tissue changes despite the detection of a tumor during exploratory surgery.

They were followed for an average of 18.3 months, during which 42 patients achieved remission as confirmed by blood tests. Of these, 34 patients did not require additional treatment; four patients needed additional surgeries to achieve control over cortisol levels; and four patients required additional radiosurgery.

Based on long-term patient outcomes, researchers were able to identify six categories of common diagnostic and surgical failures. They include:

  • persistently high cortisol levels despite the successful removal of lesions
  • the failure of tumor resection
  • recurrence of disease
  • a failure to identify the source of ACTH secretion
  • the absence of identifiable lesions during exploratory surgery
  • concurrent tumors.

While the first three are common among patients with a visible lesion on imaging scans, the latter three are characteristic of patients in whom physicians fail to detect a lesion.

Investigators believe that anticipating and recognizing these common failures may help to improve the effectiveness of surgery, symptom management, and overall treatment outcomes.

“The success of surgical intervention can be enhanced greatly by improving patient selection and surgical management by anticipating and subsequently deterring the six common failures described above,” the team concluded. They added that better imaging methods also might improve outcomes for Cushing’s disease patients.