Surgery success in Cushing’s marked by low morning cortisol levels
Results of 2 tests strongly predict long-term remission, new study finds
Written by |
After surgery for Cushing’s disease, very low levels of cortisol in the morning strongly predict that a patient will recover and remain disease-free long term, a new study from a quartet of researchers in Germany has found.
Remission was shown to be especially likely for Cushing’s patients with a good response to another test in which a small dose of the steroid dexamethasone is given at night to check if it reduces cortisol — the so-called stress hormone that helps activate the body’s fight or flight response — by the next morning. That test was done on “postoperative day five, in selected cases,” the team noted.
According to the researchers, these findings show that morning cortisol and dexamethasone tests are “reliable predictors of remission” following surgery in people with Cushing’s disease. The team suggested that both tests “should be included in routine postoperative assessment.”
The study, “Early postoperative LDDST enhances remission prediction beyond morning cortisol in cushing’s disease,” was published in the journal Pituitary.
Symptoms of Cushing’s disease are caused by excess cortisol in the body due to a tumor growing in the brain’s pituitary gland. This tumor makes the pituitary gland produce excess adrenocorticotropic hormone (ACTH), which signals the adrenal glands, located above the kidneys, to release cortisol.
The main treatment is transsphenoidal surgery, a procedure in which doctors remove the tumor from the pituitary gland through the nose. After surgery, clinicians check if cortisol normalizes, which would mean the disease is under control.
Researchers urge use of both tests after surgery in Cushing’s
Cortisol can be measured in the blood early in the day — known as a morning serum cortisol, or MSeC, test — or after giving a low dose of dexamethasone, a steroid that mimics cortisol and should reduce its levels if the body is responding normally. That’s called LDDST, for low-dose dexamethasone suppression test.
To understand how well these two tests predict short-term recovery and long-term well-being, the researchers reviewed data from 342 patients who underwent transsphenoidal surgery between 2004 and 2024. Most patients were women (82%), with an average age of 43.3 at the time of the procedure.
For 281 patients (82%), it was the first transsphenoidal surgery. The other 61 patients (18%) underwent a repeat procedure, due to recurrence in 37 (61%) and persistent Cushing’s disease in 24 (39%).
About half of the patients achieved immediate postoperative biochemical remission, according to the researchers, which is defined as morning cortisol of less than 50 nanomoles per liter of blood (nmol/L).
The dexamethasone test was done five days after surgery in more than half (58%) of the patients, mostly among those whose cortisol was not clearly low, the researchers noted. Of these 197 patients, 137 (70%) achieved complete suppression, defined as a morning cortisol level of less than 50 nmol/L after receiving a low-dose dexamethasone.
The proportion of patients achieving clinical remission at three to six months after the transsphenoidal surgery was very high — about 99% — among those who had achieved immediate postoperative biochemical remission or complete suppression. Patients with higher cortisol levels were less likely to be in remission.
Based on our findings and clinical experience, we propose a standardized postoperative protocol incorporating both [morning cortisol] and [the low-dose dexamethasone test] to optimize remission assessment and guide early management strategies.
Over an average of nine years, patients who had achieved immediate postoperative biochemical remission (94%) or complete suppression (87%) were more likely to stay in remission. Recurrence after five years, meaning the disease came back, did not exceed 7% among patients who had achieved immediate postoperative biochemical remission or complete suppression, compared with up to 71% among those who did not.
Both morning cortisol and the dexamethasone test showed strong predictive ability for remission, the researchers found.
Morning cortisol of less than 50 nmol/L had a 59% sensitivity, or ability to detect true cases of remission. Specificity, or the test’s ability to exclude false results, was 85% with morning cortisol. The dexamethasone test, meanwhile, performed better, with 86% sensitivity and 70% specificity, the data showed.
Usually, the dexamethasone test is a “supplementary diagnostic test,” the researchers wrote. However, “based on our findings and clinical experience, we propose a standardized postoperative protocol incorporating both [morning cortisol] and [the low-dose dexamethasone test] to optimize remission assessment and guide early management strategies,” the team concluded.
