Cortisol Levels Predict Remission in Cushing’s Patients Undergoing Transsphenoidal Surgery

In patients with Cushing’s disease, removing the pituitary tumor via an endoscopic transsphenoidal surgery (TSS) leads to better remission rates than microscopic TSS, according to new research.

But regardless of surgical approach, plasma cortisol levels one day after surgery are predictive of remission, researchers found.

The study, “Management of Cushing’s disease: Changing trend from microscopic to endoscopic surgery,” was published in the journal World Neurosurgery.

Because it improves visualization and accessibility, endoscopic TSS has been gaining popularity over microscopic TSS to remove pituitary tumors in Cushing’s disease patients. Yet, although this surgery has been associated with high remission rates, whether it outperforms microscopic surgery and determining the factors affecting long-term outcomes may further ease disease recurrence after TSS.

A team with the All India Institute of Medical Sciences addressed this topic in 104 patients who underwent surgery from January 2009 to June 2017. Among these patients, 47 underwent microscopic surgery and 55 endoscopic surgery. At presentation, their ages ranged from 9 to 55 (mean age of 28). Also, patients had been experiencing Cushing’s symptoms over a mean duration of 24 months.

Eighty-seven patients showed weight gain. Hypertension (high blood pressure) and diabetes mellitus were among the most common co-morbidities, found in 76 and 33 patients, respectively. Nineteen patients had osteoporosis and 12 osteopenia, which refers to lower-than-normal bone mineral density.

As assessed with magnetic resonance imaging, 68 patients had a microadenoma (a tumor diameter smaller than one centimeter) and 27 had a macroadenoma (a tumor one centimeter or larger). Only two patients had an invasive pituitary adenoma.

Two patients with larger tumors were operated on transcranially (through the skull). The surgery resulted in total tumor removal in 90 cases (86.5%). A blood loss greater than 100 milliliter was more common with endoscopic than with microscopic TSS.

Ten patients developed transient diabetes inspidus, two experienced seizures after surgery, and six of nine patients with macroadenoma and visual deterioration experienced vision improvements after TSS.

The incidence of intraoperative leak of cerebrospinal fluid — the liquid surrounding the brain and spinal cord — was 23.2%, while that of post-operative leak was 7.7% and was more common in microadenoma than macroadenoma surgery (9.8% vs. 5.0%).

Seventeen patients were lost to follow-up and two died due to metabolic complications and infections. The average follow-up was shorter for endoscopic than with microscopic surgery (18 months vs. 35 months).

Among the remaining 85 cases, 65 (76.5%) experienced remission, as defined by a morning cortisol level under 5.0 μg/dL, restored circadian rhythm (the body’s internal clock, typically impaired in Cushing’s patients), and suppression of serum cortisol to below 2 μg/dl after overnight dexamethasone suppression test.

The remission rate was 54.5% in pediatric patients and was higher with endoscopic than with microscopic TSS (88.2% vs. 56.6%). Also, patients with microadenoma showed a trend toward more frequent remission than those with macroadenoma (73.2% vs. 64.3%).

Ten of the remaining 20 patients experienced disease recurrence up to 28 months after surgery. Sixteen cases revealed signs of hypopituitarism, or pituitary insufficiency, which were managed with replacement therapy.

A subsequent analysis found that morning cortisol level on day one after surgery was the only significant predictor of remission. Specifically, a one-unit increase in cortisol lowered the likelihood of remission by 7%. A cortisol level lower than 10.7 μgm/dl was calculated as predicting remission.

Overall, the study showed that “postoperative plasma cortisol level is a strong independent predictor of remission,” the researchers wrote, and that “remission provided by endoscopy is significantly better than microscopic approach.”

From https://cushingsdiseasenews.com/2019/09/24/cortisol-levels-predict-remission-cushings-patients-undergoing-transsphenoidal-surgery/

Unilateral andrenalectomy may be valid first-line treatment for Cushing’s syndrome

Debillon E, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/jc.2015-2662.

In patients with evident Cushing’s syndrome related to primary bilateral macronodular adrenal hyperplasia, unilateral adrenalectomy of the large gland appears to be a suitable alternative to bilateral adrenalectomy as a first-line treatment, according to recent findings.

Unilateral adrenalectomy yielded normalized urinary free cortisol and improved Cushing’s syndrome, according to the researchers.

Olivier Chabre , MD, PhD, of the Service d’Endocrinologie-Diabétologie-Nutrition in France, and colleagues evaluated all patients (n = 15) with overt Cushing’s syndrome related to primary bilateral macronodular adrenal hyperplasia who underwent unilateral laparoscopic adrenalectomy of the larger gland between 2001 and 2015. Patients were seen for clinical and biological follow-up assessments at 1, 3 and 6 months postoperatively, 5 years after surgery and at the time of the last available urinary free cortisol measurement.

The study’s primary outcome measures were pre- and postoperative levels of urinary free cortisol, plasma cortisol, adrenocorticotropic hormone (ACTH), BMI, blood pressure, plasma glucose and lipids and measurements of these values on follow-up assessments. Patients were followed for a median of 60 months.

The researchers found that in early postoperative measurements, all 15 patients who underwent unilateral adrenalectomy achieved normal or low urinary free cortisol. Between 7 days and 1 month, there was a decrease in median urinary free cortisol from 2.19 times the upper limit of normal (ULN) at baseline to 0.27 ULN (P = .001). At 1 month, only one patient had elevated urinary free cortisol, and this patient went into remission by month 3 and continued to be in remission after 12 years of follow-up.

Forty percent of the patients developed adrenal insufficiency after unilateral adrenalectomy and latent adrenal insufficiency could not be excluded in two of the other patients. No predictors of postoperative adrenal insufficiency were identified.

Six of the patients had diabetes before unilateral adrenalectomy surgery; four of those were treated with antidiabetes drugs. At 12 months, only two of these patients had a continued need for antidiabetes drugs and had reductions in HbA1c despite decreases in their treatment. Recurrence occurred in two patients, demonstrating urinary free cortisol above the ULN at 7 years postoperatively and 8 years postoperatively. Both cases required treatment with mitotane, and in one of the patients, adrenalectomy of the second gland was required 9 years after the initial adrenalectomy.

According to the researchers, postoperative management and vigilant follow-up is needed in order to monitor patients for the risk for adrenal insufficiency.

“Further prospective studies are needed to better evaluate the long-term benefits of [unilateral adrenalectomy], which has one major benefit over [bilateral adrenalectomy]: if needed, [unilateral adrenalectomy] can be transformed in [bilateral adrenalectomy], while the opposite is obviously not true,” the researchers wrote. “One could propose that in further prospective studies [bilateral adrenalectomy] could be performed only if [unilateral adrenalectomy] fails to normalize [urinary free cortisol] at 1 month postoperatively.” – by Jennifer Byrne

Disclosure: The researchers report no relevant financial disclosures.

From Healio

<span>%d</span> bloggers like this: