Glucocorticoid therapy may safely await day after surgery: Study

No concerns seen in Cushing's patients with delayed replacement treatment

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A patient on a stretcher is being wheeled into an operating room.

For people who undergo surgery to treat Cushing’s disease or other forms of endogenous Cushing’s syndrome, replacement treatment with glucocorticoids may not be necessary immediately before or after the procedure, a study suggests.

Rather, findings favored “withholding perioperative glucocorticoids until the first postoperative day (or even longer),” the researchers wrote.

The study, “No requirement of perioperative glucocorticoid replacement in patients with endogenous Cushing’s syndrome – a pilot study,” was published in the journal Endocrine by scientists in Austria.

Endogenous Cushing’s syndrome occurs when cortisol, a glucocorticoid hormone, is produced in excess by the body. In Cushing’s disease, this is due to a tumor in the brain’s pituitary gland. Other forms may be caused by a tumor that forms in the adrenal glands and triggers an excessive release of cortisol.

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Evidence is limited on glucocorticoid need around the time of a surgery

First-line treatment for Cushing’s disease is transsphenoidal adenomectomy, a surgery to remove a pituitary gland tumor. Another common surgical procedure is an adrenalectomy, during which one or both adrenal glands are removed.

Because surgery cuts off the source of cortisol, many patients need lifelong treatment, replacing cortisol with a glucocorticoid. This replacement therapy maintains the hormone’s levels within an adequate range to help regulate the body’s response to stress, among other important functions.

While glucocorticoid replacement therapy is mandatory after surgery, patients may not need glucocorticoids perioperatively, or around the time of surgery, as some studies suggest. But evidence is “limited” regarding whether perioperative treatment can be safely delayed, and opinions vary about when it should be initiated, the study noted.

“If perioperative glucocorticoid replacement could be omitted, this would facilitate perioperative clinical care of patients including screening for postoperative hypocortisolism [unusually low cortisol levels], which is considered a positive predictor for surgical remission,” the researchers wrote.

A team at the Medical University of Graz measured cortisol levels in patients who didn’t receive glucocorticoids until the day after surgery. Blood samples were drawn before and right after surgery, in the evening after surgery, and in the mornings of the first and third days after surgery, before patients took their glucocorticoid dose.

The study included seven adults who underwent transsphenoidal adenomectomy to treat Cushing’s disease, and five with Cushing’s syndrome who underwent adrenalectomy or adrenal radiofrequency ablation, a procedure that uses heat to destroy tumor cells. Six adults who had pituitary surgery for reasons other than Cushing’s also were included, serving as controls.

Patients’ cortisol levels fell, but few had levels below 5 mcg/mL after surgery

Among Cushing’s patients, mean blood cortisol levels fell by about half three days after surgery compared with their values before surgery (8.5 vs. 19.9 mcg/dL). Among control patients without Cushing’s, blood cortisol levels were significantly higher right after than before surgery (31.2 vs. 15.9 mcg/dL), a difference that persisted over time.

On the third day after surgery, four (57%) Cushing’s disease patients and two people (40%) with adrenal Cushing’s syndrome saw their cortisol levels dip below 5 mcg/dL, but none developed symptoms of hypocortisolism. No control group patients had cortisol levels below 5 mcg/dL at any time point.

Right after surgery, however, the proportion of patients with cortisol levels below 5 mcg/mL was low, at 11%. This suggests that “perioperative glucocorticoid replacement in curative surgery for [Cushing’s syndrome] may be safely omitted until the first postoperative day,” the researchers wrote.

Patients were discharged after a mean of 11 days, and prescribed a mean, 26 mg daily dose of hydrocortisone, a glucocorticoid. Two Cushing’s disease patients were discharged without glucocorticoids due to signs of hypercortisolism (overly high cortisol levels) during their hospital stay.

For patients who needed hydrocortisone after being discharged from the hospital, it took a mean of 129 days for their cortisol levels to rise above 5 mcg/mL. Hydrocortisone treatment was stopped after a mean of 402 days (slightly more than one year).

None of the patients required permanent replacement treatment, but two were lost to follow-up before their cortisol levels normalized. No one developed venous thromboembolism, which refers to a blood clot that forms in a vein, due to hypercortisolism.

“There were no safety concerns for withholding glucocorticoid replacement until the morning of the first postoperative day, suggesting that this approach represents a reasonable clinical strategy,” the researchers wrote, noting that their findings should be confirmed in larger studies.