Metoclopramide Can Mask Adrenal Insufficiency After Gland Removal in BMAH Patients, Case Report Suggests

Metoclopramide, a gastrointestinal medicine, can increase cortisol levels after unilateral adrenalectomy — the surgical removal of one adrenal gland — and conceal adrenal insufficiency in bilateral macronodular adrenal hyperplasia (BMAH) patients, a case report suggests.

The study, “Retention of aberrant cortisol secretion in a patient with bilateral macronodular adrenal hyperplasia after unilateral adrenalectomy,” was published in Therapeutics and Clinical Risk Management.

BMAH is a subtype of adrenal Cushing’s syndrome, characterized by the formation of nodules and enlargement of both adrenal glands.

In this condition, the production of cortisol does not depend on adrenocorticotropic hormone (ACTH) stimulation, as usually is the case. Instead, cortisol production is triggered by a variety of stimuli, such as maintaining an upright posture, eating mixed meals — those that contain fats, proteins, and carbohydrates — or exposure to certain substances.

A possible treatment for this condition is unilateral adrenalectomy. However, after the procedure, some patients cannot produce adequate amounts of cortisol. That makes it important for clinicians to closely monitor the changes in cortisol levels after surgery.

Metoclopramide, a medicine that alleviates gastrointestinal symptoms and is often used during the postoperative period, has been reported to increase the cortisol levels of BMAH patients. However, the effects of metoclopramide on BMAH patients who underwent unilateral adrenalectomy are not clear.

Researchers in Japan described the case of a 61-year-old postmenopausal woman whose levels of cortisol remained high after surgery due to metoclopramide ingestion.

The patient was first examined because she had experienced high blood pressure, abnormal lipid levels in the blood, and osteoporosis for ten years. She also was pre-obese.

She was given medication to control blood pressure with no results. The lab tests showed high serum cortisol and undetectable levels of ACTH, suggesting adrenal Cushing’s syndrome.

Patients who have increased cortisol levels, but low levels of ACTH, often have poor communication between the hypothalamus, the pituitary, and the adrenal glands. These three glands — together known as the HPA axis — control the levels of cortisol in healthy people.

Imaging of the adrenal glands revealed they were both enlarged and presented nodules. The patient’s cortisol levels peaked after taking metoclopramide, and her serum cortisol varied significantly during the day while ACTH remained undetectable. These results led to the BMAH diagnosis.

The doctors performed unilateral adrenalectomy to control cortisol levels. The surgery was successful, and the doctors reduced the dose of glucocorticoid replacement therapy on day 6.

Eight days after the surgery, however, the patient showed decreased levels of fasting serum cortisol, which indicated adrenal insufficiency — when the adrenal glands are unable to produce enough cortisol.

The doctors noticed that metoclopramide was causing an increase in serum cortisol levels, which made them appear normal and masked the adrenal insufficiency.

They stopped metoclopramide treatment and started replacement therapy (hydrocortisone) to control the adrenal insufficiency. The patient was discharged 10 days after the surgery.

The serum cortisol levels were monitored on days 72 and 109 after surgery, and they remained lower than average. Therefore she could not stop hydrocortisone treatment.

The levels of ACTH remained undetectable, suggesting that the communication between the HPA axis had not been restored.

“Habitual use of metoclopramide might suppress the hypothalamus and pituitary via negative feedback due to cortisol excess, and lead to a delayed recovery of the HPA axis,” the researchers said.

Meanwhile, the patient’s weight decreased, and high blood pressure was controlled.

“Detailed surveillance of aberrant cortisol secretion responses on a challenge with exogenous stimuli […] is clinically important in BMAH patients,” the study concluded. “Caution is thus required for assessing the actual status of the HPA axis.”