Metyrapone lowers systolic blood pressure in mild autonomous cortisol secretion

Key takeaways:

• Adults with mild autonomous cortisol secretion using metyrapone had greater reductions in blood pressure than controls.
• There were no reports of adrenal crises among adults receiving metyrapone.

An oral 11‐beta hydroxylase inhibitor administered during the evening reduced systolic and diastolic blood pressure for adults with mild autonomous cortisol secretion, researchers reported in Clinical Endocrinology.

Metyrapone (Metopirone, Esteve) is a medication used in conjunction with tests to diagnose adrenal insufficiency, but it is not FDA-approved for the treatment of mild autonomous cortisol secretion, according to prescriber information from Esteve Pharmaceuticals.

Miguel Debono, MD, FRCP, PhD, clinical director and consultant endocrinologist at Sheffield Teaching Hospitals NHS Foundation Trust and University of Sheffield in the U.K., said multiple guidelines recommend patients with a unilateral adenoma undergo an adrenalectomy, but assessing the effects of pharmacotherapy is necessary for adults with bilateral adenomas as well as those who cannot or do not want to undergo surgery.

“This [study] demonstrates a potential route to medical management of mild autonomous cortisol secretion by lowering of blood pressure when using metyrapone,” Debono told Healio.

Researchers collected electronic health record data from 15 adults with mild autonomous cortisol secretion who received metyrapone off-label at Sheffield Teaching Hospitals NHS Foundation Trust from January 2016 to January 2023. Those receiving metyrapone were matched by age and sex with 15 adults who did not receive the drug. Metyrapone was initiated with a 500 mg dose at 6 p.m. and a 250 mg dose at 10 p.m., though a lower dose at 6 p.m. was used for people with frailty or if an individual experienced intolerable adverse events with the higher dose. Morning serum cortisol was collected to assess for adrenal oversuppression at 2 weeks. Researchers assessed BP, HbA1c, body weight and non-HDL cholesterol at baseline and 6 months.

Improvements in blood pressure

Among nine adults receiving metyrapone who had BP data available, there was a 17.7 mm Hg decline in systolic BP from baseline to 6 months (P = .021). The absolute change in diastolic BP during that timeframe was not significant.

Those using metyrapone had greater reductions in both systolic BP (mean change, 17.7 mm Hg vs. +8.7 mm Hg; P = .008) and diastolic BP (mean change, 9.9 mm Hg vs. +3 mm Hg; P = .024) compared with controls who did not use the drug.

The percentage of adults receiving metyrapone who achieved a systolic BP of 140 mm Hg or lower increased from 33% at baseline to 77.8% at 6 months; and the proportion of those who had a diastolic BP of 80 mm Hg or less increased from 44.4% at baseline to 100% at 6 months.

From baseline to 6 months, one adult in the metyrapone group started a new antihypertensive drug vs. four in the control group.

Change in HbA1c, body weight and non-HDL cholesterol were similar between the metyrapone and control groups.

Safety outcomes

Adults who used metyrapone had a median morning serum cortisol of 365 nmol/L. Median adrenocorticotropic hormone increased from 4.5 ng/L at baseline to 7.5 ng/L at 6 months (P = .032).

Two of 15 adults who initiated metyrapone stopped the drug due to adverse events, with one patient discontinuing therapy due to diarrhea at 1 week and the second patient being a woman who experienced increased serum testosterone and dehydroepiandrosterone sulfate levels. No adrenal crises were reported during metyrapone therapy. All other adverse events were deemed to be transient and tolerated, according to the researchers.

“We were pleased to note that the drug is safe to use for this indication but do suggest a cautious approach by monitoring and educating patients about the risk of adrenal insufficiency whilst on this medication,” Debono said.

Debono added that the findings need to be replicated in a well-powered randomized controlled trial.

“It would be interesting to design studies to assess whether medical management can be used to identify those who would benefit most from surgery by testing whether mild autonomous cortisol secretion is the cause or a bystander of an individual’s cardiometabolic risk factors,” Debono said.

For more information:

Miguel Debono, MD, FRCP, PhD, can be reached at m.debono@sheffield.ac.uk or miguel.debono@nhs.net.

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