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Persistent adrenal insufficiency may follow adrenalectomy to treat primary aldosteronism
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Unilateral adrenalectomy to treat primary aldosteronism can lead to both transient and persistent adrenal insufficiency, and clinicians should perform postoperative adrenocorticotropic hormone stimulation testing to avoid potential adrenal crisis in patients, according to an analysis of registry data.
“In this study, we prospectively investigated [primary aldosteronism] patients who underwent unilateral adrenalectomy and identified a surprisingly high number of cases with postoperative adrenal insufficiency,” Daniel A. Heinrich, MD, a clinician scientist at LMU Munich, and colleagues wrote. “Even though, at average, the biochemical presentation was less severe and of shorter duration than in other entities of endogenous hypercortisolism, clinicians treating [primary aldosteronism] patients should to be aware of the risk of development of postoperative adrenal insufficiency as a potentially life-threatening condition.”
Heinrich and colleagues analyzed data from 100 consecutive patients (51 men) who underwent unilateral adrenalectomy between 2014 and 2018 to treat primary aldosteronism as well as postoperative adrenocorticotropic hormone (ACTH) stimulation testing at discharge to identify adrenal insufficiency; 67 patients also underwent preoperative ACTH stimulation testing. Moderate adrenal insufficiency was defined as a serum cortisol level between 13.5 µg/dL and 17 µg/dL; severe adrenal insufficiency was defined as a serum cortisol level of less than 13.5 µg/dL.
Within the cohort, 13 patients (six men) had postoperative ACTH stimulation cortisol levels of less than 13.5 µg/dL, and 14 patients (four men) had stimulation serum cortisol values between 13.5 µg/dL and 17 µg/dL. There were no between-group differences in baseline characteristics in patients with moderate, severe or no adrenal insufficiency, according to researchers.
Among the 67 patients who underwent a preoperative ACTH stimulation test, none had abnormal results, the researchers wrote (mean stimulated serum cortisol, 23 µg/dL). The researchers noted that 1 mg overnight dexamethasone suppression testing, salivary cortisol and urinary cortisol excretion before surgery failed to predict which patients developed adrenal insufficiency.
Among patients who developed severe or moderate adrenal insufficiency, 17 underwent repeat ACTH stimulation testing at least once after diagnosis (median follow-up, 293 days). Hydrocortisone therapy was continued for a median of 340 days. During follow-up, one patient with severe adrenal insufficiency was hospitalized for an acute adrenal crisis.
“Based on our findings we suggest performing postoperative ACTH stimulation tests in all [primary aldosteronism] patients undergoing adrenalectomy,” the researchers wrote. “Further analysis is required to identify markers that would predict the development of clinically relevant postoperative adrenal insufficiency.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
Perspective
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John W. Funder, MD, PhD, FRACP, FRCP
This study brings a timely reminder that after unilateral adrenalectomy, the contralateral adrenal may be sluggish in responding to ACTH. Twenty-seven of the 100 consecutive patients showed cortisol levels in response to ACTH of less than 13.5 ug/dL (n=13: severe adrenal insufficiency) and between 13.5 ug/dL and 17 ug/dL (n=14 moderate adrenal insufficiency). There would appear to be no pre-adrenalectomy test able to predict the likelihood of subsequent adrenal insufficiency. However, without questioning the data presented, there are a number of issues that might be addressed before the extent (not the existence) of adrenal insufficiency post-surgery occurs in other centers.
First, it would be good to know whether or not there are data on cortisol levels on either side from adrenal venous sampling and, if so, whether these might (or might not) correlate with the post-operative state. Second, there is a clear difference between the severe and moderate urinary cortisol values (81 vs. 170 ug per 24 hours), but none for plasma cortisol (13.1 vs. 13.3 ug/dL). Third, in all groups, median plasma potassium levels are between 3.4 mmol/L and 3.6 mmol/L, suggesting that over a quarter of the patients in all groups did not achieve biochemical success on the Primary Aldosteronism Surgical Outcome (PASO) criteria.
Fourth, it may be instructive to know how long the patients had been diagnosed with hypertension before they underwent adrenalectomy; note that the severe group was 5 years older than the moderate group. Fifth, it would similarly be instructive to know how the three groups compared in terms of total, partial and absent biochemical or clinical success. Finally, the authors might speculate as to the cause of the persistent adrenal insufficiency in the two patients now approaching the third year of requiring supplemental hydrocortisone and to seek possible differences between these two and the other eleven in the severe cohort.
These are questions arising rather than criticisms; the report reinforces studies previously published and appropriately acknowledged. Just as there is now compelling evidence that all primary aldosteronism patients with bilateral disease on mineralocorticoid receptor antagonists should have plasma renin measured 6 months after starting medication (Hundemer GL, et al. Lancet Diabetes Endocrinol. 2018; doi:10.1016/S2213-8587(17)30367-4.), the present study clearly demonstrates the importance of routinely measuring cortisol as well as aldosterone after surgery for an aldosterone-producing adenoma.
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