Ambulatory Report: Adrenal Incidentaloma

We had a great Ambulatory Report today with the help of our own Christian Ngo and Endocrinologist Dr. Abramowitz, teaching us how to workup/manage adrenal incidentalomas:

Basics:

  • All patients:
    • cortisol (1mg dex suppression test: am cortisol <1.8 rules out and >5 rules in). 24 hour urine cortisol is only used in patients where suspicion for Cushings is high or in patients (ie on HRT or with liver disease) where binding globulins may interfere with the results.
    • metanephrines/catecholamines (24 hour urine: >4x ULN rules in). Free serum metanephrines are only useful in patients who you have a very high suspicion of a pheo.  Remember that TCAs and SNRIs can lead to falsely elevated metanephrines/catecholamines.  
  • Only patients with HTN (no matter how mild):
    • Renin/Aldo. Abramowitz recommends using the “Texas Two-Step” guidelines by Dr. Auchus.  The most important lesson to learn from this paper is that a suppressed renin is more important than an elevated aldosterone.  A renin <1 and aldosterone >15 gives you the diagnosis. Avoid using the ratio of >20 that we learned for Step 1. Remember that aldosterone antagonists (aldactone) will completely interfere with the test. ACE-I/ARBs do to a lesser extent so if their renin/aldo studies are +, then you have the diagnosis, however, if their studies are indeterminate/negative, either refer to Endocrine for assistance or, if it’s safe to do, change them to a CCB or BB for ~ 1 month and then repeat screening.  

Refer to Endocrinology if patient has:

  • Any worrisome features on imaging (>10HU, >4cm, irregular, >50% washout, calcifications, growth >1cm)
  • A functioning adenoma
  • Their tests are indeterminate (especially patients on SNRIs/TCAs whose metanephrine/catecholamine screen might be falsely + or a patient on ACE-I/ARB/aldactone that you feel might be interfering with the tests).

Long term monitoring: (there are no set guidelines)

  • Repeat imaging: 6mo, 12mo, then 24mo and if no changes, you can stop imaging.
  • Repeat labs (cortisol, metanephrines/catecholamines) yearly x 4 years (Dr. Abramowitz is confident you can stop after 2 years if imaging and hormonal studies are all negative/stable).

To Summarize (per Dr. William Young, NEJM):

ai

One thought on “Ambulatory Report: Adrenal Incidentaloma”

  1. Thank you for your thorough post on the management of AI. The recommendation to test every adrenal incidentaloma (AI) for cushing’s brings up 3 important teaching pearls for how to interpret and apply evidence. If anyone has interest in EBM and/or endocrinology and would like to write this up as an editorial/perspective article, please contact me. I think there is a strong case to be made to change practice and guidelines (see #2 and #3 below).

    1) The guideline recommendation to test every patient with an AI is AACE/AAES Grade C level of evidence 3 (which basically means this is weakly supported). An EBM pearl is that any recommendation supported by a weak level of evidence, is unlikely beneficial if uniformly applied to all patients.

    2) Incidence for clinically meaningful cushing’s disease is very low (likely 0.5%). Assuming a 90% sens and 90% spec for 1 mg Dexa suppression test (which I think is a bit optimistic), the LR+ = 9. Thus, if a patient tests positive on low dose DST, the post-test probability is only 5%, meaning 95% of patients will have a false positive result. In the absence of moderate to high prestest probability for Cushing’s disease, you will be chasing down rabbit holes most of the time and subjecting your patient to more and more unnecessary testing.

    3) The incidence of subclinical cushing’s is a bit higher at 5-8%. By definition these patients lack manifestation of full blow Cushing’s syndrome, but may have other more subtle manifestations (DM, HTN) due to prolonged exposure to higher than normal cortisol levels. However, in the absence of any manifestations of subclinical cushing’s, should you refer ALL of your patients with subclinical cushing’s for adrenalectomy? This is an evidence void area — meaning no RCTs or prospective studies. Current consensus is NO, and to only CONSIDER referring younger patients with some manifestation that could plausibly be related to excess cortisol level (DM, HTN, obesity). Even then, we have no idea if taking out adrenal glands in folks with biochemical abnormalities is a good thing or not since the prevalence of DM, HTN, and obesity are so high and caused by many factors (my hunch is no). The moral of the story here is, if you are not going to refer someone for adrenalectomy, don’t test for subclinical cushing’s. Labeling people with a ‘disease’ based on abnormal biochemical results does not help improve quality or quantity of life.

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