Hyperaldosteronism??  1/6/2018

QUESTION--I have a question about a patient who is showing abnormal lab values. She is 36 y/o female with history of hypertension postpartum at age 34 with no other past history. Her BP were ranging 160/70's-180/100s. She was put on Labetolol 200mg twice daily and her blood pressure are now ranging 115/60-130/70's. She does not have a significant family history of hypertension, early stroke or CAD. She had her Renin concentration and Aldosterone levels checked while on labetolol and came to me with following numbers:

1st check) Renin Concentration (not activity):  <2.0 microIU/mL  (2.8-39.9 )
Aldosterone Concentration:  308 pmol/L ( 118-946)

2nd Check) Renin: 2.5 microIU/mL  (2.8-46.1)
Aldosterone: 150 pmol/L (118-946)
A/R ratio: 60 pmol/L/microIU/mL (normal 90.99)

3rd check)  Renin: 2.7 microIU/mL (2.8-46.1)
Aldosterone: 313 pmol/L (118-946)
A/R ratio: 115 pmol/L/microIU/mL (normal 90.99)

4th Check) different lab, performed during follicular phase of menses
Renin 1.0 ng/L (2.8-46.1 )   Aldosterone 221 pmol/L (118-946 )
A/R ratio 221 pmol/ng (normal <53) Her K ranges in 4.5-5.0 and catecholamines and metanephrines are normal.

She has low renin, normal aldosterone, and elevated AR ratio each check and I am trying to figure out the next step?Should I try taking her off Labetolol as I read this can interfere with the hormone assay causing false elevation of AR ratio due to beta-adrenergic effect, switch to a non interfering BP medication, then check aldosterone and renin levels again?  Or should I just go straight for the salt loading test and check the urine Aldosterone and Na levels?

RESPONSE- Labetalol has beta 1/2 and alpha 1 receptor (ratio approx. 3:1) blocking effects.. In general, betablockers can reduce the concentrations of aldosterone and renin and may lead to a false elevation of the ARR. Central alpha blocking agents may also lead to an elevation of the ARR.
Taking a look at the Endocrine Society Guideline from 2016 on “The management of primary aldosteronism: case detection, diagnosis, and treatment. The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 5, 1 May 2016, Pages 1889–1916’--
Tables 3, 4, and 5 nicely summarize important points in evaluating patients with possible primary aldosteronism. Table 3 depicts factors that may lead to false positive or false negative ARR results. Table 4 suggests an approach how to best measure the ARR including which medications to withdraw before measuring aldosterone and renin concentrations. Table 5 lists medications with minimal effects on plasma aldosterone levels that can control hypertension during case finding and confirmatory testing for primary aldosteronism.

Regarding the 4 checks on aldosterone and renin levels in this patient, the absolute aldosterone level certainly should be taken into account as well as the menstrual cycle. Plasma aldosterone concentrations measured during the menses or the proliferative phase are similar to those in men but rise briskly in the luteal phase. Renin levels are typically lower in premenopausal women, therefore the ARR higher than in men for all phases of the menstrual cycle. False positives can occur during the luteal phase if renin is measured as DirectRC and not PRActivity. To screen women at risk for primary aldo in the follicular phase is reasonable.

Looking at the absolute plasma aldosterone level in all 4 blood checks, the highest one was "only" approx. 11 ng/dL and the lowest one approx. 5 ng/dL, all measured while K was above 4 mmol.

I assume this patient did not have any clinical features of hypercortisolism and that a 1 mg dexamethasone suppression test had not been performed. Certainly, there could be mineralocorticoids other than aldosterone alone, i.e. DOC etc. which could stimulate the MR. However, I doubt that this patient does have "true" / pure primary aldosteronism / aldosterone excess. Obviously, the BP is controlled with the current antihypertensive and certainly, there are forms of "normotensive" PA in the spectrum of patients with PA.

One could certainly look at Table 4 of the Endocrine Society Guidelines and consider point 4a and then recheck the ARR. From a practical standpoint, my recommendation would be to perform the salt loading test and see if plasma / urinary aldosterone is suppressible (considering urinary Na).
Christian Koch, MD