Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism

J Clin Endocrinol Metab. 2016 Nov;101(11):3989-3996. doi: 10.1210/jc.2016-1963. Epub 2016 Jul 18.

Abstract

Context: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA).

Objective: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening.

Participants: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241). Positive screening for PA was defined as: plasma renin activity (PRA) less than or equal to 1.0 ng/mL · h with serum aldosterone more than or equal to 6 ng/dL. PA was confirmed by a 24-hour urinary aldosterone excretion more than or equal to 12 mcg with urinary sodium more than 200 mmol.

Results: Only 33% (79/241) of participants with an ARR more than 20 had a positive PA screen on HS. On LS, 56% (44/79) of these participants no longer met criteria for positive PA screening. When compared with participants with positive PA screening on both diets, participants with a positive screen on HS but negative on LS exhibited a significantly higher PRA on both diets. Remarkably, of the 48/79 participants who had PA confirmed, 52% had negative PA screening on LS. The distinguishing feature of these participants with "discordant" screening results was a larger rise in PRA on LS resulting in normalization of the ARR and higher Caucasian race prevalence.

Conclusions: Sodium restriction is recommended in hypertension; however, it can significantly raise PRA, normalize the ARR, and result in false interpretation of PA screening. Milder phenotypes of PA, where PRA is not as suppressed, are most susceptible to dietary sodium influences on renin and ARR. Optimal screening for PA should occur under conditions of HS.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aldosterone / blood
  • Aldosterone / urine
  • Algorithms
  • Cohort Studies
  • Diagnostic Errors* / prevention & control
  • Diet, Sodium-Restricted / adverse effects*
  • Down-Regulation*
  • False Negative Reactions
  • Female
  • Humans
  • Hypertension / diet therapy*
  • Hypertension / etiology
  • Hypoventilation / blood
  • Hypoventilation / congenital*
  • Hypoventilation / diagnosis
  • Hypoventilation / physiopathology
  • Hypoventilation / urine
  • Male
  • Mass Screening
  • Middle Aged
  • Practice Guidelines as Topic
  • Renin / blood
  • Retrospective Studies
  • Severity of Illness Index
  • Sleep Apnea, Central / blood
  • Sleep Apnea, Central / diagnosis*
  • Sleep Apnea, Central / physiopathology
  • Sleep Apnea, Central / urine
  • Sodium, Dietary / administration & dosage

Substances

  • Sodium, Dietary
  • Aldosterone
  • Renin

Supplementary concepts

  • Congenital central hypoventilation syndrome