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					                                                                                               CAT 1.4.05
                                                               Primary hyperaldosternoism and hypokalemia
                                                                               Genji Terasaki & EBM class
Clinically Appraised Topic
Evidence-Based Medicine (January 4, 2005)
Theme: Diagnosis

Clinical Bottom Line:
There is no evidence to suggest that potassium levels can be used to predict primary hyperaldosteronism.

Question: What is the diagnostic value of hypokalemia in predicting hyperaldosteronism in hypertensive

Search strategies:

Cochrane             “hyperaldosteronism”                       1 review: not relevant
Clinical Evidence    Search “hyperaldosteronism” OR             No relevant articles.
                     “aldosteronism”                            No relevant articles under ‘Endocrine” or
                                                                “Cardiovascular” sections either.
TRIP                 “hyperaldosteronism”                       61 diagnosis articles: none related to potassium

                                                                1 EBM hit: Massien-Simon C. article with a nice
                                                                summary and LRs for potassium <4.0.
PubMed               Clinical queries
                     “Hyperaldosteronism”                       61 items  none specifically related to potassium

                                                                Note: one review article by Rayner on screening
                                                                for hyperaldosteronism mentions that
                                                                “hypokalaemia is a poor screening test with 70%
                                                                of proven cases having normal serum potassium
                     ("Potassium/blood"[MAJR] OR                47 items  really no relevant articles except for a
                     "Potassium/diagnostic use"[MAJR]) AND      French study by Massien-Simon C.
                     "Hyperaldosteronism"[MeSH]                     ** a ‘relevant articles’ search did not yield

                     "Potassium"[MeSH] AND                      839 items  too many.
                     "Hyperaldosteronism"[MeSH]                    ** limited to ‘RTC’  4 articles, of which
                                                                were none relevant.

         1) a difficult search with only one relevant article published in France.
         2) I did some additional background reading on the subject (Up-To-Date). The presence of
hypokalemia is apparently dependent on the sodium intake and volume status of the patient; sodium
depleted or deprived patients with primary hyperaldosteronism can be normokalemic.
                   “Hypokalemia is present at some time in most patients with primary aldosteronism who
                   are on an adequate sodium intake [1,13]. Two factors contribute to the urinary potassium
                   wasting in this setting: the hypersecretion of aldosterone, which directly promotes
                   potassium secretion in the cortical collecting tubule; and adequate delivery of sodium and
                   water to the distal secretory site [16]. As an example, increasing sodium intake and
                   therefore distal delivery will exacerbate the hypokalemia in this setting, since aldosterone
                   secretion will not be appropriately suppressed by the volume expansion [17]. If, on the
                   other hand, distal flow is reduced because of effective circulating volume depletion, then
                   normal potassium balance may be maintained despite the excess mineralocorticoid.”

Massien-Simon et al: Presse Medicale 1995; 24 (27): 1238-1242.
                                                                                                 CAT 1.4.05
                                                              Primary hyperaldosternoism and hypokalemia
                                                                                Genji Terasaki & EBM class
This article is in French but an EBM group reported the following information from their critical appraisal:
       Design: 159 patients (aged mean ~45, 52% female) : 60 with Conn's adenoma, 50 with primary
       hypertension and 49 normal controls. Non-independent unblinded reference standard, applied in
       some patients from a non-consecutive inappropriate spectrum. Reference standard is defined as
       hypertension, potassium < 3.9 mmol/l, supine plasma aldosterone > 150 pg/ml, erect plasma renin <
       15 pg/ml, unilateral adrenal tumour on CT, and lateralised secretion of aldosterone on adrenal vein

      Relevant results:
                           Primary Hyperaldo          Normal
      K<4.0 mmol/L                 58                 4

      The calculated +LR and –LR are astonishing: 24 and 0.035, respectively.

      Comments: There are several fatal flaws but the most obvious lies in the reference standard for
      primary aldosteronism which among other things includes potassium level <3.9 mmol/l.

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