At a Glance

Pseudohypoaldosteronism (PHA) is a rare inherited disorder in which there is impaired response to aldosterone. There are two types of PHA that have very different presentations. Type I PHA usually presents soon after birth. Similar to mineralocorticoid deficiency, there is volume contraction, hyponatremia, hyperkalemia, and renal salt wasting. Blood pressure is low with orthostatic changes. Aldosterone levels are high. The genetic defect can be autosomal dominant or recessive with defects in the mineralocorticoid receptor or a sodium transporter.

Type II PHA has been diagnosed in adolescence or adulthood as hyperkalemia unresponsive to mineralocorticoids. Type II PHA has been referred to as adolescent hyperkalemic syndrome, Spitzer-Weinstein syndrome, subtype renal tubular acidosis IV, Gordon syndrome, mineralocorticoid-resistant hyperkalemia, and chloride shunt syndrome. It appears to result from impaired regulation of chloride channels. Hypertension can be present and basal renin and aldosterone levels are variable.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

For type I PHA, check serum electrolytes, serum pH, plasma renin and aldosterone, urine sodium, and potassium. The disorder is characterized by hyponatremia, hyperkalemia, renal tubular acidosis, high plasma renin and aldosterone, and inappropriately high sodium and low potassium in urine. Glomerular filtration rate is normal, but there is a renal tubular acidosis. Checking serum creatinine helps rule out renal failure as a cause of hyperkalemia. Family history may be informative.

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For type II PHA, the main indicators are hyperkalemia and acidosis unresponsive to mineralocorticoids. Some patients are hypertensive, and basal plasma renin and aldosterone may be normal or decreased. (Table 1)

Table 1.
Serum Potassium Plasma Aldosterone Plasma pH
High High (variable in Type II)


Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Antagonists of aldosterone, such as spironolactone, block the activity of aldosterone and lead to retention of potassium. Sodium intake, intravenous fluid intake, potassium binding resins, mineralocorticoid therapy, and diuretics can affect laboratory measurements.

A number of factors can lead to factitiously high measured values of potassium. Excessive tourniquet time or fist clenching during specimen collection can lead to increases in serum potassium. Hemolysis of specimens and prolonged storage of serum on the clot can lead to increases in potassium. High platelet counts increase serum potassium due to release of potassium from platelets during specimen clotting.

What Lab Results Are Confirmatory?

Evaluation of urinary sodium and potassium in relation to serum electrolytes helps identify an apparent decreased response of the kidney to aldosterone or defects in ion transport. Therapeutic trials can support the diagnosis. Therapy for type 1 PHA commonly includes sodium supplementation, volume replacement, and potassium binding resins. Therapy for Type II PHA usually includes sodium restriction and thiazide diuretics.

Gene sequencing is increasingly coming into use to identify specific gene defects. For type I PHA, mutations have been found in the mineralocorticoid receptor and in subunits of the epithelial sodium channel. Type II PHA has been associated with genetic changes affecting expression or function of WNK1 or WNK4, which are kinases that regulate a sodium-chloride co-transporter. Interpretation of genetic sequencing may be difficult if patients have previously unidentified mutations.