Pseudohypoaldosteronism Treatment & Management

Patients with pseudohypoaldosteronism (PHA) who are experiencing hypovolemia and shock should receive fluid resuscitation with isotonic sodium chloride solution at 20 mL/kg over 30-60 minutes. Fluid boluses may be repeated until signs of improved perfusion to vital organs are observed.

Patients with severe hyperkalemia should receive intravenous (IV) 10% calcium gluconate 0.5-1 mL/kg to protect the heart muscle and sodium bicarbonate to shift potassium intracellularly until cation exchange resins start to lower the serum potassium level. IV administration of glucose 0.5-1 g/kg and insulin 0.1 U/kg over 30 minutes should also be considered in severe hyperkalemia.

Agents that may be used in the management of PHA include the following (see Medications):

• Potassium-binding resins
• Prostaglandin inhibitors
• Alkalizing agents
• Hydrochlorothiazide (in PHA type II [PHA-II])

Angiotensin-converting enzyme (ACE) inhibitors should not be used in patients with PHA-II, because they can aggravate hyperkalemia, which may be life threatening.

No surgical management is needed in most cases. Consultations with an endocrinologist and a nephrologist are appropriate. Genetic counseling should be provided to the patient by a qualified professional.

Renal pseudohypoaldosteronism type I

Patients with renal PHA type I (PHA-I) exhibit a characteristic lack of improvement despite administration of large doses of mineralocorticoids. Therapy consists of fluid and sodium supplementation, with requirements being higher early in infancy and tending to diminish over time. Large doses may be necessary to correct serum electrolyte abnormalities.

Sodium chloride supplementation is followed by significant clinical improvement and correction of electrolyte abnormalities. Expansion of extracellular fluid (ECF) increases renal tubular flow and sodium chloride delivery to the distal nephron, thereby creating a favorable gradient for secretion of potassium despite the lack of mineralocorticoid action.

Multiple target organ defects pseudohypoaldosteronism type I

Although administration of exogenous mineralocorticoids is ineffective in correcting the abnormalities in multiple target organ defects (MTOD) PHA-I, ingestion of a high-sodium and low-potassium diet is generally effective in preventing volume depletion and in partially reducing, though not completely correcting, the hyperkalemia. Patients may require oxygen for episodes of dyspnea and cyanosis associated with lower respiratory tract infections.

Pseudohypoaldosteronism type II

In some patients with PHA-II, restriction of dietary sodium has resulted in normalization of blood pressure and of plasma potassium, plasma aldosterone, plasma renin, and urinary calcium levels. However, correction of acidosis with bicarbonate administration does not correct the hyperkalemia.

In patients with renal PHA-I, sodium chloride supplementation during infancy can reverse hyponatremia and hyperkalemia, improve symptoms, and permit improved growth. Ingestion of a high-sodium (10-15 mEq/kg/day) and low-potassium (0.6 mEq/kg/day) diet is generally effective in preventing both volume depletion and hyperkalemia.

After infancy, reduction or discontinuance of sodium chloride supplementation is possible when patients develop an appetite for salt and are asymptomatic while eating a normal diet. Symptoms may recur with salt restriction in older children and adults.

For patients with MTOD PHA-I, dietary sodium supplementation (10-15 mEq/kg/day) and a low-potassium diet (0.6 mEq/kg/day) are recommended. Patients typically respond poorly to sodium chloride supplementation alone.

In patients with PHA-II, dietary sodium supplementation and potassium restriction may correct the hyperkalemia and acidosis.

No activity restrictions are necessary once adequate replacement therapy is instituted.

The rare occasions on which unintentional salt or fluid restriction is most likely to occur include hospitalization, surgery, major accidental trauma, and life-threatening emergency. Thus, wearing lifelong medical identification (eg, a MedicAlert necklace or bracelet) is imperative as another means of alerting healthcare professionals who may be unfamiliar with the patient’s rare medical condition.

Ensure that the IV fluids the patient is receiving contain no potassium. Once fluid and sodium deficits are corrected, administer maintenance fluids at 120-160 mL/kg/day, and provide sodium supplementation at 20-40 mEq/kg/day. If differentiating adrenal insufficiency from PHA-I is impossible at presentation, treat patients with glucocorticoids once electrolytes, blood sugar, cortisol, and adrenocorticotropic hormone (ACTH) concentrations are obtained until the diagnosis of PHA-I is confirmed.

While in the hospital, patients should be closely monitored and frequently reevaluated. Monitor weight and fluid intake and output every 12 hours, and recalculate the infusion rate if fluid balance becomes negative. Monitor blood pressure and serum and urine electrolytes closely, watching for normalization of blood pressure as well as of serum electrolyte levels. Electrocardiographic (ECG) monitoring is warranted.

In the outpatient setting, maintain fluids at 120-160 mL/kg/day. Ensure that the patient follows a high-sodium and low-potassium diet. Sodium supplementation at 20-40 mEq/kg/day until patients are aged 1-2 years may be provided as 20% sodium chloride (at 3 mEq/mL) every 6 hours and added to patients’ feedings.

Closely monitor serum electrolytes, blood pressure, weight, and height. Watch for dehydration and hypovolemia. Observe patients with MTOD PHA-I for episodes of respiratory distress.