A 20-year-old woman with fatigue and palpitations
2. Which is the most likely cause of hypokalemia in this patient?
- Vomiting
- Liddle syndrome
- Bartter syndrome
- Gitelman syndrome
- Diuretic use
Her laboratory tests reveal hypokalemia and hyponatremic-hypochloremic metabolic alkalosis with compensatory respiratory acidosis. In metabolic alkalosis, the expected respiratory compensation is an increase of 0.7 mm Hg in Pco2 for each 1-mEq/L increase in bicarbonate. Therefore, the expected Pco2 is 67, close to the patient’s actual value of 69.
Protracted vomiting with loss of gastric acid juices could be a cause of the metabolic disturbances in this young woman, although she did not mention vomiting during the history.
Liddle syndrome, or pseudoaldosteronism, is a rare autosomal dominant disorder characterized by altered renal epithelial sodium channels, excessive sodium retention, and resultant hypertension. Hypokalemia and alkalosis are seen in Liddle syndrome, but the absence of hypertension in our patient makes Liddle syndrome unlikely.
Bartter syndrome is an inherited autosomal recessive disorder of the sodium-potassium-chloride cotransporter in the thick ascending loop of Henle, resulting in impaired reabsorption of chloride and sodium. Bartter syndrome mimics chronic loop-diuretic use and is associated with hypercalciuria. Bartter syndrome is possible in this patient; however, patients with Bartter syndrome are usually diagnosed in infancy or childhood and have evidence of growth impairment.
Gitelman syndrome is an autosomal recessive disorder of the thiazide-sensitive sodium-chloride cotransporter. Although Gitelman syndrome is more common than Bartter syndrome and presents at older ages, it is not usually associated with such profound metabolic alkalosis. Gitelman syndrome mimics chronic use of thiazide diuretics and is associated with hypocalciuria.
Diuretic use could also cause the metabolic disturbances described; however, the patient denied taking diuretics.
The most common cause of hypokalemia in clinical practice is diuretic use.4 In this young woman with unexplained hypokalemia, the most likely cause is either undisclosed self-induced vomiting or diuretic abuse. The degree of metabolic alkalosis suggests vomiting, since metabolic alkalosis this severe is usually seen only with protracted vomiting. Bartter and Gitelman syndromes are included in the differential diagnosis, but they are much less common than hypokalemia associated with diuretics or self-induced vomiting.5
3. Which test could help elucidate the cause of hypokalemia in this patient?
- Ratio of plasma aldosterone to rennin
- Urine chloride
- Ratio of urinary potassium to creatinine
- Urinary anion gap and urinary pH
APPROACH TO HYPOKALEMIA
Determining the cause of hypokalemia starts with a thorough history and physical examination. The history should focus on drugs such as diuretics and laxatives. Women should be asked about their menstrual history since irregular periods may suggest an eating disorder. The physical examination should focus on signs that suggest self-induced vomiting, such as dry skin, dental erosions, enlarged parotid glands, and calluses or scars on the knuckles.
Patients with an unclear cause of hypokalemia after a thorough history and physical examination can be categorized into one of three groups based on blood pressure and acid-base status:
- Hypokalemia, hypertension, metabolic alkalosis
- Hypokalemia, normal blood pressure, metabolic acidosis
- Hypokalemia, normal blood pressure, metabolic alkalosis.
Hypokalemia, hypertension, metabolic alkalosis
The blood pressure provides an important clue in the evaluation of hypokalemia. The combination of hypertension, hypokalemia, and alkalosis should raise concern for hyperaldosteronism or pseudoaldosteronism. Primary hyperaldosteronism from an adrenal adenoma (Conn syndrome) is characterized by a plasma aldosterone-renin ratio of greater than 20.6,7 In contrast, patients with secondary hyperaldosteronism due to renovascular disease have a plasma aldosterone-renin ratio of less than 10. Patients with pseudoaldosteronism have low aldosterone and renin levels and hypertension. Since our patient has a normal blood pressure, testing the plasma aldosterone and renin levels would not help determine the cause of her hypokalemia.
Hypokalemia, normal blood pressure, metabolic acidosis
Patients with normal blood pressure, hypokalemia, and normal plasma anion gap acidosis either have renal tubular acidosis or have lost potassium because of diarrhea or laxative abuse. In a patient who denies taking laxatives or denies a history of diarrhea, checking the urinary anion gap and urinary pH may help differentiate the cause of acidosis and hypokalemia.
The urinary anion gap, calculated by the equation sodium + potassium − chloride, is an indirect estimate of hydrogen excretion in the form of ammonium ion8; the normal value is 0 to 10 mEq/L. A negative value represents increased hydrogen excretion in response to systemic acidosis from gastrointestinal or renal loss of bicarbonate (proximal renal tubular acidosis). A urinary pH greater than 5.5 in the setting of systemic acidosis suggests impaired ability of the kidneys to acidify urine and raises the possibility of renal tubular acidosis.
This patient has metabolic alkalosis, so calculation of the urinary anion gap would not be helpful.
Hypokalemia, normal blood pressure, metabolic alkalosis
Patients such as ours, with normal blood pressure, hypokalemia, and alkalosis, have been vomiting, have used diuretics, or have an inherited renal tubulopathy such as Bartter or Gitelman syndrome. Usually, differentiating Bartter and Gitelman syndromes from chronic vomiting or diuretic use is done with the history and physical examination. However, in patients with a questionable history and a lack of findings on physical examination, checking the urinary chloride, potassium, calcium, and creatinine may be helpful.
A urinary potassium-creatinine ratio greater than 15 suggests renal loss, whereas a ratio less than 15 suggests extrarenal loss.9
Patients who are taking a diuretic or who have Bartter or Gitelman syndrome have a high urinary chloride concentration, ie, greater than 20 mmol/L, whereas patients with hypokalemia and alkalosis from chronic vomiting tend to have a concentration less than 10 mmol/L.10
Table 1 summarizes an approach to the evaluation of unexplained hypokalemia based on blood pressure and acid-base status.
A HIDDEN HISTORY
On further questioning, the patient admits to an 8-year history of daily self-induced vomiting in an attempt to lose weight, in addition to multiple hospitalizations for hypokalemia and a previous diagnosis of an eating disorder.
