Case Quiz  (April 2016)

A 2.5-year-old female was referred for evaluation of polydipsia and polyuria. She was the third child of related parents. Both parents and her two older siblings were healthy and none of her relatives were known to have polydipsia or polyuria. The pregnancy was uneventful and the delivery was spontaneous at term. Since 6 months of age, the patient was noted to have a conspicuously high fluid consumption and poor solid food intake. In addition, she was noted to urinate frequently, perhaps as frequently as every 30-60 min.

Physical examination at that time revealed an alert, thin girl. Her height was 84 cm (<25th percentile) and her weight was 9.5 kg (<5th percentile). The head circumference was 47 cm (5th percentile). The systolic BP was 120-140 mmHg and the diastolic 80-100 mmHg. No other abnormal findings were noted on physical examination. Initial laboratory data showed the specific gravity of random urine specimens to be between 1002 and 1010. The reaction was acidic or neutral. The urine sediment was normal at all times and multiple cultures of clean-voided urine specimens were negative. Biochemical analysis of serum revealed the following values: sodium, 138 mEq/l; potassium, 2.4 mEq/l; chloride, 94 mEq/l; pH, 7.5; carbon dioxide content, 35 mEq/l. Serum calcium concentration was 9.7 mg/dl and serum phosphorus level was 4.2 mg/dl. Serum creatinine level was 0.4 mg/dl and blood urea nitrogen was 8 mg/dl. The daily fluid intake averaged 2000 ml. The maximum urine concentration after fluid deprivation for 12 h was 1010 and this concentrating defect was also vasopressin-resistant. Serum aldosterone level (2.5 ng/dl) and plasma renin activity (15 µg/ml) were at the lower limits of normal. The following additional tests were normal: IVP, VCUG, bone age, serum urinary and blood steroid levels (cortisol, deoxycorticosterone, progesterone and pregnanetriol), and thyroid function studies.

Hypertension was corrected initially with hyralazine and subsequently with captopril. Hypokalemia worsened by medications (2.1 mEq/l). With correction of hypokalemia and a behavioral conditioning program, the percentage of calories taken as solid food increased from 20% to 60%, with a total daily calorie intake of more than 100 Kcal/kg. The significant failure to thrive at presentation was partially corrected; however, the patient remained below the 5th percentile on the growth curve for height and weight. An improvement in the polyuria was also noted; however, the patient was unable to concentrate her urine to a specific gravity of more than 1010.

Hydralazine and captopril were discontinued and the correct medication was given.

Case Answer (April 2016)

Liddle's syndrome is a rare disorder of tubular transport simulating primary aldosteronism but with negligible aldosterone secretion. Patients with this syndrome fail to respond to spironolactone but are sensitive to triamterene or amiloride. Invariable features of this disorder are salt retention, hypertension, renin suppression, hypokalemia and metabolic alkalosis. Review of the literature suggests that growth failure is also a significant feature of this syndrome.Characteristic symptoms and laboratory findings including polyuria, hypertension, hypokalemic alkalosis and hyporeninemic hypoaldosteronism, suggested the diagnosis of Liddle's syndrome in this patient. Furthermore, the lack of therapeutic response to spironolactone with a good response to triamterene confirmed this diagnosis. Growth failure was not a prominent feature and several other reports either did not mention growth, or found it to be normal. However, failure to thrive was a significant clinical manifestation in our patient at the time of presentation. Growth failure is a frequent concomitant of other syndromes manifesting polyuria and polydipsia such as Bartter's syndrome, nephrogenic diabetes insipidus and primary aldosteronism. It is postulated that children with polydipsia fail to grow and gain weight because they constantly imbibe a low caloric intake. In our patient we were able to decrease the polydipsia and increase the caloric intake to over 100 cal/kg per day, so that the failure to thrive was partially corrected and a stable growth velocity was achieved.Liddle's syndrome should be considered in any infant or young child who presents with failure to thrive and/or polyuria and polydipsia. An elevated blood pressure in conjunction with hypokalemic alkalosis would be suggestive of the diagnosis of Liddle's syndrome.