Case Quiz (April 2021)
A third-born female child to consanguineous parents (born at 34 weeks of gestation) was admitted to NICU because of feeding difficulties as she was small for gestational age. Her perinatal history revealed intrauterine growth retardation and oligohydramnios. Laboratory tests showed a mild hypokalemia (K = 3.2 meq/L) with metabolic alkalosis (pH= 7.52 and HCO3 = 33 meq/L) and normal serum Na (139 meq/L). She was subsequently discharged at 5 days of life in good clinical condition with no further investigations.
At 6 months of age, due to her failure-to-thrive, laboratory tests were repeated, and mild hypokalemia (K = 3.1 meq/L) with metabolic alkalosis (pH= 7.52 and HCO3 = 31 meq/L) and normal serum Na (137 meq/L) was confirmed, this time associated with low renin (2.1 mg/dl) and aldosterone (3.5 mg/dl) values, which had not been tested for previously.
An abdominal U/S revealed nephrocalcinosis and echocardiographic examination yielded normal results. Other laboratory tests were as follows: Na 139 mq/l, creatinine 0.3 mg/dl, Cl 101 meq/L and normal urine Ca/Cr ratio. Due to the association of hypokalemia, nephrocalcinosis and failure to thrive, a classic Bartter syndrome type III was suspected, but not confirmed by genetic testing. Blood pressure measurements were not evaluated at this time.
At 8 months of age, she was admitted again to a pediatric nephrology unit for persistent growth failure. Mild polyuria with a urine output of 4 mL/kg/hour and low urine osmolality (108 mOsm/kg) were observed. Urine K/Cr ratio was high (17 mmol/mmol), while FENa was 0.7%.
A new echocardiographic examination revealed mild ventricular septal hypertrophy (thickness of interventricular septum at end diastole IVSD 6.3 mm), which was referred to follow up after 3 months; BP readings taken daily over the four-day hospital stay were occasionally very high. During the following months, the polyuria worsened (8.5 mL/kg/hour), urine Ca/Cr ratio was elevated (0.8), and supine and standing blood pressure values were consistently elevated (>99th percentile for sex, age, and height). Echocardiographic examination at 15 months showed ventricular hypertrophy (IVSD 7–8 mm), which led to the introduction of antihypertensive therapy with calcium antagonists and beta-blockers, with little benefit.
Subsequent laboratory tests showed normal deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycortisol levels.
Diagnostic test was done
Case Answer (April 2021)
Apparent Mineralocorticoid Excess (AME) AME is characterized by ihypertension due to excessive sodium retention and plasma volume, it is caused by a mutation in the HSD11B2 gene encoding the oxydoreductase enzyme 11 β -hydroxysteroide dehydrogenase type 2
High blood pressure values associated with hypokalemia and low renin and aldosterone levels were suggestive of a monogenic form of hypertension. Liddle and Geller syndromes were excluded. Congenital adrenal hyperpeplasia types IV and V had been excluded by routine neonatal screening performed during the first days of life.
Elevated ratio of tetrahydrocortisol (THF) + allo-tetrahydrocortisol (5α-THF) to tetrahydrocortisone (THE) (ratio of 20 for a normal range of 0.75–1.50) together with normal deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycortisol levels is diagnostic.
