P2.248: Unmasking Secondary Hypertension in a Teenager: The Genetic Clue to Non-Classical 11β-Hydroxylase Deficiency

Introduction: Hypertension is an increasing problem in children and adolescents, affecting an estimated 4% of the pediatric population. The most common type is essential hypertension; however, screening for secondary hypertension is an important part of the evaluation in those without typical risk factors. Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency is a rare cause of secondary hypertension that classically presents with virilization of external genitalia in females and precocious puberty in males. This case represents a unique presentation of congenital adrenal hyperplasia diagnosed during the workup for hypertension in an adolescent.

Case Description: A 13-year-old male presented to the nephrology clinic for initial evaluation after an incidental finding of elevated blood pressure (>170/120) at a recent Urgent Care visit. The patient was asymptomatic with no growth or developmental delays. He had a normal BMI and a family history of hypertension in his maternal grandmother. Initial laboratory workup revealed normal electrolytes, renal function, and thyroid function. He also had a normal echocardiogram and renal ultrasound.
Further workup revealed low aldosterone and low renin, with normal plasma metanephrines. Genetics ultimately completed a hypertension-specific gene panel. This resulted for one pathogenic and one likely pathogenic mutation in CYP11B1, consistent with autosomal recessive CYP11B1 related 11-beta-hydroxylase deficiency. The patient was urgently referred to endocrinology where he was started on fludrocortisone and hydrocortisone for the treatment of hypertension and congenital adrenal hyperplasia.

Discussion: In pediatric patients over the age of six years with a family history of hypertension, AAP guidelines do not currently recommend extensive evaluation for secondary causes of hypertension, such as renin and aldosterone levels. Given that this patient presented with severe hypertension that lacked typical features of primary hypertension such as elevated BMI or family history of early-onset hypertension, additional workup was pursued.
Although laboratory studies revealed hyporeninemic hypoaldosteronism, this patient lacked the classical feature of 11-beta-hydroxylase deficiency: premature adrenarche, pseudoprecocious puberty, and hypokalemia. This more subtle presentation can make early diagnosis challenging, especially in the absence of hallmark signs. Patients with 11-beta-hydroxylase deficiency remain at risk for adrenal crises, adrenal rest tumors, and hypertension-mediated end-organ damage if left untreated. Therefore, timely diagnosis and initiation of corticosteroid therapy are essential to improve patient outcomes.

Conclusion: In the initial evaluation of hypertension in children and adolescents, it is vital to keep a broad differential diagnosis. This case is a reminder of the importance of a thorough workup in patients whose clinical picture does not quite fit primary hypertension. There is not currently strong evidence to support the extent of workup for hypertension, thus further research is needed to better understand which patients require detailed workup.