Endocrine Abstracts

Introduction: Primary aldosteronism (PA) is the most frequent cause (55%) of secondary arterial hypertension (HTN) in individuals under 40 years old. Hereditary forms, known as familial hyperaldosteronism (FH), should be considered in patients under 20 years of age, and in cases of a family history of early-onset HTN, PA, cerebral hemorrhage before the age of 40, or bilateral adrenal hyperplasia.

Case Report: We report the case of a 17-year-old asymptomatic patient with no personal medical history, referred for incidentally discovered HTN, secondary to PA (aldosterone 605ng/l, renin <2.1mU/l) with normal adrenal glands on abdominal CT-scan. The patient’s father had a history of HTN diagnosed following a cerebral hemorrhage at the age of 26. No mutations associated with FH had been identified. Our patient’s workup confirmed a glucocorticoid-remediable aldosteronism (aldosterone 47ng/l after Liddle’s test). Long-read DNA sequencing using Oxford Nanopore Technologies revealed a pathogenic heterozygous CYP11B1-CYP11B2 chimeric gene (PMID 1472060), confirming a diagnosis of FH type 1 (FH-I). The patient’s HTN has since been managed with Dexamethasone.

Discussion: FH-I accounts for 1% of PA cases and is caused by a chimeric gene resulting from the fusion of the CYP11B1 promoter with the coding region of CYP11B2. This leads to ectopic ACTH-dependent aldosterone production in the zona fasciculata. Transmission is autosomal dominant. This case highlights the diagnostic value of long-read DNA sequencing in the molecular diagnosis of FH-I. This technique detects certain mutations, such as structural genetic rearrangements, which are often missed by conventional short-read sequencing methods. Accurate molecular diagnosis allows a targeted treatment and facilitates genetic family screening.

Keywords: Endocrine hypertension, familial hyperaldosteronism, genetic diagnosis