Endocrine Abstracts

Familial hyperaldosteronism type I (FH-I) is a rare subset of primary aldosteronism (PA) with an autosomal domintant pattern of inheritance. The molecular basis was determined to be from the unequal crossing over of the 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in a chimeric gene duplication. This in turn leads to the ectopic synthesis of aldosterone in the zona fasciculata of the adrenal glands under the regulation of adrenocorticotropin along with hybrid steroids. While affected subjects typically have early onset hypertension, there is considerable phenotypic diversity. We describe the first ever series of three individuals with FH-I in a Singaporean kindred. The proband, an 18-year-old Chinese male, was initially diagnosed with primary aldosteronism during evaluation of normokalemic hypertension detected at health screening. A strong family history of early onset hypertension prompted further assessment of the proband’s affected family members. His brother (aged 20) was diagnosed with essential hypertension, and his father (aged 50) had a personal history of early onset hypertension and coronary artery disease. Biochemical evaluation of both the proband and his brother revealed hyperaldosteronism, suppressed plasma renin activity with an elevated plasma aldosterone to renin ratio. Intravenous saline loading failed to suppress plasma aldosterone confirming primary aldosteronism. Computed tomographic imaging did not reveal any adrenal adenoma or hypertrophy. As FH-I was suspected, genetic analysis with long polymerase chain reaction was performed and all three subjects tested positive for the chimeric CYP11B1/B2 gene. The proband and his brother were initially treated with low-dose dexamethasone up to 0.5 mg/day and while this led to improvement in hypertension, blood pressure readings did not normalize. Due to the development of steroid-induced acne and weight gain, dexamethasone was switched to spironolactone with good effect. The proband’s father was managed at another centre and declined a change in therapeutics as his blood pressure control was satisfactory. To our knowledge, this is the first report of FH-I in a Singaporean Chinese kindred and possibly the first in the region. This contributes to our local experience in managing this rare hereditary form of PA, and forms the basis for genetic screening and surveillance of this pedigree. In agreement with the Endocrine Society Clinical Practice Guidelines for PA, we recommend genetic testing for FH-I in subjects with young onset of PA (<20 years), in those with a family history of PA or strokes at a young age (<40 years).