27 Dizygotic twin with glucocorticoid-remediable aldosteronism and different phenotypes
Rood, J.A.J., Geelen, J.A. van, Simsek, S.
Locatie(s): Auditorium 1
Categorie(ën): Parallelsessie
Introduction: Glucocorticoid-remediable aldosteronism (GRA) is a rare form of primary hyperaldosteronism (PHA). This autosomal dominant form of PHA consists of an unequal crossing-over of the CYP11B1 gene (coding for 11-β-hydroxylase, an enzyme involved in the synthesis of cortisol) and CYP11B2 gene (coding for the aldosterone synthase), resulting in an ACTH dependent aldosterone production in the zonae glomerulosa and fasciculata of the adrenal gland. Treatment of GRA consists of ACTH lowering therapy, such as dexamethasone.
Case: Patient 1, a 23-year old Caucasian man was referred to our outpatient clinic with hypertension. Despite the use of irbesartan the blood pressure was 150/100 mmHg. Laboratory tests without renin suppressive medication revealed: aldosterone 1023 pmol/l, renin 6 ng/l, aldosterone renin ratio (ARR) 170.5 pmol/ng, potassium 3.6 mmol/l. MRI of the adrenal glands showed no abnormalities. Because of a family history of hypertension genetic testing was performed, which demonstrated the chimaeric gene, compatible with GRA.
The twin brother, patient 2, was also referred to our outpatient clinic with hypertension taking labetalol. Apart from a blood pressure of 220/160 mmHg, physical examination showed no abnormalities. Laboratory tests revealed: aldosterone 896 pmol/l, decreasing to 120 pmol/l after ACTH suppression, potassium of 5.0 mmol/l. MRI imaging of the adrenal glands showed no abnormalities. Also, in patient 2 the chimaeric gene was found. Patient 2 was treated with dexamethasone daily 1.5 mg, later reduced to 0.25 mg combined with eplerenon 25 mg, with a blood pressure of 135/85 mmHg. Surprisingly, patient 1 responded very well to only nifedipine 60 mg, and was not treated with ACTH lowering therapy.
Discussion: Young patients with PHA and an increased ARR, with on imaging no abnormalities of the adrenal glands, and no lateralisation on venous sampling, should be tested for GRA with a long-PCR test. Despite the same chimaeric genes, the response to antihypertensive treatment may be different. Possible explanations include differences in sodium consumption and concomitant inheritance of genetic factors influencing the blood pressure. In addition, patients with GRA have two normal copies of the aldosterone synthase, as well as 11-β-hydroxylase, besides the chimeric gene, which supresses or stimulate the regulation of this chimaeric gene.