Prevalence and Characteristics of Familial Hyperaldosteronism

Abstract

Abstract-Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients. (Hypertension. 2011; 58:797-803.)Key Words: familial hyperaldosteronism Ⅲ endocrine hypertension Ⅲ primary aldosteronism Ⅲ aldosterone P rimary aldosteronism (PA) is the most frequent cause of secondary hypertension; it accounts for 5% to 15% of hypertensives, depending on the severity of the disease.

An update on novel mechanisms of primary aldosteronism

“…In the hypertensive adult population, FH1 accounts for 0.5 to 1.0% of PA and occurs equally among women and men (Jackson et al 2002, Pizzolo et al 2005, Mulatero et al 2011Figure 2). However, in the pediatric population, a recent study has described a prevalence of 3% of the chimeric CYP11B1/CYP11B2 gene in hypertensive children (Aglony et al 2011).…”

Visinin-Like 1 Is Upregulated in Aldosterone-Producing Adenomas With KCNJ5 Mutations and Protects From Calcium-Induced Apoptosis

“…FH-I (or glucocorticoidremediable aldosteronism) accounts for Ͻ1% of PA patients. 3 The molecular basis of FH-I is an unequal crossing over between the genes encoding 11␤-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) to produce a chimeric gene transcribed under the control of adrenocorticotropic hormone. 4,5 FH-II is a nonglucocorticoid-remediable form of hyperaldosteronism that displays linkage with chromosomal region 7p22 6 but is of unknown etiology.…”

“…4,5 FH-II is a nonglucocorticoid-remediable form of hyperaldosteronism that displays linkage with chromosomal region 7p22 6 but is of unknown etiology. FH-II is the most frequent form of FH (Յ6% of PA patients) 3 and its diagnosis requires the confirmation of PA in Ն2 family members and FH-I and -III exclusion. 1,2 Finally, FH-III is an autosomaldominant form of PA that has been described in only 2 families so far 7,8 and is caused by germline mutations in the KCNJ5 gene that encodes the potassium channel Kir3.4 (potassium inwardly rectifying channel, subfamily 1, member 5).…”

Update in diagnosis and management of primary aldosteronism

“…In a study of 300 consecutive patients with PA, two patients were diagnosed with FH type I (prevalence of 0.66%). In the remaining 199 families, 12 were diagnosed with FH type II (6%) [16].…”