Apparent mineralocorticoid excess and the long term treatment of genetic hypertension

Razzaghy-Azar, Maryam; Yau, Mabel; Khattab, Ahmed; New, Maria I.

doi:10.1016/j.jsbmb.2016.02.014

Cited by 23 publications

(12 citation statements)

References 24 publications

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“…with AME are often found to be the offspring of consanguineous families, like our patient [10]. Multiple hydrogen bonds and salt bridges between polar residues stabilize the tertiary structure of 11 β-HSD2, and some mutations causing loss of these interactions result in severe AME.…”

Section: Discussionmentioning

confidence: 81%

Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child

Gülhan¹,

Unsal

Baltu³

et al. 2022

Blood Pressure Monitoring

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A genetic defect of 11 β-hydroxysteroid dehydrogenase causes apparent mineralocorticoid excess syndrome. Since 50 days of life, our patient was hospitalized several times for various reasons including hypokalemia. At the age of 3.3 years, she was diagnosed with severe hypertension (160/120 mmHg). She also had left ventricular hypertrophy and hypertensive retinopathy and referred to our center. Her renal function and electrolytes were normal except for hypokalemia. She was on captopril treatment; nifedipine and propranolol were added. Plasma renin and aldosterone concentrations were 1.13 pg/ml (1–8.2 pg/ml) and 12.2 ng/dl (35–300 ng/dl), respectively. Severe hypertension, hypokalemia, low renin and aldosterone levels pointed to the diagnosis of apparent mineralocorticoid excess syndrome. Strict salt-restricted diet and potassium citrate were ordered. Genetic analysis of the HSD11B2 gene showed c.623G>A (p.Arg208His). Spironolactone was initiated. On follow-up, amiloride was added and her blood pressure was controlled. In patients with severe HSD11B2 mutation, combination therapy of spironolactone with amiloride could be effective in controlling blood pressure.

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Section: Discussionmentioning

confidence: 81%

Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child

Gülhan¹,

Unsal

Baltu³

et al. 2022

Blood Pressure Monitoring

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“…The goal of AME treatment is to control BP and correct electrolyte disturbance [33][34][35]. Therapeutically, it is important to reduce dietary sodium [36].…”

Section: Discussionmentioning

confidence: 99%

“…However, dexamethasone cannot correct hypertension and hypokalemia in AME patients, and long-term medication has major adverse effects [37]. Therefore, the treatment of AME with low-dose dexamethasone (1.5-2 mg/day) should be initiated in a monitored setting [35]. Use of a calcium channel blocker as an adjunctive treatment to control hypertension was reported to be helpful [24].…”

Section: Discussionmentioning

confidence: 99%

Apparent mineralocorticoid excess caused by novel compound heterozygous mutations in HSD11B2 and characterized by early-onset hypertension and hypokalemia

Peng

Yang

et al. 2020

Endocrine

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Purpose Apparent mineralocorticoid excess (AME) is an ultrarare autosomal recessive disorder resulting from deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) caused by mutations in HSD11B2. The purpose of this study was to identify novel compound heterozygous HSD11B2 mutations in a Chinese pedigree with AME and conduct a systematic review evaluating the AME clinical features associated with HSD11B2 mutations. Methods Next-generation sequencing was performed in the proband, and Sanger sequencing was used to identify candidate variants in family members, 100 hypertensives, and 100 healthy controls. A predicted structure of 11βHSD2 was constructed by in silico modeling. A systematic review was used to identify cases of HSD11B2-related AME. Data for genotyping and clinical characterizations and complications were extracted. Results Next-generation sequencing showed novel compound heterozygous mutations (c.343_348del and c.1099_1101del) in the proband with early-onset hypertension and hypokalemia. Sanger sequencing verified the monoallelic form of the same mutations in five other relatives but not in 100 hypertensives or 100 healthy subjects. In silico structural modeling showed that compound mutations may simultaneously perturb the substrate and coenzyme binding pocket. A systematic review of 101 AME patients with 54 HSD11B2 mutations revealed early-onset hypertension, hypokalemia and homozygous mutations as common features. The homozygous HSD11B2 mutations correlated with low birth weight (r = 0.285, P = 0.02). Conclusions We report novel compound heterozygous HSD11B2 mutations in a Chinese teenager with early-onset hypertension, and enriched genotypic and phenotypic spectrums in AME. Genetic testing helps early diagnosis and treatment for AME patients, which may avoid target organ damage.

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“…In common with other Mendelian disorders, high blood pressure in AME is thought to originate in the kidney [ 63 ]. Renal transplant reverses AME in humans [ 64 ]; selective deletion of 11βHSD2 in the renal tubule induces key features of AME, including salt-sensitive hypertension [ 65 ••]. However, this view is too simplistic.…”

Section: βHsd2 and Hypertensionmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases and Hypertension in the Metabolic Syndrome

Bailey

2017

Curr Hypertens Rep

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The metabolic syndrome describes a clustering of risk factors—visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension—that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25–30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome. This is not increased systemic in circulating cortisol, rather increased bioavailability of active glucocorticoids within tissues. This review examines the role of covert glucocorticoid excess on the hypertension of the metabolic syndrome. Here, the role of the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine and paracrine control over glucocorticoid signalling, is examined. 11βHSD1 amplifies glucocorticoid action in cells and contributes to hypertension through direct and indirect effects on the kidney and vasculature. The deactivation of glucocorticoid by 11βHSD2 controls ligand access to glucocorticoid and mineralocorticoid receptors: loss of function promotes salt retention and hypertension. As for hypertension in general, high blood pressure in the metabolic syndrome reflects a complex interaction between multiple systems. The clear association between high dietary salt, glucocorticoid production, and metabolic disorders has major relevance for human health and warrants systematic evaluation.

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Apparent mineralocorticoid excess and the long term treatment of genetic hypertension

Cited by 23 publications

References 24 publications

Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child

Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child

Apparent mineralocorticoid excess caused by novel compound heterozygous mutations in HSD11B2 and characterized by early-onset hypertension and hypokalemia

11β-Hydroxysteroid Dehydrogenases and Hypertension in the Metabolic Syndrome

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