Adult Patients with Congenital Adrenal Hyperplasia Have Elevated Blood Pressure but Otherwise a Normal Cardiovascular Risk Profile

Mooij, Christiaan F.; Kroese, Jeanne Margot; Sweep, Fred C.G.J.; Hermus, A.R.M.M.; Tack, Cees J.

doi:10.1371/journal.pone.0024204

Cited by 34 publications

(21 citation statements)

References 23 publications

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“…The mineralocorticoid receptor p.Ile180Val SNP has been associated with an increased hypertension risk [28]. As CAH patients have a tendency to develop elevated blood pressure [29,30], the role of this SNP in CAH patients might be important with respect to their cardiovascular risk profile. We showed that the hMR p.Ile180Val SNP does not affect transactivation of the hMR by aldosterone.…”

Section: Discussionmentioning

confidence: 99%

Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

et al. 2015

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Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to accumulation of steroid precursors and adrenal androgens. These steroids may have a biological effect on the steroid receptor with clinical consequences on diagnostics and treatment in CAH patients. Therefore, we analysed the effect of accumulated steroids [17-hydroxyprogesterone (17OHP), progesterone, androstenedione and testosterone] on aldosterone-mediated transactivation of the human mineralocorticoid receptor (hMR). Methods: A transactivation assay using transiently transfected COS7 cells was employed. Cells were co-transfected with hMR-cDNA, MMTV-luciferase and renilla-luciferase expression vectors. Transfected cells were incubated with six different steroid concentrations in addition to aldosterone (10^-10M). Luciferase and renilla activities were measured to quantify hMR transactivation. Results: Linear regression analysis showed statistically significant linear inhibition of transactivation of the hMR by 10^-10M aldosterone in the presence of increasing 17OHP [F(1,5) = 11.34, p = 0.019] and progesterone [F(1,5) = 11.08, p = 0.021] concentrations. In contrast, neither androstenedione nor testosterone affected hMR transactivation by aldosterone at a concentration of 10^-10M. Conclusion: Our study shows for the first time that neither androstenedione nor testosterone has a biological effect on aldosterone-mediated transactivation of the hMR. 17OHP and progesterone have an anti-mineralocorticoid effect in vitro that may clinically lead to an increased requirement of mineralocorticoids in poorly controlled CAH patients.

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Section: Discussionmentioning

confidence: 99%

Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

et al. 2015

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“…In contrast, in 21OHD blood pressure is usually low at diagnosis but long-term hypertension is often found in treated patients, presumed due to overtreatment of glucocorticoids and/or mineralocorticoids, even in children [12,80,98,99]. However, others have not found any increased risk of hypertension in 21OHD [25,[100][101][102].…”

Section: Blood Pressurementioning

confidence: 96%

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2016

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Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is a rare autosomal recessive genetic disorder. It is caused by reduced or absent activity of 11β-hydroxylase (CYP11B1) enzyme and the resultant defects in adrenal steroidogenesis. The most common clinical features of 11 beta-hydroxylase deficiency are ambiguous genitalia, accelerated skeletal maturation and resultant short stature, peripheral precocious puberty and hyporeninemic hypokalemic hypertension. The biochemical diagnosis is based on raised serum 11-deoxycortisol and 11-deoxycorticosterone levels together with increased adrenal androgens. More than 100 mutations in CYP11B1 gene have been reported to date. The level of in-vivo activity of CYP11B1 relates to the degree of severity of 11 beta-hydroxylase deficiency. Clinical management of 11 beta-hydroxylase deficiency can pose a challenge to maintain adequate glucocorticoid dosing to suppress adrenal androgen excess while avoiding glucocorticoid-induced side effects. The long-term outcomes of clinical and surgical management are not well studied. This review article aims to collate the current available data about 11 beta-hydroxylase deficiency and its management.

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“…Blood pressure has not been shown to be severely affected in 21-hydroxylase deficiency, although studies have shown partly contradictory results [10,12,28,60,65,87,113,126,129,[144][145][146][147][148][149][150][151].…”

Section: Blood Pressurementioning

confidence: 99%

Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome

2015

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Nonclassic congenital adrenal hyperplasia (NCAH) is one of the most frequent autosomal recessive disorders in man with a prevalence ranging from 0.1 % in Caucasians up to a few percent in certain ethnic groups. Most cases are never diagnosed due to very mild symptoms, misdiagnosing as polycystic ovary syndrome, or ignorance. In contrast to classic CAH, patients with NCAH present with mild partial cortisol insufficiency and hyperandrogenism and will survive without any treatment. Undiagnosed NCAH may result in infertility, miscarriages, oligomenorrhea, hirsutism, acne, premature pubarche, testicular adrenal rest tumors, adrenal tumors, and voice problems among other symptoms. A baseline measurement of 17-hydroxyprogesterone can be used for diagnosis, but the ACTH stimulation test with measurement of 17-hydroxyprogesterone is regarded as the golden standard. The diagnosis can be verified by CYP21A2 mutation analysis. Treatment is symptomatic and usually with glucocorticoids alone. The lowest possible glucocorticoid dose should be used. Long-term treatment with glucocorticoids will improve the symptoms but will also result in iatrogenic cortisol insufficiency and may also lead to long-term complications such as obesity, insulin resistance, hypertension, osteoporosis, and fractures. Although the complications seen in NCAH patients have been assumed to be related to the glucocorticoid treatment, some may, in fact, be associated with prolonged hyperandrogenism. Different risk factors and negative consequences should be monitored regularly in an attempt to improve the clinical outcome. More research is needed in this relatively common disorder.

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Adult Patients with Congenital Adrenal Hyperplasia Have Elevated Blood Pressure but Otherwise a Normal Cardiovascular Risk Profile

Cited by 34 publications

References 23 publications

Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome

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