Early central blood pressure elevation in adult patients with 21-hydroxylase deficiency

Rosenbaum, David; Lethielleux, G; Bruckert, Éric; Lévy, Bernard; Tanguy, Marie Laure; Jérôme, D.; Dahmoune, Nora; Salem, Joe‐Elie; Bittar, Randa; Leban, Monique; Girerd, Xavier; Touraine, Philippe; Bachelot, Anne

doi:10.1097/hjh.0000000000001850

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…There have been many studies on CAH that indicate an increased cardiometabolic risk, including insulin resistance (4,6,81,89,125,137,145,146,147,148,149,150), but very few indicating an increased frequency of established cardiovascular disease (129,151) or diabetes (including gestational diabetes) (81,103,151). Since most studies have been performed in children and adolescents and most of the adults in the CAH studies have been aged less than 50 years, this is to be expected because cardiovascular disease and diabetes usually develop later in life (64).…”

Section: Cardiovascular Disease and Diabetesmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Nordenström

Falhammar

2019

European Journal of Endocrinology

115

129

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Non-classic congenital adrenal hyperplasia (NCAH) is a relatively common disorder regardless of ethnicity, but most cases are never diagnosed, especially in males. A baseline 17-hydroxyprogesterone measurement may be used for screening, but 17-hydroxyprogesterone measurement after ACTH stimulation is the gold standard. We advocate a CYP21A2 mutation analysis to verify the diagnosis, for genetic counselling and for better prognostic and treatment guidance. Most patients are diagnosed in adolescence and adult life with hirsutism, acne, a PCOS-like picture and fertility issues. Many men with NCAH never seek medical attention and escape diagnosis. Although treatment is somewhat controversial, an early diagnosis and start of treatment may have positive implications on growth and be relevant for preventing and ameliorating the symptoms and consequences of androgen excess that develop over time, including fertility issues. Long-term treatment with glucocorticoids will improve the androgen symptoms but may result in long-term complications, such as obesity, insulin resistance, hypertension, osteoporosis and fractures. The glucocorticoid doses should be kept low. However, complications seen in NCAH, assumed to be caused by the glucocorticoid treatment, may also be associated with long-term androgen exposure. Oral contraceptive pills are a common treatment option for young females with NCAH. Regular clinical monitoring to improve the clinical outcome is recommended. It is important to acknowledge that glucocorticoid treatment will lead to secondary cortisol insufficiency and the need for stress dosing. Studies focusing on the specific difficulties patients with NCAH face, both those with a late clinical diagnosis and those with a neonatal diagnosis obtained by screening, are warranted.

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Section: Cardiovascular Disease and Diabetesmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Nordenström

Falhammar

2019

European Journal of Endocrinology

115

129

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“…For every patient with CAH, a healthy control matched for sex, age, and smoking status was prospectively included in the CARDIOHCS study (NCT01807364) between May 2011 and August 2015 (8,9,10). Patients with CAH and healthy controls were all assessed at the Clinical Investigation Center Paris-Est (CIC-1421, Pitie-Salpetriere University Hospital, Paris, France).…”

Section: Study Population and Settingmentioning

confidence: 99%

Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Nguyen

Rouas‐Freiss

Funck‐Brentano

et al. 2019

European Journal of Endocrinology

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Background HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. Methods In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. Results Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35–1.27) and −0.44 (−0.94, −0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04–0.41), P = 0.001) and estradiol (β = −0.22 (−0.57, −0.02), P < 0.001). Conclusion CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.

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“…The majority of studies including adults and children with CAH have reported an increased body fat mass assessed by DXA [96,101,102,106,107], which enables separation between lean mass (which may be increased due to hyperandrogenism) from fat mass. Elevated cardiometabolic risk, including insulin resistance [4,94,[108][109][110][111][112][113][114][115][116][117], has been reported in a large number of studies on CAH, with a few reporting increased rate of established cardiovascular disease [103,118], and diabetes (including gestational diabetes) [81,109,118]. Very few individuals with CAH above 50 years of age have been included in studies, and thus it could be expected that the rate will increase since cardiovascular disease and diabetes usually develop later in life [1].…”

Section: Obesity Diabetes and Cardiovascular Diseasementioning

confidence: 99%

Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency

2019

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Purpose 3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare variant of congenital adrenal hyperplasia (CAH) causing less than 0.5% of all CAH. The aim was to review the literature. Methods PubMed was searched for relevant articles. Results 3βHSD2D is caused by HSD3B2 gene mutations and characterized by impaired steroid synthesis in the gonads and the adrenal glands and subsequent increased dehydroepiandrosterone (DHEA) concentrations. The main hormonal changes observed in patients with 3βHSD2D are elevated ratios of the Δ5-steroids over Δ4-steroids but molecular genetic testing is recommended to confirm the diagnosis. Several deleterious mutations in the HSD3B2 gene have been associated with saltwasting (SW) crisis in the neonatal period, while missense mutations have been associated with a non-SW phenotype. Boys may have ambiguous genitalia, whereas girls present with mild or no virilization at birth. The existence of non-classic 3βHSD2D is controversial. In an acute SW crisis, the treatment includes prompt rehydration, correction of hypoglycemia, and parenteral hydrocortisone. Similar to other forms of CAH, glucocorticoid and mineralocorticoid replacement is needed for long-term management. In addition, sex hormone replacement therapy may be required if normal progress through puberty is failing. Little is known regarding possible negative long-term consequences of 3βHSD2D and its treatments, e.g., fertility, final height, osteoporosis and fractures, adrenal and testicular tumor risk, and mortality. Conclusion Knowledge is mainly based on case reports but many long-term outcomes could be presumed to be similar to other types of CAH, mainly 21-hydroxylase deficiency, although in 3βHSD2D it seems to be more difficult to suppress the androgens.

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Early central blood pressure elevation in adult patients with 21-hydroxylase deficiency

Abstract: We found an early rise in central SBP in CAH patients whereas sublinical arterial damages markers were normal. Our study suggest that vascular damages and increased cardiovascular risk could be mainly BP-driven.

Cited by 13 publications

References 39 publications

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency

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