Novel treatments for congenital adrenal hyperplasia

Schröder, Mariska A M; Grinten, Hedi L Claahsen-van der

doi:10.1007/s11154-022-09717-w

Cited by 16 publications

(8 citation statements)

References 96 publications

(174 reference statements)

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“…Adult patients usually require hydrocortisone at 15–25 mg/day fractioned in 2–3 doses. In Addison’s disease, dual-release hydrocortisone has demonstrated an improved metabolic profile and quality of life [ 21 ], especially when administered in fractionated daily doses [ 22 ]. Similar hydrocortisone modified-release formulations have been developed for CAH patients, showing an efficient suppression of the early morning ACTH peak and a more physiological circadian rhythm [ 23 ].…”

Section: Congenital Adrenal Hyperplasiamentioning

confidence: 99%

“…Other than hydrocortisone, prednisone, prednisolone, and methylprednisolone twice daily and dexamethasone once daily are being used. 21-OHD patients show adequate androgen suppression when treated with dexamethasone [ 21 , 25 ]. However, dexamethasone and, to a lesser extent, prednisone, are associated with worse long-term outcomes compared to hydrocortisone in classical 21-OHD [ 26 ].…”

Section: Congenital Adrenal Hyperplasiamentioning

confidence: 99%

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Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

Cera

Locantore

Novizio

et al. 2022

JCM

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Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases that may cause cortisol insufficiency together with other hormonal alterations. The most common form is 21-hydroxylase deficiency, in which the lack of pituitary negative feedback causes an increase in ACTH and adrenal androgens. Classical forms of CAHs can lead to severe adrenal failure and female virilization. To date, the appropriate management of pregnant CAH patients is still debated regarding appropriate maternal therapy modifications during pregnancy and the risks and benefits of prenatal treatment of the fetus. We conducted a literature search of relevant papers to collect current evidence and experiences on the topic. The most recent and significant articles were selected, and current international guidelines were consulted to update current recommendations and guide clinical practice. Given the lack of randomized clinical trials and other high-quality scientific evidence, the issue is still debated, and great heterogeneity exists in current practice in terms of risk/benefit evaluation and pharmacological choices for pregnancy and prenatal treatment. Glucocorticoid therapy is advised not only in classical CAH patients but also in non-classical, milder forms. The choice of which glucocorticoid to use, and the safety and benefits of dexamethasone therapy aimed at preventing genital virilization are still debated issues. Several advances, however, have been made, especially in terms of fertility and reproduction. This review aims to present the most recent scientific and real-world updates on pregnancy and prenatal management of CAH, with the presentation of various clinical scenarios and specific case-by-case recommendations.

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Section: Congenital Adrenal Hyperplasiamentioning

confidence: 99%

Section: Congenital Adrenal Hyperplasiamentioning

confidence: 99%

Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

Cera

Locantore

Novizio

et al. 2022

JCM

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“…Individuals diagnosed with CAH require continuous medical intervention to compensate for deficient hormones and to regulate elevated androgen levels. Previous studies have shown that complications have persisted due to exposure to high doses of glucocorticoids and the continued high level of adrenal androgens [10]. Over the last few years, there has been substantial improvement in the development of new drugs and therapies for CAH.…”

Section: Introductionmentioning

confidence: 99%

A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia–CYP21A2-R484Q Mutant Mouse

Thirumalasetty,

Schubert,

Naumann

et al. 2024

IJMS

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Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2, causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.

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“…Overall, CAH remains a challenging condition in terms of best management, adequate hormonal substitution (to avoid both over and under treatment), and most practical surveillance protocol [41][42][43]. Adrenal tumours in these patients are generally associated with a late CAH diagnosis and a poor disease control [28].…”

Section: Introductionmentioning

confidence: 99%

Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia

Carsote,

Gheorghe,

Nistor

et al. 2023

Biomedicines

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Our aim is to update the topic of adrenal tumours (ATs) in congenital adrenal hyperplasia (CAH) based on a multidisciplinary, clinical perspective via an endocrine approach. This narrative review is based on a PubMed search of full-length, English articles between January 2014 and July 2023. We included 52 original papers: 9 studies, 8 case series, and 35 single case reports. Firstly, we introduce a case-based analysis of 59 CAH-ATs cases with four types of enzymatic defects (CYP21A2, CYP17A1, CYP17B1, and HSD3B2). Secondarily, we analysed prevalence studies; their sample size varied from 53 to 26,000 individuals. AT prevalence among CAH was of 13.3–20%. CAH prevalence among individuals with previous imaging diagnosis of AT was of 0.3–3.6%. Overall, this 10-year, sample-based analysis represents one of the most complex studies in the area of CAH-ATs so far. These masses should be taken into consideration. They may reach impressive sizes of up to 30–40 cm, with compressive effects. Adrenalectomy was chosen based on an individual multidisciplinary decision. Many tumours are detected in subjects with a poor disease control, or they represent the first step toward CAH identification. We noted a left lateralization with a less clear pathogenic explanation. The most frequent tumour remains myelolipoma. The risk of adrenocortical carcinoma should not be overlooked. Noting the increasing prevalence of adrenal incidentalomas, CAH testing might be indicated to identify non-classical forms of CAH.

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Novel treatments for congenital adrenal hyperplasia

Cited by 16 publications

References 96 publications

Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia–CYP21A2-R484Q Mutant Mouse

Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia

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