Management of Infants with Congenital Adrenal Hyperplasia

Dabas, Aashima; Vats, Pallavi; Sharma, Rajni; Singh, Preeti; Seth, Anju; Jain, Vandana; Batra, Prerna; Gupta, Neerja; Kumar, Ravindra; Kabra, Madhulika; Kapoor, Seema; Yadav, Sangeeta

doi:10.1007/s13312-020-1735-8

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…The recommended glucocorticoid for pediatric CAH patients is hydrocortisone (HC, name of synthetic cortisol) due to its short half-life and lower risk for adverse events ( Oprea et al, 2019 ). To mimic the circadian rhythm of cortisol biosynthesis, oral administration of 10–15 mg/m 2 hydrocortisone daily is recommended, divided into two to three doses, and with the highest dose in the morning ( Kamoun et al, 2013 ; Khattab and Marshall, 2019 ; Dabas et al, 2020 ). It is essential to monitor cortisol replacement in CAH patients frequently and adjust dosages according to the patients’ individual needs, based on the body surface area, laboratory parameters, and symptoms evaluation ( Bornstein et al, 2016 ) as too high or too low cortisol exposure can cause adverse events, such as Cushing’s syndrome, and or lead to an adrenal crisis ( Merke and Bornstein, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis

et al. 2022

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Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling. Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations. In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions. In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.

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Section: Introductionmentioning

confidence: 99%

Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis

et al. 2022

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“…Thesegeneswereincludedduetothehighprevalenceof theassociateddisordersandpublichealthrelevance.CAH isanendocrinedisorder;thatispotentiallylife-threatening in the absence of early diagnosis and treatment and typically requires lifelong therapy with steroids. The timely initiation of corticosteroid therapy and regular follow-up can lead to a reduction in associated mortality (Dabas et al, 2020). Even though MCAD is considerably rarer, it canbeaffordablymanagedbymaintainingahigh-glucose diet,avoidingfastingandglucosesupplementationduring illness (Merritt&Chang, 1993).Althoughwedidnotfind mutationsinallfourgenesaddedduetotheirassociation withchildhoodmortality,itisimportanttonotethatidentifyingtheriskvariantswillleadtoearlyinterventions.Also, datafromstudieslikethiscouldhelpdetectrareandpathogenic variants and estimate their population frequencies.…”

Section: Discussionmentioning

confidence: 99%

Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts

Oladayo

Gowans

Awotoye

et al. 2023

Molec Gen & Gen Med

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IntroductionThe frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large‐scale population genomic studies. The availability of data from the first whole‐genome sequencing for orofacial clefts in an African population motivated this investigation.MethodsIn total, 130 case‐parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM).ResultsWe identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP.ConclusionThis study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations.

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“…В случае назначения данного препарата рекомендуются более низкие дозы. У взрослых пациентов (у детей препаратом первой линии является гидрокортизон [65]) решение вопроса о назначении гидрокортизона или преднизолона принимается с учетом дополнительных факторов.…”

Section: влияние блокирующей терапии глюкокортикоидами на костный обмunclassified

Effect of glucocorticoids on bone metabolism in replacement therapy of adrenal insufficiency. Literature review

et al. 2020

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Adrenal insufficiency (AI) is a syndrome caused by disturbance in the synthesis and secretion of hormones of the adrenal cortex, which ensure the vital activity, energy and water-salt homeostasis. The widest hormonal deficiency is observed in primary hypocorticism, when the synthesis of not only glucocorticoids (GC) and adrenal androgens, but also mineralocorticoids is disrupted. Lifelong replacement therapy with GCs for this pathology may be associated with a risk of bone loss and osteoporosis. However, at present, there are no clear guidelines for diagnosis of bone condition, including and bone mineral density (BMD) monitoring during treatment with GCs in patients with AI. This review summarizes collected data on the key pathogenetic links of glucocorticoid-induced osteoporosis, incidence of decreased BMD and fractures in patients with AI. In this review factors that influence bone metabolism in this cohort of patients are considered: the type and the dose of prescribed GCs, the type (primary, secondary, HH in congenital adrenal cortex dysfunction) and the duration of AI, age, gender, and the presence of concomitant endocrine disorders (hypogonadism, growth hormone (GH) deficiency). In addition, the review presents data on the effect of adrenal androgen replacement therapy and recombinant GH therapy on bone metabolism in secondary AI.

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Management of Infants with Congenital Adrenal Hyperplasia

Cited by 9 publications

References 23 publications

Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis

Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis

Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts

Effect of glucocorticoids on bone metabolism in replacement therapy of adrenal insufficiency. Literature review

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