An integrated PK-PD model for cortisol and the 17-hydroxyprogesterone and androstenedione biomarkers in children with congenital adrenal hyperplasia.

Aims: The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH).

Methods: A nonlinear mixed-effect modelling approach was used to analyse cortisol, 17-hydroxyprogesterone and androstenedione concentrations obtained over 6 hours from children with CAH (n = 50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH.

Health-related quality of life in children with congenital adrenal hyperplasia.

Background: Children with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement and have daily intermittent hyper/hypocortisolemia and hyperandrogenemia. Health-related quality of life (HRQL) is important for understanding the impact the disease and therapy have on physical, mental, emotional, and social functioning. Little is known about HRQL in CAH.

Obesity in children with congenital adrenal hyperplasia in the Minnesota cohort: importance of adjusting body mass index for height-age.

Objectives: To evaluate obesity and overweight in children with congenital adrenal hyperplasia (CAH) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index-for-height-age (BMI ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall-for-age stature.

Design: Longitudinal.

Executive functioning in children with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder characterized by impaired cortisol synthesis leading to excessive production of adrenal androgens. Prenatal and postnatal exposure to excess androgens may increase neural vulnerability to insult and affect cognitive functions, particularly dopamine-dependent neural circuits responsible for executive functioning (EF). Our study aimed to investigate relationship between more pronounced androgen exposure and EF-related behaviors in children with CAH, as well as sex differences in these associations.

Hypertension in children with congenital adrenal hyperplasia.

Objectives: Estimates of high blood pressure (BP) incidence in children with congenital adrenal hyperplasia (CAH) vary widely; risk factors are poorly understood. We estimated incidence of hypertension by CAH subtype and sex, and assessed its association with body mass index, hydrocortisone and fludrocortisone.

Design: Longitudinal.

Use of Automated Bone Age for Critical Growth Assessment.

Background: We compared the variability of bone age (BA) rating between clinicians and an automated system in children with congenital adrenal hyperplasia (CAH).

Method: A total of 126 radiographs assessed by 3 clinicians blinded to patient details using Greulich and Pyle (GP) (readers 1, 2, and 3) and BoneXpert (BX).

Results: Comparing BA rating with each other, the mean of the absolute differences varied from 0.

The relation of peripubertal and pubertal growth to final adult height in children with classic congenital adrenal hyperplasia.

Objectives: To determine the relationships between peripubertal and pubertal timing and growth, along with glucocorticoid exposure, to the reduced final adult height seen in patients with congenital adrenal hyperplasia (CAH).

Study Design: Chart review of 104 children with classic CAH (41 males: 28 salt-wasting, 13 simple-virilizing; 63 females: 38 salt-wasting, 25 simple-virilizing) were selected from a cohort from 3 medical institutions in Minnesota. Triple logistic modeling of longitudinal data was performed to determine patterns of peripubertal and pubertal growth.

Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia.

Unlabelled: Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated.

Objectives: (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters.

Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets.

The Endocrine Society Clinical Practice Guidelines on congenital adrenal hyperplasia (CAH) recommend against using hydrocortisone suspension based on a study that examined a commercial suspension. Our objective was to examine the absorption of an extemporaneously prepared hydrocortisone suspension and compare it to tablets. Secondary objectives were to evaluate the 17-hydroxyprogesterone and androstenedione adrenal steroid responses.