scholarly journals Management of Altered Hydrocortisone Pharmacokinetics in a Boy with Congenital Adrenal Hyperplasia Using a Continuous Subcutaneous Hydrocortisone Infusion

2009 ◽  
Vol 94 (9) ◽  
pp. 3477-3480 ◽  
Author(s):  
Sinead M. Bryan ◽  
John W. Honour ◽  
Peter C. Hindmarsh
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Insulin Pump ◽  
Serum Cortisol ◽  
Adrenal Hyperplasia ◽  
Adrenal Androgen ◽  
Valuable Adjunct ◽  
Rapid Control ◽  
High Doses ◽  
17 Hydroxyprogesterone ◽  
Oral Doses

Background: Conventional hydrocortisone dosing schedules do not mimic the normal circadian rhythm of cortisol, making it difficult to optimize treatment in congenital adrenal hyperplasia (CAH). Case Details: We report a 14.5-year-old boy with CAH who had reduced bioavailability [42% (normal 80% orally and 100% by im route)] and increased clearance [half-life 50 min (normal range, 70–100 min)] of oral doses of hydrocortisone leading to ambient serum 17-hydroxyprogesterone concentrations of 400 nmol/liter (14.5 ng/ml) and androstenedione concentrations of 24.9 nmol/liter (7.1 ng/ml). Intervention: Using a continuous but variable sc hydrocortisone infusion via an insulin pump, rapid control of his CAH was attained with a normal cortisol circadian profile. Average daily hydrocortisone dose was 17.4–18.6 mg/m2, which produces on average 24-h serum cortisol and 17-hydroxyprogesterone concentrations of 316 nmol/liter (115 ng/ml) and 4.3 nmol/liter (1.4 ng/ml), respectively. Therapy has been maintained over 4 yr with suppression of normal adrenal androgen production and normal progression through puberty. Conclusions: Continuous sc infusion of hydrocortisone may prove a valuable adjunct to therapy for CAH, particularly in patients requiring high doses of oral hydrocortisone and in those with abnormal hydrocortisone pharmacokinetics. A boy is described with congenital adrenal hyperplasia and altered hydrocortisone pharmacokinetics managed by continuous subcutaneous hydrocortisone infusion.

scholarly journals Serum Cortisol and 17-Hydroxyprogesterone Interrelation in Classic 21-Hydroxylase Deficiency: Is Current Replacement Therapy Satisfactory?

2001 ◽  
Vol 86 (10) ◽  
pp. 4679-4685 ◽  
Author(s):  
Evangelia Charmandari ◽  
David R. Matthews ◽  
Atholl Johnston ◽  
Charles G. D. Brook ◽  
Peter C. Hindmarsh
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Serum Cortisol ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Group 2 ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Pituitary Adrenal Axis ◽  
Serum Acth ◽  
Group 1

One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1–18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9α-fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when administered as a single dose (0.3 or 0.5 mg/m2) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9μ g/dl (sd = 2.1) and 66.2 ng/dl (sd = 92.7), respectively, in group 1 and 4.1 μg/dl (sd = 2.5) and 4865.7 ng/dl (sd = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400–0900 h. In group 2, 17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600–2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r =− 0.187; P < 0.0001), peaking at lag time 60 min (r = −0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m2 in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400–1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress.

Screening for Congenital Adrenal Hyperplasia: The Delfia Screening Test Overestimates Serum 17-Hydroxyprogesterone in Preterm Infants

PEDIATRICS ◽  
1996 ◽  
Vol 97 (1) ◽  
pp. 100-102 ◽  
Author(s):  
Saad Al Saedi ◽  
Heather Dean ◽  
William Dent ◽  
Elizabeth Stockl ◽  
Catherine Cronin
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Preterm Infants ◽  
Gestational Age ◽  
Adrenal Hyperplasia ◽  
Blood Spots ◽  
Healthy Infants ◽  
Extraction Step ◽  
Postconceptional Age ◽  
17 Hydroxyprogesterone ◽  
Over Time

Objective. To compare 17-hydroxyprogesterone (17-OHP) levels measured by quantitative serum radioimmunoassay (RIA), including an extraction step, and by screening fluoroimmnoassay (FIA) on blood spots in preterm infants. Methods. Subjects were 39 healthy infants born at less than 31 weeks' gestational age. Each infant had weekly blood sampling, and RIA and FIA were performed on each sample. Results. Two hundred twenty-seven samples were taken at 28 to 41 weeks' postconceptional age. Mean ± SD 17-OHP measured by RIA was 11.4 ± 11.1 nmol/L (0.4 ± 0.4 µg/dL), and decreased over time. Mean ± SD 17-OHP measured by FIA was 38.96 ± 37.3 nmol/L, greater than 17-OHP (RIA). Log(δFIA-RIA) was inversely related to postconceptional age (R2 = .39). Conclusion. Screening FIA of blood spots overestimates levels of 17-OHP in preterm infants and should not be used to determine the likelthood of congenital adrenal hyperplasia in this population. We have abandoned FIA screening for congenital adrenal hyperplasia in infants weiging less than 1500 g.

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