Tildacerfont for the treatment of patients with classic congenital adrenal hyperplasia: results from a 12-week phase 2 clinical trial in adults with classic CAH

2021 ◽  
Author(s):  
Richard Auchus ◽  
Deborah Merke ◽  
Madu Ivy-Joan ◽  
Samer Nakhle ◽  
Kyriakie Sarafoglou ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Congenital Adrenal Hyperplasia ◽  
Phase 2 ◽  
Adrenal Hyperplasia ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Phase 2 Clinical Trial ◽  
Classic Cah

scholarly journals Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

2016 ◽  
Vol 174 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Brigitte Odenwald ◽  
Uta Nennstiel-Ratzel ◽  
Helmuth-Günther Dörr ◽  
Heinrich Schmidt ◽  
Manfred Wildner ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hospital Admissions ◽  
Discharge Summary ◽  
Severe Illness ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

ObjectiveTo evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH).DesignAnalysis of data extracted from a population-based prospective long-term follow-up study of children detected in neonatal screening.MethodsData of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary.ResultsA total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6–8.8).ConclusionsCrisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients.

scholarly journals Real-World Evidence of Clinical Outcomes in Patients With Assumed Classic Congenital Adrenal Hyperplasia in the United States

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A93-A94
Author(s):  
Mallory Farrar ◽  
Robert Farber ◽  
Ginny P Sen ◽  
Charles Yonan ◽  
Jean Lin Chan
Keyword(s):  
United States ◽  
Congenital Adrenal Hyperplasia ◽  
Real World ◽  
Pediatric Patients ◽  
The United States ◽  
Adrenal Hyperplasia ◽  
Medical Claims ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Real World Evidence ◽  
Classic Cah

Abstract Background: Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, usually due to a deficiency in the 21-hydroxylase enzyme, that results in impaired cortisol synthesis and excess androgen production. Patients with classic CAH experience both disease-related features from excess androgens and treatment-related complications from the chronic, supraphysiologic use of glucocorticoids (GCs) often required for androgen control. This study was conducted to evaluate the demographics and clinical characteristics of adult and pediatric patients in the United States (US) with assumed classic CAH based on International Classification of Diseases (ICD) codes, GC prescriptions, and medical claims. Methods: Analyses were based on longitudinal patient-level data from the Decision Resources Group Real World Evidence repository, which links medical claims, prescription claims, and electronic health records from >300 million US patients. Data were analyzed for patients aged ≥18 years (adult) and <18 years (pediatric) with assumed classic CAH based on ICD 9/10 codes associated with “adrenogenital disorders” and whose proportion of days covered with a GC in 2018–2019 was >75%. These patients were matched 1:3 with a control cohort based on age, gender, geographic region, and insurance type. Both assumed CAH and control cohorts had continuous coverage with at least 1 medical claim and 1 pharmacy claim in each year, 2018–2019. Results: Of 1,111 patients with assumed classic CAH, 778 were ≥18 years old (65% female; mean age [±SD], 43±17 years) and 333 were <18 years old (51% female; mean age [±SD], 11±4.7 years). Both adult and pediatric patients with assumed classic CAH were more likely than matched controls (adult N=2334; pediatric N=999) to experience events that could be related to chronic GC use, including infection (adult: 49.9% vs 37.3% [control]; pediatric: 49.5% vs 40.0%), weight gain (adult: 5.9% vs 2.5%; pediatric: 9.0% vs 2.6%), and moon face (adult: 44.0% vs 0.1%; pediatric: 37.8% vs 0.1%); all P<0.01 vs control. Adult patients were more likely than matched controls to experience acne (6.0% vs 3.6%), hirsutism (8.1% [47/508] vs 5.5% [84/1524]), and infertility (1.7% vs 0.4%); all P<0.01. Pediatric patients were more likely to experience pubertal development issues (10.5% vs 1.8%), acne (8.4% vs 5.1%), and advanced bone age (1.2% vs 0.1%); all P<0.05. Conclusions: Compared to matched controls, both adult and pediatric patients with assumed classic CAH had significantly more disease-related comorbidities and potential GC treatment-related conditions, indicating the challenges with current GC treatments. This study was limited by the assumed nature of classic CAH due to lack of a specific ICD code, but the combination of chronic GC use (>75% days) with the diagnosis code most likely used in these patients (adrenogenital disorder) supports the validity of this analysis.

scholarly journals Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry

2021 ◽  
Author(s):  
Heike Hoyer-Kuhn ◽  
Angela Huebner ◽  
Annette Richter-Unruh ◽  
Markus Bettendorf ◽  
Tilman Rohrer ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Daily Practice ◽  
Linear Regression Models ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Comprehensive Information ◽  
Custom Made ◽  
Classic Cah ◽  
Simple Virilizing

Objective: Treatment in classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH, but recommendations regarding dosage/administration are inconsistent. Aim of the study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicentre CAH registry. Design: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. Methods: A custom-made electronic health record software is used at the participating centres. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. Results: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean [lower-upper quartiles] daily HC dose [mg/m² body surface area] was 19.4 [18.9-19.8] for patients <3 months (n=329), 15.0 [14.6-15.3] age ≥3-12 months (n=463), 14.0 [13.7-14.3] age 1-5.9 years (n=745), 14.2 [14.0-14.5] age 6 years-puberty entry (n=669), and 14.9 [14.6-15.2] during puberty-18 years (n=801). Fludrocortisone was administered in 74.1% of patients (median daily dosage 88.8 µg). Conclusion: Our analyses demonstrated still a high proportion of children with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

scholarly journals Patients with Classic Congenital Adrenal Hyperplasia Have Decreased Epinephrine Reserve and Defective Glycemic Control during Prolonged Moderate-Intensity Exercise

2007 ◽  
Vol 92 (8) ◽  
pp. 3019-3024 ◽  
Author(s):  
Liza Green-Golan ◽  
Catherine Yates ◽  
Bart Drinkard ◽  
Carol VanRyzin ◽  
Graeme Eisenhofer ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Congenital Adrenal Hyperplasia ◽  
Moderate Intensity ◽  
Brisk Walking ◽  
Adrenal Hyperplasia ◽  
Moderate Intensity Exercise ◽  
Post Exercise ◽  
Glucose Levels ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah

Abstract Context: Patients with classic congenital adrenal hyperplasia (CAH) have adrenomedullary dysplasia and hypofunction, and their lack of adrenomedullary reserve has been associated with a defective glucose response to brief high-intensity exercise. Objective: Our objective was to assess hormonal, metabolic, and cardiovascular response to prolonged moderate-intensity exercise comparable to brisk walking in adolescents with classic CAH. Subjects and Methods: We compared six adolescents with classic CAH (16–20 yr old) with seven age-, sex-, and body mass index group-matched controls (16–23 yr old) using a 90-min standardized ergometer test. Metabolic, hormonal, and cardiovascular parameters were studied during exercise and recovery. Results: Glucose did not change throughout exercise and recovery for controls, whereas CAH patients showed a steady decline in glucose during exercise with an increase in glucose in the postexercise period. Glucose levels were significantly lower in CAH patients at 60 (P = 0.04), 75 (P = 0.01), and 90 (P = 0.03) min of exercise and 15 (P = 0.02) min post exercise, whereas glucose levels were comparable between the two groups early in exercise and at 30 min (P = 0.19) post exercise. As compared with controls, CAH patients had significantly lower epinephrine (P = 0.002) and cortisol (P ≤ 0.001) levels throughout the study and similar norepinephrine, glucagon, and GH levels. Patients with CAH and controls had comparable cardiovascular parameters and perceived level of exertion. Despite having lower glucose levels, insulin levels were slightly higher in CAH patients during the testing period (P = 0.17), suggesting insulin insensitivity. Conclusion: CAH patients have defective glycemic control and altered metabolic and hormonal responses during prolonged moderate-intensity exercise comparable to brisk walking.

scholarly journals Characteristics of growth in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency during adrenarche and beyond

2021 ◽  
Author(s):  
Tobias Troger ◽  
Grit Sommer ◽  
Mariarosaria Lang-Muritano ◽  
Daniel Konrad ◽  
Beatrice Kuhlmann ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adult Height ◽  
Final Height ◽  
Bone Age ◽  
Growth Patterns ◽  
Adrenal Hyperplasia ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency ◽  
The Impact

Abstract Context Patients with classic congenital adrenal hyperplasia (CAH) often fail to achieve their full growth potential. Adrenarche may accelerate bone maturation and thereby result in decreased growth in CAH. Objective To analyze the impact of growth during adrenarche on final height of adequately treated classic CAH patients. Design Retrospective, multi-center study. Setting Four academic pediatric endocrinology centers. Participants Fourty-one patients with classical CAH, born between 1990 and 2012. Main outcome measures We assessed skeletal maturation (bone age), growth velocity and (projected) adult height outcomes, and analyzed potential influencing factors, such as sex, genotype, and glucocorticoid therapy. Results Patients with classic CAH were shorter than peers (-0.4SDS±0.8SD) and their parents (corrected final height -0.6SDS±1.0SD). Analysis of growth during adrenarche revealed two different growth patterns: patients with accelerating bone age (49%), and patients with non-accelerating bone age compared to chronological age (BA-CA). Patients with accelerating BA-CA were taller than the normal population during adrenarche years (p=0.001) and were predicted to achieve a lower adult height SDS (-0.9SDS, 95%CI -1.3;-0.5) than non-accelerating patients when assessed during adrenarche (0.2SDS, 95%CI -0.3;0.8). Final adult height was similarly reduced in both accelerating and non-accelerating BA-CA groups (-0.4SDS, 95%CI -0.9;0.1 vs -0.3SDS, 95%CI -0.8;0.1). Conclusions Patients with and without significant bone age advancement, and thus differing height prediction during adrenarche, showed similar (predicted) final height when reassessed during pubertal years. Bone age alone should not be used during adrenarche as clinical marker for metabolic control in CAH treatment.

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