A model for measuring the health burden of classic congenital adrenal hyperplasia in adults

Hummel, S; Sadler, Susannah; Whitaker, Martin J.; Ara, Roberta; Dixon, Simon; Ross, R. J. M.

doi:10.1111/cen.13060

Cited by 10 publications

(4 citation statements)

References 34 publications

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“…Interestingly, the daily doses of conventional regimen and dual-release hydrocortisone were similar, suggesting that for anthropometric and metabolic parameters, the improvement in serum cortisol profile was more important than reducing daily drug dose to prevent glucocorticoid overtreatment. Congenital or acquired adrenal hyperplasia is a unique clinical model to investigate the effects of overreplacement therapy with glucocorticoids on different clinical outcomes since glucocorticoids are used for both hormonal replacement and suppression purposes (148). In a recent study, treatment with modified-release hydrocortisone (i.e.…”

Section: Discussionmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects

Mazziotti

Formenti

Frara

et al. 2017

European Journal of Endocrinology

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The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.

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Section: Discussionmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects

Mazziotti

Formenti

Frara

et al. 2017

European Journal of Endocrinology

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“…The main sources of calcium are dairy products, bread, eggs, and citrus fruits. To achieve peak bone mass, and to prevent its loss with age, calcium has been identified as the most important nutrient [53][54][55][56]. However, some studies have not found any relationship between calcium intake and BMC [57].…”

Section: Discussionmentioning

confidence: 99%

Bone Mass in Young Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Reyes¹,

González²,

Alonso³

et al. 2021

Horm Res Paediatr

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Background: The effects of hyperandrogenism and steroid treatment on bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH) are controversial. Objectives: The objectives of this study were to characterize BMD and fractures in patients with CAH and to identify whether there is an association between alterations in BMD, nutritional status, and variables related to the disease. Methods: A cross-sectional descriptive study was conducted to explore clinical, hormonal, dairy consumption, physical activity, and BMD variables in patients with CAH due to 21-hydroxylase deficiency and controls matched by age, gender, skin color, body mass index, and Tanner scale. Results: Fifty subjects (CAH n = 25; females n = 42 [84%]) with a mean age of 15.9 ± 5.8 years were included in the study. White skin color predominated in 34 subjects (68%), mestizo in 11 (22%), and black in 5 (10%). In patients with CAH, BMD lumbar spine was decreased compared to that in controls (0.83 ± 0.23 vs. 0.98 ± 0.26 g/cm3, p = 0.004). BMD femur was also decreased in patients with CAH; however, this was not significant (0.95 ± 0.20 vs. 1.04 ± 0.24 g/cm3, p = 0.17). There was a positive relationship between age at diagnosis, age of initiation of glucocorticoid treatment, and testosterone levels with all measurements of BMD. The daily glucocorticoid dose was negatively related to BMD. No fractures were found. Conclusions: Patients with CAH had decreased BMD, especially in lumbar spine. Increased androgen exposure seemed to improve, while increased glucocorticoid dose impaired BMD.

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“…Patients with childhood-onset adrenal insufficiency, including the genetic disease congenital adrenal hyperplasia (CAH), have an increased morbidity and mortality in adult life that may, in part, relate to excess glucocorticoid therapy in childhood (1,2,3,4,5,6,7,8). Adrenal crisis, however, is the leading cause of death in adrenal insufficiency (9), and lower hydrocortisone doses are associated with a greater risk of adrenal crisis (10).…”

Section: Introductionmentioning

confidence: 99%

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children

Michelet

Melin

Parra-Guillén

et al. 2020

European Journal of Endocrinology

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Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing`s syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate 7 different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the 7 treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC24h within the 90% reference range for healthy children except in neonates where 2 regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 hours were outside the 90% reference range for healthy individuals in 50%, 55% - 65% and 70% - 75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC24h but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.

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A model for measuring the health burden of classic congenital adrenal hyperplasia in adults

Cited by 10 publications

References 34 publications

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects

Bone Mass in Young Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children

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