Endocrine Abstracts

Background: In men there is a strong relationship between androgens and erythropoiesis; however this has not been shown in women. Patients with congenital adrenal hyperplasia (CAH) if uncontrolled may have high androgen levels and if over treated with glucocorticoids low androgen levels. Therefore CAH provides a potential model to examine the relationship between androgens and erythropoiesis in women.Aim: To investigate the relationship between androgens...

Cortisol has a distinct circadian rhythm; levels rise from 0300 h to peak within an hour of waking and gradually decline until 1800 h before a quiescent period lasting from 1800 to 0300 h. Current hydrocortisone replacement regimens are unable to replicate this rhythm and we have been investigating modified release technology. Our initial formulation, using tableting technology, demonstrated it was possible to replicate the overnight rise in cortisol but the tablet had reduced...

BackgroundCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder characterized by insufficient cortisol production resulting in excess adrenocorticotropic hormone (ACTH) and adrenal androgen production. Standard-of-care therapy with glucocorticoids (GC) is suboptimal due to the difficulty of balancing control of the ACTH-driven androgen excess against the serious long-term side effects associated...

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

Introduction: First-line treatment for congenital adrenal hyperplasia (CAH) is hydrocortisone1. When adequate control is not achieved, prednisolone (or its prodrug prednisone) are often used. However, there has been no formal comparison of disease control in CAH comparing prednis(ol)one vs hydrocortisone and patients are often on a glucocorticoid dose that exceeds the guideline recommended dose of hydrocortisone (≤25 mg/day)1,2. We report an interim...

Background: Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD-CAH) have poor health outcomes due to failure of currently available glucocorticoid preparations to control adrenocorticotropic hormone-driven androgen excess. We investigated whether modified-release hydrocortisone (MR-HC), which mimics the physiological circadian cortisol rhythm, could improve androgen control.Methods: 122 patients with 21-OHD-CAH ...

Background: Patients with congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency have poor health outcomes. We compared disease control in CAH adults treated with modified release hydrocortisone (MRHC, Chronocort®, Diurnal Ltd) versus standard glucocorticoid (GC).Methods: 6-month, Phase 3 study in 122 patients randomised to either MRHC twice daily or standard GC followed by safety extension study on MRHC. Patients had 24-hr 17...

Background: The therapeutic goal in CAH is androgen control on the lowest achievable glucocorticoid dose, preferably an adrenal replacement dose (15-25 mg hydrocortisone a day)1. However, the glucocorticoid dose required to control androgens frequently exceeds that required for adrenal replacement2. Modified-release hydrocortisone (MRHC) capsules, (Efmody, Diurnal Ltd, Cardiff, UK), replicate cortisol diurnal rhythm and improve CAH control compared to sta...

Background: Patients with salt-wasting congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency require glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy. Recently, it was shown that twice daily modified-release hydrocortisone hard capsules (MRHC, Efmody®, Diurnal Ltd) improved control of CAH with most patients showing good disease control versus standard GC therapy. However, no data has been reported on the renin-angiotens...

Background: Fertility in CAH women is impaired: 0.25 live births vs 1.8 in the UK population and 45% have irregular menses vs 13.6% in healthy women1. Male fertility is also impaired in CAH with oligospermia reported in 48%2. Treatment of infertility usually involves increasing the glucocorticoid dose to normalise adrenal androgens and progesterone to facilitate ovulation and implantation, respectively. Modified-release hydrocortisone (MRHC) capsules, (Ef...