Endocrine Abstracts

Background: Measurement of salivary glucocorticoids is gaining popularity as it offers a non-invasive collection technique, enabling sampling in the community or home environment, allowing tailored capture of steroid circadian rhythm and improved patient experience. Current popular salivary collection methods cannot be used in very young children due to choking and the requirement for active participation. There is little data on saliva stability during home collection.<p ...

Introduction: Measuring serum cortisol to evaluate the normal circadian rhythm and adequacy of hydrocortisone replacement levels requires multiple readings; an expensive, cumbersome process. Conversely, salivary cortisone, a surrogate marker for free cortisol levels is non-invasive and well suited for out-patient settings. We hypothesised that salivary cortisone predicts circulating cortisol levels and can be used as an alternative marker of serum cortisol in a physiological s...

Background: Current standard treatment for adrenal insufficiency in neonates and infants is unsatisfactory as unlicensed adult dosage formulations are used. These are generally difficult to administer and may give rise to inconsistencies in dose as the content uniformity of the dosage form cannot be verified.Methods: Infacort is a newly-developed immediate release formulation of hydrocortisone that is provided in appropriate unit dosage units (0.5, 1, 2,...

Background: Replacing physiological cortisol levels is important for the long-term health of patients with adrenal insufficiency and congenital adrenal hyperplasia (CAH). Modified-release formulations of hydrocortisone are one strategy being used to replace the cortisol circadian rhythm in adult patients but there is no data in children. Physiologically based pharmacokinetic (PBPK) modelling is a valuable tool for paediatric drug development1; however, there are no ...

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...

Introduction: The 250µg Short Synacthen test (SST) is the reference standard for a diagnosis of adrenal insufficiency (AI) in most endocrine centres. The test is expensive and time consuming, requiring clinic attendance. We hypothesised that a cheaper home waking salivary cortisone (WSC) is predictive of the SST 30-minute cortisol >430 nmol/l cut-off and carried out a diagnostic accuracy study to assess the predictive value of the WSC in diagnosing and excluding AI. W...

Clinical Endocrinology, 2018, 88(1): 21–29 (DOI: https://doi.org/10.1111/cen.13447)...

The prevalence of metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), continues to escalate. Glucocorticoids (GCs) and bile acids (BAs) are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver, where it inactivates steroid hormones and catalyses a fundamental step in BA synthesis. We have previously demonstrated that AKR1D1 modulates hepatic GC availability and GC recept...

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...