Endocrine Abstracts

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: Excess glucocorticoids are well recognised as a cause of osteoporosis; they inhibit osteoblast function and increase osteoblast and osteocyte apoptosis resulting in thinning of the trabeculae. The circadian rhythm of bone turnover, which is linked to cortisol rhythm, is abnormal in osteoporosis. Furthermore, some studies show abnormal cortisol metabolism in osteoporosis. The aim of our study was to evaluate the day–night rhythm of cortisol and to relate cortis...

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 ...

Introduction: Current testosterone replacement therapies have limited acceptability: gels can be messy and risk inadvertent dosing of others; injections are painful; and oral testosterone undecanoate (TU) delivers variable testosterone levels, requires concurrent ingestion of a fatty meal and may produce supraphysiological dihydrotestosterone (DHT) levels1. We present the first human trial of an oral native testosterone preparation formulated to deliver testosterone...

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...

The commonest cause of acquired hypopituitarism is a benign pituitary adenoma. However, in patients with non-pituitary malignancy different diagnoses need to be considered. We describe three oncology patients presenting with hypopituitarism and/or a pituitary mass where the cause was related either to malignant disease or its treatment.Case 1: A 56-year-old man with known metastatic melanoma presented with increasing lethargy. Investigation showed a larg...

Background: The development of recombinant biologics has had a major impact on many diseases. However, most biologics are rapidly cleared from the body and therefore require frequent injection regimens. There is therefore a need for technologies that allow the half-lives of these molecules to be extended in a predictable manner.HypothesisIncreasing numbers of N-linked glycosylation motifs between two GH molecules leads to gradually...

Background: The development of recombinant biologics such as interferon, insulin and Growth Hormone (GH) has had a major impact on the management of diseases including hepatitis, diabetes and GH-deficiency. However, most biologics undergo rapid renal filtration and proteolytic degradation, necessitating frequent dosing regimens. Pegylation can successfully delay clearance but has several drawbacks including potential toxicity, expense and reduced activity. There is therefore n...

Background: Cortisol is an essential stress hormone and deficient patients suffering a systemic inflammatory response (SIR) will rapidly die if not replaced. However, controversy remains on the definition for a normal adrenal response in critically ill patients. We investigated cortisol status in patients undergoing coronary artery bypass surgery (CABG), surgery frequently associated with a SIR, varying in severity from sub-clinical, to life-threatening....