Endocrine Abstracts

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...

Introduction: GH signalling is essential for post-natal linear bone growth. The systemic/local mechanisms responsible for GH action remain unclear as the importance of liver derived IGF1 on linear growth has recently been challenged.Aim: To unravel the underlying mechanisms of linear bone growth we exploited the suppressor of cytokine signalling-2 (SOCS2) KO mice which have enhanced linear growth despite normal systemic IGF1 and GH levels.<p class="a...

GH is anabolic to the skeleton but its mode of action is unclear. Clues are available from the study of the suppressor of cytokine signalling-2 (SOCS2) KO mouse which has increased bone mass despite normal systemic IGF1 levels. Whilst suggesting direct GH effects on bone forming osteoblasts the precise signalling mechanisms remain unclear. The aims of this study were, therefore, to further detail the bone phenotype of SOCS2 KO mice and determine if GH promotes bone mass by mec...

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: There is uncertainty as to whether glucocorticoid receptor (GCR) polymorphisms play a role in the development of glucocorticoid-related side-effects in individuals receiving hydrocortisone replacement for Addison’s disease.Method: One-hundred-and-forty-seven Addison’s patients were age, gender, ethnicity and body mass index (BMI) matched with 147 control subjects. Genotyping was performed using polymerase chain reaction (PCR) for th...

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...

Tanycytes line the wall of the third ventricle sitting at the boundary between the cerebral spinal fluid (CSF) and the hypothalamus. Tanycytes actively take up substances from the CSF using their villi-like apical projections that extend into the third ventricle. Retinol is one such compound and can be oxidized by these cells to retinoic acid, which can be released to regulate transcription in the hypothalamus via specific nuclear receptors. Two retinal dehydrogenases (RALDHs)...

Aims/hypothesis: Adrenal incidentaloma (AI) are very common, but optimal management of patients with AI and low-grade excess cortisol secretion is not established. Uncontrolled studies reporting outcomes of adrenalectomy suggest improvements in cardiovascular risk, but all are subject to selection bias, and it is unclear if benefits are due to removal of excess cortisol. We reasoned that short-term use of mifepristone, a rapidly-acting glucocorticoid receptor (GR) antagonist, ...