Endocrine Abstracts

Introduction: Immunotherapy has become standard treatment for an increasingly wide range of cancers. Checkpoint inhibitors (ICT; CTLA4, PD1 & PD-L-1) can cause endocrine toxicity, principally affecting the pituitary and thyroid glands. We have studied the clinical management and outcome of patients with endocrine adverse effects over 5 years at our cancer centre.Methods: All patients treated with ICT agents between 1 Jan 2014 to 31 Jan 2019 were incl...

Introduction: Immune checkpoint therapies are novel cancer agents, which have been associated with the development of endocrine toxicities. ESMO and SfE endorsed management guidelines have been helpful for the early recognition of these toxicities, but in clinical practice, having early access to specialist endocrine advice improves the decision making and effective use of these agents when toxicities occur. In response to need we developed an easily accessible interdisciplina...

Whereas G-protein coupled receptors (GPCRs) have long been believed to signal via cyclic AMP (cAMP) exclusively at the cell surface, our group has shown that GPCRs also stimulate cAMP production from the cell interior once internalized together with their ligands. This phenomenon, which we originally described for the thyroid stimulating hormone receptor (TSHR) in thyroid follicles, has now also been shown for several other GPCRs. However, the involved subcellular compartment(...

Introduction: Falsely high FT4 and FT3 with concurrent falsely low TSH have been reported in patients taking biotin and in a few case reports of patients with IgG anti-streptavidin antibody. However, other isotypes and effects on other immunoassays have not been reported.Case: A 77 year female presented with worsening fatigue with a background of hyperthyroidism on carbimazole. Clinically she appeared hypothyroid. Her results on Roche Cobas platform were...

Background: Both undernutrition and chronic inflammation impair linear growth through resistance to GH. Fibroblast growth factor 21 (FGF21) is known as an important regulator of the metabolic adaptation to fasting. Elevated expression of FGF21, secondary to prolonged undernutrition has been identified to develop GH resistance and subsequent attenuation of skeletal growth and growth plate chondrogenesis in both mice and human. However, the mechanism of FGF21’s actions rema...

Background: Fibroblast growth factor 21 (FGF21) is a key metabolic regulator in the adaptation to fasting. In food-restricted mice, inhibition of skeletal growth appears to be mediated by the antagonistic effect of FGF21 on GH action in the liver and in the growth plate (Kubicky et al. 2012, Yu et al. 2012). The role of FGF21 in growth regulation in humans is currently unknown.Objective and hypothesis: To provide mechanistic insights in...

Introduction: The osteoblast derived bone formation marker osteocalcin has been reported to decrease adipose tissue in mice. In elderly men, osteocalcin was reported to correlate inversely with fat mass.Aim: To examine the relationship between osteocalcin and regional fat depots.Method: The Odense Androgen Study is a population-based, cross-sectional study of 779 randomly selected men aged 20–29 years. Total, central, upper ex...

Introduction: The Gli-family of zinc-finger transcription factors regulates the Sonic Hedgehog (Shh) signalling pathway, critical for normal CNS development. Gli2 is essential for early pituitary and ventral forebrain development in mice, with mutations described in humans with holoprosencephaly (HPE), isolated hypopituitarism (HP) and cranial/midline facial defects. SHH mutations have been associated with phenotypes including HPE but not HP, despite murine studi...

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are important neuropeptides that are structurally related. They have been found to exert many physiological and pathophysiological effects through the activation of three specific receptors: PAC1R, VPAC1R, and VPAC2R. In tetrapods, PACAP and VIP are potent agonists to VPAC2R. In teleosts, we have previously identified a PHIR in goldfish which shares high level of sequence similarity ...

Children diagnosed with either Growth Hormone deficiency (GHD) or Turner syndrome (TS) are both treated with GH titrated against either weight or area. The response to such treatment however, is highly variable and, at least in part, diagnosis dependent. The precise mechanisms underlying this variability are unknown. As basal GH levels differ between GHD and TS and, as GH elicits its effects through changes in gene expression, the basal gene expression profiles of GHD and TS s...