Searchable abstracts of presentations at key conferences in endocrinology

ea0083erco5 | Endocrine-related Cancer | EYES2022

PD-1, PD-L1 and CTLA-4 immune checkpoint expression – Is there a prognostic impact on adrenocortical carcinoma?

L Landwehr , I Sbiera , B Altieri , H Remde , S Kircher , S. Sbiera , M. Kroiss , M. Fassnacht

Adrenocortical carcinoma (ACC) is a very severe endocrine malignancy with poor prognosis. While cancer immunotherapies have revolutionized the treatment of several cancer entities, the results of initial studies of different immune checkpoint inhibitors in ACC were heterogeneous and clinically substantial responses were observed only in a subset of patients. Expression of immune checkpoint molecules - programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T Lymphocytes...

ea0083erco2 | Endocrine-related Cancer | EYES2022

Ablation of Znrf3 & Trp53 induces metastatic adrenocortical carcinoma in mice

J. Wilmouth JR , J. Olabe , L. Landwehr , L. Pucheu , D. Dufour , F. Roucher-Boulez , C. Lucas-Rodrigues , D. Garcia-Garcia , C. Damon-Soubeyrand , M. Kroiss , M. Fassnacht , A. Lefrancois-Martinez , A. Martinez , P. Val

Background: Adrenocortical carcinoma (ACC) is an aggressive cancer originating from steroidogenic cells within the adrenal cortex. Unfortunately, half of patients present with metastatic spread upon initial diagnosis, and there is no curative therapy for advanced disease. Genomic analysis has identified that the most aggressive subgroup of ACC patients have overlapping alterations in the WNT/β-catenin pathway and the p53/RB signaling pathway.Objecti...

ea0083erco6 | Endocrine-related Cancer | EYES2022

Outcome of immuncheckpoint inhibitor therapy in adrenocortical carcinoma – A multicenter retrospective study

H Remde , L Schmidt-Pennington , M Reuter , L Landwehr , M Jensen , H Lahner , K Laubner , J Schreiner , J Bojunga , S Kircher , A Pohrt , M. V. Teleanu , D Hubschmann , A Stenzinger , H Glimm , S Frohling , M Fassnacht , K Mai , M. Kroiss

Background: Adrenocortical carcinoma is a rare endocrine malignancy with poor prognosis and few treatment options in advanced disease. Immune checkpoint inhibitors (ICI) have been studied in few clinical trials with a limited number of patients in ACC. No real-life data are available so far. In the present study we aimed at evaluating treatment response and safety of ICI treatment in advanced ACC and identifying clinical, biochemical, histological and molecular markers for pre...

ea0011p830 | Thyroid | ECE2006

Increase of L-thyroxine requirement during pregnancy

Russo L , Tonacchera M , Gianetti E , Perri A , Vitti P , Pinchera A

In pregnant women with thyroid diseases an increased amount of LT4 may be required for the correction of hypothyroidism or treatment of nodular goiter. Aim of this study was to assess the amount of the variations of LT4 requirement in pregnant women with thyroid diseases. To address this issue, we retrospectively evaluated a cohort of 107 women treated with LT4 divided in two groups: 42 euthyroid (E) (affected by nodular goiter (NG) treated with LT4 suppressive therapy) and 65...

ea0026p30 | Adrenal cortex | ECE2011

Is plasma mitotane level >30 mg/l a serious adverse event in patients with adrenocortical carcinoma (ACC)?: a retrospective analysis of the French COMETE network

Mauclere-Denost S M D , Tabarin A T , Drui D D , Chaillous L C , Salenave S S , Leboulleux S L , Chabre O C , Do-Cao C D C , Dubourg H D , Cuvelier M L C , Young J Y , Baudin E B

Background: Mitotane antitumor efficacy is related to plasma levels. Objective responses have been associated with mitotane plasma levels >14 mg/l. However, high plasma levels >20 or >30 mg/l are at higher risk of toxicity, especially neurotoxicity. National-based survey is lacking to evaluate the frequency and severity of high mitotane plasma levels. Our aim was to retrospectively describe serious adverse events (SAE).Methods: Mitotane plasm...

ea0009p55 | Growth and development | BES2005

Constitutional delay of growth and puberty (CDGP)is associated with the GPR54 gene but not with Leptin (L), Leptin Receptor (LR) and Cocaine and Amphetamin Regulated Transcript (CART) genes

Banerjee I , Trueman J , Patel L , Hall C , Price D , Hirschhorn J , Palmert M , Read A , Clayton P

CDGP is a common growth disorder, often dominantly inherited. Genetic association is thus very likely. There are many possible candidates but none are yet linked to CDGP. We assessed the possible contribution of L, LR genes (mutations in each cause very delayed or absent puberty), CART (mediates the effect of L on GnRH pulse generation), and GPR54 (a hypothalamic G-protein coupled receptor, which is mutated in familial hypogonadotrophic hypogonadism) genes.<p class="abstex...

ea0034p199 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

The effect of L-cysteine on appetite in humans

Amin Anjali , Agahi Amy , Martin Niamh , Ghatei Mohamed , Bloom Steve , Murphy Kevin

High protein diets suppress appetite and facilitate weight loss, but are difficult to adhere to. Understanding the mechanisms by which protein suppresses appetite may establish targets for more acceptable interventions to treat or prevent obesity. Of particular interest is the concept of functional foods or novel products, which aim to potentiate satiety.Receptor systems that respond to amino acids have been identified. However, the specific mechanisms r...

ea0006p52 | Bone | SFE2003

sRANK-L AND OPG ARE INCREASED IN SOME OSTEOPOROTIC PATIENTS

Jabbar S , Weston C , Drury J , Varey J

The importance of the sRANK-L / RANK / Osteoprotegerin (OPG) system in osteoclast function has clearly been demonstrated in the rat. Activating and inactivating mutations lead to severe disturbances of bone remodelling.Since this early animal work, there have been several studies designed to assess the importance of sRANK-L / RANK / OPG in diseases of the human skeleton. sRANK-L and OPG are measurable in blood.This cross-sectional ...

ea0029p1226 | Obesity | ICEECE2012

Curcumin inhibits the upregulation of cathepsin L by palmitate in fat

Yoo J. , Lee Y. , Kim J. , Kang S. , Nam J. , Park J. , Ahn C. , Song Y. , Kim K.

Objective: Cathepsin L can control adipogenesis and relate to acute coronary syndrome. However, it is not clear whether cathepsin L can be affected by saturated fatty acid and decrease by curcumin. We examined the hypothesis that palmitate upregulates cathepsin L expression in adipose tissue and curcumin can be block that effect.Methods: 3T3-L1 cells were fully differentiated for 8 to 10 days and treated with palmitate, LPS, IL6, TNF-α, IL6 neutrali...

ea0086op4.2 | Metabolism, Obesity and Diabetes | SFEBES2022

Differential effects of L- and D-lactate on HCAR1 signalling

Milner Annabelle , Brown Alastair , Frost Gary , Hanyaloglu Aylin

Lactate is a metabolite that activates the G-protein coupled receptor, Hydroxycarboxylic acid Receptor 1 (HCAR1) to regulate physiological processes such as lipolysis, cancer cell survival, and neuroprotection. Lactate exists in two forms, L+ and D-, with the L isoform predominant in the human body. Interestingly, both isoforms are only found together in the gastrointestinal tract. L-lactate is synthesised as a by-product of anaerobic respiration, whereas D-lactate, is a produ...