Endocrine Abstracts

11Beta-Hydroxylase and aldosterone synthase catalyse the synthesis of corticosterone and aldosterone in the rat adrenal cortex and are encoded by the CYP11B1 and CYP11B2 genes respectively. These genes are also expressed in distinct regions of the CNS and cardiovascular system where they may play a key role in behavioural response and blood pressure homeostasis. However, it is unclear whether this extra-adrenal expression is regulated by, or contributes to, circulating levels ...

Objectives: Mutations in SECISBP2 cause deficiency of selenoproteins, resulting in a multisystem disorder with abnormal circulating thyroid hormone and selenium levels and features due to lack of specific selenoproteins or loss of antioxidant selenoenzymes. Having observed early-onset, aneurysmal thoracic aortic dilatation in four patients with this disorder, we studied zebrafish and murine Secisbp2 mutant models to determine whether the aortic phenotype and selenopro...

Paltusotine is a once-daily, oral selective nonpeptide somatostatin receptor type 2 (SST2) agonist, which is in clinical development for the treatment of acromegaly. Maintenance of insulin-like growth factor 1 (IGF-1) control and toleration was demonstrated in phase 2 studies evaluating paltusotine in biochemically controlled (IGF-1 ≤1xULN) [ACROBAT Evolve (NCT03792555)] and uncontrolled (1> IGF-1 ≤2.5xULN) [ACROBAT Edge (NCT03789656)] patients with acromegaly ...

Paltusotine is a once-daily, oral, nonpeptide somatostatin receptor type 2 (SST2) specific agonist, in development for the treatment of acromegaly and neuroendocrine tumors. We report interim results from ACROBAT Advance (NCT04261712), an ongoing, multicenter, open-label, long-term extension study of paltusotine in subjects with acromegaly who previously completed either Phase 2 study ACROBAT Edge (NCT03789656) or Evolve (NCT03792555). ACROBAT Edge enrolled 47 subjects with el...

Nuclear Receptors control many developmental and physiological processes by regulating the expression of networks of genes. Their ability to activate or repress gene transcription depends on the recruitment of coactivators and corepressors that function as scaffolds for the binding of chromatin remodelling enzymes. RIP140 is a ligand dependant corepressor for most, if not all, nuclear receptors with key roles in energy homeostasis and reproduction.RIP140...

Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include short stature and pubertal delay. The underlying mechanism of endocrinopathies in RASopathies has not been fully elucidated. We report four BRAF mutations (two of which are novel) in four children with congenital hypopituitarism and RASopathy features. To demonstrate the functional role of the variants we performed phosphoproteomic analyses...

IGF-I is a marker of activity of the growth axis. It is accepted that the interpretation of IGF-I values requires age- and gender-specific reference ranges (RR).We have studied IGF-I assay performance by circulating 2 blood samples with different clinical scenarios to 23 centers [IDS-OCTEIA (n=2), DPC-Immulite (3), DPC-Immulite 2000 (4), in-house RIA (1), Nichols-Advantage (10) and Nichols-IRMA (3)] participating in the UK-NEQAS IGF-I scheme. Participant...

Objectives: GH measurements during OGTT have profound effects on therapy and follow-up management of acromegaly. To minimize the discordance between immunoassays, it is recommended to calibrate them using 22 kDa-GH-preparation instead of the use of pituitary-derived calibrants. The aim of our study was to evaluate the between-method discrepancies in GH determinations by assays using different calibrants considering further confounders like age, gender, and BMI.<p class="ab...

Objectives: Besides the measurement of IGF-1, GH suppression during OGTT to assess the biochemical status in acromegaly is recommended. However, as a consequence of the development of highly sensitive and specific GH assays a critical re-evaluation of the criteria for the diagnosis and follow-up management of acromegaly is mandatory. The aim of our study was to evaluate the between-method discrepancies in GH determinations by different immunoassays considering further confound...

Plasma aldosterone concentration (PAC) to active renin concentration (ARC) ratio (ARR) is an established screening tool for primary aldosteronism. Previously we provided reliable cut-offs measuring PAC by a radioimmunoassay (RIA; Byk&DiaSorin) und ARC by an established immunoluminometric assay (Nichols Institute Diagnostics). Since the latter one is not longer available, we aimed to establish cut-offs for currently available assays.One hundred seven ...