Endocrine Abstracts

Context: Somatostatin receptor ligands (SRLs) are the cornerstone medical treatment of acromegaly, however many patients remain uncontrolled under SRLs. Well-established predictive markers of response are needed.Objective: We aimed to explore the relationship between responsiveness to SRLs, on one hand, and somatostatin (SST)2A and 5 receptor expression, adenoma granulation, and T2-weighted MRI signal intensity (T2WSI), on the other hand.<p class="ab...

Introduction: Paradoxical increase of GH following oral glucose load has been described in ~30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing’s syndrome. Patients...

Background: Acromegaly is associated with an increased left ventricular mass, as reported in echo-based and more recently in few cardiac MRI studies. One possible explanation of this increased ventricular mass could be water retention and consequently edema of the ventricular wall.Methods: In this prospective, cross-sectional study 26 patients with active acromegaly and 31 control subjects of comparable age and sex were investigated by cardiac MRI. Patie...

Background: Hyperphagia leading to craniopharyngioma-related obesity (CRO) is a common and serious sequel of treatments of craniopharyngiomas. The few therapeutic approaches that have been tested until now for the control of eating behaviour and weight have poor efficacy. Glucagon-like peptide-1 (GLP-1) analogues might be an option. Methods: This multicentre, randomised, double-blind superiority trial was conducted in France. Adults with CRO (BMI > 3...

Introduction: PBMAH is an heterogeneous disease from the clinical, hormonal, and morphological point of view. ARMC5 inactivating mutations have been reported as a cause of PBMAH. PDE11A4 variants have been associated with PBMAH and NR3C1 variants with bilateral adrenal incidentalomas.Aim: To analyse the frequency of ARMC5 pathogenic mutations and PDE11A4 and NR3C1 variants in PBMAH patients.<p cla...

Dopamine agonists (DAs), used as first line therapy in patients with macroprolactinomas, and antipsychotics have opposite effects on dopamine receptors (D2R). In patients with severe psychiatric conditions treated with antipsychotics, the rare occurrence of a macroprolactinoma, particularly with optic chiasm compression, represents a therapeutic challenge. Indeed, on one hand, antipsychotics by their antagonistic effect on D2R, could decrease or even abolish the effects of DAs...

NC-CAH is diagnosed in pubertal/post-pubertal women because of androgen excess however, the risk of potential adrenal insufficiency is not known, and indication of systematic glucocorticoid replacement therapy is controversial.Design: Prospective controlled clinical study in a tertiary referral center. 20 women with NC-CAH (serum stimulated 17-OHP >10 ng/ml/250 μg, Synacthen) comparatively to matched healthy women, were included if they had not ...

Introduction: Heterozygous mutations in the AIP gene are associated with young-onset pituitary adenomas while homozygous loss of AIP in animal models is lethal. As early diagnosis could lead to better outcomes, family members of AIP mutation-positive patients need follow up. The R304Q variant is commonly described as pathogenic based on clinical assessment. However, it is also present in the general population (minor-allele-frequency (MAF) 0.0007&#15...

ATL1103 is a second generation antisense 20mer intended to inhibit expression of the GH receptor (GHR) gene. Phosphorothioate and 2′-O-methoxyethyl modifications to nucleotides increase its plasma half-life and affinity for the target RNA to allow post-hybridization RNaseH degradation. We previously reported a phase 2, randomised, open-label, parallel group study of ATL1103 in 26 patients with acromegaly which demonstrated a fall in serum IGF-I of 26% with 200 mg twice w...

ATL1103 is a second generation antisense oligomer directed at the GH receptor. It is a 20mer with a phosphorothioate backbone and 2′-O-methoxyethyl modifications of the five nucleotides at either end intended to increase its plasma half-life and affinity for the target RNA to allow post-hybridization RNaseH degradation. We report a phase 2 randomised, open-label, parallel group study of subcutaneously administered ATL1103 in patients with active acromegaly. Appr...