Endocrine Abstracts

Adrenocortical carcinoma (ACC) is part of the Li-Fraumeni tumour syndrome which is due to germline mutations in TP53. Recent studies demonstrate low penetrance mutations leading to later tumour manifestation. Furthermore, in ACC mutations outside the hotspot region have been found. TP53-polymorphisms have also been described to impact on p53 function. We, therefore investigated TP53 sequence alterations in a large cohort of adult patients with ACC.Method...

Objective: Isolated ACTH-deficiency (IAD) is considered a rare autoimmune endocrinopathy most frequently associated with autoimmune thyroid diseases (ATD). We have previously diagnosed IAD in four patients with primary hypothyroidism and negative TPO antibodies. The aim of this study was to determine the prevalence of undiagnosed IAD in patients with ATD.Methods: We studied 45 patients with ATD on stable L-thyroxine replacement (dose range...

ContextPrenatal dexamethasone (Dex) therapy is used in female foetuses with congenital adrenal hyperplasia (CAH) to suppress adrenal androgen excess and prevent virilisation of the external genitalia. The prenatal dexamethasone dose of 20 µg/kg per day has been used for decades in prenatal CAH and is associated with risks for the treated mother and potentially for the unborn child. Despite the high medical need, no prospective, clinical studies had ...

ContextE47 is a transcription factor mostly known for its role in B and T cell lineage commitment. Recently E47 was identified as a modulator of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. Patients with Cushing’s syndrome (CS) suffer from an endogenous glucocorticoid excess due to tumour formation associated with a variety of metabolic comorbidities seriously affecting patients&#1...

Background: In 2020, DSD-Care, a collaborative project involving endocrine reference centres, support groups, and research institutes in Germany was launched funded by the German Ministry of Health. The aim of the project was to improve the quality of care for people with differences in sex development (DSD), who often report feeling poorly treated by healthcare providers and a lack of access to detailed information about their condition. Congenital adrenal hyperplasia (CAH) i...

Background: Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) require lifelong glucocorticoid replacement therapy, including stress dose adjustment to prevent life-threatening adrenal crises (AC). Previous studies indicate a high incidence of inadequate stress dose adjustment and AC in patients with CAH. The aim of this study was to prospectively assess AC incidence, frequency and details of stress dose adjustment as well as knowledge of the d...

Background: Mutations of 21-hydroxylase (CYP21A2) cause congenital adrenal hyperplasia. Its severe (classic) form constitutes a life-threatening disease. Patients suffer a significant disease burden due to co-morbidities that are often treatment-related. The current therapeutic situation is unsatisfying and demands novel treatment approaches. In silico modelling suggests protein misfolding and intracellular retention to play a significant role in the pathogenesis of C...

Congenital adrenal hyperplasia due to P450 oxidoreductase (POR) deficiency (ORD) results in disordered sex development (DSD) in individuals of both sexes. POR provides electrons to CYP17A1 thereby facilitating synthesis of the major androgen precursor dehydroepiandrosterone (DHEA). ORD disrupts this enzymatic step, resulting in deficient synthesis of 5α-dihydrotestosterone (DHT) via DHEA, readily explaining undervirilisation (46,XY DSD) in male ORD neonates. Female virili...

Introduction: 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4) are new biomarkers for hyperandrogenic disorders. Steroids can be measured in saliva, allowing non-invasive sampling by patients. We modified a published LC-MS/MS method1 for quantification of 11-oxygenated androgens in saliva with respect to sample volume, extraction procedure and equipment, and assessed the potential impact of different sampling devices on results.<p class="a...

Background: Distinction of benign testicular adrenal rest tumours (TART) and potentially malign Leydig cell tumors (LCT) is challenging but important to prevent unnecessary surgery of TART. Ultrasound or magnetic resonance imaging can reliably detect but not distinguish between both tumour entities.Methods: Functional imaging results using the specific CYP11B1/2-inhibitor 123I-IMAZA were investigated in seven adult male patients with classic c...