Endocrine Abstracts

Objectives: Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormones and is a target for autoimmune responses in autoimmune thyroid disease. TPO autoantibody (TPOAb) binding epitopes have been mapped on the peroxidase domain (POD) and the complement control protein like domain (CCP). This study aimed to solve the molecular structures of TPO bound to TPO antibodies.Methods: An extracellular domain (ECD) of human TPO (amino acids; aa 1...

Objectives: TSH receptor (TSHR) autoantibodies (TRAb) which mimic the actions of TSH are responsible for hyperthyroidism in Graves’ disease (GD) which is often associated with Graves’ orbitopathy (GO). K1-70 is a TSHR specific human monoclonal autoantibody which binds to the TSHR with high affinity and prevents stimulation of the TSHR by TSH and TRAb. Safety, tolerability, pharmacokinetic, pharmocodynamic and immunogenic effects of K1-70 in patients with GD were asse...

Background: A diagnosis of Addison’s disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality, as well as a risk of unexpected adrenal crisis. We wished to explore whether immunomodulatory therapy at an early stage of autoimmune Addison’s disease could lead to preservation or improvement in adrenal steroidogenic function.Design: We conducted an open-label, p...

Objectives: The crystal structures of the TSH receptor (TSHR) leucine rich repeat domain (LRD) bound to TSHR stimulating monoclonal autoantibody M22TM or to TSHR blocking monoclonal autoantibody K1-70TM and antibody free have been solved previously. Cryo-electron microscopy (cryo-EM) was now used to solve the structure of full length TSHR in complex with K1-70TM.Methods: Recombinant human TSHR expressed in CHO cells was i...

Despite lifelong glucocorticoid and mineralocorticoid replacement, there is excess morbidity and mortality associated with autoimmune Addison’s disease (AAD). Adrenal cortical cells undergo continuous self-renewal from a population of subcapsular progenitor or stem cells, under the influence of ACTH. We aimed to determine if synthetic ACTH analogue could revive adrenal steroidogenic function and ameliorate AAD.We performed an open-label trial of syn...