Endocrine Abstracts

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...

IntroductionAdrenocortical Carcinoma (ACC) is a rare aggressive cancer which carries a poor prognosis. Adjuvant mitotane improves survival but is limited by poor response rates and resistance following tumour recurrence. Mitotane’s efficacy has been attributed to intracellular accumulation of toxic free cholesterol (FC) predominantly through inhibition of cholesterol storage through SOAT1. Yet SOAT1 specific inhibitors demonstrate inferior efficacy ...

Klotho (Kl), initially identified as an antiaging gene, plays a critical role in the regulation of renal and adrenal dependent fluid homeostasis. A previous study reported that haplodeficiency of Kl in mice resulted in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone and high blood pressure. This phenotype was presumed to result from diminished Kl expression in zona glomerulosa (zG) of the adrenal. To examine whether Kl expressed in zG is indeed...

The adrenal glands serve as central organs of the endocrine system by producing steroid hormone essential for organismal homeostasis. Mechanisms ensuring proper adrenal homeostasis and function are therefore crucial for maintaining human life. ACTH, released by the pituitary corticotrope, is required for the differentiation of the inner part of the adrenal cortex (the zona fasciculata) and the resultant stimulation of cortisol production. Perturbation of ACTH signaling can lea...

Background: Cushing’s syndrome (CS) is a rare but very severe condition with high morbidity and mortality. Patients are often diagnosed late in the course of the disease, many years after onset of symptoms. New approaches like extended screening of at risk populations, alternative biomarkers and clinical scores have been developed to improve diagnostic accuracy. However, there is still a debate, whether certain patient populations should be screened for CS outside the fra...

Introduction: The differential diagnosis between arginine vasopressin deficiency (AVP-D), formally known as central diabetes insipidus, and primary polydipsia (PP) is challenging. In clinical routine, psychopathologic findings are often used as a hallmark for diagnosing PP; thus, it is often referred to as psychogenic polydipsia. Yet, psychopathologic characteristics are barely assessed in patients with AVP-D, and to date, no data exist comparing AVP-D and PP with regard to th...

Background: Cyclic Cushing’s syndrome (cCS) is a sub-entity of Cushing’s syndrome (CS) associated with diagnostic and therapeutic challenges. It describes a condition, in which phases of clear-cut biochemical hypercortisolism are followed by spontaneous troughs of normal or subnormal cortisol secretion. We conducted the first systematic literature review to identify common features of cCS.Methods: We searched MEDLINE (via PubMed) for eligible s...

Background: Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism. Somatic mutations explain the excess aldosterone production in the majority of patients with APA with mutations in the potassium channel KCNJ5 the most prevalent. In contrast, mechanisms driving cell proliferation are largely unresolved.Objective: To identify genes that modulate cell growth in APAs.Methods: Quantitative transcripto...

In a previous study we found mutations in the main catalytic subunit of protein kinase A (PKA Cα) to be responsible for cortisol-secreting adrenocortical adenomas (ACAs). These mutations interfere with the formation of a stable holoenzyme, thus causing constitutive PKA activation. More recently, we identified additional mutations affecting PKA Cα in ACAs associated with overt Cushing syndrome: Ser213Arg_Leu212_Lys214insIle-Ile-Leu-Arg, Cys200_Gly201insVal, Trp197Arg,...

Introduction: Mutations activating USP8 have been detected in a high proportion of pituitary adenomas causing Cushing’s disease and have been linked to an increase of ACTH production in corticotroph cells. Whether USP8 mutations are involved in the tumorigenesis of the ectopic Cushing’s syndrome (ECS) caused by neuroendocrine tumors has not been studied.Patients and methods: In this work we evaluate the role of USP8 in a series of 17 t...