Endocrine Abstracts

Background: Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). Although adverse effects (AEs) associated to its use are frequent, detailed information are very limited. Aim was to evaluate the AEs of mitotane monotherapy in ACC patients. Methods: We performed a retrospective multicenter study including 311 ACC patients (F=200, median age 49 yrs) treated with mitotane as first line of medical treatment. Presence and grade of AEs were collect...

Clinical vignette: We investigated a 33-year-old woman diagnosed during pregnancy with a 7cm unilateral adrenal mass associated with severe ACTH-independent glucocorticoid and androgen excess, a steroid phenotype usually indicative of adrenocortical carcinoma. Pregnancy had been achieved with in-vitro fertilisation on the assumption of underlying PCOS. Neonatal death occurred soon after emergency delivery due to foetal growth arrest at 26 weeks gestation. Hist...

Background: DNA mismatch repair (MMR) maintains genomic integrity and stability. Inactivation of the MMR genes MLH1, PMS2, MSH2, and MSH6 by somatic or germline variants or gene methylation causes MMR deficiency (dMMR) leading to microsatellite instability (MSI) and high tumour mutational burden. In many tumour entities, patients with dMMR/MSI respond well to immune checkpoint inhibitor (ICI) therapy. The clinical relevance of dMMR and MSI i...

Background: Pheochromocytomas and paragangliomas (mPPGL) are rare neuroendocrine tumors. Therapeutic options in advanced and irresectable mPPGL are limited. Two small retrospective studies demonstrated the effectiveness of temozolomide in patients with mPPGL and suggested that patients with mutation in the succinate dehydrogenase B (SDHB) gene might benefit more than SDHB wildtype cases.Aim: To re-evaluate safety and effectiveness of temozolomide in a la...

Background: Treatment of adrenocortical carcinoma (ACC) is unsatisfactory in advanced stages. Oral mitotane remains a mainstay of treatment. Response rates of ACC to immune checkpoint inhibition (ICI) are disappointing and markers of response have not been identified. Tumoural infiltration with cells of the adaptive immune system is sparse in ACC tissue. Growth/differentiation factor 15 (GDF-15) is a cytokine that has been described to impair tumoral immune infiltration and is...

Background: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome. Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess has never been studied before.Methods: We investigated a woman with a large, heterogeneous 7 cm adrenal mass (with a radiologically normal contralateral adrenal) and adrenocorticotropic hormone (ACTH)-independent glucocorticoid and androge...

Introduction: Pheochromocytomas and paragangliomas (PPGLs) exhibit an up to 20% malignancy rate. Various clinical, genetic, and pathological features have been proposed as predictors of malignancy. However, until present there are no robust indices to reliably predict metastatic PPGLs.Aim: The aim of the present study was to prospectively validate the value of methoxytyramine as risk marker of metastatic disease and establish a machine learning (ML) mode...

Background: Adrenal incidentalomas (AI) are found in approximately 5% of the adult population. Most AIs are benign; however, small-scale studies have indicated that 20–50% of patients harbouring a benign AI show biochemical evidence of mild autonomous cortisol excess (MACE), previously termed subclinical Cushing’s syndrome. MACE is differentiated into MACE-1 (serum cortisol after overnight suppression with 1 mg dexamethasone (1 mg-DST) 50–140 nmol/l) and MACE-2 ...

Background: Adrenal incidentalomas (AI) are found in approximately 5% of the adult population. Most AIs are benign; however, small-scale studies have indicated that 20–50% of patients harbouring a benign AI show biochemical evidence of mild autonomous cortisol excess (MACE), previously termed subclinical Cushing’s syndrome. MACE is differentiated into MACE-1 (serum cortisol after overnight suppression with 1 mg dexamethasone (1 mg-DST) 50–140 nmol/l) and MACE-2 ...

Background: The main challenge in the diagnosis of arginine vasopressin deficiency (AVP-deficiency, formerly known as central diabetes insipidus), is its distinction against primary polydipsia. Hypertonic saline stimulated copeptin showed a high diagnostic accuracy of 97% in distinguishing between AVP-deficiency and primary polydipsia (Fenske W, Refardt J, NEJM 2018), but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showe...