Endocrine Abstracts

Some elegant clinical observations of dysregulated cortisol-secretion in cases of ACTH-independent macronodular hyperplasia (AIMAH) and more rarely adrenocortical adenomas (ACA) have led to the concept of ‘aberrant’ or ‘illegitimate’ membrane receptors (AR) in adrenal Cushing syndrome. It this situation cortisol secretion is regulated by an extra-cellular ligand that usually does not stimulate cortisol secretion in normal adrenals. This abnormal response mi...

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochem...

Mitotane (o.p’DDD, Lysodren) is used to treat adrenortical carcinoma and Cushing syndromes. It is catabolised into o.p’DDA and o.p’DDE. It is lowly protein-bound but its tropism for lipids is high. It has multiple side effects on the digestive gut increasing alkaline phosphatases and cholesterol. Patients treated with mitotane have been described as having decreased FT4 levels without any signs of hypothyroidism. We wanted to know whether this is due to an analy...

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

Introduction: In chronic hypoparathyroidism (cHP), hypercalciuria is frequent, the mechanism of which remains unclear. The repetition of episodes of urinary tract obstruction by lithiasis can play a key role in the progressive deterioration of renal function. Taking advantage of the prospective cohort Epi-Hypo, we examined the relationship between nephrolithiasis and hypercalciuria.Methods: The Epi-Hypo cohort started in 2016 in France and is still activ...

Introduction: In Chronic hypoparathyroidism (cHP), secretion of parathyroid hormone (PTH) is insufficient to maintain blood calcium concentration (PCa) steady. More than 70% of cases result from neck surgery and therefore in insufficient secretion of PTH as in mutations of genes involved in PTH synthesis, while mutations of the calcium-sensing receptor (CaSR) and its signaling pathway may result in a remaining secretion of PTH. cHP can exert nephrocalcinosis and/or nephrolithi...

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to metyrapone. It has become increasingly used in recent years for treatment of Cushing’s Syndrome (CS). However, few in vivo studies are currently available to accurately compare both drugs characteristics. The objective of our study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent CS.Me...

Introduction: Biological diagnosis of Cushing syndrome relies on three parameters: 24 hours-free urinary cortisol; serum cortisol after 1 mg dexamethasone suppression test; late-night serum or salivary cortisol. These tests allow the diagnosis of cortisol excess but do not help in etiological diagnosis, particularly in the distinction between pseudo-Cushing and ACTH-dependent Cushing syndrome, which is often challenging. The aim of this study was to evaluate the performances o...

Background: Cushing syndrome due to PPNAD is the main endocrine disorder of CNC, an autosomal dominant multiple neoplasia caused by germline inactivating mutations of the subunit type 1A (PRKAR1A) of the protein kinase A (PKA). In addition, germline inactivating mutations in the gene encoding phosphodiesterase 11A (PDE11A) have been identified in patients with PPNAD.Aim of the study: To investigate the role of PDE11A genetic alterati...

Diagnosing malignancy and assessing the prognosis of adrenocortical tumors is challenging. The aim is to identify molecular predictors of malignancy and of survival.Patients and methods: Of 153 unilateral adrenocortical tumors were studied by microarray (n=92) or RT-qPCR (n=148). A 2-gene predictor of malignancy was built using the disease-free survival as the end-point in a training cohort (n=47), then validated in an independent va...