Endocrine Abstracts

Introduction: Adrenal Cushing due to bilateral multiple adrenal tumors known as Primary Pigmented Nodular Adrenocortical Disease (PPNAD) can be observed in the multiple neoplasia syndrome Carney Complex or as an isolated disease. In both situations germline inactivating mutations of PRKAR1A (regulatory subunit R1A of PKA) can be observed. The loss of PKA R1A results in an increased PKA activity. Comparison of the transcriptome of PPNAD and stably transfected H295R adr...

Introduction: Steroid profiling by mass spectrometry approaches consists in the simultaneous measurement of several steroid molecules in a biological sample, allowing an optimal characterization of steroidogenesis alterations, particularly in the context of adrenal tumors. Twenty-four hours urine samples have the advantage of being non-invasive and of giving an integrated view of steroidogenesis. Urinary steroid profiling has thus been shown to be particularly useful in the di...

Introduction: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare aetiology of Cushing syndrome. Familial clustering suggests a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat containing 5 (ARMC5) gene.Clinical case: A 70 years old female admitted due to femoral neck fracture in May 2014, presented central obesity, rubeosis and hypertension. Laboratory work up reveale...

Bilateral Adrenal Hyperplasias (BAH) are responsible for approximately 10% of ACTH-independent Cushing syndrome and are classified as either micronodular or macronodular. Whereas Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) are two types of micronodular hyperplasia, Primary Macronodular Adrenal Hyperplasia (PMAH) is a macronodular BAH. These tumors are classified differently based on clinical, histological and geneti...

The cyclic AMP (cAMP) signalling cascade is one of the main pathways involved in the pathogenesis of adrenocortical tumors (ACT). PRKARIA or PRKARIIb are involved in the proliferation/apoptosis in a subset of tumors.Majors alterations of genes involved in both cell proliferation and the cell cycle have been described by transcriptome and miRNome analysis in various types of adrenocortical tumors (ACC, ACA, AIMAH, and PPNAD). In addition...

Illegitimate membrane receptors are known to play a role in cortisol secretion in adrenal adenomas and ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing’s syndrome. Conversely, illegitimate receptors have never been described in primary pigmented nodular adrenal disease (PPNAD). In the normal adrenal gland, serotonin (5-HT) has been shown to stimulate cortisol secretion through activation of 5-HT receptor type 4 (5-HT4) whereas, in some AIMAH tissu...

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...

The cAMP signaling pathway plays an important role in cell proliferation and differentiation, and can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Inactivating mutations of PRKAR1A are observed in CNC (a dominant autosomal hereditary disease responsible for primary pigmented nodular adrenocortical disease, cardiac myxoma and lentiginosis). Most PRKAR1A mutations lead to mRNA unstability and protein degrad...

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...

Introduction: MSC is a simple and reliable mean to diagnose hypercortisolism, yet its value to asses the outcome of treatment has rarely been addressed.Objective: Compare MSC and other classical parameters, to assess the outcome of TSS in CD.Patients and methods: Sixty-eight patients from a single Center operated for CD between 1996 and 2006. Outcome was assessed between 6–12 months post TSS. Remission was defined as: morning ...