Endocrine Abstracts

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 ...

cAMP/PKA pathway activation is frequently involved in endocrine tumors with overactivity. The Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome which associates cardiac myxomas, spotty skin pigmentation and endocrine overactivity. Mutations in the PRKAR1A gene located at 17q22-24 and encoding for the R1A regulatory subunit of protein kinase A have been found in about 60% of CNC. These mutations are heterozygous germline mutations leading to ab...

CNC is an autosomal dominant multiple neoplasia syndrome, responsible mainly for cardiac myxomas, pigmented skin lesions and endocrine tumors (acromegaly, thyroid and testicular neoplasms and primary pigmented nodular adrenocortical disease: PPNAD). The PRKAR1A gene was previously found to be mutated in about 41% of CNC kindreds. Most mutations lead to nonsens mediated mRNA decay and preclude expression of the mutant protein. 102 patients (64 with PPNAD and 38 with CNC)...

Introduction: The inactivating mutations of the Carney complex gene PRKAR1A (regulatory subunit RIA of PKA) cause bilateral adrenocortical tumors (PPNAD: Primary Pigmented Nodular Adrenocorticel disease) over-secreting cortisol. This leads to stimulation of PKA activity, however the mechanisms of adrenal tumorigenesis and cortisol dysregulation are not fully understood. In order to identify target genes of PRKAR1A inactivation in adrenal cortex we undertook a comparat...

Introduction: Insulinoma is the most frequent functional endocrine tumor of the pancreas but remains rare with an incidence of less than 5 cases by million and by year. It is often sporadic but can occur in the context of MEN1 in about 5% of cases, being then readily multiple. Clinically, it is typically responsible for fasting hypoglycemic episodes. Only one case of multiple insulinomas, with no obvious argument for MEN1 context, has previously been reported (Babic an al., <e...

BackgroundARMC5 is a putative tumor suppressor gene that is frequently mutated in primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing’s syndrome. The function of ARMC5 is poorly known, aside the fact that it regulates cell apoptosis and adrenal steroidogenesis in by mechanisms still unknown. Tumor suppressor genes play an important role in oxidative stress.MethodsIn this s...