Endocrine Abstracts

We previously identified mutations in PRKACA, coding for the catalytic a (Ca) subunit of protein kinase A (PKA), as the main genetic alteration in cortisol-producing adrenal adenomas (CPAs) responsible for Cushing’s syndrome. Here, we further investigated the mechanism of action of all PRKACA mutations identified so far by our team (L206R, L199_C200_insW, S213R_L212_K214insIILR, C200_GlyinsV, W197R, del244-248+E249Q and E32V). Five out of seven mutants s...

Introduction: Alteration in the expression of clock-related genes has been observed in various diseases. Adrenal sensitivity to adrenocorticotropic hormone (ACTH) apart from the hypothalamo-pituitary-adrenal axis is also regulated by the intrinsic adrenal clock. A link between clock genes and glucocorticoid adrenal production has been suggested by in vitro and animal studies. In the present study we investigated clock genes expression in human benign tumors of the adr...

Adrenal insufficiency is a rare endocrine disorder characterized by low levels of cortisol associated with increased mortality, also due to inadequate replacement therapy. The replacement with the thrice-daily immediate release hydrocortisone (IRH), in contrast to the once-daily modified-release hydrocortisone (MRH), more appropriately mimicking the physiological circadian rhythm of cortisol (PCRC), is associated with metabolic disorders, mainly due to the non-physiological pe...

Introduction: Adrenal insufficiency requires life-long glucocorticoid replacement. Conventional therapies fail to mimic endogenous cortisol circadian rhythm. Clock genes are essential components of the molecular machinery controlling organ’s circadian function and are influenced by glucocorticoids. However, clock genes expression has never been investigated in patients with adrenal insufficiency (AI).Aim: To evaluate the effect of the timing of gluc...

Introduction: ARMC5 germline and somatic inactivating mutations were discovered in patients treated by adrenalectomy for hypercortisolism due to primary bilateral macronodular adrenal hyperplasia (PBMAH). Since then, several ARMC5 germline variants have been described in PBMAH patients. Genetic alterations are spread all over ARMC5 coding sequence and many are missense variants. For them, geneticist conclusions are based on in silico predictions. As ...

Background: Adrenal myelolipoma (AML) is a relatively common and invariably benign tumor composed of adipose tissue and hematopoietic elements. Due to the variable proportion of fat and hematopoietic elements, it is sometimes challenging to differentiate AML from adrenocortical carcinoma (ACC). MicroRNAs have been identified as promising biomarkers in many tumors, including adrenocortical neoplasms, but the microRNA expression of adrenal myelolipoma has not been investigated, ...

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: Neuroendocrine tumors (NET) arise from tissue mucosal cells known as enterochromaffin cells. The clinical behavior of NET has been recognized over the past 30 years and genome analysis are needed for further follow up. Here we conduct integrated genome analyses on data from chromosomal gene copy number and transcriptome sequencing as well as analysis of overal survival of patients diagnosed with NET.Material and methods: The study accrued 6...

Background: Currently, the European Society of Endocrinology guidelines asserted against additional imaging during follow-up (FUP) in patients with non-functioning adrenal masses <4 cm in size with clear benign features on imaging studies. Our analysed literature data suggests that an increase (minimum 1 cm) in an initially benign adrenal mass during follow-up occurs in 3.5–20% of patients with adrenal incidentalomas.Aim: To analyse the change i...

Hypercortisolism is associated with high prevalence of psychiatric disorders and major depression occurs in 50–60% of patients. According to the available literature it is still unknown if patients with (possible) autonomous cortisol secretion ((P)ACS) carry the risk of depressive disorders. The Beck Depression Inventory II (BDI-II) is a commonly used instrument for detecting and quantifying levels of depression and its validity as a screening instrument is well establish...