Cell-To-Cell Communication in Bilateral Macronodular Adrenal Hyperplasia Causing Hypercortisolism

Abstract

It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes, and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia (BMAH), a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events, which cause the disease, favor abnormal adrenal differentiation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms, which are likely to play a role in the pathophysiology of BMAH-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment

“…Paracrine and autocrine regulation of adrenal glands by peptides or neurotransmitters secreted by chromatin cells, nerve endings, or immune cells has been previously demonstrated [106][107][108].…”

Immunohistochemical study on the expression/hyperexpression of aberrant/eutopic receptors in patients with bilateral macronodular adrenal hyperplasia

“…Ранее была выявлена экспрессия мРНК MC2R в кортизолпродуцирующих аденомах надпочечников, которая отсутствовала в окружающей атрофичной ткани [65,66] ков. В данном случае при ИГХ-исследовании выявляется диффузное клеточное окрашивание в гиперпластической коре надпочечников, а также его полное отсутствие в мозговом веществе и неизмененной коре надпочечников [37,67]. В работе Louiset и соавт.…”

Diagnosis and management of primary bilateral macronodular adrenal hyperplasia

“…Although recent research has unraveled many aspects of PBMAH (Lefebvre et al 2015), the pathophysiology of this disorder remains largely unclear, due to the perplexity of the mechanisms involved in the processes of adrenal growth as well as hormonal hypersecretion and, also, to the intrinsic heterogeneity of this disorder. Different pathogenetic processes may lead to similar phenotypes of adrenal enlargement with formation of nodules and various degrees of cortisol hypersecretion.…”

“…Of note, aberrant hormone receptors have been shown to also regulate the paracrine secretion of ACTH creating an autocrine/paracrine loop that promotes adrenal growth and steroid secretion , Cavalcante et al 2018. Paracrine regulatory loops involving ligands such as serotonin or vasopressin have also been implicated in the pathophysiology of steroid hypersecretion (Lefebvre et al 2013(Lefebvre et al , 2015.…”