5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer

Abstract

Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland.

Concurrent pituitary and adrenocortical lesions on computed tomography imaging in dogs with spontaneous hypercortisolism

“…With time, it may be difficult to distinguish between adrenal nodular hyperplasia and AT. It might even be hypothesized whether they occur independently of each other or the AT transitioned from initial hyperplasia …”

ITRAQ-based proteomic analysis reveals possible target-related proteins in human adrenocortical adenomas

“…In addition, the discrimination of distinct prognosis between ACA and adrenocortical carcinoma (ACC) deserves our close attention. ACA is a curable neuroendocrine tumor that is usually treated via surgery, whereas ACC is a malignant tumor with a low five-year mortality rate and very poor prognosis [41, 42]. Therefore, future proteomic studies may focus on meaningful markers that allow the differentiation between ACA and ACC [6].…”

Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004–2014)

“…[12][13][14] Recently, genetic studies in humans elucidated the relationship between adrenocortical hyperplasias and their progression to benign and malignant tumours. 15 Similarly, benign thyroid lesions may undergo malignant transformation. 16 17 Likewise, long-standing benign thyroid lesions in cats are assumed to progress to thyroid carcinomas.…”

“…The progression from endocrine tissue hyperplasia to benign or malignant tumour is a common phenomenon of MEN syndrome, and it is presumed that hyperplasia represents a precursor state of neoplasia 12–14 . Recently, genetic studies in humans elucidated the relationship between adrenocortical hyperplasias and their progression to benign and malignant tumours 15 . Similarly, benign thyroid lesions may undergo malignant transformation 16 17 .…”