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Christian A. Koch, George P. Chrousos, Is the Diminuto/Dwarf1 Gene Involved in Physiologic Adrenocortical Size Regulation and Tumor Formation?, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 11, 1 November 2001, Pages 5127–5129, https://doi.org/10.1210/jcem.86.11.8118
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In this issue of JCEM, Sarkar et al. (1) report very interesting data on the diminuto/dwarf1 gene in benign cortisol-producing adrenocortical adenomas. Adrenal nodules are now frequently discovered by contemporary imaging modalities, with an overall prevalence of about 4% (2, 3). These are in accordance with earlier autopsy series, which reported adrenal adenomas in up to 8% of cases (4, 5). The majority of these nodules are hormonally inactive, but when they produce hormones, these are mostly cortisol and/or aldosterone. The molecular pathogenesis of most adrenocortical adenomas and carcinomas remains unknown, but the majority of these lesions are of monoclonal origin (6–8).
An early and proven approach to elucidate tumorigenesis has been by analyzing hereditary neoplasms, since these already have an identifiable “first hit,” the inherited gene defect. Indeed, subsequent hits may be easier identified in familial than in sporadic tumors (9, 10). Signal transduction systems, including G protein-coupled receptors and G proteins, when activated chronically/constitutively in endocrine tissues, may cause an increase in intracellular levels of cAMP and hormone hypersecretion and/or cell proliferation. This is the case for at least 40% of somatotropinomas and toxic thyroid adenomas, in which the GHRH and TSH signaling systems are pathogenetically involved. However, analysis of components of the ACTH receptor (ACTHR) signal transduction system in adrenocortical adenomas or carcinomas has suggested that these are not involved in a major fashion in the pathogenesis of these tumors (7, 11, 12), yet aberrant expression of ectopic G-coupled receptors, such as those of GIP and the catecholamines, have been determined to be of pathophysiologic significance in some adrenal adenomas (13). On the other hand, investigations focused on the involvement of growth factors, such as IGF-II, and components of apoptotic pathways, such as p53, have yielded useful information about the pathogenesis of malignant adrenal neoplasms (7, 11, 12, 14).
