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Molecular Pathology, Diagnostics, and Therapeutics of Adrenal Incidentalomas
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Molecular Pathology, Diagnostics, and Therapeutics of Adrenal Incidentalomas

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 13773

Special Issue Editor

Dr. Valentina Morelli

E-Mail Website
Guest Editor
Unit of Endocrinology and Metabolic Diseases, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, University of Milan, Milan, Italy
Interests: adrenocortical tumors; adrenal insufficiency; steroids measurement; osteoporosis

Special Issue Information

Dear Colleagues,

The detection of adrenal lesions, both unilateral and bilateral, during radiological examinations for unrelated diseases, is an emerging condition and requires extensive and adequate evaluation. Indeed, the term adrenal incidentaloma includes a wide range of lesions that are, frequently, although not always, benign. Primitive, rare, or secondary malignancy has to be excluded, as well as the presence of pheochromocytoma, infiltrative diseases, or congenital enzymatic mutations if bilateral. New radiological algorithms and metabolomics have been proposed so as to better characterize suspicious lesions; however, areas of uncertainty remain. Although the majority of adrenocortical masses are nonfunctioning adenomas, hormone-secreting tumours may cause Cushing's syndrome, primary aldosteronism, or virilisation. Clinical presentations vary in relation to the degree of steroid secretion, which are frequently mild. One of the main challenges is to identify patients with adrenal incidentaloma that present an increased risk of developing cardiovascular or bone complications, thus limiting unnecessary assessments. The adequate treatment of adrenal incidentaloma still needs to be defined—new drugs could be helpful when surgical excision is not feasible, for example in secreting cases.

This Special Issue will focus on all of these aspects, in particular the pathophysiology and preclinical approach of adrenocortical lesions, differential diagnosis, clinical consequences of mild hypersecretion, the role of new steroid measurement techniques, and biochemical inflammation markers in this setting, as well as possible therapeutic approaches. Both original research and review articles are welcome.

Dr. Valentina Morelli
Guest Editor

Manuscript Submission Information

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Keywords

  • adrenal incidentalomas
  • differential diagnosis of adrenal masses
  • subclinical hypercortisolism
  • genetics of adrenal tumours
  • adrenalectomy
  • steroidogenesis inhibitors
  • cardiovascular risk factors
  • secondary osteoporosis and vertebral fractures
  • biochemical markers
  • metabolomics

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Published Papers (3 papers)

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Review

17 pages, 2391 KiB  
Review
Pathophysiological Link between Insulin Resistance and Adrenal Incidentalomas
by Jordan A. Higgs, Alyssa P. Quinn, Kevin D. Seely, Zeke Richards, Shad P. Mortensen, Cody S. Crandall and Amanda E. Brooks
Int. J. Mol. Sci. 2022, 23(8), 4340; https://doi.org/10.3390/ijms23084340 - 14 Apr 2022
Cited by 12 | Viewed by 3498
Abstract
Adrenal incidentalomas are incidentally discovered adrenal masses greater than one centimeter in diameter. An association between insulin resistance and adrenal incidentalomas has been established. However, the pathophysiological link between these two conditions remains incompletely characterized. This review examines the literature on the interrelationship [...] Read more.
Adrenal incidentalomas are incidentally discovered adrenal masses greater than one centimeter in diameter. An association between insulin resistance and adrenal incidentalomas has been established. However, the pathophysiological link between these two conditions remains incompletely characterized. This review examines the literature on the interrelationship between insulin resistance and adrenal masses, their subtypes, and related pathophysiology. Some studies show that functional and non-functional adrenal masses elicit systemic insulin resistance, whereas others conclude the inverse. Insulin resistance, hyperinsulinemia, and the anabolic effects on adrenal gland tissue, which have insulin and insulin-like growth factor-1 receptors, offer possible pathophysiological links. Conversely, autonomous adrenal cortisol secretion generates visceral fat accumulation and insulin resistance. Further investigation into the mechanisms and timing of these two pathologies as they relate to one another is needed and could be valuable in the prevention, detection, and treatment of both conditions. Full article
(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Adrenal Incidentalomas)
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27 pages, 1471 KiB  
Review
Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside
by Vittoria Favero, Arianna Cremaschi, Chiara Parazzoli, Alberto Falchetti, Agostino Gaudio, Luigi Gennari, Alfredo Scillitani, Fabio Vescini, Valentina Morelli, Carmen Aresta and Iacopo Chiodini
Int. J. Mol. Sci. 2022, 23(2), 673; https://doi.org/10.3390/ijms23020673 - 8 Jan 2022
Cited by 15 | Viewed by 5951
Abstract
Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently [...] Read more.
Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation). Full article
(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Adrenal Incidentalomas)
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12 pages, 1404 KiB  
Review
Diagnostic Accuracy of CT Texture Analysis in Adrenal Masses: A Systematic Review
by Filippo Crimì, Emilio Quaia, Giulio Cabrelle, Chiara Zanon, Alessia Pepe, Daniela Regazzo, Irene Tizianel, Carla Scaroni and Filippo Ceccato
Int. J. Mol. Sci. 2022, 23(2), 637; https://doi.org/10.3390/ijms23020637 - 7 Jan 2022
Cited by 24 | Viewed by 3432
Abstract
Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); [...] Read more.
Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20–356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions. Full article
(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Adrenal Incidentalomas)
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