Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives

Abstract

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2-3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10-40% of the cases by autonomous cortisol hypersecretion, and in 1-10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients.

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

“…However, ECS is the most frequent endocrine paraneoplastic syndrome reported in NET [47]. It has well demonstrated that cortisol excess has a negative impact on bone health [48][49][50]. Osteoporosis induced by glucocorticoid excess is due mainly to a direct effect on osteoblasts, osteocytes, and osteoclasts, which express glucocorticoid receptors (GR; Figure 3) [49].…”

“…It has well demonstrated that cortisol excess has a negative impact on bone health [48][49][50]. Osteoporosis induced by glucocorticoid excess is due mainly to a direct effect on osteoblasts, osteocytes, and osteoclasts, which express glucocorticoid receptors (GR; Figure 3) [49]. In osteoblasts, cortisol excess induces a reduction of bone formation mediated by an upregulation of peroxisome proliferator-activated receptor (PPAR)-γ and an inhibition of the wnt pathway, which promotes, in turn, osteoblast apoptosis and differentiation of mesenchymal progenitors into adipocytes.…”

“…Sclerostin secreted by osteocytes induces osteocyte apoptosis and inhibits the wnt pathway. Moreover, the increase of the receptor activator for NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, together with the increased macrophage colony-stimulating factor (M-CSF), stimulates osteoclastogenesis and bone resorption ( Figure 3) [49].…”

Osteoporosis and adrenal incidentaloma: To be or not to be?

“…The excess of pure adrenal androgens is extremely rare in cases without other secretions and these cases are not usually asymptomatically at presentation so they can barely fit to the diagnosis of adrenal incidentaloma (7,8). The cortisol excess (even subclinical) is more frequent in subjects with bone loss or vertebral fractures (4,9).…”

“…The finding has an age-dependent pattern (2,3). The diagnosis actually includes two aspects: one is the radiological or imaging detection through any of the mentioned procedures, and the other aspect is related to the clinical and endocrine assessment that finally decides that the incidental tumour is a "true" incidentaloma meaning that overall there is a negative secretor profile and the route to its detection was accidental (4,5). However, a possible or a probable autonomous cortisol production is included and thus some long term complications might be expected, ignored or considered "idiopathic" or just "age-related" as seen in subjects diagnosed with high blood pressure, hyperlipemia and osteoporosis especially in menopausal women (1,5,6).…”