Pathophysiological Link between Insulin Resistance and Adrenal Incidentalomas

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 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.

Characterisation of the urinary steroid profile of patients with nonfunctioning adrenal incidentalomas: A matched controlled cross‐sectional study

“…They propose that hyperinsulinemia caused by insulin resistance, could result in the birthing of diverse masses throughout the body, including adrenal masses. 36 Patients with NFAI had higher levels of free urinary cortisol than the healthy-adrenal group. Other previous studies 17,37,38 reported that patients with NFAI had higher THF and THS than patients without adrenal tumours.…”

“…In this line, some authors have suggested that AIs may be part of the metabolic syndrome in patients with insulin resistance. They propose that hyperinsulinemia caused by insulin resistance, could result in the birthing of diverse masses throughout the body, including adrenal masses 36 …”

Management of Adrenal Cortical Adenomas: Assessment of Bone Status in Patients with (Non-Functioning) Adrenal Incidentalomas

“…Longitudinal studies have reported an increased frequency of complications, including of osteoporotic fractures, in patients with AIs/ACS [ 62 , 79 , 80 ]. Additionally, the management (short- and long-term medical and surgical strategies) needs to integrate bone status into the larger panel of cardiovascular and metabolic complications due to ACS/SCS [ 108 , 109 , 110 ], as well as generally in patients with AIs/non-functioning AIs [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. “Non-functional” does not necessarily mean harmless, and insulin resistance, obesity, high blood pressure, diabetes, and dyslipidaemia are identified in the same patients who display a higher risk of osteoporosis and VFs [ 118 , 119 , 120 , 121 , 122 , 123 , 124 ], as is increased arterial intima-media thickness-associated endothelial dysfunction [ 125 , 126 ], elevated uric acid [ 127 ], and pro-coagulation status [ 128 , 129 ], as well as potential elevated all-cause mortality [ 130 ].…”

Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure—A Diabetic Perspective

“…Perturbations in insulin sensitivity in HAAF may be influenced by changes at the level of the adrenal gland. It is known that cortisol secreted by the adrenal glands acts on the pancreas to increase glucagon release and reduce insulin release [40]. Furthermore, it is known that the adrenal cortex and the adrenal medulla regulate the release of cortisol and adrenaline, respectively, in a synchronised bidirectional manner [41,42].…”