In humans, the adrenal cortex comprises three concentric zones including the zona glomerulosa, zona fasciculata, and zona reticularis that under normal conditions respond to bodys physiological demands for steroid hormones. The adrenal cortex is considered a dynamic organ in which senescent cells are replaced by newly differentiated cells. This constant renewal facilitates organ remodeling which contributes to dynamic characteristics of the adrenal cortex. correspondingly, the developmental physiology of the adrenal cortex is believed to play a pivotal role in formation of the adrenocortical tumors. Hence, the molecular mechanisms involved in normal development of the adrenal glands are like double edged swords that can lead to the formation of tumors within the adrenal cortex. Moreover, recent studies suggest that mutations affecting the molecular pathways of the adrenocortical region can stimulate abnormal proliferation and tumor formation. Through these studies, the cyclic AMP-dependent protein kinase A signaling has been identified as a key mediator of cortisol secretion, and the mutations associated with the dysregulation of cyclic AMP - protein kinase A pathways have been implicated in the adrenocortical pathophysiology. Pathophysiology
If functional, adrenocortical adenomas can affect the normal activities of the adrenal cortex. Located within the adrenal glands are the three zones that are responsible for secretion of the three major classes of adrenal steroids. Hence, functional adrenocortical adenomas can induce over-secretion of adrenal steroids associated with pure or mixed endocrine syndromes, a condition commonly known as hyperadrenalism.
Diagnosis
Due to their asymptomatic nature, most reported cases of adrenal adenomas have been discerned fortuitously through autopsy, or during medical imaging, particularly CT scan (computed tomography) and magnetic resonance imaging. Hence, they have earned the title incidentaloma referring to small adenoma discovered incidentally. Though adrenocortical adenomas are considered challenging to differentiate from the normal adrenal cortex, they appear as well-circumscribed lesions once isolated.Imaging Diagnostics

Computed Tomography (CT scan)
Magnetic Resonance Imaging (MRI)
Laboratory Tests

CRH Stimulation Test
High-dose-dexamethasone suppression test

Gross Description
Well-circumscribed lesion
Size ≤ 5 cm
Weight ≤ 50 grams
often appear as golden-yellow color mass(may have focal dark regions corresponding to hemorrhage, lipid-depletion, and increased lipofuscin)

Histopathology
The microscopic histopathology analysis of the tissue samples obtained from the adrenal cortex of individuals presenting with adenoma-associated symptoms such as primary aldestronism (PA) indicates that adenoma cells are relatively larger with different cytoplasm, and increased variation in nuclear size. This indication is based on comparison between the healthy (normal) and affected (adenoma-associated) adrenal cortex tissue samples. Adrenocortical adenomas are most commonly distinguished from adrenocortical carcinomas (their malignant counterparts) by the Weiss system, as follows:
Total score indicates:
0-2: Adrenocortical adenoma
3: Undetermined
4-9: Adrenocortical carcinoma

Treatment
Non-functioning cases of adrenocortical adenoma can be managed through long-term followups and monitoring. The treatment approach for the functioning cases of adrenocortical adenoma depends on the type of disorders they induce and their advancement.