The adrenal glands are small, triangular organs situated on top of each kidney, forming part of the body’s endocrine system. They consist of an outer cortex and an inner medulla, each responsible for producing different hormones that regulate essential bodily functions. The cortex specifically produces steroid hormones, including cortisol, aldosterone, and small amounts of androgens. “Overactive adrenal glands” describes a condition where one or both glands secrete an excessive amount of these hormones. This hormonal overproduction disrupts the body’s internal balance, leading to distinct health problems based on which hormone is being over-secreted.
Causes of Excess Cortisol Production (Hypercortisolism)
Excessive production of the stress hormone cortisol, known as hypercortisolism, is most frequently caused by an internal disruption of the body’s hormonal control system. This system involves a complex chain of command, starting in the brain and ending at the adrenal glands. The most common endogenous cause is Pituitary-Dependent Cushing’s Disease, which accounts for up to 80% of cases. This condition originates from a benign tumor, called an adenoma, located in the pituitary gland at the base of the brain.
The pituitary adenoma autonomously secretes an excessive amount of adrenocorticotropic hormone (ACTH). ACTH is the chemical messenger that normally signals the adrenal glands to produce cortisol. The high level of ACTH circulating in the bloodstream then overstimulates the adrenal glands, causing them to hypertrophy and increase their cortisol output. This constant stimulation overrides the normal negative feedback loop that would typically suppress cortisol production.
Another group of causes originates directly within the adrenal glands, leading to ACTH-independent hypercortisolism. In this scenario, the adrenal gland produces cortisol in excess, regardless of the low levels of ACTH being sent from the pituitary gland. The most common adrenal-based cause is a benign tumor, or adenoma, located on one of the adrenal glands. This adenoma produces cortisol autonomously, and the resulting high cortisol levels suppress the pituitary’s release of ACTH.
Adrenal and Ectopic Tumors
In rarer instances, the cause can be a malignant tumor, or carcinoma, of the adrenal cortex, which also drives uncontrolled cortisol production. A less common internal cause is the Ectopic ACTH Production syndrome. This occurs when a tumor located outside of the pituitary gland, often in the lung, pancreas, or thymus, starts to secrete ACTH. This ectopic source of ACTH then overstimulates the adrenal glands, leading to hypercortisolism. The tumors involved are frequently neuroendocrine tumors.
Causes of Excess Aldosterone Production (Primary Aldosteronism)
The overproduction of the mineralocorticoid hormone aldosterone, referred to as primary aldosteronism, stems from issues within the adrenal cortex. Aldosterone’s primary function is to regulate salt and water balance, which directly affects blood pressure and potassium levels. The resulting hormonal imbalance leads to hypertension that is often resistant to conventional blood pressure medications.
The single most common cause of primary aldosteronism is the presence of an Aldosterone-Producing Adenoma (APA). This is a non-cancerous tumor that develops on one adrenal gland and secretes aldosterone without regulation. This localized overproduction is responsible for a significant portion of all primary aldosteronism cases.
In a large percentage of patients, the cause is Bilateral Idiopathic Adrenal Hyperplasia (BIAH), where both adrenal glands become enlarged. This enlargement is accompanied by an overgrowth of the aldosterone-producing tissue within the adrenal cortex, causing both glands to secrete excess aldosterone. While the precise reason for this bilateral overgrowth is not known, it represents a generalized overactivity of the adrenal cortex.
Rare Causes and Effects
Rarer causes of primary aldosteronism exist, including inherited familial hyperaldosteronism and, exceptionally infrequently, an aggressive Aldosterone-Producing Adrenocortical Carcinoma. All of these primary causes result in the kidneys retaining too much sodium and excreting too much potassium, leading to high blood pressure and, often, low blood potassium levels.
External Factors Leading to Adrenal Overactivity
Adrenal overactivity can be induced by factors that originate outside the body’s natural endocrine system. The most frequent overall cause of hypercortisolism is Iatrogenic Cushing’s Syndrome, caused by the medical administration of synthetic glucocorticoid medications. These drugs, such as prednisone or dexamethasone, are widely prescribed to treat inflammatory conditions like asthma, arthritis, and autoimmune diseases.
These synthetic drugs are structurally and functionally similar to the body’s natural cortisol. Taking them at high doses or for prolonged periods mimics the effect of internal cortisol overproduction. The body sees the external medication as its own hormone, leading to the same effects as an internal adrenal tumor.
This external input of glucocorticoids creates an “overactive” state without an actual tumor or internal hormonal cascade driving it. The high concentration of the medication forces the body into a state of hormonal excess. This highlights the distinction between disease arising from a body malfunction and a condition induced by medical therapy.