Bilateral Adrenal Hyperplasia (BAH) is a medical condition characterized by the abnormal enlargement of both adrenal glands. This non-malignant growth, known as hyperplasia, leads to the overproduction of hormones. This hormonal excess can disrupt normal bodily functions, resulting in significant health problems. This article examines the causes, symptoms, diagnosis, and treatment of BAH.
Understanding the Adrenal Glands
The adrenal glands are small, triangular-shaped endocrine glands situated on top of each kidney. They are composed of the outer cortex and the inner medulla. The cortex produces steroid hormones essential for life.
These steroid hormones fall into three main categories: glucocorticoids, mineralocorticoids, and androgens. Cortisol, the primary glucocorticoid, is involved in stress response, metabolism, and immune function. Aldosterone, the main mineralocorticoid, regulates blood pressure and the balance of salt and water. The adrenal cortex also produces androgens, which are precursor sex hormones.
Hormone production is tightly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. The pituitary gland releases adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce cortisol. Disruption in this feedback loop can lead to an excess or deficiency of adrenal hormones.
Defining Bilateral Adrenal Hyperplasia
Bilateral Adrenal Hyperplasia (BAH) refers to the simultaneous enlargement of both adrenal glands. Hyperplasia indicates an increase in the number of cells within the tissue, causing the organ to become larger than normal, which is distinct from a tumor.
The enlargement manifests in different physical forms. Micronodular hyperplasia involves numerous small nodules, less than one centimeter in diameter. Macronodular hyperplasia features larger, more pronounced nodules exceeding one centimeter. In both types, the increased cell mass results in the functional overproduction of one or more adrenal hormones.
The Mechanisms of Adrenal Enlargement
The cause of Bilateral Adrenal Hyperplasia depends on whether growth is driven by pituitary signals (ACTH-dependent) or autonomous changes within the adrenal cells (ACTH-independent).
ACTH-dependent hyperplasia, or secondary hyperplasia, occurs when the pituitary gland secretes excessive ACTH. This constant stimulation acts as a growth factor on the adrenal cortex, causing the glands to enlarge. This mechanism is most commonly seen in Cushing’s disease, where a benign pituitary tumor overproduces ACTH.
ACTH-independent hyperplasia, or primary hyperplasia, is driven by factors intrinsic to the adrenal glands. In this scenario, the body’s ACTH levels are suppressed due to the negative feedback of excessive cortisol, yet the adrenal glands continue to grow and secrete hormones autonomously. A common form is Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), often caused by genetic mutations, such as those in the ARMC5 gene.
This independent growth often involves the abnormal expression of G-protein-coupled receptors on the adrenal cell surface. These aberrant receptors allow adrenal cells to be stimulated by hormones they would normally ignore, such as those related to digestion or stress. This leads to unregulated cell growth and hormone production.
Recognizable Symptoms and Health Consequences
The symptoms of Bilateral Adrenal Hyperplasia relate directly to which hormone is overproduced. The most common presentation involves an excess of cortisol, leading to Cushing’s syndrome.
Patients often experience a characteristic pattern of weight gain, accumulating fat in the central body, face, and neck, while the limbs remain thin. This hypercortisolism also causes protein catabolism, leading to muscle weakness, particularly in the hips and shoulders, and skin fragility resulting in easy bruising.
Another frequent consequence is high blood pressure (hypertension). If aldosterone production is primarily affected, the resulting hyperaldosteronism causes the body to retain sodium and excrete potassium. This leads to low potassium levels (hypokalemia), which can cause muscle cramps, fatigue, and increased urination.
Diagnostic Testing and Treatment Options
Diagnosing Bilateral Adrenal Hyperplasia requires confirming hormonal overproduction and identifying the underlying cause and morphology. Imaging techniques like Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) visualize the adrenal glands to confirm bilateral enlargement or the presence of nodules.
Specialized blood and urine tests measure hormone levels. Measuring plasma ACTH levels is a key step; suppressed ACTH alongside high cortisol confirms an ACTH-independent problem originating in the adrenal glands. Suppression tests, such as the 1 mg dexamethasone suppression test, determine if cortisol production is autonomous. For hyperaldosteronism, the plasma aldosterone-to-renin ratio (ARR) is measured, and Adrenal Vein Sampling (AVS) may be performed to confirm both glands are the source of excess aldosterone.
Treatment strategies depend on the mechanism driving the hyperplasia. For hyperaldosteronism caused by BAH, medical management uses mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, to block aldosterone action and control blood pressure and potassium levels.
For hypercortisolism, medication like ketoconazole can block cortisol production. If medical therapy fails to control severe hypercortisolism, especially in ACTH-independent cases, a bilateral adrenalectomy (surgical removal of both glands) may be necessary. This procedure cures the hormone excess but requires the patient to take lifelong glucocorticoid and mineralocorticoid replacement therapy to manage the resulting adrenal insufficiency.