The Adrenal Gland
The adrenal glands are small, triangular-shaped glands located above each kidney. The adrenal glands are part of the endocrine system. Each adrenal gland consists of two main parts: the adrenal cortex and the adrenal medulla.
The adrenal cortex produces three types of hormones: cortisol, aldosterone, and sex hormones. Cortisol helps manage stress, metabolism, and immune response. Aldosterone regulates blood pressure and electrolyte balance. The sex hormones from the adrenal glands are only a minor component of androgen (testosterone) and estrogen production in the body.
The adrenal medulla produces catecholamines like adrenaline and norepinephrine. Catecholamines rev up the body's fight-or-flight response, preparing the body to respond to stress or danger.
In the picture to the left (or above) you see the adrenal gland in its location relative to the kidney. It sits above the kidney within the perinpheric fatty tissue that surrounds the kidney.
The layers of the adrenal gland are seen in the picture to the right (or below). The medullary adrenal makes the “fight or flight” hormones such as adrenaline. Th layer labelled glomerulosa makes the hormone aldosterone. The fasciculata layer makes cortisol. Sex hormones are made in the reticularis layer.
Adrenal Gland Pathology
Pathologies of the adrenal glands can lead to significant health issues, categorized mainly into hyperfunction, hypofunction, and tumors.
Hyperfunction
Cushing's Syndrome: Characterized by excessive cortisol production, it can result from adrenal tumors, pituitary adenomas, or ectopic ACTH production. Common symptoms include weight gain, hypertension, diabetes, and characteristic skin changes.
Conn's Syndrome (Primary Hyperaldosteronism): This condition arises from an aldosterone-secreting adenoma or bilateral adrenal hyperplasia. Patients typically present with hypertension, hypokalemia, and metabolic alkalosis.
Pheochromocytoma: A rare tumor of the adrenal medulla that secretes catecholamines (epinephrine and norepinephrine). Symptoms may include episodic hypertension, headaches, palpitations, and sweating.
Hypofunction
Addison's Disease: This primary adrenal insufficiency occurs due to the destruction of adrenal cortical tissue, often from autoimmune processes, tuberculosis, or metastatic disease. Patients may experience fatigue, weight loss, hyperpigmentation, and hypotension.
Secondary Adrenal Insufficiency: This results from inadequate ACTH production by the pituitary gland, commonly due to chronic use of glucocorticoids. Symptoms are similar to Addison's disease but may lack hyperpigmentation.
Tumors
Adrenal Adenomas: These are benign tumors that can be functional or non-functional. Functional adenomas often cause Cushing's syndrome or Conn's syndrome.
Adrenal Carcinoma: A rare malignant tumor that may present with signs of hyperfunction or may not produce hormones. A tumor less than 4 cm has a low chance of malignancy. Surgical removal is the primary treatment.
Metastatic Disease: The adrenal glands are common sites for metastasis from other cancers, including lung and breast cancer. Diagnostic imaging and biopsy may be required for differentiation.
Diagnosis and Treatment
Diagnosis of adrenal gland pathologies can involve a combination of blood tests to measure hormone levels, imaging studies (CT or MRI), and biopsy when indicated. Treatment varies widely based on the specific pathology and may include surgical intervention, medical management, or hormone replacement therapy in cases of insufficiency.
In addition to imaging, every patient with a newly diagnosed AI should receive hormonal screening, including a 1 mg dexamethasone suppression test and plasma-free and/or urinary fractionated metanephrine levels. If the patient has hypertension, a renin/aldosterone level should also be drawn.
Adrenal incidentalomas are defined as any unsuspected adrenal mass ≥1cm detected incidentally on radiologic imaging obtained for another indication. Based on imaging and autopsy studies, the estimated prevalence is approximately 5%. Currently, up to 20% of adrenal incidentalomas are estimated to be metabolically active.
The clinical and biochemical evaluation of an adrenal incidentaloma should specifically assess for signs and symptoms of hypercortisolism (Cushing syndrome), hyperaldosteronism only in patients with hypertension or hypokalemia, , pheochromocytoma, and malignant tumor. The relevant clinical signs and symptoms of hormonal excess may variably include substantial unintended weight gain, central obesity, easy bruising, striae, severe and uncontrolled hypertension, diabetes, virilization, proximal muscle weakness, or fatigue. It is important to obtain a careful history regarding extra-adrenal malignant disease, as an estimated 19-58% of patients with a history of metastatic cancer and an incidental adrenal mass will have a metastatic lesion within the adrenal gland.
All adrenal incidentalomas should undergo biochemical testing unless the imaging is unequivocal for myelolipoma (e.g., low CT attenuation of -10 to -20 Hounsfield units or the presence of macroscopic fat) in which case biochemical testing is not mandatory. However, if there is a clinical suspicion for endocrine functionality based on the clinical history, then a biochemical evaluation should be completed as a small subset of myelolipomas (10-15%) can be functional. Conversely, recent data suggest that if the incidentaloma has HU <10 HU in the non-contrast phase, then testing for pheochromocytoma is not necessary.
