Adrenal

The adrenal glands are small, triangular organs located above the kidneys. They are vital for producing hormones that regulate metabolism, blood pressure,  and immune and stress responses. Each adrenal gland consists of two main parts: the cortex (the outer layer) and the medulla (the inner layer).

• Cortex: Responsible for producing aldosterone, cortisol, and androgens.
• Medulla: Produces epinephrine and norepinephrine, hormones involved in the body’s fight-or-flight response.

NORMAL HISTOLOGY OF THE ADRENAL GLAND: 

The adrenal cortex has three distinct zones, each responsible for producing different hormones:

• Zona Glomerulosa: Produces aldosterone, which helps control blood pressure by regulating salt and water balance.
• Zona Fasciculata: Produces cortisol, a key hormone in the stress response and glucose metabolism.
• Zona Reticularis: Produces androgens, involved in the development of secondary sexual characteristics.

The adrenal medulla contains chromaffin cells, which release catecholamines (epinephrine and norepinephrine) into the bloodstream, aiding in the body’s immediate response to stress.

NON-NEOPLASTIC PATHOLOGY OF THE ADRENAL GLAND:

• Adrenal Insufficiency
  • Acute: Characterized by sudden hormone deficiency, commonly caused by adrenal hemorrhage, as seen in Waterhouse-Friderichsen Syndrome (below).

• • Chronic: Known as Addison’s Disease, often caused by autoimmune destruction, infections like tuberculosis, or metastatic cancer. It results in a gradual decline in adrenal hormone production, leading to symptoms like fatigue, weight loss, and low blood pressure.

• Cushing Syndrome results from an excess of glucocorticoids (usually cortisol). This condition can be caused by:
  • An adrenal adenoma (a benign tumor)
  • Cushing’s disease (ACTH-producing pituitary adenoma)
  • Or, ectopic ACTH production (lung or other non-endocrine cancers)

• Primary Hyperaldosteronism (Conn Syndrome)
  • Characterized by overproduction of aldosterone, leading to high blood pressure and low potassium levels. Most cases are caused by an adrenal adenoma or bilateral adrenal hyperplasia.

NEOPLASTIC PATHOLOGY OF THE ADRENAL GLAND:

• Adrenal Adenomas
  • These are benign, well-circumscribed tumors that arise in the adrenal cortex (left images below). While many adenomas are non-functional, some can lead to excess hormone production, resulting in syndromes like Cushing’s syndrome or Conn’s syndrome.

• Adrenocortical Carcinoma
  • A rare and aggressive cancer that may cause hormone excess (e.g., cortisol, aldosterone) or present as a large, destructive mass. Histologically, these tumors often show pleomorphic cells, necrosis, and hemorrhage (center images below).

• Pheochromocytoma
  • A tumor of the adrenal medulla that secretes catecholamines, leading to episodic hypertension, headaches, and palpitations.
    • Pheochromocytomas exhibit a characteristic zellballen pattern, with polygonal tumor cells arranged in nests, supported by a vascular stroma, showing granular cytoplasm, round nuclei with “salt and pepper” chromatin (images on the right).
  • Known for the rule of 10s (10% malignant, 10% bilateral, 10% extra-adrenal), pheochromocytomas may be sporadic or linked to familial syndromes, including:
    • RET (associated with MEN 2A/2B)
    • VHL (linked to von Hippel-Lindau syndrome)
    • And SDH mutations (in familial pheochromocytomas)

NOTE: The adrenal glands are a common site for metastatic cancers, most often from lung cancer, but also from breast cancer, kidney cancer, and melanoma. These metastatic tumors frequently replace large portions of adrenal tissue, and while they may be asymptomatic, they can sometimes cause adrenal insufficiency if both glands are involved.