Adrenal Cortex Hyperfunction (Hypercortisolism)
Excessive production of adrenocortical hormones is most commonly associated with tissue hyperplasia or hormonally active tumors (adenomas and carcinomas).
- Cushing Syndrome: Results from cortisol excess. Causes include ectopic ACTH production, carcinomas, or adrenocortical hyperplasia. If bilateral adrenalectomy is performed in a patient with this syndrome, 8–10% of patients may develop Nelson syndrome — the formation of an ACTH-secreting pituitary adenoma, causing severe skin hyperpigmentation.
- Primary Hyperaldosteronism: Aldosterone excess that is entirely independent of the renin-angiotensin-aldosterone system. In 70% of cases, it is caused by a benign tumor (aldosteroma), known as Conn syndrome. It presents with hypertension, paresthesias, and muscle weakness in the setting of hypokalemia and hypernatremia.
Clinical pearl: Liddle syndrome (pseudohyperaldosteronism) is a hereditary renal pathology where receptors are hypersensitive to aldosterone, even though the blood level of the hormone itself remains normal.
Congenital Adrenal Hyperplasia (CAH)
CAH is a group of autosomal recessive disorders caused by congenital enzymatic defects. Due to the enzymatic block, glucocorticoid levels drop, which stimulates the pituitary gland to secrete massive amounts of ACTH. This leads to massive bilateral adrenal hyperplasia (gland weight may exceed 60 g).
21-Hydroxylase deficiency accounts for 90% of cases. There are two main forms:
- Virilizing form: Excess precursors are shunted toward testosterone synthesis. Females develop female pseudohermaphroditism, while males develop macrogenitosomia. Children grow rapidly, but epiphyseal growth plates close early, resulting in short stature.
- Salt-wasting form (10% of cases): The enzyme is completely absent, making aldosterone synthesis impossible. It is accompanied by severe renal wasting of sodium and chloride. Without hormone replacement therapy, it rapidly leads to death.
Adrenal Cortex Hypofunction (Hypocortisolism)
Adrenal insufficiency manifests only when at least 80–90% of the cortical layer is destroyed bilaterally.
- Addison Disease (chronic form): In more than half of cases, it is autoimmune in origin (antibodies are directed against the cytoplasm of cortical cells). Notably, in autoimmune destruction, the adrenal medulla remains intact. If the cause is generalized tuberculosis, both layers are destroyed. Classic symptoms include generalized melanosis (skin darkening), hypotension, weakness, and weight loss.
- Acute Insufficiency (Adrenal Crisis): Can occur upon rapid withdrawal of glucocorticoids or massive hemorrhage into the glands. A prominent example is Waterhouse–Friderichsen syndrome, which develops in young children with severe bacterial infections (especially meningococcal). Due to bilateral hemorrhagic infarction of the adrenals, catecholamines are depleted, blood vessels dilate pathetically, blood pressure drops, and coma ensues.
Adrenal Medulla Pathology
The primary pathology of the medullary tissue is pheochromocytoma, a rare tumor arising from mature chromaffin cells that actively secretes catecholamines (most commonly norepinephrine).
- Features: About 10% of these tumors are malignant. The tumor can also be located extra-adrenally (e.g., in the Zuckerkandl organ or aortic paraganglia).
- Clinical Presentation: Characterized by paroxysmal crises. Triggers can include physical exertion or stress. During an attack, there is a sharp spike in blood pressure, tachycardia, headache, profuse sweating, and skin pallor.
- Complications: Excess catecholamines can lead to myocardial infarction, stroke, or sudden cardiac death during anesthesia induction.