Adrenal Gland Disorders

Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison disease, is caused by adrenal gland disorder (autoimmune disease, infections, and malignancy, among others). Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Diagnosis is by demonstrating hypocortisolism (via cortisol and ACTH levels and ACTH-stimulation test) and determining the etiology (adrenal autoantibodies, imaging). Glucocorticoid replacement is needed in all forms of AI. Additionally, in primary AI, mineralocorticoid is given to prevent volume depletion, salt loss, and hyperkalemia. Adrenal crisis is a medical emergency; management requires prompt IV hydration and administration of IV glucocorticoids without waiting for initial hormone results.

Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytomas are frequently familial and associated with genetic syndromes. Approximately 90% of pheochromocytomas are benign and surgical resection is the only curative treatment. Prognosis is generally good for benign, sporadic tumors that have been completely resected. Familial forms are associated with higher recurrence rates and malignant potential.

Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis, although recent studies have suggested that hypokalemia is less common than originally thought in primary hyperaldosteronism. Patients with hypertension who are treatment resistant and/or associated with hyperkalemia should be screened for hyperaldosteronism by determining their plasma aldosterone concentration and plasma renin activity. Confirmatory tests and an abdominal CT scan are required to conclusively diagnose primary hyperaldosteronism. Management involves the use of aldosterone receptor antagonists and surgical excision of any aldosterone-secreting tumors.

The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. The outer zona glomerulosa secretes mineralocorticoids (primarily aldosterone); the middle zona fasciculata secretes glucocorticoids (primarily cortisol); and the innermost zona reticularis secretes androgens. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. The medullary cells function more like neurosecretory postsynaptic neurons rather than traditional endocrine cells. The adrenal glands have a rich vascular supply and complex relationships with their surrounding organs.

Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by adrenal gland disorder (autoimmune disease, infections, and malignancy, among others). Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Diagnosis is by demonstrating hypocortisolism (via cortisol and ACTH levels and ACTH-stimulation test) and determining the etiology (adrenal autoantibodies, imaging). Glucocorticoid replacement is needed in all forms of AI. Additionally, in primary AI, mineralocorticoid is given to prevent volume depletion, salt loss, and hyperkalemia. Adrenal crisis is a medical emergency; management requires prompt IV hydration and administration of IV glucocorticoids without waiting for initial hormone results.

Cushing's syndrome or hypercortisolism is a disorder characterized by features resulting from chronic exposure to excess glucocorticoids. Cushing's syndrome may be exogenous, due to chronic glucocorticoid intake, or endogenous, due to increased adrenal secretion of cortisol or adrenocorticotropic hormone (ACTH) production from the pituitary gland or ectopic sources. Exogenous or iatrogenic hypercortisolism is the most common cause. Typical clinical features of hypercortisolism include central obesity, thin and bruisable skin, abdominal striae, secondary hypertension, hyperglycemia, and proximal muscle weakness. The initial diagnostic approach is to establish hypercortisolism via urinary and salivary cortisol tests along with low-dose dexamethasone suppression test. Once the elevated cortisol levels are confirmed, the etiology is determined based on ACTH levels, confirmatory biochemical tests, and subsequent imaging studies. Treatment options depend on the cause, and include surgery and medical therapy.

Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytomas are frequently familial and associated with genetic syndromes. Approximately 90% of pheochromocytomas are benign and surgical resection is the only curative treatment. Prognosis is generally good for benign, sporadic tumors that have been completely resected. Familial forms are associated with higher recurrence rates and malignant potential.