The adrenal glands are two small, triangular glands that sit on top of each kidney. Despite their small size, they produce hormones that are essential for life — including cortisol, aldosterone, DHEA, and adrenaline (epinephrine). Adrenal disorders arise when these glands produce too much or too little of these critical hormones.

Anatomy and Function

Each adrenal gland has two distinct parts:

  • Adrenal cortex (outer layer): Produces corticosteroids — cortisol (stress response, metabolism), aldosterone (blood pressure/sodium regulation), and DHEA/androgens
  • Adrenal medulla (inner core): Produces catecholamines — epinephrine (adrenaline) and norepinephrine, the "fight or flight" hormones

Cushing's Syndrome — Excess Cortisol

Cushing's syndrome results from prolonged exposure to excess cortisol. The most common cause is exogenous (from taking corticosteroid medications). Endogenous Cushing's may be caused by a pituitary adenoma producing excess ACTH (Cushing's disease), an adrenal tumor, or an ectopic ACTH-secreting tumor.

Symptoms: Central obesity with a "buffalo hump" (fat between shoulders), moon face, purple stretch marks (striae), easy bruising, muscle weakness, hypertension, high blood sugar, osteoporosis, and depression.

Diagnosis: 24-hour urine free cortisol, late-night salivary cortisol, or overnight low-dose dexamethasone suppression test. MRI of the pituitary or CT of the adrenals identifies the source.

Treatment: Surgical resection of the causative tumor. Medical therapies (metyrapone, ketoconazole, osilodrostat) may be used if surgery is not possible or while awaiting surgery.

Adrenal Insufficiency — Too Little Cortisol

Adrenal insufficiency occurs when the adrenal glands cannot produce adequate cortisol. Primary adrenal insufficiency (Addison's disease) involves the adrenal glands themselves — most commonly autoimmune destruction. Secondary adrenal insufficiency results from pituitary ACTH deficiency, most commonly from prolonged steroid use causing adrenal suppression.

Symptoms: Fatigue, weakness, weight loss, low blood pressure, dizziness, nausea, abdominal pain, and hyperpigmentation (primary only — due to elevated ACTH). Can precipitate an adrenal crisis — a life-threatening emergency with extreme hypotension and shock — during illness, surgery, or trauma.

Treatment: Lifelong hydrocortisone replacement (or prednisone). Patients must double or triple their dose during illness, fever, or surgery ("sick day rules") and carry emergency injectable hydrocortisone for crises.

🚨 Adrenal Crisis: People with adrenal insufficiency who are severely ill, vomiting, or cannot take oral medications need emergency hydrocortisone injection. This is life-threatening — always carry a glucocorticoid emergency injection kit and wear medical alert identification.

Primary Aldosteronism (Conn's Syndrome)

Excess aldosterone from the adrenal gland is a cause of secondary hypertension, accounting for 5–10% of all hypertension cases. It causes high blood pressure that is difficult to control, and often low potassium. Diagnosed by elevated aldosterone-to-renin ratio. Treatment is surgical (if unilateral) or with aldosterone-blocking medications (spironolactone/eplerenone).

Pheochromocytoma

A pheochromocytoma is a rare tumor arising from the chromaffin cells of the adrenal medulla — the inner portion of the adrenal gland. These tumors produce and release excess catecholamines (epinephrine and norepinephrine), which can cause dangerous surges in blood pressure and other serious symptoms.

Symptoms — The Classic Triad

The hallmark presentation of pheochromocytoma is episodic (paroxysmal) symptoms, often triggered by physical activity, stress, certain foods, or changes in body position:

  • Severe hypertension — often episodic, sometimes persistent; may be resistant to multiple blood pressure medications
  • Pounding headache — typically sudden onset, severe
  • Profuse sweating — diaphoresis, often drenching
  • Palpitations — rapid or irregular heartbeat
  • Other symptoms may include pallor, tremor, anxiety, nausea, and weight loss

Not all patients experience the classic triad — some have persistent hypertension only, and some are asymptomatic (discovered incidentally on imaging).

Diagnosis

Biochemical testing is the cornerstone of diagnosis:

  • Plasma free metanephrines — the most sensitive initial test (sensitivity ~97%); recommended by the Endocrine Society as the first-line biochemical test
  • 24-hour urine metanephrines and catecholamines — high specificity; often used to confirm diagnosis
  • Imaging (CT or MRI of the adrenal glands) — performed after biochemical confirmation to localize the tumor
  • MIBG scintigraphy or DOTATATE PET — used when extra-adrenal tumors (paragangliomas) are suspected or for staging

Important: Imaging should NOT be performed before biochemical testing, as many adrenal masses are benign and non-functional. Biochemical confirmation must come first.

Paraganglioma — A Related Condition

A paraganglioma is essentially a pheochromocytoma that arises outside the adrenal gland — along the sympathetic and parasympathetic nerve chains from the skull base to the pelvis. The most common location is the organ of Zuckerkandl near the aortic bifurcation. Paragangliomas behave similarly to pheochromocytomas and require the same evaluation and treatment approach.

Hereditary Pheochromocytoma

Up to 30–40% of pheochromocytomas and paragangliomas have an underlying genetic cause — making genetic counseling and testing an important part of the evaluation. Associated genetic syndromes include:

  • Multiple Endocrine Neoplasia type 2 (MEN2) — RET proto-oncogene mutation; associated with medullary thyroid cancer and hyperparathyroidism
  • Von Hippel-Lindau (VHL) disease — VHL gene mutation
  • Neurofibromatosis type 1 (NF1)
  • SDHx mutations (succinate dehydrogenase subunit genes) — particularly SDHB, which is associated with malignant/metastatic disease

Genetic testing is recommended for all patients diagnosed with pheochromocytoma or paraganglioma, regardless of family history.

Treatment

The treatment for pheochromocytoma is surgical removal of the tumor. However, surgical management requires careful preparation:

  • Alpha-adrenergic blockade first (mandatory): Patients must be pre-treated with an alpha-blocker (phenoxybenzamine or doxazosin) for at least 7–14 days before surgery to control blood pressure and prevent hypertensive crisis during tumor manipulation. This is the most critical pre-operative step.
  • Beta-blockade second: A beta-blocker may be added after adequate alpha-blockade is established (never before, as unopposed alpha stimulation can cause severe hypertension)
  • Laparoscopic adrenalectomy is the preferred surgical approach for most adrenal pheochromocytomas
  • Post-operative biochemical testing at 2–6 weeks to confirm cure
  • Long-term surveillance is required — pheochromocytomas have a recurrence risk of 5–17%, and metastatic disease can appear years later
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District Endocrine — Pheochromocytoma Evaluation

Our providers have experience in the evaluation and management of pheochromocytoma and paraganglioma — including biochemical testing (plasma and urine metanephrines), coordination of appropriate imaging, genetic counseling referral, and pre-operative alpha-blockade management. If you have been told you have an adrenal mass, unexplained hypertension, or a family history of pheochromocytoma, we encourage you to schedule a consultation.

Adrenal Incidentaloma

An adrenal mass discovered incidentally on imaging done for another reason. Found in 3–5% of CT scans. Most are benign non-functioning adenomas requiring only monitoring. Evaluation includes hormonal assessment (rule out subclinical Cushing's, pheochromocytoma, aldosteronism) and imaging characterization to assess malignancy risk.

Key Takeaways

  • The adrenal glands produce cortisol, aldosterone, and adrenaline — all essential hormones
  • Cushing's syndrome (excess cortisol) causes central obesity, stretch marks, and metabolic complications
  • Adrenal insufficiency (Addison's) requires lifelong steroid replacement and emergency preparedness
  • Primary aldosteronism is an underdiagnosed cause of difficult-to-control hypertension
  • Adrenal incidentalomas are common and most are benign — but all require hormonal evaluation
Medical Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider before making any changes to your treatment plan. Individual medical decisions should be made in partnership with your physician based on your specific circumstances.