Can adrenal nodules cause anxiety?

Can Adrenal Nodules Cause Anxiety?

Yes, adrenal nodules can cause anxiety, particularly when they secrete excess hormones that affect the body's stress response system. This relationship is most evident with functional adrenal tumors that produce hormones like catecholamines (pheochromocytoma) or cortisol (Cushing's syndrome).

Hormone-Secreting Adrenal Nodules and Anxiety

Pheochromocytoma

• Pheochromocytomas can directly cause anxiety attacks as part of their clinical presentation, along with headaches, sweating, and palpitations 1
• These tumors secrete excess catecholamines, which trigger the body's "fight or flight" response, mimicking severe anxiety 1
• Screening for pheochromocytoma should be performed in patients with adrenal incidentalomas that display ≥10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess 1

Cortisol-Producing Adrenal Nodules

• Adrenal adenomas that produce excess cortisol (Cushing's syndrome) can cause anxiety, depression, and sleep disturbances 1
• Even mild autonomous cortisol secretion (MACS) from adrenal nodules can cause psychological symptoms including anxiety 1
• Cortisol excess affects the hypothalamic-pituitary-adrenal (HPA) axis, which is known to be altered in anxiety disorders 2

Mechanisms Linking Adrenal Function and Anxiety

• Intermediaries of cortisol synthesis, especially dehydroepiandrosterone sulfate (DHEAS), can act as antagonists of the GABA-A receptor and exert anxiogenic effects 3
• Carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency show impaired cortisol production and demonstrate higher anxiety scores, suggesting a link between adrenal function and anxiety vulnerability 4
• Studies have shown a significant correlation between morning salivary aldosterone concentrations and trait anxiety scores, particularly in women 2

Diagnostic Approach for Suspected Hormone-Secreting Adrenal Nodules

Clinical Features Suggesting Hormone Excess

• For pheochromocytoma: anxiety attacks, headaches, palpitations, sweating, severe hypertension, tachycardia 1
• For cortisol-producing tumors: weight gain, central obesity, fatigue, depression, sleep disturbances, proximal muscle weakness 1
• For aldosterone-producing tumors: hypertension, hypokalemia, muscle cramping and weakness, headaches 1

Recommended Screening Tests

• All patients with adrenal incidentalomas should be screened for autonomous cortisol secretion using 1 mg dexamethasone suppression test (DST) 1
• Plasma free metanephrines or 24-hour urinary metanephrines for suspected pheochromocytoma 1
• Aldosterone/renin ratio for suspected primary aldosteronism in patients with hypertension and/or hypokalemia 1

Treatment Considerations

• Surgical removal (adrenalectomy) is recommended for functional adrenal tumors causing significant hormone excess and symptoms 1
• Medical management with specific medications may be appropriate in some cases:
  • Ketoconazole or mitotane for hypercortisolism 1
  • Spironolactone or eplerenone for hyperaldosteronism 1
  • Mifepristone has shown benefit in mild autonomous cortisol secretion due to adrenal adenomas 5
• Treatment of hormone excess from adrenal nodules has been shown to improve anxiety symptoms 3

Pitfalls and Caveats

• Not all adrenal nodules are functional - many are non-secreting incidentalomas that don't cause symptoms 6
• Anxiety can have multiple causes, and the presence of an adrenal nodule doesn't automatically explain anxiety symptoms 1
• Imaging characteristics alone cannot always reliably distinguish between benign and malignant adrenal masses, or functional vs. non-functional tumors 1
• Pheochromocytomas can be misdiagnosed as primary anxiety disorders, leading to dangerous delays in treatment 7
• Some adrenal nodules may cause subclinical hormone excess that still contributes to anxiety symptoms but might be missed on routine testing 1