Do adrenal adenomas cause increased metanephrines (metanephrine levels)?

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From the Guidelines

Adrenal adenomas typically do not cause increased metanephrines. Most adrenal adenomas are non-functional (incidentalomas) and do not produce excess hormones. When adrenal adenomas do secrete hormones, they commonly produce cortisol, aldosterone, or sex hormones rather than catecholamines. Elevated metanephrines are characteristic of pheochromocytomas, which are different types of adrenal tumors that specifically arise from the chromaffin cells in the adrenal medulla. Pheochromocytomas produce excess catecholamines (epinephrine and norepinephrine), which are metabolized to metanephrines and normetanephrines that can be measured in blood or urine. If a patient with an adrenal mass shows elevated metanephrines, this would raise suspicion for a pheochromocytoma rather than a typical adrenal adenoma, as suggested by the recent guideline 1. This distinction is important because pheochromocytomas require specific preoperative management to prevent potentially dangerous blood pressure fluctuations during surgery. Key points to consider in the diagnosis and management of adrenal masses include:

  • Screening for pheochromocytoma with plasma or 24-hour urinary metanephrines in patients with adrenal incidentalomas that display ≥ 10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess, as recommended by the guideline 1.
  • Testing serum levels of various hormones, such as dehydroepiandrosterone (DHEA-S), testosterone, and others, to confirm androgen hypersecretion, which is more commonly associated with adrenal adenomas than with pheochromocytomas 1.

From the Research

Adrenal Adenomas and Metanephrines

  • Adrenal adenomas are benign neoplasms of the adrenal cortex that can be functional or non-functional 2.
  • Functional tumors can manifest as Cushing syndrome, and rarely, they can be associated with high levels of metanephrine due to pheochromocytoma 2.
  • A case report described an adrenal adenoma associated with raised metanephrine levels, but no histopathological evidence of medullary changes, suggesting that Cushing syndrome due to cortisol-secreting adrenal adenoma can be associated with biochemical and clinical features suggestive of pheochromocytoma 2.

Relationship Between Adrenal Adenomas and Metanephrines

  • The study found that the patient's metanephrine levels were elevated, which is a rare occurrence in adrenal adenomas without pheochromocytoma 2.
  • The patient's symptoms, such as resistant hypertension, severe refractory hypokalemia, decreased sleep, fearfulness, anxiety, and palpitation, were consistent with both Cushing syndrome and pheochromocytoma 2.
  • After laparoscopic adrenalectomy, the patient's symptoms improved dramatically, suggesting that the adrenal adenoma was the cause of the elevated metanephrine levels 2.

Other Adrenal Diseases and Metanephrines

  • Other studies have discussed the medical management of adrenal diseases, including the treatment of Cushing's syndrome, congenital adrenal hyperplasia, and neoplastic adrenomedullary disease 3.
  • However, these studies do not provide direct evidence for the relationship between adrenal adenomas and metanephrines 3, 4, 5, 6.
  • Overall, the available evidence suggests that adrenal adenomas can be associated with elevated metanephrine levels, although this is a rare occurrence 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adrenal adenoma associated with raised metanephrine level: A case report.

International journal of surgery case reports, 2023

Research

Cardiovascular and metabolic consequences in patients with asymptomatic adrenal adenomas.

Current opinion in endocrinology, diabetes, and obesity, 2021

Research

Primary aldosteronism: current knowledge and controversies in Conn's syndrome.

Nature clinical practice. Endocrinology & metabolism, 2007

Research

Abnormal body composition in patients with adrenal adenomas.

European journal of endocrinology, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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