Based on WHO | Can adrenal cancer cause fever, and how can I differentiate tumor-related fever from an infection?

Overview

Yes, adrenal cancer (adrenocortical carcinoma) can be associated with fever, although this is relatively uncommon. Fever may arise from the cancer itself (often called tumor-related or paraneoplastic fever) or from an infection, which is far more frequent in people with cancer, especially during or after treatment. Distinguishing tumor-related fever from infectious fever is essential because the management is very different. ^{[1] [2]}

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Can adrenal cancer cause fever?

• Fever has been reported as a presenting symptom in a subset of adrenal tumors, including nonfunctional adrenocortical carcinoma. Historical case series suggest fever can occur and may even be prolonged in some adrenal tumor patients. ^[3]
• In nonsecretory adrenal cortical carcinoma, clinical features can include fever, pain, weight loss and distant metastasis, reflecting systemic effects of the tumor. Surgical removal is the primary treatment for ACC, but recognition that fever can be a tumor manifestation helps avoid delays. ^[1]

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Why cancer can cause fever

• Tumors may release inflammatory substances (such as cytokines), or develop areas of necrosis (tissue death), both of which can trigger fever. These non-infectious mechanisms are well-recognized in solid tumors and can complicate diagnosis. ^[2]
• Paraneoplastic fever is a diagnosis of exclusion: infectious causes must be thoroughly ruled out before labeling a fever as tumor-related. ^[2]

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Infections are common and dangerous in cancer

• Infection is the most frequent and potentially life-threatening cause of fever in people undergoing cancer care; prompt action is vital. A temperature of 38°C (100.4°F) or higher warrants urgent medical evaluation, especially if you are on chemotherapy or immunosuppressive therapy. ^{[4] [5]}
• Many cancer treatments increase infection risk and can cause neutropenia (low white blood cells). Guidelines recommend treating any post‑therapy fever as a medical emergency with rapid empiric antibiotics until neutropenia is excluded. ^[6]

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Practical clues: tumor fever vs. infection

Fever patterns and associated signs can offer hints, but none are definitive on their own. Use these clues as guidance while pursuing a full work-up. ^[2]

• Tumor-related (paraneoplastic) fever:

  • Often persists or recurs despite antibiotics. May partially improve with nonsteroidal anti-inflammatory drugs (NSAIDs), reflecting cytokine-driven fever. ^[2]
  • Less likely to have focal infectious symptoms (localized redness, swelling, purulent discharge), though this is not absolute. Can accompany other systemic cancer features like weight loss and malaise. ^{[2] [1]}

• Infectious fever:

  • Frequently accompanied by new localizing symptoms (cough, dysuria, catheter site pain, skin redness) or systemic signs (chills, rigors). Antibiotics typically lead to clinical improvement and falling infection markers. ^[2]
  • In neutropenic or post‑chemotherapy settings, treat as infection first and urgently. Time to antibiotics is critical to reduce complications. ^[6]

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Diagnostic approach

A structured evaluation helps separate infection from tumor-related fever. The goal is to rapidly identify and treat life‑threatening infections while recognizing non‑infectious causes. ^[2]

Core steps

• Full history and exam:
  • Recent treatments, indwelling devices (ports, catheters), surgical sites, urinary symptoms, respiratory complaints, skin changes. Look carefully for subtle infection signs. ^[2]
• Initial tests:
  • Complete blood count with differential (to assess neutropenia). Basic metabolic panel and liver tests to evaluate organ function. ^[2]
  • Inflammatory markers (CRP, ESR) and procalcitonin (PCT). PCT is particularly helpful: higher early rises point toward bacterial infection; lower or unchanged levels suggest non‑infectious fever. ^{[7] [8] [9]}
  • Blood cultures (two sets), urine culture and urinalysis. Culture any suspicious sites: sputum, wound, catheter insertion sites. ^[2]
  • Chest X‑ray or targeted imaging based on symptoms. If persistent fever without source, consider broader imaging. ^[2]

Advanced imaging

• FDG PET/CT can help identify hidden infectious foci in persistent fever, especially in severe neutropenia when conventional work-up is unrevealing. Studies show PET/CT can detect deep infections and alter management in most cases of prolonged febrile neutropenia. ^[10]

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Biomarkers: how they help

Biomarkers are supportive, not definitive, but can guide decisions. Interpreting them alongside clinical context improves accuracy. ^[7]

• Procalcitonin (PCT):

  • Rises early and significantly in bacterial infections, including bacteremia and sepsis; falls with effective antibiotic therapy. ^{[8] [9]}
  • Lower or stable PCT values suggest non‑infectious etiologies, including tumor fever; however, severe cancer or metastasis can modestly increase baseline PCT. Trend over time is informative. ^[9]

• C‑reactive protein (CRP) and ESR:

  • Commonly elevated in both infection and inflammation, so less specific; persistent elevation without infectious source may align with tumor-related inflammation. ^{[7] [8]}

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When to suspect tumor-related fever

Consider paraneoplastic fever when:

• Cultures are negative, imaging fails to identify infection, and antibiotics do not improve fever. ^[2]
• PCT remains low or does not show the typical infectious rise, while CRP/ESR may stay elevated. Fever responds to NSAIDs but returns after the effect wears off. ^{[7] [2]}
• There are other signs of active cancer burden (large mass, metastases, weight loss) without infectious features. In adrenal cortical carcinoma, nonsecretory tumors may present with fever and systemic symptoms. ^[1]

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Management principles

• If you are on or recently completed chemotherapy or have indwelling devices, seek urgent care for any fever ≥38°C (100.4°F); clinicians often start empiric antibiotics while evaluating. ^{[6] [4]}
• If infection is confirmed, targeted antibiotics and source control (e.g., catheter removal, drainage) are essential. ^[2]
• If infection is excluded and tumor fever is likely:
  • Treat the underlying cancer (surgery, systemic therapy) to reduce cytokine production and tumor necrosis; fever often improves as cancer burden decreases. ^[1]
  • Symptomatic control with NSAIDs may help; corticosteroids are sometimes used short‑term when appropriate, balancing risks. Always coordinate with oncology. ^[2]

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Quick comparison table

Feature	Tumor-related fever	Infectious fever
Onset/Pattern	Persistent, may wax and wane; sometimes long-standing	Often acute with chills/rigors; may localize
Response to antibiotics	Little to no sustained improvement	Improves with appropriate antibiotics
NSAID response	Often partial/temporary relief	Variable; relief less diagnostic
PCT trend	Low or minimal rise	Early, significant rise; falls with treatment
CRP/ESR	Elevated but non-specific	Elevated; overlaps with tumor fever
Cultures/imaging	Negative for infection	Positive cultures or imaging evidence
Context	Known/advanced malignancy; nonsecretory ACC may present with fever	Neutropenia, catheters, recent procedures, focal symptoms

PCT behavior and antibiotic response have the strongest practical discriminatory value, but no single test replaces a comprehensive evaluation. ^{[8] [9] [7] [2]}

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Key takeaways

• Adrenal cancer can cause fever, but infection is the more common and urgent cause to rule out. ^{[3] [1]}
• Start with an infection‑focused work‑up and timely antibiotics when appropriate, especially if you are immunosuppressed or recently treated. ^{[6] [4]}
• If repeated evaluations do not reveal infection and fever persists, consider tumor-related fever, using biomarkers (especially PCT), imaging, and clinical context to guide the diagnosis. ^{[7] [9] [10] [2]}