Fatigue and Adrenal Cancer: How Common Is It, and Why Does It Happen?

Fatigue can be part of the symptom profile in adrenal tumors, but it varies by tumor type and hormone activity. Many adrenal cancers (adrenocortical carcinoma) produce excess hormones, most often cortisol, leading to Cushing’s syndrome with muscle weakness, weight gain, and metabolic changes that can feel like persistent tiredness. ^[1] These hormone-driven changes are well described as typical features of adrenal cancer and can indirectly manifest as fatigue through muscle weakness, poor sleep, high blood pressure, and high blood sugar. ^[2] At major centers, lists of adrenal tumor symptoms include fatigue among possible manifestations, especially when tumors disrupt normal hormone balance. ^[3] Benign adrenal tumors often cause no symptoms, and malignant adrenal cancers are uncommon, so fatigue alone is not specific; however, when fatigue occurs with endocrine signs (easy bruising, fluid retention, high blood pressure), an adrenal source is considered. ^{[4] [3]}

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How Adrenal Tumors Cause Persistent Tiredness

Multiple biologic mechanisms can contribute to chronic fatigue in adrenal tumors; some relate to hormone excess, others to tumor biology or treatment effects.

• Cortisol excess (Cushing’s syndrome):

  • Adrenal cancer frequently secretes cortisol, causing weight gain, muscle weakness, high blood pressure, and high blood sugar. ^[1] These changes strain energy systems and sleep quality, leading to perceived fatigue. ^[2]
  • Cortisol dysregulation also alters daily stress-hormone rhythms, which is linked to fatigue and sleep-wake disruption in cancer more broadly. ^[5]

• Other hormone excess:

  • Some adrenal tumors elevate hormones like aldosterone, epinephrine, norepinephrine, and androgens, which can lead to high blood pressure, rapid heart rate, sweating, easy bruising, fatigue, and low potassium each a contributor to tiredness and muscle weakness. ^{[6] [7]}

• Non-secretory adrenal cancers:

  • When the tumor does not secrete hormones, systemic effects such as fever, pain, cachexia (weight loss and muscle wasting), anorexia, and exhaustion have been reported historically, reflecting cancer-related fatigue from inflammatory and paraneoplastic processes. ^[8] These patterns are consistent with general paraneoplastic syndromes where tumors drive remote effects via cytokines or immune mechanisms. ^{[9] [10]}

• Cancer-related fatigue pathway:

  • Across cancers, disrupted circadian rhythms of stress-related hormones (hypothalamic–pituitary–adrenal axis) are strongly associated with chronic fatigue and sleep disturbance, offering a shared mechanism relevant to adrenal malignancies that perturb cortisol biology. ^[5]

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After Treatment: Adrenal Insufficiency and Fatigue

Treatment of hormone-secreting adrenal cancer (surgery, mitotane, or other therapies) can lead to adrenal insufficiency (low cortisol), which often causes significant fatigue even with replacement therapy. ^[11] In clinical studies, a considerable proportion of people with adrenal insufficiency whether primary, secondary, or after Cushing’s treatment report severe fatigue, driven by psychological distress, sleep disturbance, and functional impairments; interestingly, salivary cortisol levels did not correlate with momentary fatigue, underscoring a multifactorial cause. ^[12]

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What Symptoms to Watch For

• When adrenal cancer secretes cortisol, common signs include muscle weakness, weight gain, purple stretch marks, easy bruising, high blood pressure, and high blood sugar; fatigue may accompany these. ^{[1] [2]}
• Non-hormone–secreting tumors may present with abdominal or back pain, unintended weight loss, and loss of appetite, and fatigue can be part of the systemic picture. ^[13]
• Clinical overviews of adrenal tumors include fatigue among symptoms linked to hormonal excess (including low potassium and fluid retention). ^{[6] [3]}

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Practical Takeaways

• Fatigue is not the most specific symptom of adrenal cancer, but it commonly occurs through hormone excess (especially cortisol) and cancer-related physiology that disrupt sleep, metabolism, muscles, and blood pressure. ^{[1] [2] [5]}
• After treatment, adrenal insufficiency can sustain or worsen fatigue, requiring careful replacement and lifestyle strategies. ^{[12] [11]}
• Because fatigue is common across many conditions, it’s most informative when paired with endocrine features (e.g., easy bruising, high blood pressure, high blood sugar, low potassium), body-shape changes, or abdominal/back symptoms context that raises suspicion for an adrenal source. ^{[1] [6] [13] [3]}

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When to Seek Medical Assessment

If persistent fatigue is accompanied by muscle weakness, easy bruising, high blood pressure, high blood sugar, abdominal/back pain, or unintentional weight changes, an evaluation for adrenal disease including hormone testing and imaging may be appropriate. ^{[1] [13]} A thorough endocrine work‑up helps identify hormone-secreting tumors and guides treatment to reduce symptoms and improve energy. ^{[1] [2]}