Based on PubMed | Can melanoma cause unexplained weight loss, and when should this symptom prompt a medical evaluation?

Can Melanoma Cause Unexplained Weight Loss?

Yes, melanoma especially when it has spread (metastasized) to other organs can be associated with unexplained weight loss. While early, localized melanoma typically presents as changes on the skin, advanced melanoma can affect the body systemically, leading to symptoms such as loss of appetite (anorexia), fatigue, and weight loss due to cancer-related metabolic changes. Cancer-related weight loss often stems from a syndrome called cachexia, which involves muscle and fat loss driven by tumor- and inflammation-related signals, and may not fully respond to normal eating. ^{[1] [2]} This process includes reduced appetite, increased resting energy expenditure, and altered carbohydrate, protein, and fat metabolism, all of which contribute to continued weight loss. ^{[1] [2]}

How Melanoma Leads to Systemic Symptoms

• Metastatic melanoma can involve organs like the liver, lungs, bone, brain, and gastrointestinal tract; when the gastrointestinal tract is affected, nonspecific symptoms such as abdominal pain, anemia, and weight loss can occur. ^{[3] [4]} Melanoma’s tendency to spread to the lymph nodes and visceral organs increases the likelihood of systemic symptoms beyond the skin. ^[5]

• Cancer cachexia is common across many cancers and is driven by tumor and host factors (including cytokines like IL‑6 and TNF‑α), causing anorexia, muscle wasting, increased thermogenesis, and inefficient energy cycles (e.g., the Cori cycle), which collectively result in progressive weight loss. ^{[6] [1]} These metabolic changes mean that even adequate nutrition may not fully reverse the weight loss until the underlying cancer is controlled. ^{[2] [7]}

Treatment-Related Weight Changes

Some melanoma treatments (particularly immune checkpoint inhibitors such as nivolumab and ipilimumab) can contribute to reduced appetite and weight changes. Loss of appetite (anorexia) and weight loss are recognized side effects, and nutrition strategies like small frequent meals and calorie-dense foods are often recommended. ^{[8] [9]} In addition, immune-related thyroid problems (both underactive and overactive thyroid states) can occur during immunotherapy and affect weight, energy, and mood, which may indirectly lead to weight changes. ^{[10] [11]}

When Unexplained Weight Loss Should Prompt Medical Evaluation

Most clinicians consider unexplained weight loss to warrant medical evaluation when it reaches certain thresholds or persists:

• More than 5% of body weight lost over 6–12 months should generally prompt a medical assessment, especially in older adults. ^{[12] [13]}
• Initial evaluation typically includes a thorough history, physical exam, and basic blood and urine tests to look for common causes. Imaging to search for hidden cancers is usually not the first step unless there are additional clues in the history or exam. ^{[14] [15]}
• If an initial workup does not reveal a cause, a period of watchful waiting (often 1–6 months) may be reasonable, while monitoring for new symptoms or further weight changes unless red flags emerge sooner. ^[14]

Red Flags Requiring Sooner Workup

If unexplained weight loss occurs alongside any of the following, a more urgent evaluation is reasonable:

• New or changing skin lesion (asymmetry, irregular border, color variation, diameter growth, or evolving features)
• Persistent fatigue, anemia, or gastrointestinal symptoms (e.g., abdominal pain, black stools, or bleeding), which can be seen with GI metastases. ^{[3] [4]}
• Neurologic symptoms (headaches, visual changes), bone pain, shortness of breath, or liver-related symptoms in the context of known melanoma’s common spread patterns. ^[5]
• Symptoms suggestive of thyroid dysfunction during or after immunotherapy (palpitations, heat/cold intolerance, sweating, constipation, hair loss, mood changes). ^{[10] [11]}

Practical Steps If You’re Experiencing Unexplained Weight Loss

• Track your weight weekly and note appetite changes, fatigue, and any new skin or systemic symptoms. If you have a history of melanoma or a suspicious skin lesion, reach out to a clinician sooner. ^[5]
• Request an appointment for a focused evaluation if you’ve lost more than 5% of your body weight over 6–12 months, or sooner if other concerning symptoms are present. ^{[12] [13]}
• Ask about nutrition support; small, frequent, calorie- and protein-dense meals can help manage anorexia and support energy levels during evaluation or treatment. ^{[8] [9]}

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Key Takeaways

• Melanoma can cause unexplained weight loss, most commonly when it has spread and triggers systemic metabolic changes (cancer cachexia). ^{[1] [2]}
• Loss of appetite and weight changes can also arise as side effects of immunotherapy or from treatment-related endocrine issues like thyroid dysfunction. ^{[8] [10]}
• Seek medical evaluation if weight loss exceeds 5% over 6–12 months, or earlier if you have other symptoms or a history suggestive of melanoma. ^{[12] [14]}