High Calcium in Skin Cancer: What It Means and What to Do

High calcium levels in the blood (hypercalcemia) can sometimes occur in people with cancer, including certain types of skin cancer, and it deserves prompt attention. While mild elevations may have several benign causes, significant or sudden high calcium in someone with cancer can signal a cancer-related process and may require urgent evaluation and treatment. ^[1] Hypercalcemia can affect the kidneys, bones, heart, and brain, so identifying the cause and treating it quickly is important. ^{[1] [2]}

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What “High Calcium” Means

• Definition: Hypercalcemia means the calcium level in your blood is above the normal range; severity and symptoms vary by how high and how fast it rises. ^{[1] [3]}
• Common causes in general: Overactive parathyroid glands, cancer, certain medicines or diseases, and excess calcium/vitamin D intake. ^{[4] [5]}
• In cancer: Some cancers raise calcium through bone spread or by releasing substances that drive calcium up. ^{[6] [1]}

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How Skin Cancer Can Cause High Calcium

• Humoral hypercalcemia of malignancy (HHM): Some skin squamous cell carcinomas can produce parathyroid hormone–related protein (PTHrP), which raises blood calcium even without bone metastases. This is less common but well documented. [PM18] In reported cases, elevated PTHrP was the hallmark, and outcomes were often serious if the underlying tumor was not controlled. [PM18]
• Inflammatory cytokines: In some cutaneous squamous cell carcinoma cases, cytokines like TNF‑α and IL‑6 were also elevated alongside PTHrP, contributing to hypercalcemia. [PM19]
• Melanoma with bone metastases: Melanoma can cause hypercalcemia, typically when there are aggressive, lytic bone metastases; this is rare but associated with advanced disease and short survival. [PM8]
• HS‑associated SCC and paraneoplastic syndromes: In long‑standing hidradenitis suppurativa, cutaneous SCC may develop and can be linked to paraneoplastic hypercalcemia, among other syndromes. [PM10]

Bottom line: In skin cancer, high calcium most often points to advanced disease or a tumor making PTHrP, and it is considered a potentially urgent complication. [PM18] [PM8]

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Symptoms to Watch For

• Kidneys: Intense thirst and frequent urination. ^[7]
• Digestive: Nausea, vomiting, abdominal pain, constipation. ^[8]
• Brain: Fatigue, confusion, drowsiness, in severe cases coma. ^[1]
• Bones/Muscles: Bone pain, weakness; prolonged hypercalcemia can thin bones. ^{[2] [8]}

If you have cancer and develop these symptoms, you should seek prompt medical help. ^{[1] [7]}

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Why It Matters

• Medical urgency: Hypercalcemia can lead to kidney stones, dehydration, heart rhythm problems, and neurological changes; severe cases can be life‑threatening without treatment. ^{[2] [1]}
• Prognostic signal: When hypercalcemia is tied to cancer, it often indicates advanced disease and requires focused management of both calcium and the underlying cancer. [PM8] [PM22]

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How Doctors Evaluate High Calcium

• Blood tests: Total and ionized calcium, albumin (to correct calcium), PTH, PTHrP, vitamin D, kidney function. Low PTH with high calcium suggests non‑parathyroid causes like cancer; elevated PTHrP supports HHM. [PM18] [PM21]
• Imaging: Bone scans or CT/MRI to look for bone metastases, and imaging of the primary tumor and lymph nodes. [PM8]
• Cancer review: Pathology and staging to identify PTHrP production or extent of spread. [PM21]

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Treatment Options

Immediate Calcium-Lowering Measures

• IV hydration: Restores fluid balance and helps the kidneys clear calcium. ^[9]
• Calcitonin: Acts quickly to lower calcium; effect is short‑term. ^[9]
• IV bisphosphonates (e.g., zoledronic acid): Commonly used to lower calcium due to cancer by blocking bone resorption; onset within 2–4 days. ^[10]
• Denosumab: An effective option, especially if bisphosphonates fail or are contraindicated; responses often occur within 10 days, with meaningful durations. [PM31] It is an approved therapy for hypercalcemia of malignancy and can help in refractory cases. [PM32] [PM29]

Treating the Underlying Cancer

• Definitive tumor control: Surgery, radiation, chemotherapy, or immunotherapy tailored to the skin cancer type and stage; controlling the tumor can normalize calcium, as shown in PTHrP‑producing cutaneous SCC cases. [PM21] When surgical removal is possible in PTHrP‑mediated cases, calcium and PTHrP levels can rapidly normalize. [PM9]
• Palliative focus: In advanced, refractory scenarios, care may prioritize symptom control and quality of life. Persistent HHM in metastatic cutaneous SCC carries a poor prognosis. [PM22]

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What You Can Do Right Now

• Get your calcium rechecked promptly if you’ve had a high result ask for albumin‑corrected calcium or ionized calcium and PTH/PTHrP testing. ^[9] [PM18]
• Tell your care team about any symptoms like confusion, severe fatigue, vomiting, constipation, intense thirst, or reduced urination. ^{[7] [11]}
• Review medicines and supplements, especially high‑dose calcium or vitamin D, which can add to the problem. ^[5]
• Discuss antiresorptive therapy options (bisphosphonate vs denosumab) and the plan for definitive cancer treatment, since lowering calcium without addressing the tumor often leads to recurrence. [PM31] [PM32]

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Key Takeaways

• High calcium in someone with skin cancer is not automatically dangerous, but it can be a sign of a serious cancer‑related complication and warrants prompt evaluation. ^[1]
• Cutaneous squamous cell carcinoma can occasionally cause high calcium via PTHrP (HHM), even without bone spread; melanoma‑related hypercalcemia usually occurs with bone metastases and advanced disease. [PM18] [PM8]
• Effective management includes rapid calcium‑lowering treatments (hydration, calcitonin, bisphosphonates, denosumab) and controlling the underlying cancer. ^[10] [PM31] [PM32]

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When to Seek Urgent Care

• Seek urgent care if you have cancer and develop confusion, severe lethargy, vomiting, or very frequent urination and thirst, as these can indicate severe hypercalcemia. ^{[7] [11]}

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Possible Explanations to Consider

• It could be related to tumor secretion of PTHrP (more typical for some squamous cell carcinomas). This often presents with low PTH and high PTHrP. [PM18] [PM21]
• It could stem from bone metastases (seen in melanoma and other cancers) causing calcium release from bone. [PM8]
• It could reflect non‑cancer causes like primary hyperparathyroidism or supplement overuse, which are also common and treatable. ^{[4] [5]}

Discussing these possibilities with your clinician, along with targeted testing, can help clarify the cause and guide the right treatment path. ^[9]