Hypophosphatemia, a condition characterized by abnormally low levels of phosphate in the blood, can occur in individuals with cancer. Phosphate is a vital mineral involved in numerous bodily processes. This article explores the role of phosphate in the human body and details how cancer can disrupt its balance, leading to reduced levels.
The Role of Phosphate in the Body
Phosphate is a mineral and electrolyte found in body fluids like blood. It is a fundamental component of every cell, playing a central role in maintaining overall health. Approximately 85% of the body’s phosphate is stored in bones and teeth, providing strength to the skeletal structure.
Phosphate is also essential for energy production within cells, forming adenosine triphosphate (ATP), the body’s main energy currency. It fuels various cellular functions, including muscle contraction and nerve impulses. Phosphate also contributes to DNA and RNA formation, components of cell membranes, and helps regulate the body’s pH balance. In adults, a normal serum phosphate level ranges between 2.5 and 4.5 milligrams per deciliter (mg/dL).
How Cancer Affects Phosphate Levels
Cancer can lead to low phosphate levels through several mechanisms, affecting how the body absorbs, uses, or excretes this mineral. These mechanisms range from tumor-secreted substances to broad effects of the disease and its treatments.
Tumor-Induced Osteomalacia
Tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome, is a cause of low phosphate in cancer patients. This condition arises when certain tumors, often small mesenchymal tumors, produce excessive amounts of fibroblast growth factor 23 (FGF23).
FGF23 acts on the kidneys, causing them to excrete too much phosphate into the urine. It also interferes with vitamin D activation, which is needed for phosphate absorption, leading to phosphate loss and impaired bone mineralization.
Paraneoplastic Syndromes
Beyond TIO, other paraneoplastic syndromes can indirectly influence phosphate metabolism. Cancer cells can produce substances, such as hormones or cytokines, that disrupt normal phosphate regulation. For example, paraneoplastic Cushing syndrome, linked to certain cancers, can interfere with phosphate levels by affecting FGF23 production or reducing intestinal phosphate absorption.
Nutritional Deficiencies and Malabsorption
Cancer and its treatments often contribute to poor nutritional status, directly impacting phosphate levels. Many patients experience reduced appetite, nausea, vomiting, or diarrhea, making it difficult to consume or absorb sufficient nutrients. Malabsorption can also occur due to gastrointestinal tumors, surgical resections, or radiation therapy, limiting phosphate uptake from food.
Direct Tumor Effects
Certain cancers can directly influence phosphate distribution within the body. Rapidly dividing cancer cells, such as those in leukemias, can consume excessive phosphate, shifting it from the bloodstream into the cells. Extensive bone metastases, particularly from prostate cancer, might also sequester phosphate within bone tissue, lowering its circulating levels.
Chemotherapy Side Effects
Cancer therapies can contribute to low phosphate levels. Some chemotherapy agents, including cisplatin, ifosfamide, methotrexate, and certain tyrosine-kinase or mTOR inhibitors, can damage kidney tubules. This kidney damage impairs the organs’ ability to reabsorb phosphate, leading to its excessive loss in the urine. Chemotherapy may also harm the intestinal lining, reducing the body’s capacity to absorb dietary phosphate.
Signs of Low Phosphate
Symptoms of low phosphate levels can vary and are often non-specific. In mild cases, individuals may experience fatigue, muscle weakness, and a diminished appetite.
As phosphate levels drop, more noticeable symptoms can emerge, including bone pain, increased irritability, and confusion. Severe low phosphate can impact muscle function, leading to difficulty breathing due to diaphragm weakness, and may contribute to cardiac arrhythmias.
In the most severe instances, very low phosphate levels (below 1.0 mg/dL) can lead to complications such as muscle breakdown (rhabdomyolysis), impaired red and white blood cell function, seizures, and coma.
Diagnosis and Management of Low Phosphate
Diagnosing low phosphate levels begins with a blood test measuring serum phosphate concentration. A level below 2.5 mg/dL in adults indicates hypophosphatemia. Once detected, further tests may be necessary to determine the underlying cause.
These evaluations can include measuring urine phosphate levels to assess kidney function and identify excessive excretion, or checking fibroblast growth factor 23 (FGF23) levels if tumor-induced osteomalacia is suspected. Imaging studies may also locate tumors contributing to the imbalance.
Managing low phosphate in cancer patients involves a multi-faceted approach, primarily focusing on addressing the underlying cancer. Phosphate supplementation, administered orally for mild cases or intravenously for severe deficiencies, is a common treatment. For conditions like tumor-induced osteomalacia, specific medications such as burosumab, which targets FGF23 effects, may be used. Dietary adjustments, including foods rich in phosphate like dairy products, meats, and nuts, can also support phosphate levels. Healthcare professionals must always oversee the diagnosis and management of low phosphate levels.