A pancreatic neuroendocrine tumor secreting parathyroid hormone-related peptide (PTHrP) caused severe, treatment-resistant hypercalcemia that ultimately proved fatal — highlighting how a peptide secreted by tumors can be more dangerous than the cancer itself.
1.1% of pNET casesPTHrP secretion from pancreatic neuroendocrine tumors is extremely rare but carries an outsized mortality risk — the resulting hypercalcemia is often refractory to standard medical therapy
What the researchers found
A 56-year-old woman with a pancreatic neuroendocrine tumor (pNET) developed severe hypercalcemia caused by tumor secretion of PTHrP — a complication reported in only 1.1% of pNET cases.
Despite treatment with IV fluids, bisphosphonates, calcitonin, and denosumab (a RANKL inhibitor), hypercalcemia recurred repeatedly. Adjunctive somatostatin analog therapy also failed to control calcium levels. The patient was not a candidate for curative surgery (cytoreduction). She died from refractory hypercalcemia — the metabolic complication, not the tumor itself, was the cause of death.
Why it matters
Pancreatic neuroendocrine tumors are often slow-growing and manageable, but when they secrete PTHrP, the resulting hypercalcemia can be rapidly fatal and resistant to standard treatments. This case underscores the need for early identification of PTHrP-secreting tumors so that surgical cytoreduction — the most effective treatment — can be attempted before the metabolic complications become uncontrollable.
How the study worked
Single-patient case report documenting clinical presentation, diagnostic workup (identifying PTHrP secretion as the cause of hypercalcemia), treatment attempts, and outcome over the disease course.
What this study cannot tell us
As a single case report, no generalizable treatment conclusions can be drawn. The patient was unfit for curative surgery, so the potential benefit of cytoreduction couldn't be assessed. Alternative therapies (cinacalcet, newer anti-PTHrP approaches) were not discussed.
How to read the evidence
This is a single case report (n=1), the lowest level of clinical evidence. While it documents an important clinical scenario, it cannot inform treatment guidelines or establish risk factors.
When this study was published
Published in 2024, this case report is recent and contributes to the small but growing literature on PTHrP-secreting pancreatic neuroendocrine tumors.
The bigger picture
PTHrP is one of the most clinically important tumor-secreted peptides — it's the leading cause of humoral hypercalcemia of malignancy, most commonly seen with solid tumors like lung and renal cancer. Its occurrence with pNETs is much rarer but particularly dangerous because the otherwise treatable nature of pNETs creates a false sense of security. This case adds to growing calls for routine PTHrP measurement in pNET patients presenting with hypercalcemia.
Questions still open
- Could earlier surgical intervention have controlled the hypercalcemia before it became refractory?
- Are there emerging targeted therapies that directly neutralize PTHrP or block its receptor to treat tumor-induced hypercalcemia?
- Should PTHrP levels be routinely measured in all pNET patients, even without hypercalcemia, to enable early detection?
Common questions
What is PTHrP and how does it cause dangerously high calcium?
Why couldn't the doctors control the calcium levels?
Read the original research
Parathyroid Hormone-Related Peptide Secretion From a Pancreatic Neuroendocrine Tumor: A Rare Case Report of Severe Hypercalcemia.
AACE clinical case reports, 10(4), 160-163
Citation
Foley, Erin; Hari Dass, Prashanth; O'Sullivan, Esther. (2024). Parathyroid Hormone-Related Peptide Secretion From a Pancreatic Neuroendocrine Tumor: A Rare Case Report of Severe Hypercalcemia.. AACE clinical case reports, 10(4), 160-163. https://doi.org/10.1016/j.aace.2024.04.009