Gastrointestinal stromal tumors (GISTs) can cause hypercalcemia through a calcitriol-mediated mechanism, as confirmed in a case study published in Frontiers in Endocrinology.

Hypercalcemia is common in patients with cancer, the main cause of which is the secretion of parathyroid hormone-related protein and metastasis. However, calcitriol secretion is a rare cause of hypercalcemia, and hypercalcemia caused by calcitriol seems to be associated with worse outcomes. This suggests that calcitriol might be a marker of high-grade tumors.

Researchers led by Aura D. Herrera-Martínez, MD, PhD, from Reina Sofia University Hospital in Córdoba, Spain showed that tumor cells obtained from a patient with GIST expressed 25-hydroxyvitamin D3-1-hydroxylase and vitamin-D receptors. The patient was a woman with a 23-cm gastric GIST and severe hypercalcemia.


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“Our case is the first one that demonstrate tumor 1α-hydroxylase activity and vitamin D receptor expression, which could explain the increased levels of calcitriol and subsequent hypercalcemia,” the researchers wrote.

The tumor also expressed the endotoxin recognition factors cluster of differentiation 14 and toll-like receptor 4. This, the researchers said, suggests an inflammatory mediated mechanism. Finally, the expression of somatostatin-receptors could play a role in the clinical evolution and prognosis of the disease in this patient.

The woman was given medical treatment to control her calcium levels and then treated with targeted-directed therapies using tyrosine kinase inhibitors. Subsequently, she had surgery to resect the tumor. She remained disease-free for 2 years following surgery.

“To the best of our knowledge, this is a very rare case of calcitriol secretion with appropriate control calcium levels before [tyrosine kinase inhibitors] use,” the researchers said. Only 3 cases of GIST with calcitriol-mediated hypercalcemia have been reported in the literature so far.

Reference

Herrera-Martínez Y, Contreras González MJ, Pedraza-Arévalo S, et al. Calcitriol-mediated hypercalcemia, somatostatin receptors expression and 25-hydroxyvitamin D3-1α- hydroxylase in GIST tumors. Front Endocrinol. 2022;26(12):812385. doi:10.3389/fendo.2021.812385