Hypercalcemia and large abdominal mass.

An 85-year-old woman with chronic renal insufficiency presented with appetite loss and abdominal fullness. Laboratory data showed serum creatinine levels of 5.46 mg/dL, urea nitrogen 42 mg/dL, corrected calcium 15.3 mg/dL, intact PTH - parathyroid hormone 15.1 pg/mL (N 10–65), calcitriol 63.4 pg/mL (N 20–60), PTH-related protein 5.5 pmol/L (N < 1.0), cortisol of 4.3 pg/mL (N 6.2–19.4), ACTH - adrenocorticotropic hormone 304 pg/mL (N 7.2–63.3) and soluble interleukin-2 receptor of 2335 U/mL (N 206–713). These results signify that the patient suffered from exacerbation of chronic renal failure, adrenal insufficiency and severe hypercalcemia probably caused by excessive calcitriol and PTH-related protein. Magnetic resonance imaging and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging disclosed giant masses bilaterally in the adrenal glands (Figure 1A and B); the masses were histologically diagnosed as extranodal malignant B-cell lymphoma (Figure 2A), which was also positive for 25-hydroxyvitamin D3-1-alpha-hydroxylase (Figure 2B), suggesting extra-renal overproduction of calcitriol. Hypercalcemia was normalized (8.9 mg/dL) shortly after hydrocortisone and zoledronate treatment concomitant with serum calcitriol decline (20.6 pg/mL) and serum cortisol increase (16.3 pg/mL), although PTH-related protein remained high (5.5 pmol/L). Additionally, serum FGF23 - fibroblast growth factor 23 (FGF23) level decreased from 9050 to 258 pg/mL (N 10–50). The patient died 2 months after hospitalization due to lymphoma progression.

Fig. 1.

Imaging of the abdominal masses. (A) Magnetic resonance imaging and (B) fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging revealed giant masses originating bilaterally in the adrenal glands and partially invading the abdominal aorta.

Fig. 2.

Histopathology of the abdominal mass. Percutaneous biopsy of the adrenal glands was performed. Histological examination revealed the huge bilateral masses in the adrenal glands to be diffuse, large B-cell lymphoma (A), and lymphoma cells were stained with 25-hydroxyvitamin D3-1-alpha-hydroxylase antibody (sc-67261; Santa Cruz Biotechnology Inc., Santa Cruz, CA) (B), signifying extra-renal overproduction of calcitriol.

Hypercalcemia is occasionally seen in malignant lymphoma [1]. Common causes of lymphoma-related hypercalcemia include overproduction of calcitriol and PTH-related protein and local osteolysis induced by inflammatory cytokines [2]. In the present case, hypercalcemia was caused by excessive calcitriol and PTH-related protein. Besides, adrenal insufficiency, which was normalized after hydrocortisone treatment, might also contribute to the development of hypercalcemia [3]. In addition, high serum FGF23 level decreased in parallel with the decline in serum calcitriol, indicating that endogeneous calcitriol overproduction stimulated the production of FGF23 in the bone.