Hypercalcemia is commonly caused by the increased production of parathyroid hormone-related protein (PTHrP) by a malignancy. In fact, the demonstration of increased PTHrP production in a patient with hypercalcemia is virtually pathognomonic of malignancy. We studied a patient with systemic lupus erythematosus (SLE), generalized lymphadenopathy, and hypercalcemia. Immunohistology of 2 biopsied lymph nodes revealed the abundant expression of PTHrP and the absence of malignant transformation. Although apparently rare, PTHrP production by nonmalignant lymphoid tissue may occur in SLE and should be considered in the differential diagnosis of hypercalcemia.Malignancy ranks among the leading considerations in the differential diagnosis of hypercalcemia and, overall, ranks comparably with primary hyperparathyroidism as the cause of hypercalcemia (1). Hypercalcemia as a paraneoplastic phenomenon was first described in the 1930s in patients with a variety of carcinomas and no detectable parathyroid abnormality (2). Since its discovery, parathyroid hormone-related protein (PTHrP) has been implicated in the pathogenesis of the hypercalcemia associated with a wide variety of tumors (3). In fact, hypercalcemia resulting from PTHrP secretion has been essentially pathognomonic for malignancy (3-5). Hypercalcemia appears to be rare as a primary manifestation of systemic lupus erythematosus (SLE). We report herein a patient with SLE in whom severe hypercalcemia developed in association with abundant PTHrP expression by nonmalignant lymph nodes.
CASE REPORTThe patient, a 29-year-old African-American male, presented in July 1995 with hypercalcemia associated with weakness and fatigue of 3 days' duration. Two years prior to admission, he developed proteinuria of 0.9 gm/24 hours and a mild persistent elevation in the serum creatinine value of 1.5-1.9 mg/dl, with positive antinuclear antibodies (titer >1:640, speckled pattern), normal C3 and C4 levels, and negative hepatitis B surface antigen. Serum protein electrophoresis revealed polyclonal hypergammaglobulinemia.Three days before admission, he noted anorexia and fatigue. His symptoms progressed to include lightheadedness, generalized weakness, and a 10-pound weight loss. Medications at the time of admission were oral verapamil 180 mgJday and 1-2 multivitamins (containing 400 IU of vitamin D) daily. The patient had discontinued a thiazide diuretic 3 weeks prior to admission.Physical examination revealed a well-developed male with normal vital signs, except for a temperature of 99.3"F orally. Diffuse lymphadenopathy was present, involving small cervical, inguinal, and axillary nodes, which were mobile and nontender bilaterally. The spleen tip was palpable. A macular hyperpigmented rash was noted on the lower extremities.The serum calcium level on admission was 13.8 mg/dl (normal 8.4-10.2), reaching as high as 14.4 mg/dl, ionized calcium was 1.94 mg/dl (normal 1.1-1.35), and phosphorus was 4.8 mg/dl (normal 2.4-4.5). The serum PTH value was <4 pdml (normal 0-200). Serum PTHrP was und...