A 23-Year-Old Woman With a Right Femoral Neck Fracture FREE

A 23-year-old woman was referred for evaluation of a right femoral neck pathologic fracture. Review of her pelvic computed tomography (CT) scan from the referring hospital revealed multiple lytic bony lesions in her pelvis bilaterally and in both proximal femurs and a right femoral neck fracture (Figure 1). On admission, she had an elevated serum calcium level (14.8 mg/dL; normal range, 8.5-10.1 mg/dL [to convert to mmol/L, multiply by 0.25]), decreased serum phosphorus level (2.3 mg/dL; normal range, 2.5-4.9 mg/dL [to convert to mmol/L, multiply by 0.323]), serum creatinine within normal limits, and an undefined anemia (hemoglobin, 7.8 g/dL; normal range, 11.3-15.2 g/dL). She was treated with intravenous fluids, pamidronate for her hypercalcemia, and a blood transfusion for her anemia. She then underwent a hemiarthroplasty.

A . Laboratory studies to rule out multiple myeloma
B . Laboratory studies to rule out primary hyperparathyroidism
C . A skeletal survey with conventional radiographs and CT scan
D. All of the above

Primary hyperparathyroidism (PHPT) of unusually early presentation

D. All of the above

The key diagnostic feature is knowing the differential diagnosis in a patient with hypercalcemia, hypophosphatemia, and multiple lytic lesions throughout the skeleton includes PHPT. The diagnosis of PHPT was confirmed by the subsequent laboratory findings of a markedly elevated serum parathyroid hormone (PTH) level (1492 pg/mL; normal range, 12-90 pg/mL) and an increased serum level of 1,25-dihydroxyvitamin D (97 pg/mL; normal range, 18-72 pg/mL [to convert to pmol/L, multiply by 2.6]). The decision was further supported by the sonographic finding of a 2.2-cm hypoechoic lesion adjacent to the left thyroid lobe.

The prevalence of PHPT varies by age and sex. Women are more commonly affected than men, with a peak incidence between 50 and 60 years of age.¹ The annual incidence among patients younger than 40 years is reportedly less than 10 per 100 000.² In a young patient, the findings might also represent skeletal manifestations of a genetic disease, such as polyostotic fibrous dysplasia in the setting of McCune-Albright syndrome. Parathyroid hormone induces serum calcium by stimulating the release of calcium from bone matrix, increasing calcium and decreasing phosphate reabsorption by the kidney, and indirectly facilitating calcium absorption from the small intestine by stimulating renal production of 1,25-dihydroxyvitamin D.³ Primary hyperparathyroidism is usually caused by a parathyroid adenoma and less frequently by hyperplasia or carcinoma. The excess PTH secretion leads to hypercalcemia in the absence of significant renal dysfunction, thus resulting in the symptoms and signs summarized by the mnemonic “stones, bones, abdominal groans, and psychiatric moans,” which refers to nephrolithiasis, bone-related complications, gastrointestinal symptoms, and effects on the central nervous system. Serum phosphorus levels are commonly low in PHPT due to the phosphaturic effect of PTH on the kidney. Moderate anemia may be seen in severe PHPT. The etiology for the anemia remains unknown; however, marrow fibrosis is thought to play a key role because it is common in such patients and has been seen to improve after parathyroidectomy.⁴

The effects of PHPT on bone largely depend on the duration of the disease and the serum level of PTH, which targets osteoblasts and induces the osteoclastogenic cytokine RANKL (receptor activator of nuclear factor κB ligand).⁵ Bone changes may not be identified in the early stages. As the disease progresses, common findings include diffuse osteopenia, bone pain, and pathologic fractures. Multifocal subperiosteal resorption is generally considered to be pathognomonic of PHPT. The earliest bone changes are typically visible in the hands, particularly in the phalanges and terminal tufts.⁶ Skeletal changes without hand changes are rare. The classic histologic appearance of long-standing PHPT in bone is “tunneling” resorption (bony trabeculae replaced in the center by fibrovascular connective tissue) and peritrabecular fibrosis. In more severe cases, lytic lesions with cyst formation (osteitis fibrosa cystica) and/or with prominent multinucleated giant cells (simulating a giant cell reparative granuloma) may be seen and are termed “brown tumors” due to their gross appearance caused by hemorrhagic debris.

Differential diagnosis in a young person with hypercalcemia includes multiple myeloma, familial hypocalciuric hypercalcemia, and hyperparathyroidism-jaw tumor syndrome. The latter are both autosomal dominant disorders.^1,7 Thus, genetic counseling and appropriate imaging and laboratory studies are needed. Once PHPT is diagnosed, the only cure is surgical removal of the parathyroid lesion. Medical treatment is reserved for patients who do not meet operative criteria.^8- 9 The diagnosis of PHPT in this patient was further complicated by the pathologic diagnosis of an aneurysmal bone cyst from the right femoral lesion, which represented a brown tumor largely replaced by a secondary aneurysmal bone cyst. A large left mandible exophytic mass was also found, the excisional biopsy of which demonstrated a giant cell reparative granuloma-like brown tumor (Figure 2). Surgical excision of the neck mass revealed a 1.34-g parathyroid adenoma. No monoclonal immunoglobulin was identified by serum or urine protein electrophoresis.