Primary hyperparathyroidism with multiple osteosclerotic lesions of the calvarium.

Abstract

PRIMARY HYPERPARATHYROIDISM (PHPT) is characterized by decalcification of bone, especially marked in the subperiosteal region. The skull classically has a homogeneous ground glass-like or salt-pepper appearance. Although some PHPT patients had focal osteosclerosis in the skull on roentgenograms in the days when diagnosis of PHPT was difficult, osteosclerosis in PHPT patients has been unusual in recent times when diagnosis of PHPT has become increasingly easy. We report herein a 26-year-old Japanese man with PHPT who developed multifocal osteosclerosis of the skull that was asymptomatic. Laboratory data disclosed hypercalcemia (11.4 mg/dl), hypercalciuria (330 mg/day), and hypophosphatemia (2.2 mg/dl). Serum intact parathyroid hormone (PTH; 286 pg/ml) and 1,25-dihydroxyvitamin D (163 pg/ml) were both elevated. Bone alkaline phosphatase (181 U/liter), osteocalcin (84 ng/ml), and urinary deoxypyridinoline (DPD; 32 nM/mM Cr) were all significantly increased, indicating a high rate of bone turnover. Blood urea nitrogen and serum creatinine were 9 and 0.6 mg/dl, respectively, negating the possibility of uremic hyperparathyroidism. Ultrasonography and computed tomography (CT) examination of the neck disclosed a mass ( 10 mm) adjacent to the upper pole of the left lobe of the thyroid gland. Multiple osteosclerotic foci, which were well-defined and not expansile, were found superimposed on a homogeneous ground glass-like appearance on skull roentgenograms (Fig. 1A). Skull CT revealed multiple high-density foci clearly demarcated from the surrounding bone tissue (Fig. 1B). Bone scintigraphy using Tc-MDP showed multiple osteosclerotic foci as hot spots with a generalized high background uptake in the calvarium. Bone mineral density (BMD) measured by DXA (Hologic QDR 4500A; Hologic Inc., Waltham, MA, USA) was 0.755 g/cm at the lumbar spine (L2–L4) and 0.479 g/cm at the distal radius 33% (Z score; –2.50 and –4.31, respectively), indicating predominant bone loss in cortical bone. Bone biopsy of the osteosclerotic foci and surrounding bone tissue (Fig. 2A) was performed when the parathyroid adenoma (4 2.7 1 cm) was excised. Serum calcium declined from 10.8 to 7.5 mg/dl within 1 day. The histology of undecalcified bone section demonstrated that the fractional volume of trabecular bone was greater and trabecular separation narrower in the osteosclerotic foci than in the surrounding area, although trabecular thickness was not markedly different (Table 1). Generalized enhancement of bone turnover was confirmed by increased numbers of osteoblasts, increased extension of osteoid, mineralized, and eroded surfaces, in both osteosclerotic and surrounding nonosteosclerotic areas. The fibrosis in marrow spaces observed in the surrounding non-osteosclerotic area was peritrabecular, a characteristic finding of osteitis fibrosa. Although bone marrow spaces in osteosclerotic area were occupied with massive fibrosis, neither mosaic bone structure characterized by irregular cement lines nor multinucleated giant osteoclasts (Pagetic giant cells) was found in the lesion that contained a predominance of woven bone. Furthermore, metastatic bone disease was negated because of the absence of malignant cells. Histomorphometric analysis confirmed that bone turnover rate in the osteosclerotic area was significantly higher than in non-osteosclerotic areas, with a predominance of inThe authors have no conflict of interest.