Departments of Medicine (C.A.M.K., S.M.S., S.J.S., J.P.B.) and Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; the Department of Endocrinology, Hospital de Clinicas, Federal University of Parana (C.A.M.K.), Curitiba, Parana, Brazil; and the Endocrine Unit, Hospital dos Servidores do Estado (C.B., D.V.), and the Endocrine Unit, Hospital Agamenon Magalhaes, Secretaria da Saude de Pernambuco, University of Pernambuco (F.B.), Recife, Pernambuco, Brazil
Address all correspondence and requests for reprints to: Carolina A. Moreira Kulak, M.D., Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032.
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this report, we describe two young women with primary hyperparathyroidism and severe osteitis fibrosa cystica who underwent successful parathyroidectomy. Dramatic, sustained, and unprecedented increases in bone density, reaching 550%, were observed. These two patients illustrate a remarkable capacity of the skeleton to be restored to normal after surgery in patients with the classical bone disease of primary hyperparathyroidism.
![]() |
Case Report 1 |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Admission laboratory tests included (see Table 1): hemoglobin, 11.8 g/dL (normal,
1216); hematocrit, 34% (normal, 3747); sodium, 141 mEq/L (normal,
135146); potassium, 3.3 mEq/L (normal, 3.24.6); chloride, 111 mEq/L
(normal, 96108); CO2, 18 mEq/L (normal, 2329);
creatinine, 0.7 mg/dL (normal, 0.51.1); and glucose, 122 mg/dL
(normal, 70105). Serum calcium was 15.2 mg/dL (normal, 8.410.2);
serum phosphorus was 2.5 mg/dL (normal, 2.74.5). Albumin was 4.5 g/dL
(normal, 3.94.8). Alkaline phosphatase activity was 2288 IU/L
(normal, 39177), and PTH was 2560 pg/mL (normal, 1065).
Twenty-four-hour urinary calcium was 1117 mg (normal, up to 250).
|
After hydration with iv sodium chloride, the patient underwent parathyroid surgery. A right inferior parathyroid adenoma (1.5 x 1.0 x 1.5 cm) was removed. Twenty-four hours after surgery, serum calcium was 9.0 mg/dL, and phosphorus was 1.9 mg/dL. Chvosteks sign was positive. She was treated with calcium gluconate iv and then with oral calcium carbonate (1 g daily). Two weeks later, the patient was discharged on supplemental calcium (1 g daily).
Two months after surgery, serum calcium had fallen further to 6.7
mg/dL. 25-Hydroxyvitamin D was 18 ng/mL (normal, 925). Calcium
carbonate was increased to 3.0 g, and ergocalciferol (50,000 U
daily) was begun. Serum calcium rose gradually into the lower range of
normal. Twenty-four-hour urinary calcium excretion normalized to 160
mg. One year after surgery, the osteocalcin level had fallen by 50%,
but was still 6 times normal (Table 1). In contrast, urinary markers of
bone resorption, pyridinium and deoxypyridinoline, had fallen by 92%
and 93%, respectively, and were only minimally elevated. The PTH level
fell, but remained elevated at 126 pg/mL. By year 2, the PTH level
normalized to 50 pg/mL. Four years after surgery, all hormonal and
biochemical values remained normal.
Bone densitometry was determined before, 5 months, 1 yr, and 4 yr after
surgery (Fig. 1). At all sites, bone
density increased markedly. By the end of the first year, lumbar spine
bone mass increased 60%, from 0.579 to 0.925 g/cm2,
corresponding to a change in the t-score from -4.55 to
-1.40. Femoral neck bone mineral density increased 250% in the first
year, from 0.388 to 0.965 g/cm2, corresponding to a change
in t-score from -5.06 to +0.71. Distal forearm bone density
showed a 42% increase from 0.334 to 0.473 g/cm2,
corresponding to an increase in the t-score from -5.83 to
-2.80.
|
|
![]() |
Case Report 2 |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Initial laboratory data revealed elevated serum calcium and PTH of 13 mg/dL and 1530 pg/mL, respectively. Serum phosphorus was 1.6 mg/dL, and alkaline phosphatase activity was 2500 U/L. Twenty-four-hour urinary calcium excretion was 380 mg. X-Rays demonstrated brown tumors in the mandible and humerous; collapsed vertebral bodies of T12, L1, and L5; and kidney stones. Bone mineral density, determined by DEXA, was markedly reduced in the lumbar spine (0.225 g/cm2) and the femoral neck (0.159 g/cm2). Forearm bone mineral density was not measured.
Surgical exploration of the neck revealed a left lower pole parathyroid adenoma (1.3 cm3), which was confirmed by histological examination. The postoperative course was complicated by symptomatic hypocalcemia, which was controlled by iv calcium gluconate. The patient was discharged on oral calcium carbonate (1 g daily) and vitamin D (400 IU daily).
Three months after successful parathyroidectomy, serum and urinary calcium, PTH, and phosphorus values all returned to normal. Serum calcium was 9.3 mg/dL, phosphorus was 3.2 mg/dL, intact PTH was 35 pg/mL, and 24-h urinary calcium was 40 mg.
Three years after surgery, these indexes were still within the normal
ranges. The patient demonstrated progressive improvement in
symptomatology and started walking 9 months later, after being bed
bound for 15 months. Lumbar bone density increased by 429% in the
first year after parathyroidectomy and continued to increase in the
subsequent years. By 3 yr after surgery, the total increase in bone
mass was 550% in the lumbar spine and femoral neck (Fig. 2).
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bone mass measurement technology provides the opportunity to apply a quantitative approach to questions regarding improvement in patients with osteitis fibrosa cystica. It is thus possible to address the potential for bone gain after surgery in such patients as well as the possibility that these gains reflect true anabolic events. The only modern report using DEXA in this regard is that of Brossard et al. (5). They reported a 63-yr-old woman with osteitis fibrosa cystica who demonstrated a 33% increase in hip (greater trochanter) bone density. Our two patients demonstrate even more dramatically the potential for bone restoration in primary hyperparathyroidism. The kinetics of the sustained increase (over 34 yr) as well as the extent of the increases, as much as 261% in case 1 and 550% in case 2, illustrate the remarkable capacity of the skeleton to restore itself. To a certain extent, the improvement in case 2 may have been aided by mineralization of an immature skeleton. However, case 1 illustrates that even the mature skeleton affected by osteitis fibrosa cystica can show vast improvement in bone mineral density. In both cases, bone mass increased from markedly osteoporotic levels (lumbar spine t-scores, -8.13 and -4.55) to t-scores that became completely normal (+0.70 and +0.10, respectively). Such improvements cannot be explained by a simple reduction in the remodeling space, because they occurred over a period of time that is much longer than such models would predict (18) and also because the magnitude of the improvement argues for a true postoperative anabolic effect. The sustained increase in markers of bone formation (alkaline phosphatase and osteocalcin) in the face of decreasing bone resorption markers supports that idea that these two patients experienced a true increment in bone mass.
Although severe primary hyperparathyroidism is seen only rarely now, the cases reported here provide additional insights into the postoperative capability of bone mass to be restored in primary hyperparathyroidism. To a more modest extent, bone mass typically improves after surgery in asymptomatic primary hyperparathyroidism. From our observations, one might infer that the greater the bone disease, the greater the likelihood that bone mass will improve postoperatively. It is possible that active bone involvement, as assessed by biochemical evidence of disease, will be associated with greater improvement in bone mass. Complete assessment of disease activity, therefore, may be useful in gaging the potential for improvement in bone mass during the postoperative period. On the other hand, when overt bone disease is present, remarkable recovery of bone loss can be expected. Although the precise mechanisms of restoration of bone mass after successful surgery have yet to be elucidated, it is likely that the postoperative changes in bone represent a true anabolic effect.
![]() |
Footnotes |
---|
Received September 26, 1997.
Revised November 6, 1997.
Accepted November 19, 1997.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|