Improved peripheral cortical bone geometry after surgical treatment of primary hyperparathyroidism in postmenopausal women.

CONTEXT: Cortical bone geometry is one of the most important components of bone strength. Excess endogenous PTH or intermittent PTH administration affects cortical bone geometry; however, the changes in cortical bone geometry in patients with primary hyperparathyroidism (pHPT) after parathyroidectomy (PTX) remain unknown. OBJECTIVE: The present study was performed to examine the longitudinal effects of treating endogenous PTH excess on cortical bone geometry in postmenopausal patients with pHPT by using peripheral quantitative computed tomography. PATIENTS: Twenty postmenopausal pHPT patients and 30 postmenopausal control subjects matched for age participated in this study. MAIN OUTCOME MEASURES: Volumetric bone mineral density (vBMD), cortical bone geometric parameters, polar strength strain index, and polar cross-sectional moment of inertia were measured using peripheral quantitative computed tomography at the radius during the year after PTX. RESULTS: After 1 yr, total and cortical vBMD significantly increased after PTX in the pHPT group (2.9 and 1.6%, respectively), whereas they significantly decreased in the control group (-2.1 and -1.3%, respectively). Significant decreases in cortical thickness and area were observed in the control group (-3.0 and -2.5%, respectively). In contrast, the pHPT group showed increases in cortical thickness and area (8.5 and 7.6%, respectively) as well as polar strength strain index 1 year after PTX. CONCLUSION: The present longitudinal study showed significant beneficial changes in volumetric BMD, cortical bone geometry, and bone strength index after PTX in postmenopausal women with pHPT.

Effects of an excess and a deficiency of endogenous parathyroid hormone on volumetric bone mineral density and bone geometry determined by peripheral quantitative computed tomography in female subjects.

Peripheral quantitative computed tomography (pQCT) is useful for evaluating volumetric bone mineral density (vBMD) as well as bone mineral density (BMD) of cortical and trabecular bones separately. Although PTH affects cortical and trabecular bones differently, the effects of endogenous PTH on vBMD and bone geometry have not previously been examined with pQCT. We, therefore, investigated the effects of an excess and a deficiency of endogenous PTH on bone by employing dual-energy x-ray absorptiometry and pQCT in 36 female patients with primary hyperparathyroidism (hyper), nine female patients with idiopathic or postoperative hypoparathyroidism (hypo), and 100 normal controls matched to age, gender, and body size (cont). Lumbar BMD by dual-energy x-ray absorptiometry was higher in the order: hypo > cont = hyper, and radius-1/3 BMD was significantly higher in the order: hypo > cont > hyper. The area of radius-1/3 was significantly higher in hyper than in cont. As for pQCT, trabecular vBMD was significantly higher in the order: hypo > cont > hyper at the 4% site (hypo, 157.5 +/- 36.7 mg/cm(3); cont, 123.4 +/- 47.5 mg/cm(3); hyper, 98.4 +/- 41.7 mg/cm(3)). Cortical vBMD was higher in the order: hypo > cont > hyper at the 20% site (hypo, 1141.1 +/- 53.1 mg/cm(3); cont, 1090.2 +/- 72.9 mg/cm(3); hyper, 1038.6 +/- 89.1 mg/cm(3)). Total bone area and endosteal and periosteal circumferences were significantly higher in hyper than in cont and hypo. Cortical area and thickness were higher in the order: hypo > cont > hyper. Bone strength indices were not significantly different among the three groups. In conclusion, vBMD evaluation revealed that an excess of endogenous PTH was catabolic for both cortical and trabecular bones, and that bone mass (especially trabecular bone mass) was preserved under a condition of deficient endogenous PTH. An excess of endogenous PTH stimulated periosteal bone formation, which might partly compensate for a decrease in bone strength induced by low BMD.

Efficacy of direct injection of calcitriol into the parathyroid glands in uraemic patients with moderate to severe secondary hyperparathyroidism.

INTRODUCTION: Secondary hyperparathyroidism (2HPT) is a common complication in uraemic patients. When medical therapy, including high doses of intravenous calcitriol, fails to suppress the pathological secretion of parathyroid hormone (PTH), one of the newly developed interventional techniques, such as percutaneous ethanol injection therapy (PEIT), is an option before taking the surgical solution. A protocol for direct calcitriol injection therapy and a discussion of its effectiveness and limitations for an enlarged parathyroid gland(s) are presented. METHODS: Nine patients were selected according to the Japanese Guideline for Selective PEIT. Using the same technique as PEIT, a dose of calcitriol that was approximately 200-300% of the calculated volume of the selected parathyroid gland was injected directly into the gland under ultrasonographic guidance. RESULTS: In six cases, the intact PTH concentration decreased to <360 pg/ml. The total volume of the enlarged parathyroid gland(s) also decreased to 54.7% of the initial volume. The blood supply to the treated glands, as evaluated by colour Doppler imaging, appeared to diminish transiently after injection, probably from the volume effect of this procedure. The number of enlarged parathyroid glands was not a limiting factor for this therapy; however, a grossly enlarged parathyroid gland (>2000 mm(3)) appeared to be resistant to this intervention and an intrathoracic parathyroid gland was found in a non-responsive case. None of the patients had any severe complications, such as nerve palsy or massive haemorrhage. CONCLUSION: This new approach to the control of 2HPT is recommended as an alternative pharmacological parathyroidectomy to surgical therapy.

Marked and sustained increase in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism; a six-year longitudinal study with or without parathyroidectomy in a Japanese population.

OBJECTIVE: Although many reports have demonstrated the sustained increase in bone mineral density (BMD) at trabecular sites in primary hyperparathyroidism (pHPT) after parathyroidectomy (PTX), there have been no data available on BMD changes over the long-term in pHPT patients with and without PTX in Japanese population. The present study was designed to investigate long-term BMD changes at both trabecular and cortical sites in Japanese pHPT patients with or without PTX. METHODS: The subjects were 97 patients who had been followed up in Kobe University Hospital for at least 1 year up to 6 years with or without PTX. PTX was recommended to all patients whose pathological parathyroid gland(s) could be determined by image diagnosis. BMD was measured at the lumbar spine (L2-L4) and at distal one-third of the radius (R1/3) by dual energy X-ray absorptiometry (QDR2000). Serum levels of calcium, alkaline phosphatase and parathyroid hormone (PTH) were determined at the time of the BMD measurement. RESULTS: Significant increases in any of the indices of BMD from the baseline values were observed within three months after PTX, followed by sustained increases over 6 years at L2-L4 even in postmenopausal women. Radial BMD also showed a marked increase six years after PTX. L2-L4 eventually reached the normal BMD but R1/3 did not. The percentage changes in L2-L4 were positively and significantly correlated with the preoperative PTH levels over the study period. However, the percentage changes in R1/3 showed a significant correlation with the preoperative PTH levels only 5 and 6 years after PTX. In the patients without PTX, no obvious changes in biochemical indices and BMD were observed over the six years. CONCLUSION: We demonstrated that PTX led to marked and sustained increases in BMD not only at L2-L4 but also at R1/3 in Japanese pHPT patients, including postmenopausal women. The preoperative PTH level could be a clinically useful index for predicting long-term BMD changes after PTX.

Trial to predict malignancy of affected parathyroid glands in primary hyperparathyroidism.

Parathyroid cancer is rare but relatively frequent in Japan compared to Western countries. Surgical parathyroidectomy is the primary choice for radical treatment of primary hyperparathyroidism (pHPT), hence it is important to distinguish malignant from benign tumor in the determination of surgical indication as well as method of operation. However, it is not easy to diagnose parathyroid cancer prior to operation. In the present study, we analyzed the background data, biochemical data and bone mineral density (BMD) of 131 patients with pHPT (111 benign and 20 malignant). BMD of the lumbar spine and mid-radius was measured by dual-energy X-ray absorptiometry. Serum levels of calcium, alkaline phosphatase (ALP), and parathyroid hormone (PTH) were significantly higher in malignant group compared to benign one. The extent of elevation of mid PTH seemed to be higher than that of intact PTH in malignant group. Age-, gender-, and race-adjusted BMD of distal one-third of radius was significantly decreased in malignant group compared to benign one, although that of lumbar spine was not significantly different between the two groups, indicating that osteopenia was marked in the region which was rich in cortical bone in malignant group. On the other hand, serum levels of calcium, ALP, and mid PTH as well as age were selected as predictors of malignancy in univariate logistic regression analysis, while serum level of intact PTH was not selected. In conclusion, radial BMD was lower in malignant group compared to benign one in pHPT. Serum levels of calcium, ALP and mid PTH were useful to predict malignancy of affected parathyroid glands in pHPT patients.

Functional giant parathyroid cyst with high concentration of CA19-9 in cystic fluid.

A 63-year-old man was admitted to our hospital for the evaluation of hypercalcemia and anterior neck mass. Laboratory findings revealed hypercalcemia, hypophosphatemia, and hypercalciuria, as well as elevated serum levels of parathyroid hormone (PTH) and alkaline phosphatase. Computerized tomography and magnetic resonance images showed that the mass contained a cystic area. Parathyroid scintigraphy using either 99mTc-sestamibi alone or 201Tl-chloride in conjunction with 99mTc-pertechnetate for thyroid image subtraction showed uptake of the radioactivity into the cyst wall, suggesting that the mass originated from the parathyroid. Fine needle aspiration biopsy revealed that the cyst fluid was serous and bloody with extremely high concentrations of both PTH and CA19-9. The patient was diagnosed as primary hyperparathyroidism caused by parathyroid cyst and cervical exploration was performed. The cyst was dissected away along with the right lobe of the thyroid gland. After tumor removal, serum calcium and PTH levels were normalized. Histological study showed that the tumor possessed malignant potential with capsular invasion as well as moderate cellular atypia with trabecular pattern in arrangement. Parathyroid cells in the wall of the cystic tumor were immunostained positively for CA19-9, suggesting that CA19-9 in the cyst fluid was produced from the cells.