Hyperparathyroidism In Postmenopausal Women Research Articles

Normocalcemic primary hyperparathyroidism in postmenopausal women: Relationship with bone metabolism

Normocalcemic primary hyperparathyroidism in postmenopausal women: Relationship with bone metabolism

Improved Peripheral Cortical Bone Geometry after Surgical Treatment of Primary Hyperparathyroidism in Postmenopausal Women

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. 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. Twenty postmenopausal pHPT patients and 30 postmenopausal control subjects matched for age participated in this study. 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. 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. 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.

Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women

The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.

Molecular mechanisms of primary hyperparathyroidism.

Several advances have been achieved toward the goal of understanding the molecular basis of parathyroid tumorigenesis. The cyclin D1/PRAD1 oncogene has been identified, and is involved in the development of several different tumor types besides those of the parathyroid. The tumor suppressor RB gene has been linked to the pathogenesis of parathyroid carcinoma. The MEN-1 gene product has been identified and mutations in MENIN shown to contribute to sporadic tumors. An understanding of the functions of MENIN will provide further insights into parathyroid disease. Mutations in the RET gene have been identified as the causal agent in MEN-2 but this gene contributes rarely to development of sporadic parathyroid tumors. Ultimately, a description of parathyroid tumorigenesis will need to account for such features as the rarity of parathyroid carcinoma, the increased incidence of tumors after neck irradiation, and the increased frequency of hyperparathyroidism in postmenopausal women. In addition, the relationship between excessive cellular proliferation and an altered set-point in the mechanism linking extracellular calcium concentration to PTH secretion requires explanation. While mutations in the CASR gene itself play a critical role in familial disease, they do not appear to be involved in sporadic parathyroid tumorigenesis, and investigation of genes important for its expression is clearly warranted.

Population based case-control study of sick leave in postmenopausal women before diagnosis of hyperparathyroidism

Objective:To analyse sick leave in women at risk of primary hyperparathyroidism before its diagnosis.Design:Case-control study nested within a screened cohort of postmenopausal women. Cases were women with hyperparathyroidism without prior...

The role of parathyroid hormone in the pathogenesis, prevention and treatment of postmenopausal osteoporosis.

Parathyroid hormone (PTH) is the principal regulator of bone remodeling in the adult skeleton. The acute in vivo effect of PTH is to increase bone resorption, although sustained increases in its circulating levels accelerate both formation and resorption. These divergent effects have focused attention on PTH as a factor contributing to bone loss in some postmenopausal women, as well as interest in its role as therapy for the disease. Sustained increases in PTH are classically seen in primary hyperparathyroidism. While still controversial, increasing evidence suggests that primary hyperparathyroidism is associated with increased rates of bone loss, particularly from cortical sites in the skeleton. It is clear that the remodeling space is increased in primary hyperparathyroidism, and that surgical correction of the disease leads to substantial increases in bone mass in patients with osteoporosis. Recently, secondary hyperparathyroidism has emerged as an important contributor to increased rates of bone turnover and bone loss in postmenopausal women. The etiology of secondary hyperparathyroidism in postmenopausal women is complex, and is probably related to alterations in vitamin D metabolism and tissue responsiveness to 1,25(OH)2vitamin D. PTH has emerged at the forefront of anabolic therapies for the treatment of postmenopausal osteoporosis. When given as a single agent, intermittent daily subcutaneous administration of PTH induces consistent gains in trabecular bone mass with more varying effects on the cortical envelope. However, recent therapeutic trials employing a second agent, most notably estrogen, give hope that this approach may provide the first truly efficacious anabolic therapy for this devastating disease.

Treatment of Postmenopausal Hyperparathyroidism With Norethindrone

The effects of norethindrone (5 mg daily) on biochemical variables and forearm mineral density were assessed in 20 postmenopausal women with mild primary hyperparathyroidism. Norethindrone produced a significant fall in plasma calcium levels and the fasting urinary calcium-creatinine and hydroxyproline-creatinine ratios after three months of treatment. There was no change in the plasma parathyroid hormone concentrations. The forearm mineral density before treatment was low in 16 of the 20 patients and there was a significant increase in forearm mineral density after norethindrone treatment. No side effects were reported. We conclude that norethindrone is an effective treatment for mild hyperparathyroidism in postmenopausal women.

The effect of ethinyloestradiol on calcium and phosphorus metabolism of post-menopausal women with primary hyperparathyroidism.

1. Eight post-menopausal women with primary hyperparathyroidism were given ethinyloestradiol (0.05 mg daily) and the effects on calcium and phosphorus metabolism were observed. 2. In every patient ethinyloestradiol produced a fall in fasting plasma and urine calcium. Calcium balance improved in seven patients on treatment and there was a significant fall in 24 h urine calcium in all eight patients; however, there was no consistent change in net or true absorption of calcium. 3. Ethinyloestradiol produced a small fall in the fasting plasma inorganic phosphorus and a fall in fasting urine phosphorus in seven cases. There was a decrease in 24 h urine phosphorus in seven of the eight cases, but there was no consistent effect on phosphorus absorption nor on phosphorus balance. 4. Bone mineralization rate and bone resorption rate were determined in seven of the patients. The administration of ethinyloestradiol produced a decrease in both these variables in all seven patients. 5. The 24 h urine hydroxyproline, used as an independent measure of bone resorption, decreased in all eight patients during ethinyloestradiol therapy. 6. It is concluded that ethinyloestradiol produces an improvement in calcium and phosphorus balance and a decrease in plasma calcium and phosphorus in primary hyperparathyroidism by decreasing bone resorption. 7. It is suggested that ethinyloestradiol may be used as a medical treatment for primary hyperparathyroidism in post-menopausal women who are either unsuitable for surgery or on whom operative procedures have failed, or in those cases in whom primary hyperparathyroidism is mild.

TREATMENT WITH ŒSTROGENS OF PRIMARY HYPERPARATHYROIDISM IN POST-MENOPAUSAL WOMEN

Ethinylœstradiol was administered to 10 post-menopausal hyperparathyroid patients. There was a gradual fall in the fasting plasma-calcium and urine-calcium and in the 24-hour- urine calcium and hydroxyproline, which was maintained up to one year in the patients who continued therapy. Œstrogen treatment of hyperparathyroidism in post-menopausal women might be expected to prevent bone disease by inhibiting bone resorption, and stone disease by reducing urine-calcium.