Neuropsychological features in primary hyperparathyroidism: a prospective study.

CONTEXT: Data regarding the presence, extent, and reversibility of psychological and cognitive features of primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: This study evaluated psychological symptoms and cognitive function in PHPT. DESIGN: This is a case-control study in which symptoms and their improvement 6 months after surgical cure of PHPT were assessed. SETTINGS: The study was conducted in a university hospital metabolic bone disease unit and endocrine surgery practice. PARTICIPANTS: Thirty-nine postmenopausal women with PHPT and 89 postmenopausal controls without PHPT participated in the study. INTERVENTION: Participants with PHPT underwent parathyroidectomy. OUTCOME MEASURES: Measurements used in the study were: Beck Depression Inventory (BDI); State-Trait Anxiety Inventory, Form Y (STAI-Y); North American Adult Reading Test (NAART); Wechsler Memory Scale Logical Memory Test, Russell revision (LM); Buschke Selective Reminding Test (SRT); Rey Visual Design Learning Test (RVDLT); Booklet Category Test, Victoria revision (BCT); Rosen Target Detection Test (RTD); Wechsler Adult Intelligence Scale-Revised Digit Symbol Subtest (DSy); Wechsler Adult Intelligence Scale Digit Span Subtest (DSpan). RESULTS: At baseline, women with PHPT had significantly higher symptom scores for depression and anxiety than controls and worse performance on tests of verbal memory (LM and SRT) and nonverbal abstraction (BCT). Depressive symptoms, nonverbal abstraction, and some aspects of verbal memory (LM) improved after parathyroidectomy to the extent that scores in these domains were no longer different from controls. Baseline differences and postoperative improvement in cognitive measures were independent of anxiety and depressive symptoms and were not linearly associated with serum levels of calcium or PTH. CONCLUSIONS: Mild PHPT is associated with cognitive features affecting verbal memory and nonverbal abstraction that improve after parathyroidectomy.

Prevention of bone loss after withdrawal of tamoxifen.

OBJECTIVE: Tamoxifen has antiestrogenic effects in the breast and estrogenlike activity in the skeletons of postmenopausal women. We hypothesized that postmenopausal women with breast cancer would experience a rapid decline in bone mineral density (BMD) after stopping tamoxifen, similar to that seen with estrogen withdrawal. The objective of this study was to assess, in a randomized, double-blind, placebo-controlled trial, whether administration of alendronate (70 mg weekly) would prevent bone loss associated with tamoxifen discontinuation. METHODS: Postmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Analyses employed repeated-measures analysis of variance. RESULTS: Patient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD T-scores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (-5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker. CONCLUSION: Differences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen therapy warrant an evaluation of their skeletal health and that bisphosphonate therapy may be useful in preventing bone loss associated with discontinuation of tamoxifen.

Clinical utility of an immunoradiometric assay for parathyroid hormone (1-84) in primary hyperparathyroidism.

The reliable diagnosis of primary hyperparathyroidism depends on the measurement of PTH. The PTH assays in widespread use measure not only the hormone but also hormone fragments, thus limiting the clinical utility of the assays. A new immunoradiometric assay (IRMA) using an antigenic determinant at the extreme amino-terminal of the PTH molecule detects only full-length PTH (1-84). We compared three PTH assays and determined the presence of PTH (1-84) and PTH fragments in serum and parathyroid adenomas of patients with primary hyperparathyroidism. We studied 56 patients with primary hyperparathyroidism. PTH levels were increased in 63% using the midmolecule RIA; in 73% in the "intact" IRMA; and in 96% in the PTH (1-84)-IRMA. The PTH (1-84)-IRMA correlated with the other assays (midmolecule RIA R = +0.736; P < 0.0001; "intact"-IRMA R = +0.951; P < 0.0001) and indices of disease activity (serum calcium R = +0.511, P < 0.0001; alkaline phosphatase R = +0.489, P = 0.001; and radius bone density R = -0.366, P < 0.01). In 21 consecutive patients undergoing parathyroidectomy, 18 had parathyroid adenomas. Intact PTH was higher than PTH (1-84)-IRMA in both serum and glandular homogenates from these patients. Similar proportions of PTH (1-84) and hormone fragments were found in both adenomas [66 +/- 3% of "intact" PTH-reflected PTH (1-84) and sera (73 +/- 2% of "intact" PTH reflected PTH (1-84)]. We conclude that the PTH (1-84)-IRMA offers improved diagnostic sensitivity in patients with primary hyperparathyroidism than other currently available assays. This study also provides evidence that both PTH (1-84) and PTH fragments are produced in parathyroid adenomas and that peripheral metabolism of hormone and fragment does not alter the proportion of bioactive hormone.