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Shonni J Silverberg

Publications and source records attributed to Shonni J Silverberg.

At least 19 recordsLinked to original sources
PubMed2006

Carotid artery plaque thickness is associated with increased serum calcium levels: the Northern Manhattan study.

BACKGROUND: Elevated serum calcium concentrations are associated with vascular calcification and cardiovascular disease. It is unknown whether there is a relationship between high-normal serum calcium levels and sub-clinical vascular effects. We investigated the association between serum calcium and carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events. METHODS: Epidemiological study of 1194 subjects from the Northern Manhattan Study cohort, a prospective community-based study designed to investigate risk factors for vascular disease in different race-ethnic groups. RESULTS: Subjects with carotid plaque had higher corrected serum calcium levels within the normal range than those without carotid plaque (2.21+/-0.09 mmol/L versus 2.19+/-0.09 mmol/L, p<0.002). The relationship between carotid plaque and serum calcium persisted after adjustment for traditional cardiovascular risk factors. Subjects in the top quintile of maximal carotid plaque thickness (>or=1.7 mm) were more likely to be in the highest quintile of serum calcium level (OR=1.64, 95% CI=1.17-2.29, p<0.004). The interaction of age and corrected serum calcium was the most significant predictor of carotid plaque thickness when traditional vascular risk factors were considered (p<0.001). CONCLUSIONS: Serum calcium levels in a multi-ethnic population of older men and women were positively associated with carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events.

Black or African American↗
PubMed2006

The diagnosis and management of asymptomatic primary hyperparathyroidism.

Classical primary hyperparathyroidism--a disease of 'bones, stones, and psychic groans'--is a rarity in the US, although it is still seen in some parts of the world. Today, most patients with primary hyperparathyroidism are asymptomatic. This change in clinical profile is not merely because of improved detection techniques, and patients with primary hyperparathyroidism who lack symptoms, if left untreated, rarely develop the 'classical' features that were common previously. Indeed, currently available data suggest that there is, today, a disorder with different, yet characteristic, effects on the end-organs of the hyperparathyroid process. In this review, the features of the skeletal, renal, neuropsychologic, cardiovascular, and gastrointestinal manifestations of 'asymptomatic' primary hyperparathyroidism will be discussed. The considerable body of data that has emerged since the recognition of the new clinical profile of primary hyperparathyroidism has allowed a reconsideration of standards of care for this disease. These data were reviewed and incorporated into new clinical guidelines at the 2002 NIH workshop on asymptomatic primary hyperparathyroidism. These recommendations highlight both what is known about the disease, and important areas that need investigation. Continued interest in the skeletal, cardiovascular, and neuropsychiatric manifestations of the disease, and therapeutic trials of medical approaches for its management, will further refine our current understanding, and could lead to additional modifications in the approach to patients with this common endocrine disorder.

Bone Diseases↗
PubMed2006

Asymptomatic primary hyperparathyroidism.

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. In adults with the disease, a single, benign adenoma is seen approximately 80 percent of the time, with multiple gland involvement comprising most of the remaining patients. Very rarely, a parathyroid cancer is responsible but it is seen in less than 0.5 percent of patients with primary hyperparathyroidism. In this article, we will review important clinical and diagnostic features of asymptomatic primary hyperparathyroidism as well as considerations for surgical or medical management of the disease.

Biomarkers↗
PubMed2005

Arterial stiffness in mild primary hyperparathyroidism.

When primary hyperparathyroidism was a more symptomatic disease, it was often associated with increased cardiovascular risk. As the clinical manifestations of the disease have changed to a milder, more asymptomatic disorder, investigation is shifting to more subtle cardiovascular abnormalities. We measured arterial stiffness in 39 patients with mild primary hyperparathyroidism [serum calcium, 2.66 +/- 0.2 mmol/liter (10.7 +/- 0.6 mg/dl); PTH, 21.7 +/- 9.5 pmol/liter (89 +/- 39 pg/ml)] and in 134 controls. Arterial stiffness was measured mathematically at the radial artery with a noninvasive device as the "augmentation index" (AIx). The AIx measures the difference between the second and first systolic peaks in the pressure waveform and correlates with increased cardiovascular risk. When physiological variables affecting augmentation index and potentially confounding cardiovascular risk factors (age, gender, heart rate, height, blood pressure, diabetes mellitus, smoking, and hyperlipidemia) were adjusted for, primary hyperparathyroidism was an independent predictor of increased augmentation index (B = 3.37; P < 0.03). A matched-pair analysis showed that 15% of the variance in AIx was uniquely accounted for by the presence of primary hyperparathyroidism. The presence of primary hyperparathyroidism was a stronger predictor of elevated AIx than age, gender, smoking, hypertension, hyperlipidemia, or diabetes mellitus. AIx was also directly correlated with evidence of more active parathyroid disease, including higher PTH levels (r = +0.42; P < 0.05) and lower bone mineral density at the distal one-third radius (r = -0.33; P < 0.05). The diagnosis of primary hyperparathyroidism was therefore an independent predictor of increased AIx, an early measure of arterial stiffness, and the increase was associated with evidence of more active parathyroid disease.

Aged↗
PubMed2004

Asymptomatic primary hyperparathyroidism: a medical perspective.

The clinical phenotype of primary hyperparathyroidism in the United States has changed markedly over the past century, with the majority of patients having minimal overt symptomatology. It has become clear, however, that "asymptomatic" primary hyperparathyroidism is a disease with distinct physiologic characteristics. Data accumulated over recent years suggest that asymptomatic patients meeting specific criteria can be safely followed without surgery. These guidelines are elucidated, and new options in the medical therapeutics of primary hyperparathyroidism are discussed.

Bone Diseases↗
PubMed2004

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial.

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

Aged↗
PubMed2004

Oxyphil parathyroid adenoma: a malignant presentation of a benign disease.

Functioning parathyroid adenomas of the oxyphil cell type are rare, and the clinical characteristics of patients with these tumors have not been well defined. We describe two cases of severe primary hyperparathyroidism (PHPT) caused by benign oxyphil parathyroid adenomas. The patients' clinical presentations mimicked parathyroid carcinoma. Both had very large tumors associated with marked elevations in PTH and serum calcium levels. Skeletal manifestations were also atypical for benign PHPT, with severe osteoporosis in one patient and osteitis fibrosa cystica in the other. These cases also highlight the remarkable capacity of the skeleton to recover after successful parathyroidectomy, previously reported in other forms of severe PHPT. Bone mineral density improved dramatically 1 yr after parathyroidectomy, with increases of 51% at the lumbar spine, 36% at the total hip, and 11% at the distal one third radius. Most of the increases occurred in the first postoperative months. Consistent with this early and accelerated skeletal response, markers of bone turnover were increased 2 months after surgery and normalized by 8 months postoperatively. In patients with PHPT who present with severe or atypical clinical features, oxyphil adenoma should be considered.

Adenoma, Oxyphilic↗
PubMed2003

Raloxifene lowers serum calcium and markers of bone turnover in postmenopausal women with primary hyperparathyroidism.

Estrogen replacement therapy (ERT) decreases total serum calcium by about 0.5 mg/dl in postmenopausal women with primary hyperparathyroidism (PHPT). We investigated the ability of raloxifene, which has skeletal antiresorptive properties similar to those of ERT, to decrease serum calcium concentrations and markers of bone turnover in PHPT. Eighteen postmenopausal women with asymptomatic PHPT were randomized to 8 wk of raloxifene (60 mg/d) or placebo, followed by a 4-wk washout. At baseline, the groups were well matched. The calcium concentration decreased significantly by 8 wk of raloxifene administration (10.8 +/- 0.2 to 10.4 +/- 0.2 mg/dl; P < 0.05), as did markers of bone resorption and formation [osteocalcin, 11.4 +/- 1.6 to 9.9 +/- 1.6 nmol/liter (P < 0.05); serum N-telopeptide, 21.2 +/- 3.4 to 17.3 +/- 2.8 nmol bone collagen equivalents/liter (P < 0.05)]. Four weeks after raloxifene was discontinued, indices were indistinguishable from baseline. Raloxifene administration did not affect serum PTH, 1,25-dihydroxyvitamin D, total alkaline phosphatase, or urinary calcium excretion. Calcium and bone marker changes were therefore similar to those observed with ERT in PHPT. This short-term study suggests that raloxifene may be a useful approach to the treatment of postmenopausal women with mild PHPT.

Biomarkers↗
PubMed2003

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.

Adenoma↗
PubMed2003

"Incipient" primary hyperparathyroidism: a "forme fruste" of an old disease.

Although primary hyperparathyroidism today is often a relatively asymptomatic disease, it has distinct biochemical and skeletal features. These features are present at diagnosis and are generally stable over time, leading to the theory of a biphasic disease course in which alterations occur during a preclinical phase. Measurement of calciotropic hormones in individuals undergoing skeletal evaluation has led to the identification of normocalcemic individuals with elevated PTH levels. We hypothesize that these patients represent the earliest manifestations of primary hyperparathyroidism Twenty-two patients had hyperparathyroidism (94 +/- 29 pg/ml) and normal corrected serum calcium levels (2.40 +/- 0.02 mmol/liter). No secondary causes of hyperparathyroidism were found. PTH levels did not correlate with urinary calcium concentration, renal function, vitamin D concentrations, or bone density. The relationship between PTH and serum calcium (regression slope, +0.004) was identical in normocalcemic and hypercalcemic hyperparathyroid patients. Preferential cortical bone loss, characteristic of patients with primary hyperparathyroidism, was not seen (T-score: spine, -1.6; hip, -1.8; distal one-third radius, -1.3). In up to 12 months of observation, three patients have developed hypercalcemia, and one has had two adenomas removed. These patients with elevated PTH levels in the absence of hypercalcemia may provide a window into this previously unrecognized stage of the disease and permit investigators to track its evolution in ways that have not heretofore been possible.

Aged↗
PubMed2002

Rheumatic manifestations of primary hyperparathyroidism and parathyroid hormone therapy.

A frequent manifestation of severe primary hyperparathyroidism was the bone disease osteitis fibrosa cystica. Rarely, excess parathyroid hormone (PTH) was associated with gout and calcium pyrophosphate crystal deposition disease. Surgical cure of primary hyperparathyroidism was occasionally associated with pseudogout. Today, primary hyperparathyroidism is generally asymptomatic. Clinically overt rheumatologic and skeletal effects are mainly of historical interest. Skeletal disease is still detectable by more sensitive techniques. In certain circumstances, PTH may be protective and anabolic for the skeleton.

Bone Diseases↗
PubMed2002

Calcimimetics: therapeutic potential in hyperparathyroidism.

Calcium homeostasis is essential for the normal function of many organ systems. The recently cloned extracellular calcium-sensing receptor plays a central role in this process and thus represents an important target for therapeutic agents aimed at treating disorders of calcium metabolism. Compounds, such as the phenylalkylamines NPS 568 and AMG 073, act as agonists of calcium at this receptor. These calcimimetic agents hold promise as potential treatments for diseases of parathyroid hyperfunction, such as primary and secondary hyperparathyroidism.

Aniline Compounds↗