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      Effect of Parathyroidectomy Upon Left Ventricular Mass in Primary Hyperparathyroidism: A Meta-Analysis

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          Abstract

          <div class="section"> <a class="named-anchor" id="d14300397e171"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e172">Context:</h5> <p id="d14300397e174">Primary hyperparathyroidism (PHPT) has been associated with increased left ventricular mass (LVM) in many studies. Most studies have been inadequately powered to assess the effect of parathyroidectomy (PTX) on LVM. </p> </div><div class="section"> <a class="named-anchor" id="d14300397e176"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e177">Objective:</h5> <p id="d14300397e179">The objective was to evaluate whether PTX has a benefit on LVM in patients with PHPT.</p> </div><div class="section"> <a class="named-anchor" id="d14300397e181"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e182">Data Sources:</h5> <p id="d14300397e184">Sources included PubMed, Medline, Cochrane Library, <a data-untrusted="" href="http://clinicaltrials.gov" id="d14300397e186" target="xrefwindow">clinicaltrials.gov</a>, review articles, and abstracts from meetings. </p> </div><div class="section"> <a class="named-anchor" id="d14300397e189"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e190">Study Selection:</h5> <p id="d14300397e192">Eligible studies included prospective studies of PTX vs observation or PTX alone in patients with PHPT who had LVM measured by echocardiography. </p> </div><div class="section"> <a class="named-anchor" id="d14300397e194"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e195">Data Extraction:</h5> <p id="d14300397e197">Two investigators independently identified eligible studies and extracted data. Random-effects models were used to obtain final pooled estimates. </p> </div><div class="section"> <a class="named-anchor" id="d14300397e199"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e200">Data Synthesis:</h5> <p id="d14300397e202">Fifteen studies (four randomized controlled trials and 11 observational) of 457 participants undergoing PTX were included. PTX was associated with a reduction in LVM (crude Hedges g <sub>u</sub> −0.290 ± 0.070, 95% confidence interval [CI] −0.423 to −0.157) of 11.6 g/m <sup>2</sup> (12.5%) on average. Effect size estimates differed by study duration ( <i>P</i> &lt; .001), with improvements seen in shorter (≤6 mo) but not longer studies. There was a trend toward greater improvement in observational studies vs randomized controlled trials ( <i>P</i> = .07), and both serum calcium and PTH were higher in the former. Using random-effects models, the estimated effect size remained significant (Hedges g <sub>u</sub> −0.250, 95% CI −0.450 to −0.050). Higher preoperative PTH but not calcium was associated with a greater decline in LVM (β = −.039, 95% CI −0.075 to −0.004). </p> </div><div class="section"> <a class="named-anchor" id="d14300397e219"> <!-- named anchor --> </a> <h5 class="section-title" id="d14300397e220">Conclusion:</h5> <p id="d14300397e222">PTX reduced LVM in PHPT, and higher preoperative PTH levels were associated with greater improvements. Because the benefit was limited to short-term studies and PHPT disease severity was not independent of study design, further work is needed to clarify the factors that influence the change in LVM and whether the benefit persists beyond 6 months after PTX. Although the clinical significance of the LVM improvement is unclear, these data indicate that PTH may underlie increased LVM in PHPT. </p> </div>

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          Estimation of effect size from a series of independent experiments.

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            Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial.

            It is unclear whether patients with asymptomatic primary hyperparathyroidism (PHPT) do better with parathyroidectomy (PTx) as compared with conservative medical management. The aim of the study was to evaluate the beneficial effect of PTx vs. conservative management in patients with mild asymptomatic PHPT. We conducted a prospective, randomized study. The study took place at a referral center. We studied 50 patients who did not meet any guidelines for parathyroid surgery as recommended by the National Institutes of Health Consensus Development Conference on Asymptomatic PHPT. Patients were randomly assigned to PTx or no PTx and were evaluated at 6 months and at 1 yr. We compared changes (percentage of basal) of lumbar spine bone mineral density (BMD) between the two groups at 1 yr. The change in BMD at lumbar spine was greater after PTx (+4.16 +/- 1.13 for PTx vs. -1.12 +/- 0.71 for no PTx; P = 0.0002). The change in BMD at the total hip was also significantly greater in the PTx group (+2.61 +/- 0.71 for PTx vs. -1.88 +/- 0.60 for no PTx; P = 0.0001). There was no difference in BMD after 1 yr between both groups at the one-third radius site. In comparison with those who did not undergo surgery, the PTx subjects, after 1 yr, showed significant differences in four quality of life measures as determined by the 36-item short form health survey scale: bodily pain (P = 0.001), general health (P = 0.008), vitality (P = 0.003), and mental health (P = 0.017). In patients with mild asymptomatic PHPT, successful PTx is followed by an improvement in BMD and quality of life. Most patients followed without surgery did not show evidence of progression.
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              Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy.

              The association between primary hyperparathyroidism (PHPT) and increased mortality mainly from cardiovascular disease is still debated. The increased mortality previously reported in PHPT was not confirmed in a recent population based study. A high prevalence of left ventricular (LV) hypertrophy was, however, reported in this disease. Although arterial hypertension is regarded as the principal factor, the pathogenesis of LV hypertrophy in PHPT is complex and not completely defined, moreover the effects of successful parathyroidectomy (PTX) are not fully elucidated. The aims of this study were: to ascertain the prevalence of LV hypertrophy in a series of patients with PHPT in comparison to a control population, to seek for relationship between biochemical markers of disease, blood pressure (BP) levels and LV measurements and to evaluate the effects of successful PTX on LV hypertrophy during short-term follow-up. Forty-three patients affected by active PHPT (16 males and 27 females, mean age 60.2 +/- 12.7 years) and 43 controls age- and sex-matched with the same prevalence of arterial hypertension were studied in a case-control analysis. Each subject underwent a M- and 2D mode echocardiographic evaluation and repeated BP measurement. In 21 PHPT submitted to surgery the echocardiographic measurement was repeated 6 months after successful PTX. Serum concentrations of parathyroid hormone (PTH), total-(Ca) and ionized calcium (iCa), phosphate, creatinine, total alkaline phosphatase (TALP) were measured in patients with PHPT at diagnosis and six months after PTX in the subgroup operated on; BP values were measured in three different occasion; mono and 2D echocardiographic evaluation was performed in control subjects and patients with PHPT either before and after PTX. LV hypertrophy, measured by LV mass index (LVMI), was present in 28/43 PHPT patients (65.1%) and in 15/43 (34.8%) controls, P < 0.05; among hypertensive subjects, 21/21 (100%) PHPT patients and 13/21 (61.9%) controls P < 0.05 were hypertrophic while among normotensive subjects, these figures were 7/22 (31.8%) for PHPT patients and 2/22 (9%) for controls, P = 0.67. At multiple regression analysis in a model including biochemical parameters and BP values, serum PTH levels were associated with LVMI values as the strongest predicting variable (0.46, P < 0.02). Six months after PTX, LVMI decreased (137.8 +/- 37.3 vs 113.0 +/- 28.5, P < 0.05) without changes in mean BP values and ratio of hypertensive patients. The present data confirm the high prevalence of LV hypertrophy in primary hyperparathyroidism also in a group of patients with an asymptomatic clinical presentation. The correlation between PTH values and left ventricular mass index suggests an action of the hormone in the pathogenesis of LV hypertrophy confirmed also by the decrease of left ventricular mass index after the reduction of PTH levels. The reversal of left ventricular mass index after parathyroidectomy could affect mortality in primary hyperparathyroidism. An echocardiographic study could be suggested in the clinical work-up of primary hyperparathyroidism in order to evaluate heart involvement and the response to successful parathyroidectomy.
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                Author and article information

                Journal
                The Journal of Clinical Endocrinology & Metabolism
                The Endocrine Society
                0021-972X
                1945-7197
                December 01 2015
                December 01 2015
                : 100
                : 12
                : 4399-4407
                Affiliations
                [1 ]Division of Endocrinology (D.J.M., A.C., C.Z., S.J.S., M.D.W.), New York Presbyterian/Columbia University Medical Center, New York, New York 10032
                [2 ]Department of Medicine, Columbia University, College of Physicians and Surgeons, and Department of Medicine (N.P.), New York Presbyterian/Columbia University Medical Center, New York, New York 10032
                [3 ]Department of Medicine, and Division of Cardiology (M.D.), New York Presbyterian/Columbia University Medical Center, New York, New York 10032
                Article
                10.1210/jc.2015-3202
                4667168
                26445115
                b725f893-6905-4a15-aa36-875c47afa7aa
                © 2015
                History

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