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      Pre-operative Serum Alkaline Phosphatase as a Predictor for Hypocalcemia Post-Parathyroid Adenectomy

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          Abstract

          Background . Post-operative hypocalcemia (POH) may complicate parathyroidectomy for primary hyperparathyroidism. This study investigates the relationship between POH and pre-operative risk factors to identify a simple method to predict POH risk.

          Methods. Retrospective data on risk factors for 29 patients was collected for age, pre-operative serum calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH), adenoma size, gender, and bisphosphonate pre-treatment. These were screened to exclude those with small effect sizes, and analyzed using Univariate General Linear Modeling (GLM) with trough serum calcium (TSC) as the dependent variable. The regression function of the significant variables against TSC was plotted with 95% CI fit lines. The cut-off regression value was read from the lower fit line for the threshold TSC of 2.0 mmol/L.

          Results. After screening, log-transformed age (r=0.600), ALP (r=-0.415), and PTH (r=-0.433) were entered into GLM analysis, which showed that only ALP was significant (p=0.016 Eta-squared=0.220). The GLM model had a partial Eta-squared of 0.559 with 98% observed power. The plot of TSC against log-ALP gave an ALP cut-off of 340 U/L.

          Conclusions. The study shows that there is a strong relationship between ALP and TSC, and that patients with a pre-operative ALP less than 340 U/L are unlikely to have symptomatic POH (100% sensitivity, 95% specificity). While vitamin D was not analyzed in this study, the ALP cut-off is conservative and should still screen out cases with severe vitamin D deficiency. We therefore recommend that pre-operative ALP be utilized to complement clinical protocols for POH management in parathyroid adenomectomy patients.

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          Most cited references17

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          Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery.

          The hospital course of 218 consecutive patients with primary hyperparathyroidism admitted over a three-year period for parathyroidectomy at the Massachusetts General Hospital was reviewed to determine the incidence and identify the risk factors for the development of the hungry bone syndrome. Twenty-five patients with the hungry bone syndrome were identified (12.6 percent). Compared to patients with uncomplicated metabolic responses to parathyroid surgery, these patients were older by a mean of 10 years; they had higher preoperative serum levels of calcium, alkaline phosphatase, N-terminal parathyroid hormone, and blood urea nitrogen; and their resected parathyroid adenomata were larger. The mean duration of hospitalization averaged three days longer in the group with hungry bone disease. Stepwise multivariate analysis of preoperative variables enabled the development of a discriminant function for prediction of postoperative hypocalcemia and hypophosphatemia. Identified predictive variables were volume of resected parathyroid adenoma, blood urea nitrogen, alkaline phosphatase, and age. When validated on an independent patient population, these readily obtainable preoperative clinical and laboratory parameters will allow identification of a subgroup of patients who are at greater risk for the development of the hungry bone syndrome following parathyroid surgery.
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            Clinical pharmacology of exogenously administered alkaline phosphatase.

            To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.
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              Bisphosphonate pretreatment attenuates hungry bone syndrome postoperatively in subjects with primary hyperparathyroidism.

              Primary hyperparathyroidism is characterized by hypercalcemia with loss of bone mass. After parathyroidectomy, hypocalcemia may develop in some patients due to unregulated bone mineralization. Preoperative administration of bisphosphonates, potent inhibitors of osteoclast activity, may prevent postoperative hypocalcemia after parathyroidectomy. We retrospectively reviewed medical records to investigate the effect of bisphosphonate pretreatment on serum calcium level changes after parathyroidectomy. Twenty-three patients with a diagnosis of primary hyperparathyroidism underwent parathyroidectomy between April 1997 and August 2002. Clinical and laboratory data were collected before and after the operation. These patients were divided into two groups; those showing hungry bone syndrome (n = 9) and those not (n = 14). None of the 9 patients with hungry bone syndrome had received bisphosphonate pretreatment. Of the 14 patients without hungry bone syndrome, 6 had received bisphosphonate pretreatment (P < 0.05). Furthermore, preoperative calcium concentration was not related to the occurrence of hypo-calcemia in those without bisphosphonate pretreatment. In conclusion, administration of bisphosphonates in primary hyperparathyroidism can prevent the occurrence of hungry bone syndrome after parathyroidectomy.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2012
                18 September 2012
                : 9
                : 7
                : 611-616
                Affiliations
                1. Institute of Gerontology (IG), Universiti Putra Malaysia, Malaysia;
                2. Tan Tock Seng Hospital (TTSH), Singapore;
                3. Singapore Institute for Clinical Sciences (SICS), Singapore
                Author notes
                ✉ Corresponding author: Dr Seng Cheong Loke. Institute of Gerontology, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, MALAYSIA. E-mail: lokesengcheong@ 123456gmail.com .

                COMPETING INTERESTS: The authors have declared that no competing interest exists.

                Article
                ijmsv09p0611
                10.7150/ijms.4861
                3461766
                23028244
                a352536d-1ccd-4165-a0df-14695b696d22
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                : 12 July 2012
                : 10 September 2012
                Categories
                Research Paper

                Medicine
                alkaline phosphatase,primary hyperparathyroidism,hypocalcemia,surgery,linear models
                Medicine
                alkaline phosphatase, primary hyperparathyroidism, hypocalcemia, surgery, linear models

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