Performance of chloride/phosphate test in patients with primary hyperparathyroidism

<33 تافسوفلا/ديرولك ةبسن صحف ةيساسح ةسارد :فادهلأا )pHPT( يلولأا ةيقردلا ةراج ددغلا طرف ضرم صيخشتل رابتخاك .مدلا يف مويسلاكلا ةبسنب هتقلاعو طرف ضربم هيصخشت تم اًضيرم 120 تانايب ضارعتسا تم :ةقيرطلا ىفشتسم ،ةحارلجا مسق يف اًيحارج مهجلاع تم ةيقردلا قوفلا ةدغلا وينوي ىتح م2010 سرام نم ةرتفلا للاخ ايلاطيا ،ازيب ،ولينازيس تايوتسلم اًقفو ةيعرف تاعومجم عبرأ ىلإ مهميسقت تم .م2011 لكل تافسوفلا/ديرولكلا ةبسن سايق تم دقو .مهدنع مويسلاكلا رثكأ ةجيتنلا نأ رابتعاب رابتخلاا ةيساسح سايق تم مث نمو ،ضيرم ينب ةقلاع دوجو نم ققحتلا ىرج مث نمو .ضرملل ةصخشم 33 نم .صحفلا ةيساسح و ةيقردلا راج نومرهلا ىوتسم تافسوفلا/ديرولك ةبسن صحف ةيساسح تناك :جئاتنلا نيذلا ىضرملل. .0.883 )0.809-0.932( لكك ةعومجملل تناك ةيداعلا تايوتسلما قوف مدلا يف مويسلاكلا نم نوناعي يتلا ةعومجلما امأ .0.9340 )0.857-0.973( صحفلا ةيساسح ىوتسم قوف )لد / مغلم( 1<مدلا سلك عافترا نم يناعت تناك ةعومجم تلكش دقو .93% صحفلا ةيساسح تناك دقف يعيبط ةيعيبطلا دودلحا نمض مهدنع مويسلاكلا ةبسن تناك نيذلا ىضرلما 0.724 صحفلا ةيساسح تغلب ةعومجلما هذهلو ؛24% يلاوح تناكو ،)0.628-0.898( 0.763 هتيصوصخو ،)0.562-0.887( ةيؤبنتلا ةميقلاو )0.536-0.864( 0.700 ةيباجيلإا ةيؤبنتلا ةميقلا ءادأ ينب ةرشابم ةقلاع يأ رهظت مل .)0.651-0.916( 0.784 ةيبلسلا .مدلا يف ةيقردلا راج نومرهلا ىوتسمو صحفلا عقوتل ةديج ةادأ لكشت تافسوفلا/ديرولك ةبسن صحف نأ :ةتماخ ىدل اًيضرم ءادأ رهظأ دقو يلولأا ةيقردلا ةراج ددغلا طرفا ضرم دودلحا نمض مهدنع مويسلاكلا ةبسن تناك نيذلا ىضرلما ةعومجم .ةيعيبطلا Objectives: To examine the sensitivity of the chloride/ phosphate )Cl/PO4( ratio with a cut-off point of <33 as a diagnostic test for primary hyperparathyroidism )pHPT( in surgically proven patients, and its performance at different calcium levels. Methods: This is a retrospective medical records based study. Data of 120 patients diagnosed with pHPT, already operated in the Department of Surgery, Cisanello Hospital, Pisa, Italy between March 2010 and June 2011 were reviewed. They were divided into 4 subgroups according to their calcium levels. The Cl/PO4 ratio was measured for each patient, with a cut-off point of 33, sensitivity of Cl/PO4 test was measured. Test sensitivity was calculated for each subgroup, and a correlation with the parathyroid hormone )PTH( level was investigated. Performance of the equation was tested for the normocalcemic patients with a suitable control group. Results: The sensitivity of Cl/PO4 ratio for the whole group was 0.883 )0.809-0.932(. The sensitivity was 0.9340 )0.857-0.973( for patients with serum calcium above normal levels. A similar result of 0.933 )0.830-0.978( was demonstrated for the subgroup with hypercalcemia <1 )mg/dL( above normal level. Normocalcemic patients constituted 24%; for this subgroup, the sensitivity test was 0.724 )0.562-0.887(, specificity was 0.763 )0.628-0.898(, positive predictive value was 0.700 )0.536-0.864(, and negative predictive value was 0.784 )0.651-0.916(. No correlation was identified between the performance of formula and serum PTH level. Conclusion: The Cl/PO4 test seems to be a good tool to anticipate pHPT and showed a fair performance in normocalcemic patients. Saudi Med J 2013; Vol. 34 (8): 801-805 From the Department of General Surgery (Mismar, Albsoul, Younes), Faculty of Medicine, University of Jordan, Amman, Jordan, and the Department of General Surgery (Materazzi, Biricotti, Miccoli), Faculty of Medicine, University of Pisa, Pisa, Italy. Received 30th April 2013. Accepted 30th June 2013. Address correspondence and reprint request to: Dr. Ayman A. Mismar, Department of General Surgery, Faculty of Medicine, University of Jordan, Amman 11942, Jordan. Tel. +962 799060822. Fax. +962 (6) 5353388. E-mail: [email protected] 801 www.smj.org.sa Saudi Med J 2013; Vol. 34 )8( 802 CL/PO4 ratio in primary hyperparathyroidism ... Mismar et al Saudi Med J 2013; Vol. 34 )8( www.smj.org.sa P hyperparathyroidism )pHPT(, which is characterized by the autonomous overproduction of parathyroid hormone, is diagnosed in approximately 100,000 patients every year in the United States.1 The classical clinical presentation of pHPT is described by the pentad painful bones, kidney stones, abdominal groans, psychic moans, and fatigue overtones.2 With the introduction of calcium screening programs and its implementation worldwide, pHPT was started to be diagnosed early. In a well-defined population in Rochester, Minnesota, the proportion of patients representing the classical symptoms or complications of pHPT decreased from 22% in the pre-screening era )1965-1974( to 8%; following the introduction of automated serum calcium screening )1974-1982( to 1.6% in the post-screening era )1983-1992(.3 Due to the early detection, severe forms of pHPT with bone diseases and renal stones are rarely diagnosed these days.4,5 High serum calcium level is the usual clue for pHPT diagnosis.6 Normal calcium levels, however, might be seen in 10-20% of patients.7 Even those patients who are thought to be asymptomatic will often show symptoms or metabolic complications when carefully evaluated with standardized health questionnaires.8,9 Truly asymptomatic pHPT is rare, occurring in only 2-5% of patients.2,10 Diagnostic lab tests include serum phosphate, chloride and parathyroid hormone )PTH( assay. The chloride/phosphate )Cl/PO4( ratio with a cut-off point of <33 was reported to be highly efficient in pHPT anticipation.11,12 Its importance is augmented in those patients who have serum calcium within normal levels or just above normal level. In this subgroup of patients, a high index of suspicion is necessary to draw attention to the pHPT possibility. There are no studies in literature on the performance of Cl/PO4 test in relation to the serum calcium level. The present study aims to examine the sensitivity of this formula in an Italian population depending on results obtained from surgically proved primary hyperparathyroid patients` records, to check its sensitivity at different calcium levels, to check a relation with parathyroid hormone concentrations and to examine its performance in the group of normocalcemic primary hyperparathyroidism. Methods. A literature review using a PubMed search looking for chloride in primary hyperparathyroidism, phosphate in primary hyperparathyroidism, chloride/ phosphate ratio in primary hyperparathyroidism and Reeves equation was carried out. A pre-hand approval by the ethical authority of the Department of Surgery, University of Pisa, Pisa, Italy according to the principles of Helsinki Declaration was achieved. Medical records of 120 patients diagnosed with pHPT, who were operated in Cisanello Hospital between March 2010 and June 2011, were reviewed. All of them had normal kidney function, normal vitamin D level in blood and a post-operative histopathological report of either parathyroid adenoma or hyperplasia. Collected data included age, gender, calcium, phosphate, chloride, parathyroid hormone )PTH( level, and pathological diagnosis; the patients who did not fulfill the previous criteria and those who had incomplete biochemical data were excluded. Whenever there was more than one reading, the highest was recorded for calcium, chloride and PTH, while the lowest was recorded for phosphate. The Cl/PO4 ratio was measured for each patient. With a cut-off point of 33, the sensitivity of Cl/PO4 test was measured. The patients were then divided into 4 groups depending on their calcium levels )<10.5, 10.5-11.5, 11.5-12.5, <12.5(. Test sensitivity was first measured for each subgroup and then compared. Then, the relation between PTH level and Cl/PO4 test performance was studied. Six patients were excluded as the PTH level was reported by the endocrinologist and no official lab record was available. Based on the pre-operative PTH level, 114 patients were stratified and divided into 4 groups with a cut-off point of 25%, 50% and 75%. Test sensitivity was measured for each group. Subgroup with calcium level <10.5 was studied separately. Data for 38 patients were collected as a control group by reviewing the hospital database with inclusion criteria: serum calcium level of 10-10.5 and a serum PTH level within the normal range, gender distribution was controlled to meet the study group. The sample size determination was based on statistical analysis of the maximum error of estimates. The analysis showed that a sample of 26 elements is statistically adequate to perform the analysis. A hypothesis test was carried out based on the comparison of the mean of 2 samples with different variances and samples size. All items of the first sample are healthy people while all the items of the second sample have pHPT. The Cl/ PO4 ratio was calculated and the average of this ratio for both samples were obtained, and the variance was calculated for both samples. The null hypothesis was Cl/PO4ratios were equal for both samples; Cl/PO4 was not a good indicator of the presence of pHPT. Whereas, the alternative hypothesis was Cl/PO4 ratio for the first sample was higher than that for the second sample. The 5% level of confidence )α=0.05( was used to carry out the hypothesis test. The statistical analysis based on t distribution was carried out and the t value of the test and the degree of