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Serum biotin interference: A troublemaker in hormone immunoassays.
Öncül, Ü, Eminoğlu, FT, Köse, E, Doğan, Ö, Özsu, E, Aycan, Z
Clinical biochemistry. 2022;:97-102
Abstract
OBJECTIVES Biotin therapy can affect the results of many immunoassay procedures. The present study investigates biotin's interference on 25-hydroxy vitamin D (25-OHD), parathyroidhormone (PTH) and thyroid-stimulating hormone (TSH) tests using four different assay systems and biotin neutralization. DESIGN AND METHODS Enrolled in the study were 50 children diagnosed with biotinidase deficiency (BTD) undergoing treatment with biotin (5-20 mg/day) who were subjected to a series of analyses involving 25-OHD (Roche Diagnostics assays, Beckman Coulter assays, HPLC, LC/MS-MS), TSH, PTH (Roche Diagnostics assays, Beckman Coulter assays) and biotin (LC/MS-MS), before and after biotin neutralization with Streptavidin-coated magnetic particles (SMP). RESULTS The median biotin concentration was found to be 175.2 [94.0-307.1] μg/L. There was no significant difference in the 25-OHD results before and after neutralization with the Beckman Coulter, HPLC and LC-MS/MS assays. In contrast, the median 25-OHD level was seen to decrease from 90.2 [35.9-105.3] ng/mL to 29.1 [22.6-37.6] ng/mL after neutralization with the Roche assay (p < 0.0001). While there was no statistically significant difference in the values recorded before and after neutralization in PTH analysis using Beckman assay, the median PTH levels increased from 7.8 [1.6-21.6] pg/mL to 28.2 [22.5-41.9] pg/mL after neutralization with the Roche assay (p < 0.0001). The cut-off values at which serum biotin interfered in the Roche assay PTH test, with 25-OHD levels determined as 51.4 μg/L and 62.9 μg/L, respectively. A significant increase was detected in the TSH levels analyzed with a Roche assay after neutralization (from 2.36 [1.85-3.00] mIU/L to 2.74 [1.93-3.70] mIU/L, p < 0.0001). CONCLUSIONS The PTH, 25-OHD and TSH results were found to be affected by high biotin concentrations in Roche assays, leading to a risk of misdiagnosis, although SMP neutralization can suppress any such interference efficiently.
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Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes.
Yang, T, Wang, W, Tang, X, Shi, P, Zhang, L, Yu, W, Xie, Y, Guo, D, Ding, F
BMC nephrology. 2019;(1):369
Abstract
BACKGROUND Numerous studies have evaluated the prevalence and importance of mineral and bone disorders among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, little is known about dysregulated mineral and bone metabolism in acute kidney injury (AKI). METHODS We evaluated the association between mineral and bone metabolites and clinical outcomes in 158 patients who underwent cardiac surgery and developed AKI between June 2014 and January 2016. The baseline characteristics of the patients were recorded, and the levels of mineral and bone metabolites, including calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25D), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-terminal fibroblast growth factor 23 (cFGF23) were measured within 12 h after establishing the clinical diagnosis. RESULTS The serum phosphate, iPTH and cFGF23 levels were significantly associated with the 28-day mortality (phosphate: Hazard Ratio [HR] =2.620, 95% CI: 1.083 to 6.338, p = 0.035; iPTH: HR = 1.044, 95% CI: 1.001 to 1.090, p = 0.046; cFGF23: HR = 1.367, 95% CI: 1.168 to 1.599, p < 0.001). Moreover, higher serum cFGF23 and BAP levels were independently associated with an increased risk of adverse outcomes. Additionally, we found that the serum cFGF23 levels rose most significantly and were associated with the severity of AKI (P < 0.001). CONCLUSIONS Mineral and bone metabolites are dysregulated and are associated with adverse clinical outcomes among patients with AKI. TRIAL REGISTRATION www.clinicaltrials.gov NCT00953992. Registered 6 August 2009.
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Maintenance of Serum Ionized Calcium During Exercise Attenuates Parathyroid Hormone and Bone Resorption Responses.
Kohrt, WM, Wherry, SJ, Wolfe, P, Sherk, VD, Wellington, T, Swanson, CM, Weaver, CM, Boxer, RS
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;(7):1326-1334
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Exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption. We used a novel intravenous iCa clamp technique to determine whether preventing a decline in serum iCa during exercise prevents increases in PTH and carboxy-terminal collagen crosslinks (CTX). Eleven cycling-trained men (aged 18 to 45 years) underwent two identical 60-min cycling bouts with infusion of Ca gluconate or saline. Blood sampling for iCa, total calcium (tCa), PTH, CTX, and procollagen type 1 amino-terminal propeptide (P1NP) occurred before, during, and for 4 hours after exercise; results are presented as unadjusted and adjusted for plasma volume shifts (denoted with subscript ADJ). iCa decreased during exercise with saline infusion (p = 0.01 at 60 min) and this was prevented by Ca infusion (interaction, p < 0.007); there were abrupt decreases in Ca content (iCaADJ and tCaADJ ) in the first 15 min of exercise under both conditions. PTH and CTX were increased at the end of exercise (both p < 0.01) on the saline day, and markedly attenuated (-65% and -71%; both p < 0.001) by Ca. CTX remained elevated for 4 hours after exercise on the saline day (p < 0.001), despite the return of PTH to baseline by 1 hour after exercise. P1NP increased in response to exercise (p < 0.001), with no difference between conditions, but the increase in P1NPADJ was not significant. Results for PTHADJ and CTXADJ were similar to unadjusted results. These findings demonstrate that bone resorption is stimulated early in exercise to defend serum iCa. Vascular Ca content decreased early in exercise, but neither the reason why this occurred, nor the fate of Ca, are known. The results suggest that the exercise-induced increase in PTH had an acute catabolic effect on bone. Future research should determine whether the increase in PTH generates an anabolic response that occurs more than 4 hours after exercise. © 2018 American Society for Bone and Mineral Research.
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Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone.
Havens, PL, Long, D, Schuster, GU, Gordon, CM, Price, G, Wilson, CM, Kapogiannis, BG, Mulligan, K, Stephensen, CB, ,
Antiviral therapy. 2018;(7):623-628
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities. METHODS Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses. RESULTS Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency. CONCLUSIONS TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health. CLINICAL TRIALS REGISTRATION NCT01751646 (ATN 109) and NCT01769469 (ATN 117).
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Intensified treatment of hyperphosphatemia associated with reduction in parathyroid hormone in patients on maintenance hemodialysis.
Chen, L, He, JX, Chen, YY, Ling, YS, Lin, CH, Guan, TJ
Renal failure. 2018;(1):15-21
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BACKGROUND This study investigated the therapeutic effect of intensive phosphorus-lowering therapy on intact-parathyroid hormone (iPTH) levels in hemodialysis patients. METHODS Ninety-five hemodialysis patients with serum phosphorus ≥1.78 mmol/L and iPTH ≥300 pg/dL were apportioned to either the treatment or control group (n = 43 and 52, respectively) based on patient commitment to treatment. The treatment group was given phosphorus-lowering therapies with phosphate binders (lanthanum, sevelamer or/and calcium reagent) combined with dietary phosphate restriction and intensified hemodialysis. The control individuals were given low doses of calcium agents, if serum calcium was <2.54 mmol/L. Percent changes in serum phosphorus and iPTH levels were compared between the two groups. In addition, based on the time required to achieve >20% decrease in serum phosphorus, the patients in the treatment group were further stratified as rapid responders (≤2 months; 27 patients) or slow responders (>2 months; 16 patients) and percent changes in iPTH were compared. RESULTS Serum phosphorus and iPTH levels decreased from baseline in the treatment group (-24.08 ± 1.93% and -9.92 ± 3.70%, respectively) but increased in the control group (22.00 ± 3.63% and 104.21 ± 23.89%; both p < .001). In the rapid responders subgroup, the iPTH decreased (-16.93 ± 3.49%), but in the slow responders subgroup the iPTH increased slightly (0.68 ± 7.37%, p < .05). CONCLUSIONS For these patients on maintenance hemodialysis, intensive treatment of hyperphosphatemia was associated with a decrease in iPTH levels, especially for those who had achieved substantial reduction in serum phosphorus within 2 months.
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Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials.
Block, GA, Bushinsky, DA, Cunningham, J, Drueke, TB, Ketteler, M, Kewalramani, R, Martin, KJ, Mix, TC, Moe, SM, Patel, UD, et al
JAMA. 2017;(2):146-155
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IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. OBJECTIVE To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. DESIGN, SETTING, AND PARTICIPANTS Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism. Trial A was conducted in 508 patients at 111 sites in the United States, Canada, Europe, Israel, Russia, and Australia from March 12, 2013, to June 12, 2014; trial B was conducted in 515 patients at 97 sites in the same countries from March 12, 2013, to May 12, 2014. INTERVENTIONS Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. MAIN OUTCOMES AND MEASURES The primary efficacy end point was the proportion of patients achieving greater than 30% reduction from baseline in mean PTH during weeks 20-27. A secondary efficacy end point was the proportion of patients achieving mean PTH of 300 pg/mL or lower. RESULTS The mean age of the 1023 patients was 58.2 (SD, 14.4) years and 60.4% were men. Mean PTH concentrations at baseline and during weeks 20-27 were 849 and 384 pg/mL vs 820 and 897 pg/mL in the etelcalcetide and placebo groups, respectively, in trial A; corresponding values were 845 and 363 pg/mL vs 852 and 960 pg/mL in trial B. Patients randomized to etelcalcetide were significantly more likely to achieve the primary efficacy end point: in trial A, 188 of 254 (74.0%) vs 21 of 254 (8.3%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.4%-72.1%) and in trial B, 192 of 255 (75.3%) vs 25 of 260 (9.6%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.3%-72.1%). Patients randomized to etelcalcetide were significantly more likely to achieve a PTH level of 300 pg/mL or lower: in trial A, 126 of 254 (49.6%) vs 13 of 254 (5.1%; P < .001), for a difference in proportions of 44.5% (95% CI, 37.8%-51.2%) and in trial B, 136 of 255 (53.3%) vs 12 of 260 (4.6%; P < .001), for a difference in proportions of 48.7% (95% CI, 42.1%-55.4%). In trials A and B, respectively, patients receiving etelcalcetide had more muscle spasms (12.0% and 11.1% vs 7.1% and 6.2% with placebo), nausea (12.4% and 9.1% vs 5.1% and 7.3%), and vomiting (10.4% and 7.5% vs 7.1% and 3.1%). CONCLUSIONS AND RELEVANCE Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, use of etelcalcetide compared with placebo resulted in greater reduction in serum PTH over 26 weeks. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT01788046.
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Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial.
Block, GA, Bushinsky, DA, Cheng, S, Cunningham, J, Dehmel, B, Drueke, TB, Ketteler, M, Kewalramani, R, Martin, KJ, Moe, SM, et al
JAMA. 2017;(2):156-164
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IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. OBJECTIVE To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. INTERVENTIONS Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. MAIN OUTCOMES AND MEASURES The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. RESULTS The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%). CONCLUSIONS AND RELEVANCE Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT1896232.
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Parathyroid reimplantation with PR-FaST technique in unselected patients during thyroidectomy. A case series with long term follow up confirming graft vitality and parathormone production.
Cavallaro, G, Iorio, O, Centanni, M, Gargano, L, Del Duca, S, Gurrado, A, Porta, N, Petrozza, V, Testini, M, De Toma, G
International journal of surgery (London, England). 2017;:202-205
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INTRODUCTION Parathyroid damage or unintentional excision still affect thyroid surgery and may cause permanent hypoparathyroidism. The only way to recover the excised or ischemic gland functionality is still reimplantation. Many sites of reimplantation have been described, each of one showing both advantages and drawbacks. The aim of this study is to verify results of a new procedure called PR-FaST: Parathyroid Reimplantation in Forearm Subcutaneous Tissue, in a series of unselected patients after long-term follow-up. MATERIALS AND METHODS From January 2013 to October 2015, 296 consecutive total thyroidectomies have been performed) to treat both benign and malignant thyroid diseases. in 42 cases (14.1%), due to an insufficient blood supply or accidental removal, one parathyroid gland was reimplanted with the PR-FaST technique. Post-operative evaluation was carried out by: total serum calcium (Ca), magnesium (Mg) and phosphorus (P) analysis in the 1st and 2nd postoperative days; Ca, Mg, P and serum iPTH from both arms analysis one week after surgery; Ca and iPTH measurement from both arms 1 months, 3, 6 and 12 months after surgery. RESULTS We observed transient hypocalcemia requiring calcium replacement therapy in 5 on 42 (11.9%) patients submitted to PR-FaST. No case of permanent hypoparathyroidism was reported. At 1 week after surgery, only 20 patients (47.6%) showed graft vitality, while the number of patients showing graft vitality arised to 33 (79%) after 1 month and to 39 (92.8%) after three and six months. At 1 year 38 (90.5%) patients showed good graft functionality. Considering levels of serum iPTH from both arms, we observed that in case of graft functionality, samples from reimplanted arm revealed in almost all cases values at least 2-3 folds higher than in non reimplanted arm. CONCLUSIONS Results from this prospective evaluation suggest that PR-FaST is a safe and effective procedure, with potential advantages when compared to other techniques of parathyroid reimplantation, that are mainly the possibility to evaluate graft functionality in the follow-up and the easy and well reproducible technique. Furthermore, it can be applied, when needed, to potentially all patients undergoing thyroidectomy.
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Single measurement of intact parathyroid hormone after thyroidectomy can predict transient and permanent hypoparathyroidism: a prospective study.
Suwannasarn, M, Jongjaroenprasert, W, Chayangsu, P, Suvikapakornkul, R, Sriphrapradang, C
Asian journal of surgery. 2017;(5):350-356
Abstract
OBJECTIVE Immediate postoperative hypocalcemia is the most common complication of bilateral thyroidectomy. Although hypocalcemia is usually transient, it can be fatal. This study aimed to find a predictor of immediate postoperative hypocalcemia by using intact parathyroid hormone (PTH) level at 4 hours after thyroidectomy (iPTH4hr) compared with the decline in the percentage of intact PTH (%iPTH). We also followed the subjects for evaluation of permanent hypoparathyroidism. METHODS This was a prospective study of 65 patients (86.2% female, mean age: 43±15 years) who planned to undergo total or subtotal thyroidectomy. Preoperative and iPTH4hr were measured. RESULTS Thirty-nine patients (60%) were diagnosed with papillary thyroid carcinoma, while the rest were multinodular goiter (21.5%) and Graves' disease (7.7%). Significant immediate hypocalcemia was observed in 25 (38.5%) patients. Both iPTH4hr <12.5 pg/mL and %iPTH decline >72% could accurately predict significant immediate hypocalcemia. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for iPTH4hr were 92%, 87.5%, 82.1%, and 94.6%, respectively. The %iPTH decline was equal in accuracy, with sensitivity, specificity, PPV, and NPV of 84%, 90%, 84%, and 90%, respectively. At 6 months after surgery, 19 patients (29.2%) displayed permanent hypoparathyroidism. The iPTH4hr <12.5 pg/mL and %iPTH decline >72% could also predict permanent hypoparathyroidism, with sensitivity, specificity, PPV, and NPV of 100%, 80.4%, 67.9%, and 100%, and 94.7%, 84.8%, 72%, and 97.5%, respectively. CONCLUSIONS Only a single measurement of iPTH4hr could be helpful in identifying patients at risk of significant immediate hypocalcemia in need prompt treatment, and subsequently facilitating early discharge of patients. Also, this parameter can precisely predict permanent hypoparathyroidism.
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Effects of Laparoscopic Sleeve Gastrectomy on Parathyroid Hormone, Vitamin D, Calcium, Phosphorus, and Albumin Levels.
Mihmanli, M, Isil, RG, Isil, CT, Omeroglu, S, Sayin, P, Oba, S, Ozturk, FY, Altuntas, Y
Obesity surgery. 2017;(12):3149-3155
Abstract
BACKGROUND Laparoscopic sleeve gastrectomy (LSG) reduces obesity-related co-morbidities, such as diabetes, hypertension, and hyperlipidemia. Endocrinological abnormalities may occur as undesired side effects. Most centers routinely prescribe folic acid, cyanocobalamin (vitB12), and protein replacement in the postoperative period, but 25-OH-vitamin-D3 (vitD) and intact parathyroid hormone (iPTH) levels are not routinely followed up. The aim of this study was to identify the effects of LSG on iPTH, vitD, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and albumin levels. METHODS Data of morbidly obese patients who underwent LSG between January and December 2014 were studied in this prospectively designed study. Serum levels of iPTH, vitD, Ca, P, folic acid, vitB12, ALP, and albumin were measured preoperatively and postoperatively at the 3rd, 6th, and 12th months. RESULTS In total, 119 patients were analyzed. All patients had normal iPTH, vitD, Ca, P, folic acid, vitB12, ALP, and albumin values preoperatively, and 31.6% had received vitD supplementation during their nutritionist observation time before surgery. At the 3rd, 6th, and 12th postoperative months, 21 (17.6%), 17 (17.3%), and 1 (0.8%) patients, respectively, had increased iPTH and ALP and decreased vitD levels. A total of 39 (32.7%) patients needed high-dose vitD treatment during a 1 year follow-up. Approximately 37.5% of the patients who received vitD supplementation preoperatively needed vitD supplementation postoperatively. Hospital records of 101 of 119 patients who underwent LSG could be screened to determine their vitD supplementation requirements previously ordered by their nutritionist for a 1-year period before LSG. Thirty-two (31.6%) of the 101 patients had received vitD supplementation during the 1-year period preoperatively. CONCLUSIONS Although serum levels of iPTH, vitD, Ca, P, vitB12, ALP, and albumin may be normal preoperatively, severe vitD insufficiency requiring high-dose vitD replacement may develop in morbidly obese patients postoperatively. Instead of iPTH and vitD, which are expensive to measure, ALP serum level, which is correlated with iPTH levels, can be a good indicator to monitor calcium metabolism.