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Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)(2)D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2), the mean serum 24,25(OH)(2)D concentrations significantly trended lower from 3.6, 3.2, 2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic black race, diabetes, albuminuria, and lower serum bicarbonate were also independently and significantly associated with lower 24,25(OH)(2)D concentrations. The 24,25(OH)(2)D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)(2)D. A 24,25(OH)(2)D concentration below the median was associated with increased risk of mortality in unadjusted analysis, but this was attenuated with adjustment for potential confounding variables. Thus, chronic kidney disease is a state of stagnant vitamin D metabolism characterized by decreases in both 1,25(OH)(2)D production and vitamin D catabolism.
Vitamin D deficiency is not a rare disorder, particularly in minority groups. The Institute of Medicine recommends serum 25-hydroxyvitamin (OH)D levels >20 ng/mL and The Endocrine Society recommends levels >30 ng/mL for good health. In contrast, the 2003-2006 National Health and Nutrition Examination Survey reported average total 25-(OH)D concentrations of 25.6 ± 0.4 ng/mL in whites, 19.5 ± 0.5 ng/mL in Mexican Americans, and 14.8 ± 0.4 ng/mL in blacks. Pediatric patients with vitamin D deficiency may be asymptomatic or may present either with rickets, hypocalcemia, or seizures. Pseudohypoparathyroidism (PHP) is a rare disorder characterized by parathyroid hormone (PTH) resistance with (type 1a) or without (type 1b) the Albright Hereditary Os-teodystrophy (AHO) phenotype of short stature, brachydactyly, and mental retardation. Patients with PHP have elevated PTH levels and may have hyperphosphatemia and hypocalcemia. However, the same laboratory values can be seen in children with vitamin D deficiency, and diagnostic confusion is common. We report two cases of vitamin D deficiency with presentations suggestive of PHP.
Copyright 2012, SLACK Incorporated.
Insulin resistance (IR) is common in chronic hemodialysis (CHD) patients and is associated with excess mortality. The gold standard for assessment of insulin sensitivity is hyperinsulinemic euglycemic clamp studies which provide the precision and accuracy necessary, especially for mechanistic studies. However, clamp studies are labor-intensive and complicated for more practical use. Accordingly, additional indices such as homeostatic model assessment of insulin resistance (HOMA), quantitative insulin sensitivity check index, and adipokine-based measurements represent appropriate alternatives for large epidemiological and interventional studies. The etiology of IR in the CHD population is complex and multifactorial. The predominant pathophysiological mechanism of 'uremic insulin resistance' is a post-receptor defect in the skeletal muscle; however, other glucose metabolism abnormalities are also present. Some of the proposed determinants of IR in CHD patients include chronic inflammation, excess visceral fat, adipokine deregulation and accumulation, metabolic acidosis, oxidative stress, vitamin D deficiency, anemia, decreased physical activity, and accumulation of uremic toxins. The relative importance of each of these abnormalities is not well-defined, although excess visceral fat and inflammation seem to be the most important correlates of IR in this patient population. There are only few interventional studies targeted at improving insulin resistance in CHD patients. Insulin sensitizers such as metformin and PPAR-γ agonists are either contraindicated or sparingly used due to their potential side effects, even in CHD patients with overt diabetes mellitus. More novel approaches to improving IR in this patient population might lead to potential strategies for preventing excess mortality.
Copyright © 2011 S. Karger AG, Basel.
This article reviews the current state of the art regarding therapy for primary hyperparathyroidism. Clinical evaluation and indications for parathyroidectomy are described, followed by a review of surgical techniques currently being practiced and possible outcomes involved. Focused parathyroidectomy has become a successful alternative to conventional bilateral cervical exploration.
BACKGROUND - Ultrasound has been used successfully to localize parathyroid glands. This study evaluates surgeon-performed ultrasound (SUS) for pre-operative parathyroid localization prior to parathyroidectomy.
METHODS - In all, 442 patients with primary hyperparathyroidism (HPT) underwent SUS at a single institution. Patients were divided into 2 groups: group 1 (n = 338) had correct localization, and group 2 (n = 104) had incorrect localization. The true-positive (TP) rate and peri-operative findings were compared. TP was defined as localization of all abnormal parathyroids resulting in operative success. A P value >.05 was considered significant.
RESULTS - Of 442 patients, 338 (76.5%) had TP results. Group 1 patients were younger (57 vs 63 years; P < .0001) with larger gland size: 2.1 versus 1.8 cm (P = .08). In group 2, 45/104 (43%) patients had false-positive SUS, and 59/104 (57%) had negative studies or missed multiglandular disease (MGD). Group 1 patients had shorter operative times (60 vs 80 min, P = .002), fewer bilateral neck explorations (BNEs) (8% vs 39%; P < .0001), and lower MGD rates (2% vs 19%; P < .0001). Operative failure was 0.3% in group 1 and 9.6% in group 2 (P < .0001).
CONCLUSION - Younger patients have a greater rate of correct localization. When SUS correlates with operative findings, MGD is significantly lower and fewer BNEs are performed. Additionally, operations are shorter with a higher success rate.
BACKGROUND - Younger individuals with hyperparathyroidism may experience severe disease with a higher incidence of multigland disease (MGD) and operative failure, thereby requiring subtotal parathyroidectomy. This study examines the characteristics and surgical outcome of younger compared with older patients with sporadic primary hyperparathyroidism (SPHPT).
METHODS - Prospectively collected data of 1101 patients with SPHPT who underwent parathyroidectomy at a single institution were retrospectively reviewed. Patients with multiple endocrine neoplasia (MEN), familial, secondary, or tertiary hyperparathyroidism, parathyroid carcinoma, rickets, or lithium induced disease were excluded. Patients were subdivided into two groups: (1) younger individuals < or = 40 y of age (n = 110) and (2) older individuals > 40 y of age (n = 991). Both age groups were compared for gender, clinical manifestations, pre- and postoperative laboratory values, MGD, operative success, and recurrent disease.
RESULTS - There was greater male predominance in younger compared with older patients treated for SPHPT (41% versus 25%, P = 0.0004). Of the clinical manifestations of SPHPT, kidney stones were more common in younger compared with older individuals (45% versus 29%, P = 0.0006). Conversely, bone pain was more common in older compared with younger patients (32% versus 14%, P = 0.0002). There was no statistical difference in biochemical values, MGD, and outcome between both groups.
CONCLUSIONS - Despite male predominance and few differences in symptoms, SPHPT is a similar disease entity in both younger and older individuals. Patients from both age groups can be similarly treated for SPHPT with a high rate of operative success. Routine BNE and subtotal parathyroidectomy is not necessary in younger individuals.
BACKGROUND - Criterion requiring intraoperative parathyroid hormone (IOPTH) drops >50% from the highest, preincision or preexcision level, 10 minutes after the abnormal gland's excision predicts operative success with 98% accuracy. The purpose of this study is to correlate IOPTH dynamics with recurrent hyperparathyroidism (RecHPT) and eucalcemia with high PTH (HPTH).
METHODS - We followed 383 consecutive patients with parathyroidectomy guided by IOPTH monitoring using the above criterion for >6 months. Calcium and PTH levels were measured for 50 months (range, 6-173). Patients were divided in 2 groups: group 1 comprised 302 participants with IOPTH levels that decrease to the normal range (NR), and group 2, with 81 participants who had >50% IOPTH decrease but remained above the normal range. The incidence of RecHPT and eucalcemia with HPTH was evaluated.
RESULTS - RecHPT was found in 2% (8/383) of patients and eucalcemia with HPTH was present in 19% (74/383). In group 1, 17% (52/302) had eucalcemia with HPTH, whereas in group 2, this incidence was 27% (22/81; P = .04). However, only 2% of those (6/302) in group 1 and 2.5% (2/81) in group 2 developed RecHPT (P = .76). Conversely, 70.5% of those (57/81) in group 2 were eucalcemic with normal PTH.
CONCLUSION - Although postoperative eucalcemia with HPTH was significantly higher among patients with IOPTH above the normal range than in patients in group 1, the incidence of RecHPT was not increased. The majority of patients in whom IOPTH did not drop to the normal range continue to be biochemically normal after the operation.
BACKGROUND - Sample collection site may affect the dynamics of intraoperative parathyroid hormone monitoring (IPM) and influence surgical decisions.
METHODS - We prospectively studied 45 patients undergoing parathyroidectomy for primary hyperparathyroidism. The IPM cure criterion was a decrease in peripheral vein (PV) parathyroid hormone (PTH) of >50% at 10 minutes after gland excision. PTH samples were collected simultaneously from PV and central vein (CV) and compared for PTH decay, the incidence of >50% PTH decay, and the incidence of normal PTH values after gland excision.
RESULTS - Mean PTH levels were significantly higher from the CV before and after gland excision. Mean PTH decay 10 minutes after gland excision was 89% PV versus 88% CV, resulting in mean PTH levels of 27 +/- 23 and 39 +/- 35 pg/mL, respectively (P < .0001). At 5 minutes, >50% decay in PTH was present in 98% PV versus 88% CV samples. By 10 minutes, the incidence of >50% PTH decay was equivalent (98%). This yielded normal range PTH levels from the PV versus CV in 90% versus 76% of patients at 5 minutes, 96% versus 89% at 10 minutes, and 95% versus 81% at 20 minutes. Of 45 patients, 44 (98%) are normocalcemic at a mean follow-up of 6.3 months. IPM predicted the single operative failure.
CONCLUSIONS - CV sampling produces significantly higher PTH levels. Surgeons sampling from a PV may observe a >50% decrease in PTH and normal range PTH values starting 5 minutes after gland excision. Surgeons who sample from the CV and require normalization of PTH levels may have to wait longer and/or continue potentially unnecessary neck exploration.
BACKGROUND - Many patients with sporadic primary hyperparathyroidism (SPHPT) have discordant preoperative Tc-99m-sestamibi (MIBI) and ultrasonography studies prior to focused parathyroidectomy (PTX). This study examines the usefulness of intraoperative parathormone monitoring (IPM) during PTX in patients with discordant preoperative localization studies.
METHODS - A retrospective series of 225 consecutive SPHPT patients with MIBI scans and surgeon performed ultrasonography (SUS) prior to focused parathyroidectomy were studied. All patient operations were reviewed, and how IPM changed operative management was determined. Correct gland localization, presence of multigland disease (MGD), and operative outcome were also examined.
RESULTS - In 225 patients, overall operative success was 97%, and IPM changed operative management in 29% of patients. In 85 patients (38%) with discordant studies, operative success was 93%; IPM changed operative management in 74% of these patients. IPM allowed for 66% (56/85) of these operations to be performed as unilateral neck exploration and confirmed removal of abnormal glands in 7 patients with MGD. In 140 patients (62%) with concordant localization, in which operative success was 99%, IPM changed operative management in only 2% (3/140) of these patients with MGD.
CONCLUSION - Although of marginal benefit in patients with concordant imaging studies, IPM remains essential for performing successful PTX with discordant or incorrect concordant localization.
HYPOTHESIS - Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear.
DESIGN - Retrospective case series.
SETTING - Tertiary referral center.
PATIENTS - Five hundred seventy-six consecutive patients with HPT.
INTERVENTION - Parathyroidectomy guided by intraoperative monitoring of PTH levels.
MAIN OUTCOME MEASURES - Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy).
RESULTS - Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency.
CONCLUSION - Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.