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Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

ABSTRACT: Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT).To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX).Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000?mg daily and 75 to calcium carbonate 1000?mg and cholecalciferol 1600?IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition.The 25-hydroxyvitamin D (25-OH-D)-level was <50?nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups.Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.

SUBMITTER: Norenstedt S

PROVIDER: S-EPMC3805017 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

Norenstedt Sophie S Pernow Ylva Y Brismar Kerstin K Sääf Maria M Ekip Ayla A Granath Fredrik F Zedenius Jan J Nilsson Inga-Lena IL

European journal of endocrinology 20131021 6

<h4>Background</h4>Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT).<h4>Objective</h4>To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX).<h4>Design and methods</h4>Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Swed ...[more]

PMID: 24026893

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Project description:ImportanceParathyroidectomy provides definitive management for primary hyperparathyroidism (PHPT), reducing the risk of subsequent fracture, nephrolithiasis, and chronic kidney disease (CKD), but its use among older adults in the US is unknown.ObjectiveTo identify patient characteristics associated with the use of parathyroidectomy for the management of PHPT in older adults.Design, setting, and participantsThis population-based, retrospective cohort study used 100% Medicare claims from beneficiaries with an initial diagnosis of PHPT from January 1, 2006, to December 31, 2016. Patients were considered to meet consensus guideline criteria for parathyroidectomy based on diagnosis codes indicating osteoporosis, nephrolithiasis, or stage 3 CKD. Multivariable logistic regression was used to identify patient characteristics associated with parathyroidectomy. Data were analyzed from February 11, 2020, to October 8, 2020.Main outcomes and measuresThe primary outcome was parathyroidectomy within 1 year of diagnosis.ResultsAmong 210 206 beneficiaries with an incident diagnosis of PHPT (78.8% women; mean [SD] age, 75.3 [6.8] years), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Among the subset of patients who met consensus guideline criteria for operative management (n = 131 723), 38 983 (29.6%) were treated with parathyroidectomy. Patients treated operatively were younger (mean [SD] age, 73.5 [5.7] vs 76.0 [7.1] years) and more likely to be White (90.1% vs 86.0%), to be robust or prefrail (92.1% vs 85.7%), and to have fewer comorbidities (Charlson Comorbidity Index score of 0 or 1, 54.6% vs 44.1%), in addition to being more likely to live in socioeconomically disadvantaged (46.9% vs 40.3%) and rural (18.1% vs 13.6%) areas (all P < .001). On multivariable analysis, increasing age had a strong inverse association with parathyroidectomy among patients aged 76 to 85 years (unadjusted rate, 25.9%; odds ratio [OR], 0.68 [95% CI, 0.67-0.70]) and older than 85 years (unadjusted rate, 11.2%; OR, 0.27 [95% CI, 0.26-0.29]) compared with those aged 66 to 75 years (unadjusted rate, 35.6%), as did patients with moderate to severe frailty (unadjusted rate, 18.9%; OR, 0.60 [95% CI, 0.56-0.64]) compared with robust patients (unadjusted rate, 36.1%) and those with a Charlson Comorbidity Index score of 2 or greater (unadjusted rate, 25.9%; OR, 0.77 [95% CI, 0.75-0.79]) compared with a Charlson Comorbidity Index score of 0 (unadjusted rate, 37.0%). With regard to operative guidelines, a history of nephrolithiasis increased the odds of parathyroidectomy (OR, 1.43 [95% CI, 1.39-1.47]); stage 3 CKD decreased the odds of parathyroidectomy (OR, 0.71 [95% CI, 0.68-0.74]); and osteoporosis showed no association (OR, 1.01 [95% CI, 0.99-1.03]).Conclusions and relevanceIn this cohort study, most older adults with PHPT did not receive definitive treatment with parathyroidectomy. Older age, frailty, and multimorbidity were associated with nonoperative management, and guideline recommendations had minimal effect on treatment decisions. Further research is needed to identify barriers to surgical care and develop tools to target parathyroidectomy to older adults most likely to benefit.

Project description:ImportanceHyperparathyroidism is associated with cardiovascular disease. However, evidence for a beneficial consequence of parathyroidectomy on hypertension is limited.ObjectiveTo investigate if parathyroidectomy improves hypertension in patients with primary hyperparathyroidism (PHPT).Design, setting, and participantsIn this cohort study and retrospective database review, patients with PHPT and hypertension between January 1, 2008, and December 31, 2016, were identified. The mean arterial pressure (MAP) and number of antihypertensive medications were compared between those who did and did not undergo parathyroidectomy. The setting was a large health care system. Primary hyperparathyroidism was defined using biochemical data, and hypertension was identified by International Classification of Diseases, Ninth Revision codes.ExposureParathyroidectomy was identified in the database by Current Procedural Terminology codes.Main outcomes and measuresThe MAP and use of antihypertensive medications were compared for patients who underwent parathyroidectomy and those who did not at 6 months, 1 year, and 2 years. Multivariable logistic regression was used to assess the adjusted odds ratios for both increased and decreased use of antihypertensive medications.ResultsIn this cohort study of 2380 participants (79.0% female), patients undergoing parathyroidectomy (n = 501) were younger (mean [SD] age, 65.3 [9.7] vs 71.9 [10.4] years; P < .001) and took fewer antihypertensive medications at baseline (mean [SD] number of medications, 1.2 [1.1] vs 1.5 [1.3], P < .001) than nonsurgical patients (n = 1879). Patients with parathyroidectomy showed greater improvement in their MAP at all follow-up time points (the median [SD] MAP change from baseline to 1 year was 0.1 [8.7] mm Hg without parathyroidectomy vs -1.2 [7.7] mm Hg after parathyroidectomy, P = .002). Nonsurgical patients were more likely vs those with parathyroidectomy to require more antihypertensive medications at 6 months (15.9% [n = 298] vs 9.8% [n = 49], P = .001), 1 year (18.1% [n = 340] vs 10.8% [n = 54], P < .001), and 2 years (17.6% [n = 330] vs 12.2% [n = 61], P = .004). By multivariable analysis, parathyroidectomy was independently associated with freedom from an increased number of antihypertensive medications at all periods (eg, adjusted odds ratio, 0.49; 95% CI, 0.34-0.70; P < .001 at 1 year). Among patients who were initially not taking antihypertensive medications, patients with parathyroidectomy were less likely vs no surgery to start antihypertensive medication treatment at all periods (eg, 10.2% [13 of 127] vs 30.4% [136 of 447], P < .001 at 1 year).Conclusions and relevanceThis study's findings suggest that, among hypertensive patients with PHPT, parathyroidectomy may be associated not only with greater decreases in their MAP but also with reduced requirements for antihypertensive medications. Parathyroidectomy decreased the number of patients who began taking antihypertensive medications. Additional study will be required to find whether there are downstream cardiovascular benefits of parathyroidectomy. Preexisting hypertension, particularly in those not already taking antihypertensive medications, should be considered when weighing surgical treatment.

Project description:BackgroundIn kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT).MethodsThis retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up.ResultsA total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68-1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65-101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode.ConclusionThere was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy.

Project description:ImportancePatients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.ObjectiveTo investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.Design, setting, and participantsThis cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.Main outcomes and measuresThe primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).ResultsA total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).Conclusions and relevanceResults of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

Dataset Information

Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

Publications

Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

Similar Datasets

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