The Risk of Fractures in Primary Hyperparathyroidism: A Meta-Analysis.
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ABSTRACT:
SUBMITTER: Narayanan N
PROVIDER: S-EPMC8046118 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose:Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in secondary or tertiary hyperparathyroidism, but the use of cinacalcet in PHPT is less clear. Methods:Searches were conducted in Medline and Embase for cinacalcet use in PHPT from induction to 10 April 2020. Articles and conferences abstracts describing the use of cinacalcet for PHPT in prospective or retrospective cohorts and randomized controlled trials restricted to English language only. We initially identified 1301 abstracts. Each article went extraction by two blinded authors on a structured proforma. Continuous outcomes were pooled with weight mean difference (WMD). Quality of included articles was assessed with Newcastle Ottwa Scale and Cochrane Risk of Bias 2.0. Results:Twenty-eight articles were included. Normalization rate of serum Ca levels was reported at 90% (CI: 0.82 to 0.96). Serum levels of Ca and PTH levels were significantly reduced (Ca, WMD: 1.647, CI: -1.922 to -1.371; PTH, WMD: -31.218, CI: -41.671 to -20.765) and phosphate levels significantly increased (WMD: 0.498, CI: 0.400 to 0.596) after cinacalcet therapy. The higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment. Age and gender did not modify the effect of cinacalcet on serum Ca levels. Conclusion:The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT.
| S-EPMC7424342 | biostudies-literature
Project description:Primary hyperparathyroidism (PHPT) is a common disorder in which parathyroid hormone (PTH) is excessively secreted from one or more of the four parathyroid glands. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumour-suppressor genes. Hypercalcaemia is the biochemical hallmark of PHPT. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcaemia. Normocalcaemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized. The clinical presentation of PHPT varies from asymptomatic disease (seen in countries where biochemical screening is routine) to classic symptomatic disease in which renal and/or skeletal complications are observed. Management guidelines have recently been revised to help the clinician to decide on the merits of a parathyroidectomy or a non-surgical course. This Primer covers these areas with particular attention to the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT.
| S-EPMC5385896 | biostudies-literature
Project description:Background/aimAlmost 15% of patients with sporadic primary hyperparathyroidism (sPHPT) present with multiple gland disease (MGD). The aim of this study was to investigate the potential role of two polymorphisms of the hsa-miR-30e, in sPHPT tumorigenesis.Patients and methodsOne-hundred twenty sPHPT patients, 77 presenting a single adenoma and 43 with MGD, and 54 healthy controls were genotyped. The SNPs were identified using the allele-specific PCR methodology, while the hsa-miR-30e expression was analyzed by real-time quantitative reverse transcriptase PCR.ResultsHsa-miR-30e expression was found to be significantly higher in patients with MGD compared to patients with single adenomas (p=0.0019), but no differences were found regarding specific genotype carriers. The genotype frequencies for ss178077483 and rs7556088 were significantly different between patients and healthy controls.ConclusionAlthough the polymorphisms cannot be used as biomarkers for the differential diagnosis of MGD, hsa-miR-30e expression could potentially serve as a biomarker for this purpose.
| S-EPMC6689336 | biostudies-literature
Project description:BackgroundOsteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT.Case presentationA 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6-10.0] mg/dl), low serum phosphate (2.2 [2.5-4.5] mg/dL), high serum alkaline phosphatase (1482 [35-105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15-65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device.ConclusionsPHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.
| S-EPMC8122575 | biostudies-literature
Project description:Epigenetic mechanisms involved in primary hyperparathyroidism are poorly understood as studies are limited. In order to understand the role of aberrant DNA promoter methylation in the pathogenesis of parathyroid tumors, we have quantified the CpG island promoter methylation density of several candidate genes including APC (promoter 1A and 1B), ?-catenin (CTNNB1), CASR, CDC73/HRPT2, MEN1, P16 (CDKN2A), PAX1, RASSF1A, SFRP1 and VDR in 72 parathyroid tumors and 3 normal parathyroid references using bisulfite pyrosequencing. Global methylation levels were assessed for LINE-1. We also compared methylation levels with gene expression levels measured by qRT-PCR for genes showing frequent hypermethylation. The adenomas displayed frequent hypermethylation of APC 1A (37/66; 56%), RASSF1A (34/66; 52%) and ?-catenin (19/66; 29%). One of the three atypical adenomas was hypermethylated for APC 1A. The three carcinomas were hypermethylated for RASSF1A and SFRP1, and the latter was only observed in this subtype. The global methylation density was similar in tumors (mean 70%) and parathyroid reference samples (mean 70%). In general, hypermethylated genes had reduced expression in the parathyroid adenomas using qRT-PCR. Among the adenomas, methylation of APC 1A correlated with adenoma weight (r = 0.306, p < 0.05). Furthermore, the methylation status of RASSF1A correlated with each of APC 1A (r = 0.289, p < 0.05) and ?-catenin (r = 0.315, p < 0.01). Our findings suggest a role for aberrant DNA promoter methylation of APC 1A, ?-catenin and RASSF1A in a subset of parathyroid tumors.
| S-EPMC3857344 | biostudies-literature
Project description:OBJECTIVE:Diabetes mellitus (DM) is associated with an increased fracture risk; however, the impact of DM and subsequent fracture at different sites and the associations according to patient characteristics remain unknown. DESIGN:Meta-analysis DATA SOURCES: The PubMed, EMBASE and Cochrane Library databases were searched from inception to March 2018. ELIGIBILITY CRITERIA:We included prospective and retrospective cohort studies on the associations of DM and subsequent fracture risk at different sites. DATA EXTRACTION AND SYNTHESIS:Two authors independently extracted data and assessed the study quality. Relative risks (RRs) with 95% CIs were calculated using a random-effects model, and the heterogeneity across the included studies was evaluated using I2 and Q statistics. RESULTS:Overall, DM was associated with an increased risk of total (RR: 1.32; 95%?CI 1.17 to 1.48; p<0.001), hip (RR: 1.77; 95%?CI 1.56 to 2.02; p<0.001), upper arm (RR: 1.47; 95%?CI 1.02 to 2.10; p=0.037) and ankle fractures (RR: 1.24; 95%?CI 1.10 to 1.40; p<0.001), whereas DM had no significant impact on the incidence of distal forearm (RR: 1.02; 95%?CI 0.88 to 1.19; p=0.809) and vertebral fractures (RR: 1.56; 95%?CI 0.78 to 3.12; p=0.209). RR ratios suggested that compared with patients with type 2?DM (T2DM), patients with type 1?DM (T1DM) had greater risk of total (RR: 1.24; 95%?CI 1.08 to 1.41; p=0.002), hip (RR: 3.43; 95%?CI 2.27 to 5.17; p<0.001) and ankle fractures (RR: 1.71; 95%?CI 1.06 to 2.78; p=0.029). Although no other significant differences were observed between subgroups, the association of DM with upper arm or ankle, vertebrae and total fracture differed according to sex, study design and country, respectively. CONCLUSIONS:Patients with DM had greater risks of total, hip, upper arm and ankle fractures, with T1DM having a more harmful effect than T2DM.
| S-EPMC6326306 | biostudies-literature
Project description:Primary hyperparathyroidism is a common condition that affects 0.3% of the general population. Primary and tertiary care specialists can encounter patients with primary hyperparathyroidism, and prompt recognition and treatment can greatly reduce morbidity and mortality from this disease. In this paper we will review the basic physiology of calcium homeostasis and then consider genetic associations as well as common etiologies and presentations of primary hyperparathyroidism. We will consider emerging trends in detection and measurement of parathyroid hormone as well as available imaging modalities for the parathyroid glands. Surgical indications and approach will be reviewed as well as medical management of primary hyperparathyroidism with bisphosphonates and calcimimetics.
| S-EPMC3124277 | biostudies-other
Project description:ImportanceApproximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown.ObjectivesTo estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing.Design, setting, and participantsThis cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020.ExposuresElevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis.Main outcomes and measuresProportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy.ResultsThe final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis.Conclusions and relevanceThis cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.
| S-EPMC7391180 | biostudies-literature
Project description:Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1-178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.
| S-EPMC8630765 | biostudies-literature
Project description:Greater body weight and fat mass have been associated with higher serum parathyroid hormone levels and a higher prevalence of primary hyperparathyroidism (P-HPTH) in women. However, prospective studies to evaluate whether greater body size associates with a higher incidence of developing P-HPTH have not been reported. We investigated whether greater body size was independently associated with a higher risk for developing P-HPTH in women. We conducted a prospective cohort study of 85,013 female participants in the Nurses' Health Study I followed for up to 26 years. Body size was measured via multiple metrics: weight, body mass index (BMI), and waist circumference (WC). Weight and BMI were assessed every 2 years from 1986 to 2012, and WC was assessed in 1986, 1996, and 2000. Detailed dietary and demographic exposures were quantified via validated biennial questionnaires. Incident cases of P-HPTH were confirmed by individual medical record review. Cox proportional hazards models were used to evaluate whether WC, weight, and BMI were independent risk factors for developing P-HPTH. Models were adjusted for demographic variables, comorbidities, medications, intakes of calcium and vitamin D, and exposure to ultraviolet light. We confirmed 491 incident cases of P-HPTH during 2,128,068 person-years of follow-up. The multivariable-adjusted relative risks for incident P-HPTH increased across quartiles of WC: Q1, ref; Q2, 1.34 (0.97, 1.86); Q3, 1.70 (1.24, 2.31); Q4, 2.27 (1.63, 3.18); p trend < 0.001. Similarly, the multivariable-adjusted risks for incident P-HPTH increased across quartiles of weight: Q1, ref; Q2, 1.23 (0.92, 1.65); Q3, 1.63 (1.24, 2.14); Q4, 1.65 (1.24, 2.19); p trend < 0.001. A similar but statistically non-significant trend was observed across quartiles of BMI (p trend = 0.07). In summary, body size may be an independent and modifiable risk factor for developing P-HPTH in women. © 2017 American Society for Bone and Mineral Research.
| S-EPMC5555811 | biostudies-literature