Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop.

The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Management of Primary Hyperparathyroidism.

Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Nontraditional Aspects of Sporadic Primary Hyperparathyroidism.

Nontraditional aspects of primary hyperparathyroidism refer to the condition's rheumatic, gastrointestinal, cardiovascular, and neuropsychological effects. Although gastrointestinal and rheumatic symptomatology were features of classical primary hyperparathyroidism, they do not seem to be a part of the modern presentation of primary hyperparathyroidism. In contrast, neuropsychological symptoms such as altered mood and cognition, as well as cardiovascular disease, have been associated with the form of primary hyperparathyroidism seen today, but the relationship is not clearly causal. Evidence does not support reversibility after parathyroidectomy and therefore none of the nontraditional manifestations are considered sole indications for recommending surgery at this time.

Long-term Bone Loss and Deterioration of Microarchitecture After Gastric Bypass in African American and Latina Women.

CONTEXT: The prevalence of obesity is burgeoning among African American and Latina women; however, few studies investigating the skeletal effects of bariatric surgery have focused on these groups. OBJECTIVE: To investigate long-term skeletal changes following Roux-en-Y gastric bypass (RYGB) in African American and Latina women. DESIGN: Four-year prospective cohort study. PATIENTS: African American and Latina women presenting for RYGB (n = 17, mean age 44, body mass index 44 kg/m2) were followed annually for 4 years postoperatively. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the spine, hip, and forearm, and body composition. High-resolution peripheral quantitative computed tomography measured volumetric bone mineral density (vBMD) and microarchitecture. Individual trabecula segmentation-based morphological analysis assessed trabecular morphology and connectivity. RESULTS: Baseline DXA Z-Scores were normal. Weight decreased ~30% at Year 1, then stabilized. Parathyroid hormone (PTH) increased by 50% and 25-hydroxyvitamin D was stable. By Year 4, aBMD had declined at all sites, most substantially in the hip. There was significant, progressive loss of cortical and trabecular vBMD, deterioration of microarchitecture, and increased cortical porosity at both the radius and tibia over 4 years. There was loss of trabecular plates, loss of axially aligned trabeculae, and decreased trabecular connectivity. Whole bone stiffness and failure load declined. Risk factors for bone loss included greater weight loss, rise in PTH, and older age. CONCLUSIONS: African American and Latina women had substantial and progressive bone loss, deterioration of microarchitecture, and trabecular morphology following RYGB. Further studies are critical to understand the long-term skeletal consequences of bariatric surgery in this population.

Risk factors for vertebral fracture in primary hyperparathyroidism.

PURPOSE: Screening for vertebral fractures (VF) in primary hyperparathyroidism (PHPT) is recommended, but there are limited data regarding which patients are at greatest risk for VF. We evaluated risk factors for VF in PHPT. METHODS: This is a retrospective cross-sectional analysis of 117 participants with PHPT. We assessed Grades 2 and 3 VF by vertebral fracture assessment (VFA) and the association of VF with the trabecular bone score (TBS), other skeletal parameters and clinical risk factors. VFA was performed only in those who met National Osteoporosis Foundation criteria for VFA screening. RESULTS: T-scores were in the osteopenic range and TBS was degraded. Overall VF rate based on VFA or other imaging was 12.8%. Serum PTH, calcium and TBS were not associated with VF. Those with VF were older (p = 0.04), had worse renal function (p = 0.04), were more likely to have received osteoporosis treatment (p = 0.03), and tended to have had a prior fracture (p = 0.06). T-scores did not differ by fracture status at any skeletal site. Those with VF had nine times the odds of osteoporosis at the hip (95% CI 2.4-34.5), but this risk factor had low sensitivity (46.7%) for VF. Hip T-score < -2.6, Age > 78.6 years, and GFR < 58.8 ml/min/1.73 m2 (thresholds maximizing sensitivity and specificity) had areas under the curve of 0.60-0.67 for VF (all p < 0.05) and low sensitivity. Findings were similar when analyses were limited to women. CONCLUSIONS: In PHPT, VF risk factors included older age, prior fracture, worse renal function and osteoporosis at the hip, but not osteoporosis at other sites, TBS or biochemical indices of PHPT. Since identified risk factors had low sensitivity and were generally inaccurate for categorizing those with VF, the data do not support limiting screening to PHPT patients with these specific VF risk factors.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.

Occult urolithiasis in asymptomatic primary hyperparathyroidism.

OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. METHODS: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. RESULTS: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)2D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)2D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)2D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. CONCLUSION: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)2D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)2D suggests screening those with higher urinary calcium may be an appropriate approach.

Classical complications of primary hyperparathyroidism.

Traditionally, classical complications of primary hyperparathyroidism are mainly represented by skeletal, kidney and gastrointestinal involvement. The old picture of osteitis fibrosa cystica is no longer commonly seen, at least in the western world. However, new imagining techniques have highlighted deterioration of skeletal tissue in patients with primary hyperparathyroidism not captured by traditional DXA measurement. Concerning the kidney, the most common consequences of excessive parathyroid hormone secretion are hypercalciuria and kidney stones; however, the exact pathogenesis of urinary stone formation is still unknown. The 2013 International Congress on the management of Asymptomatic Primary Hyperparathyroidism, emphasized the role of imaging techniques for early discovery of both skeletal and renal complications in asymptomatic patients. Gastrointestinal manifestations include acid-peptic disease, constipation, pancreatitis and gall stone disease. More studies are needed in this area to find the exact pathophysiological mechanism underlying these manifestations and the effect of parathyroid surgery.

Primary hyperparathyroidism.

In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a common endocrine disorder that is characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Most often, the presentation of PHPT is asymptomatic in regions of the world where serum levels of calcium are routinely measured. In addition to mild hypercalcaemia, PHPT can manifest with osteoporosis and hypercalciuria as well as with vertebral fractures and nephrolithiasis, both of which can be asymptomatic. Other clinical forms of PHPT, such as classical disease and normocalcaemic PHPT, are less common. Parathyroidectomy, the only curative treatment for PHPT, is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. Various medical therapies can increase BMD or reduce serum levels of calcium, but no single drug can do both. More data are needed regarding the neuropsychological manifestations of PHPT and the pathogenetic mechanisms leading to sporadic PHPT, as well as on risk factors for complications of the disorder. Future work that advances our knowledge in these areas will improve the management of the disorder.

Use of Cinacalcet and 99mTc-sestamibi Imaging During Pregnancy.

A case report is reviewed, in which two nontraditional interventions were used in a patient with gestational primary hyperparathyroidism: cinacalcet and technetium-99m methoxyisobutylisonitrile imaging. The rationale for these decisions is considered in view of the available data.

Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women.

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.

Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism.

Restoration of the euparathyroid state is associated with improvement of bone dynamics both in hypoparathyroidism and primary hyperparathyroidism. To date, no study has directly compared these two groups following correction of parathyroid hormone excess or deficiency. The study was designed to investigate changes in bone mineral density and trabecular bone score with restoration of the euparathyroid state by parathyroidectomy in primary hyperparathyroidism or recombinant parathyroid hormone [rhPTH(1-84)] replacement in hypoparathyroidism. This was a 2-year prospective intervention study in which we evaluated areal bone mineral density by DXA and trabecular bone score in 52 hypoparathyroid patients on rhPTH(1-84) replacement and 27 patients with primary hyperparathyroidism who underwent parathyroidectomy. We evaluated changes in areal bone mineral density by DXA and trabecular bone score at baseline, 6, 12, 18, and 24 months. After parathyroidectomy, areal bone mineral density increased from baseline at the lumbar spine and total hip at 6 months and at the femoral neck at 12 months, while there were no changes at the distal 1/3 radius. Treatment with rhPTH(1-84) was associated with significant increases in lumbar spine and decreases in distal 1/3 radius areal bone mineral density by 18 months in hypoparathyroid patients. At this time point, hypoparathyroid subjects demonstrated a significant increase in trabecular bone score from baseline, while there were no significant changes in trabecular bone score following parathyroidectomy. Bone mineral density increases both with administration of parathyroid hormone in a state of parathyroid hormone deficiency or removal of parathyroid hormone in a state of parathyroid hormone excess. However, only hypoparathyroid patients on rhPTH(1-84) appeared to have improvements in micro-architectural pattern as assessed by trabecular bone score.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

Fibroblast Growth Factor 23 and Cause-Specific Mortality in the General Population: The Northern Manhattan Study.

CONTEXT: An elevated fibroblast growth factor (FGF) 23 is an independent risk factor for cardiovascular disease and mortality in patients with kidney disease. The relationship between FGF23 and cause-specific mortality in the general population is unknown. OBJECTIVE: To investigate the association of elevated FGF23 with the risk of cause-specific mortality in a racially and ethnically diverse urban general population. DESIGN, SETTING, PARTICIPANTS: The Northern Manhattan Study is a population-based prospective cohort study. Residents who were > 39 years old and had no history of stroke were enrolled between 1993 and 2001. Participants with available blood samples for baseline FGF23 testing were included in the current study (n = 2525). MAIN OUTCOME MEASURES: Cause-specific death events. RESULTS: A total of 1198 deaths (474 vascular, 612 nonvascular, 112 unknown cause) occurred during a median follow-up of 14 years. Compared to participants in the lowest FGF23 quintile, those in the highest quintile had a 2.07-fold higher risk (95% confidence interval [CI], 1.45, 2.94) of vascular death and a 1.64-fold higher risk (95% CI, 1.22, 2.20) of nonvascular death in fully adjusted models. Higher FGF23 was independently associated with increased risk of mortality due to cancer, but only in Hispanic participants (hazard ratio per 1 unit increase in ln FGF23 of 1.87; 95% CI, 1.40, 2.50; P for interaction = .01). CONCLUSIONS: Elevated FGF23 was independently associated with increased risk of vascular and nonvascular mortality in a diverse general population and with increased risk of cancer death specifically in Hispanic individuals.

Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes.

CONTEXT: Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D have not been clearly established. OBJECTIVE: The objective of the study was to determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a tertiary medical center. PATIENTS: Sixteen postmenopausal women with T2D and 19 matched controls participated in the study. MAIN OUTCOME MEASURES: Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF, and circulating bone turnover markers were measured. RESULTS: BMSi was reduced by 9.2% in T2D (P = .02) and was inversely associated with the duration of T2D (r = -0.68, P = .004). Increased SAF was associated with reduced BMSi (r = -0.65, P = .006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r = -0.63, P = .01) in T2D, whereas no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (P = .03). CONCLUSIONS: Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.

Effect of Low Vitamin D on Volumetric Bone Mineral Density, Bone Microarchitecture, and Stiffness in Primary Hyperparathyroidism.

CONTEXT: Patients with 25-hydroxyvitamin D deficiency (25OHD <20 ng/ml) and primary hyperparathyroidism (PHPT) have more severe disease reflected by higher serum PTH levels compared to those with vitamin D levels in the insufficient (20-29 ng/ml) or replete range (≥ 30 ng/ml). OBJECTIVE: To study the effect of low vitamin D in PHPT on volumetric bone mineral density (vBMD), bone microarchitecture, and bone strength. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of 99 PHPT patients with and without 25OHD insufficiency and deficiency from a university hospital. OUTCOME MEASURES: Bone microarchitecture and strength were assessed with high-resolution peripheral quantitative computed tomography (HRpQCT), microfinite element analysis, and individual trabecula segmentation. RESULTS: In this cohort, 25OHD levels were deficient in 18.1%, insufficient in 35.4% and replete in 46.5%. Those with lower 25OHD levels had higher PTH (P < .0001), were younger (P = .001) and tended to weigh more (P = .053). There were no age-, weight- and sex-adjusted between-group differences (<20 vs 20-29 vs ≥ 30 ng/ml) in any HRpQCT, microfinite element analysis, or individual trabecula segmentation indices. Because few participants had 25OHD below 20 ng/ml, we also compared those with 25OHD below 30 vs at least 30 ng/ml and found only a trend toward lower adjusted cortical vBMD (3.1%, P = .08) and higher cortical porosity (least squares mean ± SEM 7.5 ± 0.3 vs 6.6 ± 0.3%, P = .07) at the tibia but not the radius. Stiffness did not differ at either site. In multiple regression analysis, 25OHD accounted for only three of the 49.2% known variance in cortical vBMD; 25OHD was not significant in the model for cortical porosity at the tibia. CONCLUSION: Low 25OHD levels are associated with higher PTH levels in PHPT, but contrary to our hypothesis, these differences did not significantly affect vBMD or microarchitecture, nor did they result in lower stiffness. Low vitamin D in PHPT using current 25OHD thresholds for insufficiency and deficiency did not significantly affect skeletal integrity as assessed by HRpQCT.

Effect of Parathyroidectomy Upon Left Ventricular Mass in Primary Hyperparathyroidism: A Meta-Analysis.

CONTEXT: Primary hyperparathyroidism (PHPT) has been associated with increased left ventricular mass (LVM) in many studies. Most studies have been inadequately powered to assess the effect of parathyroidectomy (PTX) on LVM. OBJECTIVE: The objective was to evaluate whether PTX has a benefit on LVM in patients with PHPT. DATA SOURCES: Sources included PubMed, Medline, Cochrane Library, clinicaltrials.gov, review articles, and abstracts from meetings. STUDY SELECTION: Eligible studies included prospective studies of PTX vs observation or PTX alone in patients with PHPT who had LVM measured by echocardiography. DATA EXTRACTION: Two investigators independently identified eligible studies and extracted data. Random-effects models were used to obtain final pooled estimates. DATA SYNTHESIS: Fifteen studies (four randomized controlled trials and 11 observational) of 457 participants undergoing PTX were included. PTX was associated with a reduction in LVM (crude Hedges gu -0.290 ± 0.070, 95% confidence interval [CI] -0.423 to -0.157) of 11.6 g/m(2) (12.5%) on average. Effect size estimates differed by study duration (P < .001), with improvements seen in shorter (≤ 6 mo) but not longer studies. There was a trend toward greater improvement in observational studies vs randomized controlled trials (P = .07), and both serum calcium and PTH were higher in the former. Using random-effects models, the estimated effect size remained significant (Hedges gu -0.250, 95% CI -0.450 to -0.050). Higher preoperative PTH but not calcium was associated with a greater decline in LVM (ß = -.039, 95% CI -0.075 to -0.004). CONCLUSION: PTX reduced LVM in PHPT, and higher preoperative PTH levels were associated with greater improvements. Because the benefit was limited to short-term studies and PHPT disease severity was not independent of study design, further work is needed to clarify the factors that influence the change in LVM and whether the benefit persists beyond 6 months after PTX. Although the clinical significance of the LVM improvement is unclear, these data indicate that PTH may underlie increased LVM in PHPT.