Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. OBJECTIVE AND DESIGN: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). PARTICIPANTS AND SETTING: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. METHODS AND OUTCOMES: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. RESULTS: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. CONCLUSIONS: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.

Preoperative imaging predicts change in bone mineral density after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Bone Mineral Density (BMD) improves after parathyroidectomy (PTX), but data on factors that predict bone recovery are limited. No studies have evaluated if preoperative imaging findings are associated with postoperative change in BMD. We hypothesized that larger, metabolically active glands would be associated with greater increase in BMD after PTX. METHODS: Patients with primary hyperparathyroidism (PHPT) who underwent combined Tc-99m sestamibi and 4D-CT imaging prior to PTX and had pre- and post-operative dual-energy X-ray absorptiometry (DXA) at our institution were considered for inclusion. Retrospectively, data were collected from imaging studies on each parathyroid gland, including estimated weight (using the ellipsoid formula) and contrast enhancement on 4D-CT as well as sestamibi avidity. Total estimated parathyroid weight was calculated. The main outcome measure was the percent change in BMD at the lumbar spine (LS) from pre- to post-operative DXA. Predictors of change in BMD at the LS were assessed. RESULTS: Complete DXA data was available in 25 patients. Median total parathyroid weight on 4D-CT was 270 mg, and mean change in BMD at the LS was 2.4 ± 4.3%. The increase in BMD was best predicted by higher preoperative serum calcium (p = 0.01), greater estimated parathyroid weight (p = 0.001), sestamibi avidity (p = 0.03), and increased time between DXA scans (p = 0.03) in the multivariable model (R2 = 0.79, p < 0.0001). CONCLUSION: In PHPT, higher preoperative serum calcium, parathyroid gland weight on imaging, and sestamibi avidity are associated with greater increases in BMD after curative PTX. These findings suggest that larger, metabolically active adenomas may mobilize more calcium from bone.

Vitamin D Status and COVID-19 Clinical Outcomes in Hospitalized Patients.

Context: Populations severely affected by COVID-19 are also at risk for vitamin D deficiency. Common risk factors include older age, chronic illness, obesity, and non-Caucasian race. Vitamin D deficiency has been associated with risk for respiratory infections and failure, susceptibility and response to therapy for enveloped virus infection, and immune-mediated inflammatory reaction.Objective: To test the hypothesis that 25-hydroxyvitamin D[25(OH)D] deficiency is a risk factor for severity of COVID-19 respiratory and inflammatory complications.Design: We examined the relationship between prehospitalization 25(OH)D levels (obtained 1-365 days prior to admission) and COVID-19 clinical outcomes in 700 COVID-19 positive hospitalized patients.Primary Outcomes: Discharge status, mortality, length of stay, intubation status, renal replacement.Secondary Outcomes: Inflammatory markers.Results: 25(OH)D levels were available in 93 patients [25(OH)D:25(IQR:17-33)ng/mL]. Compared to those without 25(OH)D levels, those with measurements did not differ in age, BMI or distribution of sex and race, but were more likely to have comorbidities. Those with 25(OH)D < 20 ng/mL (n = 35) did not differ from those with 25(OH)D ≥ 20 ng/mL in terms of age, sex, race, BMI, or comorbidities. Low 25(OH)D tended to be associated with younger age and lower frequency of preexisting pulmonary disease. There were no significant between-group differences in any outcome. Results were similar in those ≥50 years, in male/female-only cohorts, and when differing 25(OH)D thresholds were used (<15 ng/mL and <30 ng/mL). There was no relationship between 25(OH)D as a continuous variable and any outcome, even after controlling for age and pulmonary disease.Conclusions: These preliminary data do not support a relationship between prehospitalization vitamin D status and COVID-19 clinical outcomes.

Current anti-depressant use is associated with cortical bone deficits and reduced physical function in elderly women.

BACKGROUND: Anti-depressants, particularly selective serotonin reuptake inhibitors (SSRIs), are associated with an increased risk of fracture. The mechanism is unclear and may be due to effects on bone metabolism, muscle strength, falls or other factors. It is unknown if serotonin norepinephrine reuptake inhibitors (SNRIs) have similar effects. METHODS: We compared musculoskeletal health in current female anti-depressant users and non-users from a population-based multiethnic (35.6% black, 22.3% white and 42.1% mixed) cohort study of adults ≥65 years old in New York (N = 195) using dual x-ray absorptiometry (DXA), trabecular bone score (TBS), vertebral fracture assessment (VFA), high resolution peripheral quantitative computed tomography (HR-pQCT), body composition, and grip strength. RESULTS: Current anti-depressant users were more likely to be white than non-white (OR 1.9, 95% CI 1.2-2.9) and were shorter than non-users, but there were no differences in age, weight, BMI, physical activity, calcium/vitamin D intake, falls or self-rated health. There were more pelvic fractures in current vs. non-users (7.1% vs. 0%, p = 0.04). Age- and weight-adjusted T-score by DXA was lower in current users at the 1/3-radius (-1.6 ± 1.1 vs. -1.0 ± 1.4, p = 0.04) site only. There was no difference in TBS, vertebral fractures or fat/lean mass by DXA. Age- and weight-adjusted grip strength was 13.3% lower in current users vs. non-users (p = 0.04). By HR-pQCT, age- and weight-adjusted cortical volumetric BMD (Ct. vBMD) was 4.8% lower in users vs. non-users at the 4% radius site (p = 0.007). A similar cortical pattern was seen at the proximal (30%) tibia. When assessed by anti-depressant class, deteriorated cortical microstructure was present only in SSRI users at the radius and only in SNRI users at the proximal tibia. CONCLUSIONS: Anti-depressant use is associated with cortical deterioration and reduced physical function, but effects may be class-specific. These findings provide insight into the mechanism by which anti-depressants may contribute to the increased fracture risk in older women.

Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease.

BACKGROUND & AIMS: Guidelines advise measurement of bone mineral density (BMD) in patients with a diagnosis of celiac disease. The lumbar spine (LS) and hip sites are usually measured. Although skeletal sites rich in trabecular bone are believed to be vulnerable to osteoporosis in patients with celiac disease, most studies have not measured the cortical distal 1/3-radius. METHODS: We collected data from 721 patients (mean age, 43.6 years; 68.4% female) with celiac disease who underwent 3-site dual energy x-ray absorptiometry (DXA, at a median 1.22 years after diagnosis). We assessed skeletal site- and sex-specific osteoporosis prevalence and the incremental utility of 1/3-radius measurement by DXA. RESULTS: Mean T- and Z-scores were normal in patients, but 43.3% had osteopenia and 19.6% had osteoporosis. Osteoporosis was found in 12.1% of patients at the LS, 5.3% of patients at the total hip, 7.6% of patients at the femoral neck, and 11.5% of patients at the 1/3-radius. A greater degree of villous atrophy at diagnosis was associated with male sex and lower T-scores at the 1/3-radius (P = .03), but not other skeletal sites. Isolated forearm osteoporosis was detected in 4.9% of patients. A higher proportion of patients with isolated forearm osteoporosis were male and had a greater weight and body mass index (all P < .01, compared to patients with osteoporosis only at other sites). Z-scores were lower at the LS and 1/3-radius and osteoporosis was more common in men than women. In men, the 1/3-radius was the most frequent site for osteoporosis. Among patients 50 years or older, isolated forearm osteoporosis was present in 10.7%. CONCLUSIONS: Based on DXA analysis of patients with celiac disease, the prevalence of osteoporosis appears to be underestimated-particularly in men when BMD at the 1/3-radius is not measured. Degree of villous atrophy is associated with BMD at the 1/3-radius and nearly 5% of patients have osteoporosis limited to that site. Recommendations for osteoporosis screening in patients with celiac disease should include measurement of the distal 1/3-radius in addition to the hip and LS.

Endocrine complications of celiac disease: a case report and review of the literature.

PURPOSE: The purpose of this article is to review recent literature regarding endocrine disorders related to celiac disease (CD). METHODS: We describe a case report and review existing literature on the endocrine manifestations of CD. RESULTS: CD is an autoimmune disorder characterized by intestinal inflammation in response to gluten. CD can cause a wide range of extra-intestinal complications, including endocrine manifestations. Metabolic bone disease including osteoporosis and osteopenia, vitamin D deficiency, secondary hyperparathyroidism and less frequently osteomalacia can be seen. In CD, fracture risk is increased by 30-40%, while risk for hip fracture is approximately doubled. The risk for other endocrine disorders, particularly autoimmune endocrinopathies, is also increased in those with CD compared to the general population. Epidemiologic data indicate the risk for hypothyroidism is 3-4 times higher among those with CD, while risk of type 1 diabetes is greater than double. Risk for primary adrenal insufficiency is a striking 11-fold higher in those with versus without CD, though the absolute risk is low. Fertility is reduced in women with CD before diagnosis by 37% while male fertility in the absence of hypogonadism does not appear to be affected. Other endocrine conditions including hyperthyroidism, ovarian failure, androgen insensitivity, impaired growth and growth hormone deficiency and autoimmune polyendocrine syndromes have also been associated with CD. CONCLUSIONS: CD is associated with a wide range of endocrine manifestations.

Bone mineral density changes after parathyroidectomy are dependent on biochemical profile.

BACKGROUND: Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism. METHODS: A retrospective analysis of 92 primary hyperparathyroidism patients who underwent PTX between 2004 and 2012 with pre- and post-PTX dual-energy x-ray absorptiometry was performed. Within-person changes in BMD pre- and post-PTX were analyzed using log linear mixed models, stratified by biochemical status. RESULTS: Bone mineral density increased post-PTX in the whole cohort at the lumbar spine (+2.5%), femoral neck (+2.1%), and total hip (+1.9%) and decreased at the one-third radius (-0.9%). On comparison of BMD changes by profile, BMD increased in those with the typical profile at the lumbar spine (3.2%), femoral neck (2.9%), and total hip (2.9%) but declined at the one-third radius (-1.5%). In contrast, BMD improved only at the femoral neck (4.3%) in the normohormonal group and did not change at any site in the normocalcemic group. The typical group had a greater increase in BMD over time at the femoral neck and total hip compared with normocalcemic patients. CONCLUSION: Our results indicate that the skeletal benefit of PTX was attenuated in normocalcemic and normohormonal patients, suggesting that skeletal changes after PTX may depend on biochemical profile.

Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study.

OBJECTIVE: To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. RESEARCH DESIGN AND METHODS: The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. RESULTS: OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (ß = -0.12 per SD increment; P = 0.004) and CTX (ß = -0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. CONCLUSIONS: In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.

Primary hyperparathyroidism: recent advances.

PURPOSE OF REVIEW: The purpose of this review is to describe recent advances and changes in the evaluation and management of primary hyperparathyroidism (PHPT). RECENT FINDINGS: Although it has long been recognized that asymptomatic PHPT is associated with bone loss, particularly at cortical skeletal sites when evaluated with dual-energy X-ray absorptiometry, new imaging techniques suggest that trabecular skeletal deterioration as well as clinically silent vertebral fractures and nephrolithiasis are common. Nonclassical targets of asymptomatic PHPT as well as the effect of vitamin D deficiency and treatment upon PHPT presentation have been the subject of recent intense investigation. Randomized clinical trials are now available regarding the effect of parathyroidectomy (PTX) upon both classical and nonclassical target organs. They have confirmed results from observational studies with regard to the skeletal benefits of PTX but have not consistently shown improvements in nonclassical symptoms. SUMMARY: These findings have led to recommendations for more extensive renal and skeletal evaluation and broader criteria for PTX in PHPT. In addition to dual-energy X-ray absorptiometry, vertebral and renal imaging is recommended. When available, trabecular imaging techniques may be helpful. PTX criteria now include subclinical kidney stones, vertebral fractures and hypercalciuria, in addition to those based on age, serum calcium, bone densitometry and renal function.

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.

Parathyroid hormone is related to QT interval independent of serum calcium in patients with coronary artery disease.

BACKGROUND: Elevated serum parathyroid hormone (PTH) is associated with increased risk of cardiovascular death, including sudden cardiac death, in patients with and without parathyroid disease. In small studies, PTH levels have been associated with changes in cardiac conduction and repolarization. Changes in the corrected QT interval (QTc) in particular are thought to be mediated by the effect of PTH on serum calcium. There is limited evidence to suggest PTH may affect cardiac physiology independent of its effects on serum calcium, but there is even less data linking PTH to changes in electrical conduction and repolarization independent of serum calcium. METHODS: ECG data were examined from the PULSE database-an observational cohort study designed to examine depression after acute coronary syndromes (ACS) at a single, urban American medical center. In all, 407 patients had PTH and ECG data for analysis. RESULTS: The QTc was longer in patients with elevated PTH levels compared with those without elevated PTH levels (451 ± 38.6 ms vs. 435 ± 29.8 ms; p < .001). The difference remained statistically significant after controlling for calcium, vitamin D, and estimated glomerular filtration rate (p = .007). Inclusion of left ventricular ejection fraction in the model attenuated the association (p = .054), suggesting that this finding may be partly driven by changes in cardiac structure. CONCLUSIONS: In one of the largest series to examine PTH, calcium, and QT changes, we found that elevated PTH is associated with longer corrected QT interval independent of serum calcium concentration in ACS survivors.

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.

Predictors of improvement in bone mineral density after celiac disease diagnosis.

PURPOSE: Low bone density is frequently found in patients newly diagnosed with celiac disease (CD), and improvement is variable. This study was performed to assess changes in bone mineral density (BMD) by dual x-ray absorptiometry (DXA) at the lumbar spine, hip, and distal one-third radius as well as clinical predictors of BMD changes after the diagnosis and treatment of CD. METHODS: Adult CD patients who had serial DXA at the Celiac Disease Center at Columbia University Medical Center were included (N = 103). We assessed within-person changes in BMD with paired t-tests. Multiple regression was utilized to assess baseline clinical and laboratory predictors of BMD improvement after diagnosis and treatment. RESULTS: The mean age of our sample was 45.6 years (±SD 15.1) and 60% were female. After a median follow-up of 21 months, lumbar spine BMD increased by 1.7 ± 5.5% (p = 0.006) after CD diagnosis. There was a similar trend at the total hip (1.6 ± 6.3%, p = 0.06), but no change at the femoral neck or distal one-third radius. Lower baseline serum calcium predicted a greater increase in lumber spine BMD (ß = -0.0470 g/cm2, p = 0.002). At the hip, higher baseline creatinine clearance (ß = 0.005, p = 0.02) was associated with greater gains in BMD. CONCLUSION: BMD increases at the lumbar spine after the diagnosis of CD and greater BMD improvement is associated with lower baseline serum calcium. This suggests that those with the lowest calcium, which is likely a surrogate for the greatest malabsorption, may have the greatest potential for improvement in skeletal health after treatment of CD.

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.

Seasonal Variability in Vitamin D Levels No Longer Detectable in Primary Hyperparathyroidism.

CONTEXT: Seasonal variability in 25-hydroxyvitamin D [25(OH)D] and PTH levels in the general population has been associated with differences in bone turnover markers, bone density, and fracture risk. Seasonal variability in 25(OH)D and PTH levels has also been reported in primary hyperparathyroidism (PHPT). OBJECTIVE: Given the widespread use of vitamin D supplements, we sought to determine whether patients with PHPT still demonstrated seasonal variation in 25(OH)D levels. DESIGN AND SETTING: This cross-sectional study was conducted at a university medical center at a Northeastern U.S. latitude (New York, NY). PATIENTS: One hundred patients with PHPT participated in the study. OUTCOME MEASURES: We assessed vitamin D supplement use and seasonal variation in serum 25(OH)D. RESULTS: Patients had PHPT ([mean ± SD] calcium, 10.8 ± 1.0 mg/dL; PTH, 85 ± 48 pg/mL) with a mean 25(OH)D level of 29 ± 10 ng/mL. Although only one fifth of participants had vitamin D deficiency (19% < 20 ng/mL), more than half were either deficient or insufficient (54% < 30 ng/mL). Sun exposure varied by season, but there were no seasonal differences in levels of 25(OH)D, PTH, bone markers, or bone mineral density, or in the prevalence of 25(OH)D less than 20 or less than 30 ng/mL. Most of the participants (65%) took supplemental vitamin D (dose among users: mean, 1643 ± 1496 IU; median, 1000 IU daily), and supplement users had markedly better vitamin D status than nonusers (25(OH)D < 20 ng/mL: 8 vs 40%; P < .0001; < 30 ng/mL: 40 vs 80%; P = .0001; ≥ 30 ng/mL: 60 vs 20%; P = .0001). CONCLUSIONS: We found no evidence of seasonal variation in 25(OH)D levels or PHPT disease severity in the Northeastern United States. This change is likely due to widespread high vitamin D supplement intake, which has resulted in better vitamin D status among supplement users and can mask the effect of season on serum 25(OH)D levels.

Vitamin D in Primary Hyperparathyroidism: Effects on Clinical, Biochemical, and Densitometric Presentation.

CONTEXT: Vitamin D (25-hydroxyvitamin D [25OHD]) deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common in primary hyperparathyroidism (PHPT), but data regarding their skeletal effects in PHPT are limited. OBJECTIVE: The objective was to evaluate the association between 25OHD levels and PHPT severity. DESIGN, SETTINGS, AND PARTICIPANTS: This is a cross-sectional analysis of 100 PHPT patients with and without 25OHD insufficiency and deficiency from a university hospital setting. OUTCOME MEASURES: We measured calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual x-ray absorptiometry. RESULTS: Lower 25OHD was associated with some (PTH: r = -0.42; P < .0001; 1,25-dihydroxyvitamin D: r = -0.27; P = .008; serum PO4: r = 0.31; P = .002) but not all (serum/urine calcium) indicators of PHPT severity. Lower 25OHD was also associated with younger age, higher body mass index, male gender, better renal function, and lower vitamin D intake. Comparison of those with deficient (<20 ng/mL; 19%) vs insufficient (20-29 ng/mL; 35%) vs replete (≥30 ng/mL; 46%) 25OHD demonstrated more severe PHPT as reflected by higher PTH (mean ± SEM, 126 ± 10 vs 81 ± 7 vs 72 ± 7 pg/mL; P < .0001) but no difference in nephrolithiasis, osteoporosis, fractures, serum or urinary calcium, bone turnover markers, or BMD after adjustment for age and weight. In women, T-scores at the 1/3 radius were lower in those with 25OHD of 20-29 ng/mL, compared to those who were vitamin D replete (P = .048). In multiple regression modeling, 25OHD (but not PTH) was an independent predictor of 1/3 radius BMD. CONCLUSION: Vitamin D deficiency is associated with more severe PHPT as reflected by PTH levels, but effects on BMD are limited to the cortical 1/3 radius and are quite modest. These data support international guidelines that consider PHPT patients with 25OHD <20 ng/mL to be deficient. However, in this cohort with few profoundly vitamin D-deficient patients, vitamin D status did not appear to significantly impact clinical presentation or bone density.

Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.

OBJECTIVE: This report summarizes data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT. PARTICIPANTS: This subgroup was constituted by the Steering Committee to address key questions related to the presentation of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. EVIDENCE: Data from the 5-year period between 2008 and 2013 were presented and discussed to determine whether they support changes in recommendations for surgery or nonsurgical follow-up. CONSENSUS PROCESS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup came to agreement on what changes in the recommendations for surgery or nonsurgical follow-up of asymptomatic PHPT should be made to the Expert Panel. CONCLUSIONS: 1) There are limited new data available on the natural history of asymptomatic PHPT. Although recognition of normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism) is increasing, data on the clinical presentation and natural history of this phenotype are limited. 2) Although there are geographic differences in the predominant phenotypes of PHPT (symptomatic, asymptomatic, normocalcemic), they do not justify geography-specific management guidelines. 3) Recent data using newer, higher resolution imaging and analytic methods have revealed that in asymptomatic PHPT, both trabecular bone and cortical bone are affected. 4) Clinically silent nephrolithiasis and nephrocalcinosis can be detected by renal imaging and should be listed as a new criterion for surgery. 5) Current data do not support a cardiovascular evaluation or surgery for the purpose of improving cardiovascular markers, anatomical or functional abnormalities. 6) Some patients with mild PHPT have neuropsychological complaints and cognitive abnormalities, and some of these patients may benefit from surgical intervention. However, it is not possible at this time to predict which patients with neuropsychological complaints or cognitive issues will improve after successful parathyroid surgery.