Risk Of Primary Hyperparathyroidism Research Articles

Evaluation for primary hyperparathyroidism after radioactive iodine treatment in patients with Graves' disease

BackgroundRetrospective studies are conflicting regarding the risk of primary hyperparathyroidism after radioactive iodine treatment. We hypothesized that primary hyperparathyroidism rates are greater after radioactive iodine than after thyroidectomy and that patients with hypercalcemia after treatment for Graves' disease are not adequately evaluated for primary hyperparathyroidism, contributing to underdiagnosis of radioactive iodine–associated primary hyperparathyroidism. MethodsThis retrospective review considers patients undergoing radioactive iodine or thyroidectomy for Graves' disease at a tertiary referral center between January 1, 2000, and January 31, 2022. Patients were identified using a hospital-based cohort discovery tool; exclusions included history of head/neck radiation, primary hyperparathyroidism/parathyroidectomy, renal dysfunction diagnoses, or treatment with both radioactive iodine and thyroidectomy. Patients with an elevated calcium (>10.2 mg/dL) level measured after treatment were classified as “incomplete workup” (no parathyroid hormone), “likely primary hyperparathyroidism” (parathyroid hormone >40 pg/dL), or “unlikely primary hyperparathyroidism” (parathyroid hormone <40 pg/dL). ResultsOf 900 patients, 468 (52%) had been treated with radioactive iodine and 432 (48%) with thyroidectomy. At a median follow-up of 9.39 years (interquartile range, 5.12–13.25), 25% (n = 224) of patients did not have a serum calcium measured and 52 (8%, n = 676) patients had an elevated calcium level. Hypercalcemia was more common after radioactive iodine (10%) than thyroidectomy (6%, P = .061). Of patients with hypercalcemia, 33 (63%) were “incomplete workup,” 5 (10%) were “likely primary hyperparathyroidism,” and 14 (27%) were “unlikely primary hyperparathyroidism.” There was no difference in primary hyperparathyroidism workup rates between patients treated with radioactive iodine (n = 23) and thyroidectomy (n = 10, P = .389). ConclusionsPatients treated with radioactive iodine for Graves' disease may experience an elevated rate of hypercalcemia, but the majority are not adequately evaluated for primary hyperparathyroidism. Patients with a history of radioactive iodine should undergo regular calcium screening and, if elevated, appropriate workup for primary hyperparathyroidism.

Cardiovascular risk in primary hyperparathyroidism

Cardiovascular risk in primary hyperparathyroidism

Carotid intima-media thickness in surgically or conservatively managed patients with primary hyperparathyroidism.

Current evidence of cardiovascular (CV) risk in primary hyperparathyroidism (PHPT) is still inconsistent. To prospectively investigate changes of early atherosclerosis in patients with PHPT undergoing parathyroidectomy (PTx) or conservative management, according to Consensus criteria. Biochemical parameters of PHPT, CV risk factors (systolic and diastolic blood pressure-BP-, total-, HDL- and LDL-cholesterol, triglyceride, glycosilated hemoglobin, and HOMA-IR), and carotid intima-media thickness (IMT) and plaque were assessed in 52 consecutive postmenopausal PHPT patients both at baseline and ≥24 months after surgery (PTx: n = 22) or conservative management (no-PTx: n = 30). At baseline, PTx and no-PTx showed comparable age, BMI, renal function, 25(OH)D levels, and did not differ for CV risk factors, IMT and plaques, nor for the prevalence of smoking, diabetes mellitus, antihypertensive or statin therapy, while differing for all parameters characterizing PHPT. Follow-up length in PTx was longer (p = 0.004) than in no-PTx. Parameters characterizing PHPT significantly improved ≥24 months after surgery, whereas in no-PTx serum phosphate slightly decreased and PTH increased. Systolic and diastolic BP increased at follow-up in both groups, while other CV risk factors did not significantly vary. In PTx IMT did not significantly vary after surgery (0.85 ± 0.14 to 0.89 ± 0.22 mm, p = 0.366), whereas it significantly increased in no-PHPT (0.80 ± 0.18 to 0.93 ± 0.23 mm, p = 0.008), even adjusting for BP values. Plaque prevalence and incidence did not significantly differ in the two groups. Our results suggest that in postmenopausal PHPT patients subclinical atherosclerosis could be halted by PTx, whereas it worsens over time in not operated patients with milder disease.

A Pilot Study of the Association VDR Polymorphisms With Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder characterized by autonomous parathyroid hormone (PTH) production from one or more parathyroid glands and hypocalcemia. Vitamin D through its receptor is a principal regulator of parathyroid glands function. VDR gene polymorphisms, which affect the expression or structure of VDR protein, may be involved in the genetic pathogenesis of PHPT. The aim of this study was to investigate the role of FokI, ApaI, TaqI, and BsmI VDR gene polymorphisms as genetic predisposing factors for PHPT. Fifty unrelated patients with sporadic PHPT and an equal number of corresponding ethnicity, sex and age range healthy volunteers were enrolled in the study. Genotyping was performed with polymerase chain reaction and restriction fragment length polymorphism assay. Statistically significant difference was observed in TaqI genotype distribution between PHPT patients and controls, while no association was detected for the other studied polymorphisms. TaqI TT and TC genotypes may be associated with PHPT risk in Greek population. Further independent studies are needed to replicate and validate the role of VDR TaqI polymorphism in PHPT predisposition.

Germline CDKN1B variant type and site are associated with phenotype in MEN4.

Multiple endocrine neoplasia 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome clinically hallmarked by primary hyperparathyroidism (PHPT), pituitary adenoma (PitAd), and neuroendocrine tumors (NET), clinically overlapping MEN1. The underlying mutated gene - CDKN1B, encodes for the cell-cycle regulator p27. Possible genotype-phenotype correlations in MEN4 have not been thoroughly assessed. Prompted by the findings in three Israeli MEN4 kindreds, we performed a literature review on published and unpublished data from previously reported MEN4/CDKN1B cases. Univariate analysis analyzed time-dependent risks for developing PHPT, PitAd, or NET by variant type and position along the gene. Overall, 74 MEN4 cases were analyzed. PHPT risk was 53.4% by age 60 years (mean age at diagnosis age 50.6 ± 13.9 years), risk for PitAd was 23.2% and risk for NET was 16.2% (34.4 ± 21.4 and 52.9 ± 13.9 years, respectively). The frameshift variant p.Q107fs was the most common variant identified (4/41 (9.7%) kindreds). Patients with indels had higher risk for PHPT vs point mutations (log-rank, P = 0.029). Variants in codons 94-96 were associated with higher risk for PHPT (P < 0.001) and PitAd (P = 0.031). To conclude, MEN4 is clinically distinct from MEN1, with lower risk and older age for PHPT diagnosis. We report recurrent CDKN1B frameshift variants and possible genotype-phenotype correlations.

Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism.

Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT. Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded. Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001). Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors’ improvements on cardiovascular events.

Evaluation of subclinical cardiovascular disease by carotid intima media thickness, epicardial adipose tissue thickness, serum endocan, and nesfatin-1 levels in patients with primary hyperparathyroidism.

Data on the presence and extent of cardiovascular disease (CVD) risk in primary hyperparathyroidism (PHPT) are conflicting. In our study, we aimed to investigate the increased CVD risk in patients with PHPT by carotid intima-media thickness (CIMT), epicardial adipose tissue (EAT) thickness, and serum levels of endocan and nesfatin-1. Patients with PHPT (n = 44) and age- and sex-matched healthy control subjects (n = 40) were enrolled in this study. Demographic data of the participants were questioned. Serum endocan and nesfatin-1 concentrations were assessed using commercially available ELISA kits. Noninvasive measurements of CIMT and EAT thickness were made with high-resolution ultrasonography and B-mode echocardiography. There was no statistically significant difference in serum endocan and nesfatin-1 levels and EAT thickness in the PHPT group compared to controls. CIMT was statistically significantly higher in the PHPT group compared to controls (p = 0.001). A negative correlation was found between PTH and low-density lipoprotein cholesterol level (p = 0.001) but no significant relationship was found between other parameters. We found that CIMT is increased in patients with PHPT and consequently, CVD risk is high in these patients. More comprehensive studies are needed to identify other markers that predict increased CVD risk in patients with PHPT.

A15382 Primary Hyperparathyroidism in a Patient with Primary Aldosteronism

Objectives: Primary aldosteronism is sometimes complicated with hyperparathyroidism, which can be classified into secondary hyperparathyroidism due to increased urinary calcium excretion. Low calcium intake has been reported to be a risk of primary hyperparathyroidism, however, it is unclear whether primary aldosteronism is causally related to the occurrence of primary hyperparathyroidism. Herein, we report an interesting case of primary aldosteronism complicated with primary hyperparathyroidism. Methods: This is a case report. Results: A 58-year-old woman, who had a history of parathyroidectomy for primary hyperparathyroidism due to parathyroid adenoma at the age of 43, was admitted for 20-years history of hypertension without remarkable family histories including hypertension. Her hypertension had been gradually worsening and was not improved by the parathyroidectomy. The laboratory findings were as follows: creatinine, 0.61 mg/dL; potassium, 4.0 mEq/L; corrected alcium, 8.9 mg/dL; plasma aldosterone concentration, 156 pg/mL; plasma renin activity, < 0.1 ng/mL/h; intact PTH, 73 pg/mL. Confirmatory tests and adrenal venous sampling revealed idiopathic hyperaldosteronism. Conclusion: We presented a case of primary aldosteronism, who experienced primary hyperparathyroidism. Her hyperaldosteronism might have contributed to the development of primary hyperparathyroidism through high urinary calcium excretion. We may need to carefully consider a possible complication of not only secondary but also primary hyperparathyroidism in patients with primary aldosteronism.

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial.

Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT). The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions]. We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration rate more than 50 ml/min per 1.73 m. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks.The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9-1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) -6.3 (-9.4 to -3.3) and -3.7 (-5.7 to -1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events. In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study.

The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. Retrospective cohort study. An integrated health care delivery system. All enrollees with biochemically confirmed PHPT from 1995 to 2010. Bone mineral density (BMD) changes and fracture rate. In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (-6.6% and -7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. Retrospective study design and nonrandom treatment assignment. Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. National Institute on Aging.

Physical Activity and the Risk of Primary Hyperparathyroidism.

Primary hyperparathyroidism (P-HPTH) is relatively common and predominantly affects women. Prior studies have shown that physical activity (PA) can lower PTH levels. Our objective was to evaluate the hypothesis that lower PA is a risk factor for developing P-HPTH. This prospective cohort study included 69 621 female participants in the Nurses' Health Study I followed for 22 years. PA and other dietary and demographic exposures were quantified via detailed, and validated, biennial questionnaires. Incident P-HPTH was confirmed by medical record review after initial assessment by questionnaire. Adjusted Cox proportional hazards models were used to evaluate whether PA was an independent risk factor for developing P-HPTH. We also evaluated the risk of developing P-HPTH when combining low PA (<16 metabolic equivalent hours/week) with a previously identified independent risk factor for developing P-HPTH: low calcium intake (<800 mg/day). The relation between PA and PTH levels was evaluated in 625 participants. We confirmed 302 incident cases of P-HPTH during 1 474 993 person-years of follow-up. Participants in the highest quintile (Q) of PA had a 50% lower risk of developing P-HPTH: age-adjusted relative risks and 95% confidence intervals for incident P-HPTH by lowest to highest of PA were Q1 = 1.0 (reference); Q2 = 0.83 (0.60–1.15); Q3 = 0.84 (0.61–1.15); Q4 = 0.50 (0.34–0.74); Q5 = 0.50 (0.35–0.73); P for trend <.001. Extensive multivariable adjustments did not materially change these findings. The adjusted relative risk for developing P-HPTH among participants with the combination lower PA and lower calcium intake was 2.37-fold (1.60–3.51) higher than in participants with higher PA and higher calcium intake. PA was inversely correlated with serum PTH (ρ = −0.09, P = .03); the mean adjusted serum PTH in Q 2–5 of PA was lower than in Q 1 (36.3 vs 39.1 pg/mL, P = .02). Low physical activity may be a modifiable risk factor for developing P-HPTH in women.

Factors associated with vertebral fracture risk in patients with primary hyperparathyroidism.

To examine factors, in addition to bone mineral density (BMD), such as the common calcium-sensing receptor (CASR) gene polymorphisms, associated with vertebral fracture (VFx) risk in primary hyperparathyroidism (PHPT). A cross-sectional analysis of 266 Caucasian PHPT seen as outpatients. Serum calcium (sCa) phosphate metabolism parameters were measured. BMD was assessed by dual-energy X-ray absorptiometry (expressed as Z-score) at lumbar spine (Z-LS) and femoral neck, morphometric VFx by radiograph, and CASR A986S/R990G genotypes by PCR amplification and genomic DNA sequencing. Fractured patients (n=100, 37.6%) had lower sCa (10.8±0.7 mg/dl) and Z-LS BMD (-1.0±1.44), higher age (61±10 years), and prevalence (51%) of ≥1 S alleles of the CASR A986S single-nucleotide polymorphism (SNP; AS/SS), than those not fractured (n=166, 11.2±1.0 mg/dl, -0.57±0.97, 58±13 years, and 38% AS/SS, respectively, P<0.05 for all comparisons). Logistic regression, with VFx as dependent variable, showed independent risks associated with increased age (OR 1.03, 95% CI 1.01-1.06, P=0.006), decreased sCa (OR 1.86, 95% CI 1.28-2.7, P=0.001), and Z-LS BMD (OR 1.4, 95% CI 1.12-1.7, P=0.002) and presence of AS/SS (OR 1.8, 95% CI 1.1-2.9, P=0.05). The presence of two out of three factors (age ≥58 years, sCa <10.8 and Z-LS BMD≤-1.0, and AS/SS genotype) gave an overall OR of 4.2 (95% CI 2.25-7.85, P<0.0001). In PHPT, VFx is associated positively with age, negatively with sCa and spinal BMD, and presence of at least one copy of the CASR A986S SNP.

131I treatment for thyroid cancer and risk of developing primary hyperparathyroidism: a cohort study

To evaluate the association between (131)I therapy for thyroid cancer and risk of developing primary hyperparathyroidism. This was a nationwide population-based cohort study of patients with thyroid cancer diagnosed during the period 1997-2008. The data were obtained from the Taiwan National Health Insurance Research dataset. The cumulative (131)I dose in each patient was calculated. Hazard ratios (HRs) were calculated using a proportional hazards model to estimate the effect of (131)I therapy on the risk of developing primary hyperparathyroidism in the cohort. A total of 8,946 patients with thyroid cancer were eligible for the final analysis. Among these patients, 8 developed primary hyperparathyroidism during the follow-up period that represented 38,248 person-years giving an incidence rate of 20.9 per 10(5) person-years. (131)I was used in the treatment of 6,153 patients (68.8%) with a median cumulative dose of 3.7 GBq. The adjusted HRs were 0.21 (95% CI 0.02-1.86) and 0.46 (95% CI 0.10-2.10) for those receiving a cumulative (131)I dose of 0.1-3.6 GBq and ≥3.7 GBq, respectively, compared to no therapy. The risk of developing primary hyperparathyroidism did not increase with increasing (131)I dose (test for trend p = 0.51). No interaction was found between (131)I dose and age (p = 0.94) or (131)I dose and sex (p = 0.99). (131)I treatment for thyroid cancer did not increase risk of primary hyperparathyroidism during a 10-year follow-up in this study population. Further research with a longer follow-up period is needed to assess late adverse effects beyond 10 years.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Trabecular Bone Score (TBS)—A Novel Method to Evaluate Bone Microarchitectural Texture in Patients With Primary Hyperparathyroidism

In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. This was a cross-sectional study conducted in a referral center. Participants were 22 postmenopausal women with PHPT. Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.

A higher calcium intake reduces risk of primary hyperparathyroidism in women

A higher calcium intake reduces risk of primary hyperparathyroidism in women

A higher calcium intake reduces risk of primary hyperparathyroidism in women

A higher calcium intake reduces risk of primary hyperparathyroidism in women

Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women

Typically, in the milder form of primary hyperparathyroidism (PHPT), now seen in most countries, bone density by dual-energy X-ray absorptiometry (DXA) and detailed analyses of iliac crest bone biopsies by histomorphometry and micro-computed tomography (µCT) show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and nonvertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro-finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole-bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment, which may help to account for increased global fracture risk in PHPT.

Is the risk of primary hyperparathyroidism increased in patients with untreated breast cancer?

An increased frequency of primary hyperparathyroidism (PHP) has been reported in patients with treated breast cancer (BC). PHP has been found in about 7% of BC patients after surgery and radio-, chemio- or hormonal therapy. To evaluate the frequency of PHP in untreated BC patients. We evaluated 186 women with BC and 233 women with thyroid cancer (TC, no.=122) or benign thyroid diseases (BTD, no.=111). In all patients, serum calcium, albumin, PTH, and 25-hydroxyvitamin D (25-OH vitD) were measured before any treatment. Serum calcium concentrations were significantly higher in BC than in TC and BTD groups (median values 9.5 mg/dl, 9.3 mg/dl and 9.3 mg/dl, respectively) but, according to a logistic regression model, calcium was not significantly different between the 3 groups when age was taken into account. In all patients, serum calcium was in the normal range, indicating that no case of overt PHP was present. Five patients (1 in BC, 2 in TC, and 2 in BDT groups) had serum calcium close to the upper limit of normal range, high PTH and low 25-OH vitD, indicating a possible PHP with hypercalcemia masked by concomitant 25-OH vitD deficiency. In untreated BC group, no patient had overt PHP and 1/186 (0.5%) presented a possible PHP masked by 25-OH vitD deficiency, a PHP frequency much lower than that observed in treated BC patients. These data suggest that the treatments of BC may be responsible for the increased frequency of PHP reported in previous studies.

Coronary Microvascular Dysfunction Induced by Primary Hyperparathyroidism is Restored After Parathyroidectomy

Symptomatic primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality. However, data on the association between asymptomatic PHPT and cardiovascular risk are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic PHPT of recent onset. We studied 100 PHPT patients (80 women; age, 58±12 years) without cardiovascular disease and 50 control subjects matched for age and sex. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperemic to resting diastolic flow velocity. CFR was lower in PHPT patients than in control subjects (3.0±0.8 versus 3.8±0.7; P<0.0001) and was abnormal (≤2.5) in 27 patients (27%) compared with control subjects (4%; P=0.0008). CFR was inversely related to parathyroid hormone (PTH) levels (r=-0.3, P<0.004). In patients with CFR ≤2.5, PTH was higher (26.4 pmol/L [quartiles 1 and 3, 16 and 37 pmol/L] versus 18 [13-25] pmol/L; P<0.007), whereas calcium levels were similar (2.9±0.1 versus 2.8±0.3 mmol/L; P=0.2). In multivariable linear regression analysis, PTH, age, and heart rate were the only factors associated with CFR (P=0.04, P=0.01, and P=0.006, respectively). In multiple logistic regression analysis, only PTH increased the probability of CFR ≤2.5 (P=0.03). In all PHPT patients with CFR ≤2.5, parathyroidectomy normalized CFR (3.3±0.7 versus 2.1±0.5; P<0.0001). PHPT patients have coronary microvascular dysfunction that is completely restored after parathyroidectomy. PTH independently correlates with the coronary microvascular impairment, suggesting a crucial role of the hormone in explaining the increased cardiovascular risk in PHPT.