pHPT Patients Research Articles

Value of 123I/99mTc-sestamibi parathyroid scintigraphy with subtraction SPECT/CT in primary hyperparathyroidism for directing minimally invasive parathyroidectomy

BackgroundPrimary hyperparathyroidism/(PHPT) is one of the most common endocrinological conditions. Surgery remains the only curative option. We have evaluated the performance of double isotope 123I/99mTc-sestamibi parathyroid scintigraphy/(PS) with subtraction SPECT/CT in PHP for identifying uniglandular disease. MethodsNinety PHPT patients undergoing parathyroidectomy (December 2015–August 2016) were included. All patients were evaluated with neck ultrasound/(US), PS and SPECT/CT with a new protocol. Outcomes from imaging modalities were reported as: uniglandular disease/(UGD), multiglandular disease/(MGD), or negative, and were compared to post-operative diagnoses. ResultsPost-operatively, 72 and 18 patients had true UGD and MGD, respectively. Sensitivities and specificities of US, pinhole scintigraphy with subtraction, pinhole and SPECT/CT with subtraction, and all modalities combined were 91.7%/38.9%, 88.9%/72.2%, 93%/66.7% and 84.72%/77.78%, respectively: specificity of US + PS superior to US alone, p = 0.074. SPECT/CT enables reclassification of doubtful uptake foci. ConclusionsCombination of neck US and PS with subtraction SPECT/CT offers a higher specificity for guiding towards minimally invasive parathyroidectomy.

Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data

Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (-0.32 to 0.48) ng/dl/μU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) μU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/μU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.

Bone mineral density in primary care patients related to serum calcium concentrations: a longitudinal cohort study from Sweden

Objective: Elevated calcium concentration is a commonly used measure in screening analyses for primary hyperparathyroidism (pHPT) and cancer. Low bone mineral density (BMD) and osteoporosis are common features of pHPT and strengthen the indication for parathyroidectomy. It is not known whether an elevated calcium concentration could be a marker of low BMD in suspected pHPT patients with a normal parathyroid hormone concentration.Purpose: To study if low BMD and osteoporosis are more common after ten years in patients with elevated compared with normal calcium concentrations at baseline.Design: Prospective case control study.Setting: Primary care, southern Sweden.Subjects: One hundred twenty-seven patients (28 men) with baseline elevated, and 254 patients (56 men) with baseline normal calcium concentrations, mean age 61 years, were recruited. After ten years, 77% of those still alive (74 with elevated and 154 with normal calcium concentrations at baseline) participated in a dual energy x-ray absorptiometry measurement for BMD assessment and analysis of calcium and parathyroid hormone concentrations.Main outcome measures: Association between elevated and normal calcium concentration at base-line and BMD at follow-up. Correlation between calcium and parathyroid hormone concentrations and BMD at follow-up.Results: A larger proportion of the patients with elevated baseline calcium concentrations who participated in the follow-up had osteoporosis (p value = 0.036), compared with the patients with normal concentrations. In contrast, no correlation was found between calcium or parathyroid hormone concentrations and BMD at follow-up.Conclusions: In this study, patients with elevated calcium concentrations at baseline had osteoporosis ten years later more often than controls (45% vs. 29%), which highlights the importance of examining these patients further using absorptiometry, even when their parathyroid hormone level is normal.Key PointsOsteoporosis is common, difficult to detect and usually untreated. It is not known whether elevated calcium concentrations, irrespective of the PTH level, could be a marker of low bone mineral density.No correlation was found between calcium or parathyroid hormone concentrations and bone mineral density at follow-up.In this study, patients with elevated calcium concentrations at baseline had osteoporosis ten years later more often than controls (45% vs. 29%).

Association between neutrophil-to-lymphocyte ratio and parathyroid hormone in patients with primary hyperparathyroidism.

IntroductionPrimary hyperparathyroidism (PHPT) is associated with adverse cardiovascular outcomes which may result from an increase in systemic inflammation. Previously we have shown that serum parathyroid hormone (PTH) levels are independently associated with inflammatory indicators. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive, widely available marker of inflammation. In the present study, we aimed to assess the longitudinal changes in NLR before and after parathyroidectomy.Material and methodsThis retrospective study included 95 patients diagnosed with PHPT who underwent parathyroidectomy between 2006 and 2016. Follow-up complete blood counts were available in 31 patients.ResultsAt diagnosis, 43 (45%) patients presented with overt clinical symptoms and had higher serum calcium and PTH levels. Preoperative NLR was positively correlated with total white blood cell count (p = 0.001), serum calcium (p = 0.001), and PTH level (p = 0.013). The NLR was not associated with sex, age, comorbidities, or parathyroid weight. Among patients who were cured of PHPT, the median NLR decreased from 2.26 to 1.77 after parathyroidectomy (p = 0.037). There was no difference in hemoglobin, total white blood cells, or platelet count before and after surgery.ConclusionsWe found a positive correlation of preoperative NLR with calcium and PTH levels in PHPT patients. After curative parathyroidectomy, NLR modestly decreased without changes in other hematological parameters.

Changing Profile of Primary Hyperparathyroidism Over Two and Half Decades: A Study in Tertiary Referral Center of North India.

Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very advanced stage but in recent years the trend seems to be changing. This has been corroborated from few recently published literature from developing countries. The scope of this study is to further carry out an in-depth analysis of various clinical and biochemical parameters of PHPT patients at a tertiary care center of northern India. In this retrospective analysis, a total of 333 patients with PHPT from the year 1990 to 2016 were studied. The study population was divided into three subgroups based on the time span; 1990-1999 (n = 34), 2000-2009 (n = 112), 2010-2016 (n = 187), and clinical and biochemical parameters were compared. The clinical presentation has evolved progressively with increase in older age group (35 vs 39 vs 43.85, p < 0.001), less patients with musculoskeletal symptoms (85.3 vs 76.8 vs 61%, p = 0.002) and less patients with severe bone disease (29.4 vs 10.7 vs 10.7%, p = 0.088). Biochemical parameters also showed a changing trend with significant decrease in mean S. Alkaline phosphatase (1393 vs 965 vs 414.8IU/L, p < 0.001) and S. iPTH (837.52 vs 812.89 vs 635.74pg/mL, p = 0.02). Vitamin D nutrition status is still suboptimal but shows improvement, and more patients are insufficient as compared to previous deficient state (mean S. Vitamin D-10.31 vs 16.16 vs 25.30ng/mL, p < 0.001). Our study reveals a change in trend in PHPT which is similar to evolution of this disease in western population and positively corroborated with observations from China, Hong Kong and Turkey.

The Significance of 18F-Fluorocholine-PET/CT as Localizing Imaging Technique in Patients with Primary Hyperparathyroidism and Negative Conventional Imaging.

The essential prerequisite for focused parathyroidectomy in patients with primary hyperparathyroidism (pHPT) is proper localization of all autonomic tissue. Sensitivity of conventional imaging modalities (ultrasound, 99mTc-sestamibi scintigraphy/SPECT/CT) is influenced by different factors (i.e., size/weight and position of autonomic tissue) and decreases in the presence of a multinodular goiter. Therefore, a considerable percentage of pHPT patients have negative or equivocal localization studies before surgery. The aim of this study is to evaluate the utility of FCH-PET/CT for preoperative localization in patients with pHPT and negative/equivocal 99mTc-sestamibi scintigraphy/SPECT/CT and/or ultrasound. Between 2014 and 2017, a total of 39 patients with pHPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. In the analysis, we included those (n = 23) who had surgery and a histopathologic workup of the lesions. 19 of 23 patients demonstrated no tracer uptake with 99mTc-sestamibi scintigraphy/SPECT/CT, 6 patients had an equivocal sonographic lesion, and multinodular goiter was present in 43% (10/23). In 21 of 23 patients, hyperfunctioning parathyroid tissue was identified correctly by FCH-PET/CT [21 true positive, 1 false negative, and 1 false positive; per-patient sensitivity 95.5% (95% confidence interval {CI}, 77.2-99.9)]. 29 lesions were resected [21 true positives, 3 false negatives, 1 false positive, and 4 true negatives; per-lesion sensitivity 87.5% (95% CI, 67.6-97.3)]. All patients were classified as having surgical success according to a decrease of intraoperative parathyroid hormone of ≥50% and normalization of postoperative serum calcium levels. Despite a high prevalence of multinodular goiter, diagnostic accuracy of FCH-PET/CT in our patient group was excellent. Therefore, FCH-PET/CT is a promising new imaging tool in patients with pHPT and negative/equivocal results by conventional imaging techniques.

CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism.

Heterozygous pathogenic germline variants in CDC73 predispose to the development of primary hyperparathyroidism (pHPT) and, less frequently, ossifying fibroma of the jaw and renal and uterine tumors. Clinical information on CDC73-related disorders has so far been limited to small case series. To assess the clinical manifestations and penetrance in CDC73-related disorders and to improve case detection in pHPT. Nationwide retrospective Dutch cohort study. Tertiary referral center. We studied 89 patients with pHPT referred for germline CDC73 analysis and 43 subsequently tested relatives who proved to be mutation carriers. Germline CDC73 mutation analysis. CDC73 mutation detection yield, referral rate, and CDC73-related disease penetrance. Pathogenic germline CDC73 variants were identified in 11 of the 89 referred pHPT patients (12.4%), with (suspected) hyperparathyroidism-jaw tumor (HPT-JT) syndrome (n = 3), familial isolated pHPT (n = 5), apparently sporadic parathyroid carcinoma (n = 2), and apparently sporadic parathyroid adenoma (n = 1). The estimated penetrance of CDC73-related disorders was 65% at age 50 years (95% confidence interval, 48% to 82%) in 43 nonindex mutation carriers. Germline CDC73 analysis is recommended in individuals with (suspected) HPT-JT syndrome, familial isolated pHPT, atypical or malignant parathyroid histology, and young individuals with pHPT. These criteria would increase germline CDC73 mutation detection, enabling optimal clinical management of pHPT as well as genetic counseling and surveillance for family members at risk for developing CDC73-related disorders.

Value of 99Tcm-MIBI SPECT/CT in pre-operative diagnosis of primary and secondary hyperparathyroidism

Objective To evaluate the value of pre-operative 99Tcm-MIBI SPECT/CT in patients with HPT by comparing with planar 99Tcm-MIBI and ultrasound imaging. Methods A total of 57 patients (9 males, 48 females; average age: (52.9±15.5) years) were enrolled into this retrospective study. They all underwent 99Tcm-MIBI planar scintigraphy, 99Tcm-MIBI SPECT/CT and ultrasound during March to October in 2016. All patients received parathyroidectomy and the surgical pathology was considered as the gold standard. The diagnostic efficiencies were compared using χ2 test. Results A total of 86 HPT lesions were confirmed, including 47 lesions in 46 PHPT patients and 39 lesions in 11 SHPT patients. The sensitivities of SPECT/CT, planar, ultrasound and combined imaging (planar plus ultrasound) were 87.21%(75/86), 69.77%(60/86), 65.12%(56/86) and 84.88%(73/86), respectively. The overall sensitivity of SPECT/CT was significantly higher than that of individual planar imaging and that of ultrasound (χ2 values: 4.691 and 7.818, both P 0.05). No significant difference was observed among the specificities of all these modalities (χ2=2.219, P>0.05). For PHPT lesions, the sensitivities of SPECT/CT, planar imaging, combined imaging and ultrasound were 95.74%(45/47), 93.62%(44/47), 97.87%(46/47) and 76.60%(36/47), respectively. No statistically significant difference was found in the sensitivity of the former 3 modalities (χ2=1.044, P>0.05), but the sensitivity of ultrasound was the lowest(χ2=16.223, P 0.05). Only SPECT/CT could accurately localize 5 ectopic HPT lesions. Conclusion Compared to planar imaging and ultrasound, SPECT/CT has higher sensitivity for SHPT patients, and could provide precise localization for ectopic lesions, thus facilitating patient planning for minimally invasive surgery. Key words: Hyperparathyroidism; Tomography, emission-computed, single-photon; Tomography, X-ray computed; Technetium Tc 99m sestamibi

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density

ContextA subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. ObjectiveWe sought to identify new mechanistic indices that could inform more personalized management of PHPT. DesignPre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. Patients or Other ParticipantsAn unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Main Outcome MeasuresCalcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. ResultsParathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43–2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41–3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of −2.7, (95% CI: −3.4 to −1.9) versus 0.9, (95% CI: −2.1 to −0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of −0.35 (p=0.02). ConclusionsImpaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT.

Renal function: glomerular filtration rate and renal concentration capacity in mild primary hyperparathyroidism

Introduction. Patients with primary hyperparathyroidism (pHPT) run an increased risk of death, and in some studies cardiovascular diseases were inversely related to glomerular filtration rate (GFR) and urine osmolality.Aim: to evaluate the renal filtration function and concentration capacity in patients with mild primary hyperparathyroidism.Materials and methods. The study included 100 patients with pHPT (median age 57 [52;61]), including 33 with mild form (median age 54 [45;60]). Changes in GFR and osmolality index were evaluated in 29 patients after surgery for pHPT. Follow-up period was up to 24 months.Osmolality index was calculated as urine osmolality to blood osmolality ratio. Renal concentration capacity impairment was diagnosed with osmolality index less than 2. Glomerular filtration rate was calculated by Modification of Diet in Renal Disease Study (MDRD) formula. Chronic kidney disease stage was estimated accordingly to current recommendations.Results. Osmolality index in patients with mild pHPT was low with median 1.65 [1.4; 2.43]. We found a high prevalence of renal concentration capacity impairment in patients with mild pHPT, that was 70%. Mean GFR was 90.9 [73.3; 95.6] ml/min/1,73 m2. Prevalence of chronic kidney disease stages 3-4 was 6% in patients with mild pHPT. Changes in renal concentration capacity in long-term period after surgery for pHPT were characterized by increase of osmolality index, also in patients with mild form (initially 1.75 [1.4; 2.14], after surgery 2.38 [1.84; 2.54]), changing Me was +12.4% in 6-24 months (p=0.012). Changes in renal function in long-term period after surgery for pHPT were characterized by decrease of GFR within the limits of chronic kidney disease stages 1-2, also in patients with mild form.Conclusions. Renal concentration capacity impairment is common in mild pHPT and is restorated after surgery for pHPT. The findings of this study add cause for measurement of urine osmolality or osmolality index in all patients with pHPT. Our results confirm the requirement of estimating GFR in pHPT patients not only while active disease, but also in remission after surgery for pHPT.

The changing pattern of diagnosing primary hyperparathyroidism in young patients

BackgroundPrimary hyperparathyroidism (PHPT) is increasing in adults but rarely reported in young patients where routine blood work is obtained more judiciously. We aim to determine how PHPT is currently being diagnosed in young patients and examine surgical outcomes. MethodWe retrospectively analyzed PHPT patients 24 years of age or less who underwent parathyroidectomy from 2001 to 2014. Patients were divided into 2 time periods: 2001 to 2007 (A) and 2008 to 2014 (B). Incidentally, diagnosed patients lacked objective symptoms of PHPT and had no family history. ResultsForty young patients met inclusion criteria: 16 in group A and 24 in group B. Those in group A compared with group B had similar mean age, preoperative calcium, and parathyroid hormone (P > .05). Incidental diagnosis was more common in the contemporary group (42% vs 25%, P = .001). ConclusionsCurrent diagnosis of PHPT in young patients is increasingly incidental. This trend may be attributed to the more liberal use of labs in younger patients.

Serum calcitriol concentrations measured with a new direct automated assay in a large population of adult healthy subjects and in various clinical situations

The measurement of calcitriol [1,25(OH2)D], is important for the differential diagnosis of several disorders of calcium/phosphorus metabolism but is time-consuming and tricky. We measured serum calcitriol with a new automated direct assay on the Liaison XL platform in 888 healthy French Caucasian subjects aged 18–89years, 32 patients with a surgically-proven PHPT, 32 pregnant women at the end of the first and at the end of the third trimester, and 24 dialysis patients before and after one year of supplementation with vitamin D3 or placebo.The mean calcitriol concentration (±SD) in the healthy population was 52.9±14.5ng/L with a 95% CI interval of 29–83.6ng/L. In PHPT patients, calcitriol concentration was 81.6±29.0ng/L, 15 of them (46.9%) having a concentration >83.6ng/L. In pregnant women, calcitriol was 80.4±26.4ng/L at the end of the first trimester, and 113.1±33.0ng/L at the end of the third trimester, 12 (37.5%) and 26 (81.3%) of them having a calcitriol concentration >83.6ng/L at the first and third trimesters respectively. In 14 dialysis patients, calcitriol was 9.5±7.7ng/L and rose to 19.3ng/L after one year of supplementation with 50,000IU vitamin D3/month. In 10 other dialysis patients, calcitriol was 9.9±2.9ng/L and remained stable (12.4±3.7ng/L) after one year of placebo. In conclusion, this new automated calcitriol assay, in addition to presenting excellent analytical performances, gives the expected variations in patients compared to “normal” values obtained in an extensive reference population.

Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors

Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.

P58. Primary hyperparathyroidism mimicking multiple sclerosis? A case report

A 46-year-old Caucasian female patient was admitted to our hospital with suspected relapse of multiple sclerosis (MS). Diagnosis was made 2 years ago by unspecific white matter lesions, oligoclonal bands in the cerebrospinal fluid and a first episode with a slight hemiparesis left, which remitted in a few weeks. A treatment with interferon beta 1a was introduced. Since that there were no relapses noted. Since a few days she suffered fluctuating muscle weakness, dysarthria, fatigue and mood changes. Clinical examination revealed brisk tendon reflexes, no paresis but severe hypalgesia of both arms. After a 20 m walk she was not able to walk fast and she reported a feeling like a lead weight in her legs. A prednisolone pulse was given for 5 days. Brain MRI showed a new small single contrast enhancing lesion parieto-occipital. Patient shows a slight improvement, mainly concerning their fatigue. Few days after completed prednisolone treatment, the fluctuating muscle weakness progressed. She reported cognitive impairment and paroxysmal panic attacks. Repeated MRI (3 Tesla) oft he brain and cervical spine showed no new lesions. Prednisolone pulse was initiated repeatedly. Laboratory investigations revealed slight elevation of serum calcium. Therefore parathyroid hormone level was evaluated and showed 3-fold elevation. Further evaluations by endocrinologists showed a large adenoma oft he right caudal parathyroid gland. Surgery was planned. Retrospectively serum calcium showed elevated values 4 years ago, when patient was first admitted to a neurology department because of cerebral MRI white matter lesions without clinical symptoms. This case raises the question wether primary hyparathyroidism is a MS mimic? A recent study showed an association between plasma parathyroid hormone and white matter lesions (Hagstroem et al., 2014). Non focal muscle weakness is sometimes reported in primary hyperparathyroidism (pHPT), but severe sensory symptoms are not reported to our knowledge. In a series of pHPT patients subclinical changes of sensory nerve conduction velocity has been showed (Diniz ET, 2013). In our patient sensory electroneurography was normal, but hypalgesia was consistent in the quantitative sensory testing (QST). Our report present further neurophysiologic tests and will discuss possible underlying mechanisms oft he clinical symptoms in detail.

Risk factors for treatment failure in surgery for primary hyperparathyroidism: the impact of change in surgical strategy and training procedures.

Surgery for primary hyperparathyroidism (pHPT) has a high cure-rate and few complications. Preoperative localization procedures have permitted a dramatic shift from routine bilateral exploration to focused, minimally invasive procedures. At Odense University Hospital, Denmark, the introduction of focused surgery was combined with training of new surgeons. The objective of this study was to identify possible risk factors for treatment failure with special focus on surgical strategy and training of new surgeons. A 6-year prospective and consecutive series of 567 pHPT patients operated at Odense University hospital, Denmark, was analyzed. A shift in strategy was made in 2006 and at the same time new surgeons started training in parathyroid surgery. Biochemical-, clinical- and follow-up data were analyzed. Overall cure-rate was 90.7%. Complication rates were 1.1% for hemorrhage, 1.1% for wound infection and 0.9% for recurrent nerve paralysis. The only significant predictor of treatment failure at 6months was histology of hyperplasia (OR 4.3). Neither the introduction of minimal invasive surgical strategy nor the training of new surgeons had a significant influence on the rate of treatment failures. Hyperplasia is a significant predictor of treatment failure in pHPT surgery. A shift towards systematic preoperative localization with focused surgery as well as training of new surgeons can be done without negative impact on treatment results. Identification of the hyperplasia and multigland patients in need of bilateral cervical exploration is crucial to avoid failures and raise cure rates.

Novel inflammatory biomarkers in primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) has been associated with low-grade inflammation and increased risk of cardiovascular disease (CVD). The aim of the study was to investigate systemic levels of pro-inflammatory proteins that previously have not been examined in patients with PHPT. The selection of the pro-inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in adipose tissue from PHPT patients. A prospective study was conducted on a total of 57 patients with PHPT and a control group of 20 healthy blood donors. PHPT patients with normalisation of serum calcium levels after parathyroidectomy were followed for 6 months. Forty-two patients participated in the longitudinal study, in which blood samples were taken at inclusion, and 1, 3 and 6 months after surgery. We observed increased serum levels of MMP9 (P=0.029), S100A4 (P<0.001) and sCD14 (P=0.002) in the 57 patients with PHPT compared to the control-group. During 6 months of follow up, S100A4 (P=0.022) and sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased (P=0.025). The results demonstrate an increased inflammatory response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion. During the 6 months of follow-up, MMP9 increased further, possibly due to the tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after surgery demonstrating a partial reversal of the systemic inflammation.

The G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria: evidences from a comprehensive meta-analysis.

Background. The calcium-sensing receptor gene (CaSR) is a candidate to explain urolithiasis. A number of case-control studies were conducted to investigate associations between CaSR polymorphisms with risks of hypercalciuria and urolithiasis in humans. But the results were still inconsistent. Methods. A meta-analysis was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CaSR polymorphisms and the risk of urolithiasis. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of CaSR polymorphisms and urine calcium concentration. Results. For urolithiasis association, the SS genotype of A986S polymorphism was a risk factor for urolithiasis in Asians and PHPT patients, but a protective factor in Caucasians. The GG genotype of R990 polymorphism was associated with an increased risk of urolithiasis, especially in Caucasians and healthy population. Regarding urine calcium concentration association, individuals with the G allele had a higher level of urine calcium than the noncarriers. Conclusions. This meta-analysis revealed that the G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria. The A986S and Q1011E polymorphisms were associated with urolithiasis and hypercalciuria in specific populations.

Minimally invasive parathyroidectomy with or without intraoperative parathyroid hormone for primary hyperparathyroidism.

PurposeThe improvement of intraoperative parathyroid hormone (IOPTH) assay and localization studies has enabled a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). The aim of this study is to analyze the demographics, clinical presentations, and surgical outcomes of the pHPT patients who received surgical management with versus without IOPTH.MethodsAnalysis of a database was performed on 53 patients who underwent parathyroidectomy for pHPT from 2004 to 2013. Preoperative localization was done by both sestamibi scan and ultrasonography. We divided the patients into two groups (without IOPTH versus with IOPTH) and analyzed the surgical outcomes statistically between two groups.ResultsThe concordance rate of Technetium 99m sestamibi scan and ultrasonography was 73.6% and 90.6%, respectively. The overall cure rate of group 1 (without IOPTH) was 94.9% and that of group 2 (with IOPTH) was 100%. The decline of PTH at postoperative 5 minutes and 10 minutes was 75.2% ± 14.9% and 84.9% ± 8.6% in cured patients. On the other hand, that of noncured patients at 5 minutes and 10 minutes was 17.2% ± 9.7% and 8.2% ± 2.2%. There was a significant difference in the drop rate of IOPTH between cured and persistent patients (P < 0.01). Pathological examination showed adenoma in 41 of 53 patients (77.4%) and hyperplasia in 10 of 53 patients (18.9%).ConclusionEven though the localization studies were successful, IOPTH monitoring is essential to avoid a surgical failure in MIP.

Low 24-hour urine calcium levels in patients with sporadic primary hyperparathyroidism: is further evaluation warranted prior to parathyroidectomy?

BackgroundLow 24-hour urine calcium (uCa) levels in patients with primary hyperparathyroidism (pHPT) raise concern for familial hypocalciuric hypercalcemia. This study evaluated patients with a low 24-hour uCa level for potential differences that may guide the extent of preoperative evaluation needed. MethodsA retrospective review was conducted of 1,139 sporadic pHPT patients who underwent parathyroidectomy between December 1999 and May 2011. ResultsOf the 54 (5%) patients with greater than or equal to one low 24-hour uCa (<100 mg), 28 (52%) patients had only one low level, 9 (17%) had multiple low levels, and 17 (31%) had a repeat 24-hour uCa greater than 100. In the latter group, 4 of the 9 (53%) patients were on a thiazide and had normalization after cessation. Among the groups, differences existed only in serum creatinine (P = .0011) and glomerular filtration rate (P = .0007). ConclusionThis study suggests that sporadic pHPT patients with low 24-hour uCa levels may not require further evaluation with genetic testing for familial hypocalciuric hypercalcemia, especially if previous eucalcemia is documented.

Abstract 15844: Plasma Parathyroid Hormone is Independently Related to 24-Hour Pulse Wave Velocity in Patients With Primary Hyperparathyroidism - Insights fFom The EPATH Study

Introduction: Accumulating evidence indicated that high parathyroid hormone (PTH) is associated with increased cardiovascular risk. The impact of PTH on vascular structure and function is, however, still unclear. We evaluated the relationship between pulse wave velocity (PWV) as a novel index of arterial stiffness and circulating levels of PTH in patients with PTH-excess (primary hyperparathyroidism (pHPT)). Methods and Results: We analyzed baseline data of the ongoing randomized, double-blind, placebo-controlled “Effect of Eplerenone on Parathyroid Hormone Levels in Patients with Primary Hyperparathyroidism” (EPATH) study. Inclusion criteria were age of at least 18 years and a diagnosis of pHPT according to international guidelines. Standardized blood sampling was performed after an overnight fast and 24h PWV was measured by a validated non-invasive device for ambulatory hemodynamic monitoring (Mobil O Graph, I.E.M., Stolberg, Germany). Our analysis comprised 92 pHPT patients with a mean age of 68.5 +/- 9.7 years (71 % females) and a median PTH of 102 (IQR 81 - 132) pg/ml. Mean 24h PWV was 9.8 +/- 1.8 m/s, mean daytime and mean nighttime PWV were 10.0 +/- 1.7 m/s and 9.6 +/- 1.8 m/s, respectively. In multivariate linear regression analyses adjusted for age, sex, body mass index, smoking status, mean systolic and mean diastolic 24h blood pressure, antihypertensive medication, type 2 diabetes, 25-hydroxyvitamin D, serum calcium, intake of cinacalcet and fasting serum cholesterol PTH emerged as a strong predictor of mean 24h PWV (ß=0.30, p=0.012), daytime PWV and nighttime PWV (ß=0.30, p=0.011 and ß=0.30, p=0.019, respectively). Conclusion: In a selective cohort of patients with pHPT plasma PTH was strongly related to 24h PWV. These data strengthen the notion that PTH may impact on vascular function. Interventional and mechanistic trials are needed to evaluate modulatory effects on vasculature in patients with high PTH.