pHPT Patients Research Articles

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.

Health-related quality of life after successful surgery for primary hyperparathyroidism: no additive effect from vitamin D supplementation: results of a double-blind randomized study.

Vitamin D insufficiency is common in primary hyperparathyroidism (pHPT). Patients with pHPT frequently have a reduced health-related quality of life (HRQoL). Our objectives were to evaluate whether HRQoL in pHPT is associated with vitamin D insufficiency and whether vitamin D supplementation after parathyroidectomy (PTX) could improve HRQoL. A randomized, double-blind study (ClinicalTrials.gov identifier: NCT00982722). The study included 150 pHPT patients randomized, 6 weeks after PTX, to daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D+) or calcium carbonate alone (D-). HRQoL was estimated with SF-36 before and after PTX and after 12 months of study medication. Three-quarters (77%) of the pHPT patients had vitamin D insufficiency, defined as 25OHD <50 nmol/l. The pHPT patients scored lower than a reference population in all domains of SF-36. A total of 135 patients completed the entire study period. Improvements in nearly all domains were registered at the follow-up 6 weeks after PTX. At the end of the study medication period, the D+ group had a significantly higher median serum (s-) 25OHD concentration (76 (65; 93) (lower; upper interquartile ranges) vs 48 (40; 62) nmol/l, P<0.001) and a lower plasma (p-) parathyroid hormone concentration (40 (34; 52) vs 49 (38; 66) ng/l, P=0.01) than the D- group. The improvements in HRQoL remained unchanged at the follow-up 1 year after PTX. Postoperative vitamin D supplementation had no obvious effect on HRQoL. PTX resulted in significant improvements in HRQoL. Despite a high prevalence of vitamin D insufficiency, 1 year of postoperative vitamin D supplementation had no obvious beneficial effect on HRQoL.

Quality of life is modestly improved in older patients with mild primary hyperparathyroidism postoperatively: results of a prospective multicenter study.

The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery. A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12months). One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients<70years and with calcemia ≥10.4mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation=32.11-0.21×age-0.4×preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement. This study showed, in patients with mild pHPT, an improvement of QoL 1year after parathyroidectomy. Patients <70years and with calcemia ≥10.4mg/dL had a more significant improvement.

Low 24-hour Urine Calcium Levels in Patients with Sporadic Primary Hyperparathyroidism: Is Further Evaluation Warranted Prior to Parathyroidectomy?

Abstract Background Low 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. Methods A retrospective review was conducted of 1,139 sporadic pHPT patients who underwent parathyroidectomy between December 1999 and May 2011. Results Of the 54 (5%) patients with greater than or equal to one low 24-hour uCa ( P = .0011) and glomerular filtration rate ( P = .0007). Conclusion This 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.

Strategy of operative treatment of hyperparathyroidism using US scan and &lt;sup&gt;99m&lt;/sup&gt;Tc-MIBI SPECT/CT

We evaluated the efficacy of technetium-sestamibi ((99m) Tc-MIBI) SPECT/CT for planning parathyroidectomy in cases with primary hyperparathyroidism (pHPT), comparing with planar scintigraphy and ultrasound (US), in an aim to establish the proper surgical strategy according to the preoperative imaging studies. A retrospective review of consecutive 75 pHPT patients who had been operated on was conducted. The results of preoperative imaging modalities and the operative finding were analyzed. Seven cases were found to have multiple hyperplastic glands, and no responsible gland was found in three cases. Four cases underwent only US scan for preoperative imaging. Remaining 61 cases were found to have single adenoma, and were included in the evaluation of localization imaging. US scan, (99m) Tc-MIBI planar scan and (99m) Tc-MIBI SPECT/CT showed accurate localization in 77.0% (47/61), 75.4% (46/61) and 88.5% (46/52) of the evaluable cases, respectively. US and (99m) Tc-MIBI planar scan demonstrated consistent result in 42 cases (68.9%), and those cases showed accurate localization in 90.5% (38/42). When both US and (99m) Tc-MIBI SPECT/CT was consistent, all 37 lesions had been correctly indicated. No clinico-pathological features were suggested to influence in demonstrating the localization, other than only (99m) Tc-MIBI SPECT/CT exhibited 100% sensitivity in ectopic glands. Combination of US and (99m) Tc-MIBI SPECT/CT certainly contributes to the planning of minimally invasive operation in cases with pHPT by indicating correct localization of single adenoma.

Senile parathyroid dysfunction: Characteristics of its diagnosis and treatment

Abstract Senile parathyroid dysfunction is mainly seen in primary or secondary hyperparathyroidism (pHPT or sHPT). pHPT in the elderly usually occurs in women, with fatigue and osteoporosis as the common symptoms. Screening of blood calcium and further evaluation of parathyroid hormone (PTH) for subjects with serum calcium &gt;2.6 mmol/L can be helpful for early identification of patients. For pHPT patients with no contraindications to surgery and whose lesions can be well-localized, surgical treatment can be more beneficial. sHPT is mainly found in patients with end-stage chronic renal dysfunction necessitating hemodialysis or peritoneal dialysis. For these patients, monitoring of PTH level, early supplement of calcium preparations and use of large-dose calcitriol will facilitate maintaining levels of blood calcium and PTH.

Perioperative changes in cortical excitability, mood, and quality of life in patients with primary hyperparathyroidism: a pilot study using transcranial magnetic stimulation

Serum calcium (Ca(2)(+)) and parathyroid hormone (PTH), amongst others, modify cortical excitability. Alterations in cortical excitability were shown in patients with epilepsy as well as hyper- or hypoparathyroidism. In patients with primary hyperparathyroidism (pHPT), preoperative elevated serum calcium and parathyroidectomy (PTx) may affect mood and quality of life. We hypothesized that perioperative changes in Ca(2)(+) and PTH in pHPT will affect cortical excitability and improve subjective health. Transcranial magnetic stimulation (TMS) was performed before and after surgery in 15 pHPT patients. We measured resting motor threshold, cortical silent period (CSP), short intracortical inhibition, and intracortical facilitation. Health questionnaires were administered before, 1 day and 6 months after PTx, along with the disease-specific Pasieka's parathyroid assessment of symptoms (PAS), which was, to our knowledge, its first use in German. SURGERY WAS SUCCESSFUL IN ALL PATIENTS. TMS-MEASUREMENTS REMAINED UNCHANGED WHEN ANALYZING ALL PATIENTS IN THIS PILOT STUDY. POSTOPERATIVELY, DEPRESSION DECLINED (P=0.05) AND QUALITY OF LIFE IMPROVED SIGNIFICANTLY (P=0.001) IN THE SF-36-SUBSCALES: vitality, social functioning, mental health and subjective health transition (post-hoc analysis). The PAS proved early relief of disease-specific symptoms (P<0.001). We found unchanged cortical excitability comparing pre- and post-PTx in this pilot study. Mood and quality of life improved postoperatively. The German PAS is valuable in detecting disease-specific changes early after PTx.

Insulin sensitivity in normocalcaemic primary hyperparathyroidism

An altered glucose tolerance and an increased prevalence of diabetes mellitus in primary hyperparathyroidism have been reported due to an increased insulin resistance in these patients [1]. Furthermore, a significant relationship between hypercalcaemia and insulin sensitivity has been reported [2]. ‘‘Normocalcaemic’’ primary hyperparathyroidism (NCpHPT), recently recognized by some authors as a peculiar early presentation of symptomatic pHPT, is not well clinically characterized, as the few data in literature are questionable since its rigorous classification following all the strict diagnostic criteria often was not performed [3]. In particular, at our knowledge, only one case–control study recently reported a non-significantly different insulin sensitivity and glucose tolerance in these patients compared to healthy volunteers [4]. Thus, in our large series of pHPT patients we sought to investigate glucose tolerance, estimates of insulin sensitivity and secretion in the subset of patients rigorously classified as NCpHPT. Patients and methods

Surgery for ‘asymptomatic’ mild primary hyperparathyroidism improves some clinical symptoms postoperatively

Most primary hyperparathyroidism (pHPT) patients do not conform to the guidelines for parathyroidectomy established by an international panel of specialists and have a mild pHPT. This group is typically defined as 'asymptomatic'. The primary aim of this study was to determine symptom improvement in this 'asymptomatic' group after parathyroidectomy. Secondly, we aimed to create a preoperative clinical score predicting postoperative symptom resolution. A prospective nonrandomized study included patients with mild pHPT. A questionnaire (22 items) was given to 'asymptomatic' patients preoperatively and at 3, 6, and 12 postoperative months. A logistic regression was performed to create a preoperative clinical score. One hundred and sixteen patients were included. Postoperatively, HPT was resolved in 98% of patients. Twelve of 22 nonspecific symptoms were improved at 1 year. Subgroups analysis showed a greater improvement in patients <70 years and those with a serum calcium level ≥2.6 mmol/l preoperatively. A clinical score, based on age and five symptoms, was established to predict the clinical improvement after surgery in mild pHPT patients with a positive predictive value of 81%. Patients with asymptomatic pHPT have clinical improvement of their symptoms postoperatively even after 1 year. Younger patients and those with higher preoperative calcium levels show the best improvement.

Does parathyroidectomy in patients with primary hyperparathyroidism and renal calculi prevent further stones?

Hypercalciuria due to primary hyperparathyroidism (pHPT) is a risk factor for renal stone formation, yet only a minority of patients form calculi. Despite several studies, the effect of parathyroidectomy on the risk of developing further urolithiasis is uncertain. This study compared the biochemistry of pHPT patients with and without renal stones undergoing a parathyroidectomy with that of idiopathic stone formers, and determined the incidence of new stone disease in each group during follow-up.

Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture

The prevalence of subclinical contributors to low bone mineral density (BMD) and/or fragility fracture is debated. We evaluated the prevalence of subclinical contributors to low BMD and/or fragility fracture in the presence of normal 25-hydroxyvitamin D (25OHVitD) levels. Prospective observational study. Among 1095 consecutive outpatients evaluated for low BMD and/or fragility fractures, 602 (563 females, age 65.4±10.0 years) with apparent primary osteoporosis were enrolled. A general chemistry profile, phosphate, 25OHVitD, cortisol after 1-mg overnight dexamethasone suppression test, antitissue transglutaminase and endomysial antibodies and testosterone (in males) were performed. Serum and urinary calcium and parathyroid hormone levels were also evaluated after 25OHVitD levels normalization. Vertebral deformities were assessed by radiograph. In total, 70.8% of patients had low 25OHVitD levels. Additional subclinical contributors to low BMD and/or fragility fracture were diagnosed in 45% of patients, with idiopathic hypercalciuria (IH, 34.1%) and primary hyperparathyroidism (PHPT, 4.5%) being the most frequent contributors, apart from hypovitaminosis D. Furthermore, 33.2% of IH and 18.5% of PHPT patients were diagnosed only after 25OHVitD levels normalization. The subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D were associated inversely with age (odds ratio (OR) 1.02, 95% CI 1-1.04, P=0.04) and BMI (OR 1.1, 95% CI 1.05-1.17, P=0.0001) and directly with fragility fractures (OR 1.89, 95% CI 1.31-2.73, P=0.001), regardless of BMD. Subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D are present in more than 40% of the subjects with apparent primary osteoporosis. Hypovitaminosis D masks a substantial proportion of IH and PHPT patients.

Serum calcium (S-Ca), the forgotten test: Preliminary results of an appropriateness strategy to detect primary hyperparathyroidism (pHPT)

BackgroundWith the introduction of automated calcium measurements with multichannel continuous-flow analyzers in the 1970s, primary hyperparathyroidism (pHPT), the silent disease, began to be detected. Years later, with the first appearance of random access analyzers, laboratory tests were requested if the patient had clinical symptoms and pHPT was again overlooked. In this current scenario, serum calcium (s-Ca) is at risk of becoming a forgotten test. In consensus with endocrinologists and general practitioners (GPs), we implemented a strategy to detect asymptomatic pHPT patients. MethodsDuring a 9month period, the Laboratory Information System automatically added s-Ca to every sample of blood from primary care patients older than 45years, without a s-Ca request in the previous three years. If hypercalcemia was detected (albumin-corrected s-Ca>2.6mmol/L), phosphate, 25-hydroxy vitamin D and parathyroid hormone (PTH) were automatically processed in the same sample. We reviewed the medical record of every patient with hypercalcemia. ResultsS-Ca was automatically added to 14,461 samples, with 79 hypercalcemia results. 14 hypercalcemia results with PTH levels in the reference range were clinically justified by causes other than pHPT. Of the remaining 65 patients, 41 were referred for evaluation by endocrinology. 34 resulted in a diagnosis of pHPT and 7 are currently in study. 24 patients were not followed by GPs to find out the primary cause of hypercalcemia. After a phone call from the laboratory, they are also currently being studied for hypercalcemia. Each case represented a cost of 110.4 US dollars. ConclusionOur proposed opportunistic screening to discover pHPT seems cost-effective.

Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: Does it matter?

The clinical importance of elevated serum parathyroid hormone (PTH) levels in patients with normocalcemia after curative parathyroidectomy (PTX) for primary hyperparathyroidism (pHPT) is unclear. This study sought to determine whether these patients, when compared with those with normal PTH levels, differ in preoperative and pathologic factors and are at increased risk of recurrent pHPT. A chart review was performed of sporadic pHPT patients who underwent PTX between December 1999 and July2011. Of 1,037 patients who underwent PTX, 310 had 6-month serum calcium, vitamin D, and PTH levels evaluated. PTX was curative (normocalcemia at ≥6 months) in 97%. At 6 months, 62 (21%) had elevated serum PTH levels. Compared with patients with normal postoperative PTH levels, patients with elevated PTH levels had greater BMI (P < .0001), greater PTH levels (P < .0001), and lesser vitamin D levels (P = .014) preoperatively and lesser vitamin D levels at 6 months (P = .05). At ≥1 year follow-up, 38 (61%) patients had calcium levels checked; all remained normocalcemic. PTH levels were available for 32 patients; 17 had persistently increased PTH levels. Patients with elevated PTH levels after curative PTX do not have greater rates of recurrence than patients with normal PTH levels. The greater PTH levels and lesser vitamin D levels support postoperative vitamin D supplementation in these patients.

Surgical Management of Normocalcemic Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT), typically defined as elevated serum calcium levels associated with inappropriately elevated parathyroid hormone (PTH) levels, can occur also in patients with normal serum calcium levels. This study investigated the characteristics, workup, and surgical management of patients with normocalcemic pHPT. A retrospective chart review of a prospectively collected, single-institution parathyroid database was performed on patients with sporadic pHPT who underwent parathyroidectomy between 12/99 and 12/08. In all, 93 of 771 (12%) pHPT patients had normal serum calcium levels 3 months prior to surgery. Ionized calcium (iCa) levels were available for 58 patients and were elevated in 50 (86%). Among those with elevated iCa levels 90% had single-gland disease (SGD), whereas 63% with normal iCa levels had SGD (p = 0.07). Preoperative imaging identified SGD in 60% of patients with normal iCa and in 66% with elevated iCa levels. Intraoperative PTH (IOPTH) monitoring identified cure in 51 of 58 (88%) patients including 6 (75%) with normal iCa. At a median follow-up of 358 days, postoperative calcium and PTH levels were similar in the groups. One (1%) patient had recurrent disease. Most patients with apparent normocalcemic pHPT have elevated ionized calcium levels. For patients with normocalcemic pHPT, we recommend measuring iCa levels preoperatively, performing localization studies, and utilizing IOPTH monitoring to guide a successful operation.

Prevalence and characteristics of metabolic syndrome in primary hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is characterized by an increased frequency of glucose tolerance abnormalities associated with insulin resistance. Few studies evaluated the prevalence of metabolic syndrome (MetS) in pHPT and whether there are differences between asymptomatic pHPT patients and symptomatic ones. Thus, we sought to investigate the prevalence of MetS in pHPT patients in comparison to the prevalence of MetS in Italian population. We conducted a retrospective chart review of 294 pHPT patients, of these 154 [age (mean ± SD) 58.7 ± 13.3 yr, body mass index 25.6 ± 4.8 kg/m(2); serum calcium (11.3 ± 1.2 mg/dl) 2.8 ± 0.3 mmol/l; PTH 234.8 ± 224.3 ng/l] met the inclusion criteria. A modified National Cholesterol Educational Program (NCEP)/Adult Treatment Panel III (ATP III) definition of the MetS was used. Prevalence of MetS was compared with that reported for the Italian population (Progetto Cuore Study). The prevalence of the MetS (34/154, 22.1%) was similar to that reported in the general Italian population. Asymptomatic pHPT patients were older (62.1 ± 12.7 vs 56.4 ± 13.2 yr, p<0.008) and showed higher prevalence of MetS than symptomatic ones (30.2% vs 16.5%, p<0.045). Moreover the prevalence of nephrolitiasis or overt bone disease was not different between patients MetS+pHPT compared to MetS-pHPT, whereas femoral bone mineral density (BMD) was higher in MetS+pHPT (p<0.003). In the logistic regression model age and femoral BMD were independent predictors of MetS. The prevalence of MetS in pHPT is not increased in comparison to the general population, thus, its diagnosis is not an appropriate tool to identify the additional cardiovascular risk related to pHPT. Difference in age affects the increased prevalence of MetS in asymptomatic pHPT patients.

Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism.

Familial primary hyperparathyroidism (FPHPT) may occur due to an underlying germ-line mutation in the MEN1, CASR, or HRPT2/CDC73 genes. The disease may be undiagnosed in the absence of a history suggestive of FHPT. Young PHPT patients (≤45 years of age) are more likely to harbor occult FPHPT. A total of 1,161 (136 were ≤45 years of age) PHPT patients underwent parathyroidectomy from 2001 to 2009. Thirty-four patients declined participation. Sixteen patients were diagnosed in the clinical routine with FPHPT (11 MEN1, four MEN2A, and one HPT-JT) and were not included in the genetic analysis. Eighty-six young (≤45 years of age) patients with clinically non-syndromic PHPT underwent genetic analysis. Sanger sequencing of all coding regions of the MEN1, CASR, and the HRPT2/CDC73 genes was performed. Eight of 86 (9.3%) young patients with clinically non-familial PHPT displayed deleterious germ-line mutations in the susceptibility genes (4 MEN1, 3 CASR, and 1 HRPT2/CDC73). There was one insertion, one deletion, two nonsense, and four missense mutations, all predicted to be highly damaging to protein function and absent in 3,244 control chromosomes. Germ-line mutations in known susceptibility genes within young patients with PHPT, including those diagnosed in the clinical routine, was 24/102 (23.5%; 15 MEN1, four RET, three CASR, and two HRPT2/CDC73). We demonstrate that germ-line inactivating mutations in susceptibility genes are common in young patients with clinically non-familial PHPT. Thus, enhanced use of genetic analysis may be warranted in clinically non-familial young PHPT patients.

Evaluation of selected cognitive functions before and after surgery for primary hyperparathyroidism

Cognitive functions have been reported to be impaired in patient with primary hyperparathyroidism (pHPT). The aim of this psychological study was to evaluate cognitive disturbances in pHPT in relation to serum calcium levels before and after surgery. A prospective, case-control study with 1-year follow-up of 35 pHPT patients versus 35 matched controls was undertaken. All patients were tested before surgery and at 12-18 months following surgery with a battery of selected cognitive function psychological tools: Benton Visual Retention Test (BVRT), Wisconsin Card Sorting Test (WCST), Memory Verbal Learning Test (DCS), The Rey's Auditory Verbal Learning Test (RAVLT), Trail Making Test A & B, Verbal Fluency Test, and Beck Depression Inventory. In addition to psychological testing, serum calcium, parathyroid hormone and phosphate levels were evaluated. The following cognitive functions of pHPT patients versus controls were deteriorated before surgery: impaired concentration, decreased nonverbal learning process, difficulties in using direct memory, verbal fluency and visual constructive abilities. However, no correlation was found between serum calcium levels and the results of neuropsychological tests. In longitudinal comparison of pHPT patients before and 1 year after surgery, there was a significant improvement in visual memory, visual-constructive abilities and direct memory. pHPT patients have significantly decreased concentration level, nonverbal learning process, access to verbal resources and constructional and visual memory ability. Thus, neuropsychological testing may be useful in the decision making for early surgery in patients with mild asymptomatic disease in order to avoid further deterioration of cognitive functions.

"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density"

BackgroundPrimary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT.MethodsWe enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.ResultsRegarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).ConclusionsOur study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.

Nonlocalizing Imaging Studies for Hyperparathyroidism: Where to Explore First?

For patients with primary hyperparathyroidism (pHPT), imaging studies are obtained to facilitate minimally invasive parathyroidectomy. If imaging studies are nonlocalizing, it is not known if exploration should begin on a particular side or gland location. A retrospective review of a prospective parathyroid database was performed. The cohort consists of pHPT patients who underwent initial parathyroidectomy between December 1999 and July 2010 and had all preoperative imaging studies reported as nonlocalizing (negative or indeterminate). Of 880 patients, 151 (17%) had nonlocalizing imaging studies. Reasons for starting exploration on a particular side were identified in 78 (52%) patients and included concomitant thyroid pathology (53%), suspicion on surgeon re-review of imaging (38%), or earlier thyroidectomy (9%). Exploration began on the right in 52%, the left in 42%, and was unknown in 6%. The surgeon had suspicion on imaging in 30 patients and correctly started on the side of pathology in 19 (63%). Hyperfunctioning glands were in eutopic locations in 144 patients (95%) and 3 had intrathyroidal glands. In 111 patients (74%) with single gland disease, median adenoma weight was 320 mg (range 80 to 8,210 mg). There was no difference in adenoma laterality (p = 0.7) or location (p = 0.8). Intraoperative parathyroid hormone criteria were met in 145 (96%) patients and 149 are eucalcemic at last follow-up; 2 (0.7%) patients have persistent disease. In pHPT patients with nonlocalizing imaging, hyperfunctioning glands are not more frequently located on a particular side or anatomic position. Eutopic location is common and intraoperative parathyroid hormone monitoring should be used to guide the extent of surgery.

Patients with surgically cured primary hyperparathyroidism have a reduced quality of life compared with population-based healthy sex-, age-, and season-matched controls

Primary hyperparathyroidism (PHPT) is associated with feelings of fatigue and depression, as well as limitation to physical and mental functioning. These quality of life (QoL) characteristics improve after parathyroidectomy. However, whether former patients fully regain QoL compared with healthy controls is largely unknown. Cross-sectional study. Fifty-one former PHPT patients, successfully treated by surgery (mean time since parathyroidectomy 7.4 (range 5-15) years), and 51 sex- and age-matched healthy controls. The 36-item Short-Form Health Survey version 2 and the WHO-Five Well-being Index. The surveys included questions on overall physical and mental health, functioning, and limitation in daily life activities. Former patients scored significantly lower compared with controls in physical functioning (P=0.01), role limitation caused by emotional problems (P=0.01), vitality (P<0.001), and general health (P=0.01). Compared with the controls, cases had a lower median (interquartile range) score of physical component summary (PCS; 54.9 (47.9-58.7) vs 49.6 (45.2-55.9), P=0.03) and mental component summary (MCS; 55.4 (49.7-58.1) vs 52.5 (44.7-55.5), P=0.04). There was no association between time since operation and PCS or MCS. Compared with controls, cases had higher body mass index (BMI; 26.0±4.7 vs 28.8±6.0 kg/m(2), P<0.001) and a higher frequency of cardiovascular diseases (CVD; 41.2 vs 62.7%, P=0.03). After adjustment for differences in BMI and CVD, PCS did no longer differ between groups. However, adjustments did not change the finding of a lower MCS in cases compared with controls. Even though QoL may improve substantially after surgery, former PHPT patients still have reduced QoL compared with healthy controls.