Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

PURPOSE: To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. METHODS: Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. RESULTS: PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. CONCLUSIONS: NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

A detailed appraisal of renal manifestations in primary hyperparathyroidism from Indian PHPT registry: Before and after curative parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a systemic disorder characterized by hypercalcaemia and inappropriately elevated parathyroid hormone (PTH). Renal manifestations are one of the main presenting features both in symptomatic and asymptomatic PHPT patients. OBJECTIVES: We aimed to compare demographic, clinical and biochemical parameters of PHPT patients with and without renal manifestations and also analysed the influence of curative parathyroidectomy on renal functions. METHODS: We retrospectively analysed the data of PHPT patients from the last 25 years (1995- March 2019) and compared the demographic and clinical presentation and biochemical measurements between patients with and without renal manifestations and evaluated the changes in renal functions after 1 year of curative parathyroidectomy. RESULTS: Of the total 544 PHPT patients, 299 (55%) including 91 out of 141 (65%) males had renal manifestations. Among renal manifestations, nephrolithiasis and nephrocalcinosis were found in 41.7% and 27.6% PHPT patients, respectively. PHPT patients with renal manifestations had significantly higher creatinine (109.7 vs 79.6 µmol/L; P < .0001) and lower eGFR level (78.8 vs 93.9 mL/min/1.73 m2 ; P < .0001) compared to patients without renal manifestations. Parathyroidectomy resolved the clinical symptoms with biochemical cure in the patients from both the groups. Patients with renal manifestations showed improvement in creatinine and eGFR levels after 1 year of curative parathyroidectomy; however, patients without renal manifestations showed no change in creatinine and eGFR levels. CONCLUSION: Young age and male gender are predictors of renal manifestations in PHPT. Curative parathyroidectomy improves renal functions in PHPT patients with renal manifestations compared to PHPT patients without renal manifestation.

Morning blood pressure surge increases in patients with hypertensive primary hyperparathyroidism and is independently associated with serum calcium level.

Introduction: There is not enough data on the effects of primary hyperparathyroidism (pHPT) on morning blood pressure surge (MBPS) in the literature. We aimed to determine whether there was any change in MBPS value in patients with hypertensive pHPT and to determine the parameters related to MBPS.Method: 80 patients with newly diagnosed pHPT with hypertension (HT) and 80 controls with newly diagnosed hypertension were included. Routine laboratory examinations and ambulatory blood pressure monitoring (ABPM) were performed in all patients.Results: In patients with pHPT, blood urea nitrogen (BUN), triglyceride, hs-CRP, uric acid, serum calcium (Ca), parathormone (PTH), daytime SBP and MBPS levels are higher than others (p < 0.05). Body mass index (BMI) and Ca level were independently associated with MBPS. In patients with MBPS ≥ 25 mmHg, BMI, BUN, creatinine, uric acid, Ca and PTH levels were found to be higher than others. BMI values and Ca levels determine the patients with MBPS ≥ 25 mmHg (p < 0.05) independently. According to this analysis, increase in BMI (for each 1 unit) and Ca level (for each 0.1 mg/dL) was found to increase the probability of MBPS ≥ 25 mmHg by 17.8% and 7.7%, respectively. When the cut-off value for Ca was taken as 10 mg/dL, the patients with MBPS ≥ 25 mmHg were determined with 73.5% sensitivity and 73.1% specificity.Conclusion: MBPS significantly increases in patients with newly diagnosed hypertensive pHPT. This increase in MBPS is closely associated with increased Ca levels. In patients with pHPT, lowering the Ca level below 10 mg/dL may have clinical implications.

Mild primary hyperparathyroidism-to treat or not to treat?

INTRODUCTION: The presentation of primary hyperparathyroidism (PHPT) has shifted from a disease characterized by renal and skeletal complications to a mild or asymptomatic condition. Modern imaging allows localization of a surgical target in the majority of cases. SOURCES OF DATA: Data were collected from literature searches of online databases including PUBMED, MEDLINE and Cochrane. A narrative review was performed. AREAS OF AGREEMENT: Parathyroidectomy is the only therapy with curative potential with good outcomes and low risk of complications in experienced hands. Current guidelines advocate that surgery is offered in all symptomatic cases and in those who meet criteria depending on age, serum calcium concentration, skeletal and renal parameters. A structured monitoring approach should be offered to those who do not undergo surgery. AREAS OF CONTROVERSY: Thresholds for intervention to improve skeletal and renal outcomes are debatable. In addition, controversy persists over the benefit of surgery for non-skeletal/renal outcomes. GROWING POINTS: The role of medical management of PHPT using agents such as bisphosphonates, denosumab and cinacalcet are discussed. AREAS TIMELY FOR DEVELOPING RESEARCH: In summary, further data on the natural history and effects of treatment of mild and asymptomatic PHPT are required to determine thresholds for surgery. In particular, further investigations of non-skeletal and non-renal parameters, such as neurocognitive quality of life and cardiovascular disease are required. Data on normocalcaemic PHPT are lacking. Large-scale randomized controlled trials would be welcome in these areas, however in view of the cost implications a more pragmatic approach may be to develop collaborative multi-centre registries.

Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis.

PURPOSE: Hyperparathyroidism (HPT) is a common endocrine disorder caused by hyperfunctioning parathyroid glands (HP). The correct detection and localization of HP is challenging but crucial, as it may guide surgical treatment, particularly in patients with primary HPT. There is a growing body of data regarding the role of radiolabelled choline positron emission tomography (PET) in this setting. Therefore, we performed a systematic review and meta-analysis of the diagnostic performance of this method in detecting HP in patients with HPT. METHODS: This systematic review and meta-analysis was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE and Cochrane Library databases for studies published through May 2018 was performed using the following search algorithm: (a) "choline" or "fluorocholine" or "F-choline" or "C-choline" or "FCH" or "CH" or "FECH" or "FMCH" and (b) "PET" or "positron emission tomography" and (c) "parathyroid" or "hyperparathyroidism". The diagnostic performance of radiolabelled choline PET was expressed as sensitivity and positive predictive value (PPV) on a per-patient and per-lesion basis and as detection rate (DR) on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI) obtained using a random-effects model. RESULTS: Eighteen studies were included in the systematic review. Fourteen articles (517 patients) were selected for the meta-analysis. The meta-analysis provided the following results on a per-patient analysis analysis: sensitivity 95% (95% CI: 92-97%), PPV 97% (95% CI: 95-98%) and DR 91% (95% CI: 87-94%). On a per-lesion analysis, pooled sensitivity and PPV were 92% (95% CI: 88-96) and 92% (95% CI: 89-95%), respectively. No significant heterogeneity was found among the selected studies. CONCLUSIONS: Radiolabelled choline PET demonstrated excellent diagnostic performance in detecting HP in patients with HPT. Large multicentre studies and cost-effectiveness analyses are needed to better define the role of this imaging method in this setting.

Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy

Background/aim: Prolonged hypercalcemia impairs renal function, and a reduced glomerular filtration rate (GFR) is typical in advanced primary hyperparathyroidism (PHPT). There are scarce data related to predictors of renal impairment in patients with PHPT. Hence, we aimed to evaluate changes in kidney function in PHPT patients after parathyroidectomy (PTX) and identify factors associated with GFR variation in these patients. Materials and methods: One hundred and twenty-five patients with PHPT who underwent surgery between 2012 and 2014 were enrolled in the study. Patients were divided into two groups according to GFR values: patients whose GFR was lower than 60 mL/min/1.73 m2 and higher than 60 mL/min/1.73 m2. Demographic and laboratory parameters were compared before and 6 months after parathyroidectomy. Results: Prevalence of antihypertensive drug users and patients with renal cysts and parathormone (PTH) and alkaline phosphatase levels were higher in patients with GFR of ≥60 than in GFR of <60 mL/min/1.73 m2 (P < 0.05). Systolic BP, uric acid, and magnesium were decreased in patients with GFR of ≥60, but GFR did not change in the two groups after parathyroidectomy. After parathyroidectomy, calcium and PTH decreased but 25(OH)D3 and phosphorus increased in the two groups. In multiple regression analysis, age, calcium, and baseline GFR were independent predictors of GFR variation. Parathyroid adenoma volume and urinary calcium were not independent predictors of GFR change. Conclusion: Olderage, higher preoperative calcium, and GFR were factors associated with GFR increase in PHPT patients after parathyroidectomy. Further renal impairment was prevented by parathyroidectomy in PHPT patients

Effect of parathyroidectomy on epicardial fat thickness as a cardiovascular risk factor in patients with primary hyperparathyroidism

Background/aim: Several studies demonstrated that primary hyperparathyroidism is related to increased risk for cardiovascular diseases (CVDs), and risk is decreased by parathyroidectomy. Epicardial fat thickness (EFT) has been postulated as a new marker of CVD risk. We evaluated the impact of parathyroidectomy on EFT in patients with primary hyperparathyroidism (PHPT). Materials and methods: Thirty-four PHPT patients (29 female, 5 male) and 28 age- and sex-matched controls (19 female, 9 male) were included in the study. Demographic, anthropometric, and biochemical data were recorded both before parathyroidectomy and 6 months after the procedure. Epicardial fat thickness was measured by transthoracic echocardiography. Results: Mean age was 53.15 ± 8.44 years. Mean preoperative EFT was higher than mean EFT in the control group (0.49 ± 0.07 cm to 0.46 ± 0.08 cm, P: 0.0005), and EFT decreased after parathyroidectomy (0.49 ± 0.07 cm to 0.44 ± 0.08 cm, P: 0.0005). Systolic blood pressure and calcium, parathormone, and hsCRP levels decreased after parathyroidectomy (P < 0.05). Vitamin D levels increased (P < 0.05). Diastolic blood pressure, body mass index, carotid intima-media thickness, and HOMA-IR, fasting plasma glucose, and phosphorus levels were unchanged after parathyroidectomy (P > 0.05). Preoperatively, EFT was correlated with SBP (r: 0.360, P: 0.0285) and age (r: 0.466, P: 0.0036). Multiple linear regression used to identify independent predictors of change in epicardial fat did not find any predictor of change in epicardial fat (P > 0.05). Conclusion: EFT was decreased by parathyroidectomy in patients with primary hyperparathyroidism.However, the decrease in EFT was not correlated with any of the cardiovascular risk factors. More comprehensive studies evaluating the potential relation between PHPT and EFT need to be conducted.

Challenging pre-surgical localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism: the added value of 18F-Fluorocholine PET/CT.

PURPOSE: To evaluate the added value of 18F-Fluorocholine (18F-FCH) PET/CT in presurgical imaging of patients with primary hyperparathyroidism (HPT) and challenging localization of the hyper-functioning parathyroid glands. METHODS: We included 27 consecutive patients with primary HPT (19 F; median age: 58 years), with either (i) non-conclusive pre-surgical localization with 99mTc-sestaMIBI scintigraphy and neck ultrasonography (US), (ii) recurrence of previously operated HPT, or (iii) familiar HPT with a suspicion of multiple gland disease. Histological findings and resolution of HPT were considered as the gold standard. RESULTS: 18F-FCH PET/CT was positive in 24/27 patients. Twenty-one patients underwent surgery with 27 resected lesions (14 adenomas, 11 hyperplastic glands, two hyper-functioning histologically normal glands), with resolution of HPT in 19/21 patients (90%). 18F-FCH PET/CT localized 22 lesions in 17/21 patients (per patient: sensitivity 81%, positive predictive value (PPV) 94%; per gland: sensitivity 76%, PPV 85%, specificity 91%, negative predictive value (NPV) 86%). 18F-FCH PET/CT found eight lesions which were undetectable on both 99mTc-sestaMIBI scintigraphy and US. In patients with a familial HPT and/or a multiple gland disease, sensitivity was 100 and 79% on a per-patient and a per-gland analysis respectively, while NPV was 63%. In six patients with a persistence or recurrence of previously treated HPT, 18F-FCH PET/CT localized all lesions, both in sporadic and familiar disease. CONCLUSIONS: 18F-FCH PET/CT is a promising modality in challenging pre-surgical localization of hyper-functioning parathyroid glands, such as inconclusive standard imaging, recurrence after surgery, or suspected multiple gland disease.

Normocalcemic Primary Hyperparathyroidism: A Comparison with the Hypercalcemic Form in a Tertiary Referral Population.

Normocalcemic primary hyperparathyroidism (NPHPT) is a formally recognized variant of primary hyperparathyroidism (PHPT), characterized by normal total and ionized serum calcium concentrations and elevated parathyroid hormone (PTH) levels, in the absence of secondary causes for hyperparathyroidism. NPHPT has been studied previously, but data are limited and confounded. We aimed to compare the clinical and biochemical data of normocalcemic and hypercalcemic subjects in a hospital-based population.We retrospectively analysed the medical records of 131 subjects diagnosed with PHPT at the university hospital Brussels (UZ Brussel) between January 1st 2007 and December 31st 2016, including 25 normocalcemic and 106 hypercalcemic subjects.The mean values of age, BMI, sex, serum 25-OH vitamin D levels and urinary phosphate excretion were comparable between both groups. Subjects diagnosed with NPHPT had significantly lower plasma PTH levels, lower urinary calcium excretion and lower serum creatinine levels compared to the hypercalcemic subjects with PHPT. Corresponding eGFR values were higher in the normocalcemic group. Normocalcemic subjects (NPHPT) presented with a high prevalence of nephrolithiasis (36%), fragility fractures (12%) and osteoporosis (25%). Clinical manifestations and BMD measurements revealed no statistically significant differences between both groups.Our data show a relative prevalence of 19% NPHPT in PHPT. NPHPT may present the earliest form of PHPT with an extension in time, but is not an indolent disease state. Normocalcemic subjects should be managed as hypercalcemic subjects with PHPT. Further research regarding the pathophysiology and natural course of NPHPT is required.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 414.8 IU/L, p < 0.001) and S. iPTH (837.52 vs 812.89 vs 635.74 pg/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 25.30 ng/mL, p < 0.001). CONCLUSIONS: 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 effect of primary hyperparathyroidism on pancreatic exocrine function.

BACKGROUND: Elastase-1 is a proteolytic enzyme secreted by pancreatic acinar cells, and measurements of the concentration this enzyme are used to evaluate pancreatic exocrine function. We aimed to determine whether pancreatic exocrine function declines due to chronic hypercalcemia by measuring fecal elastase levels. METHODS: 75 patients with primary hyperparathyroidism (18 men and 47 women) and 30 healthy subjects (11 men and 19 women) participated in this study. Renal function tests, lipid parameters, bone mineral density, and serum calcium, phosphorus, vitamin D, parathormone, glucose, and thyroid stimulating hormone levels as well as fecal elastase concentrations, were determined in these patients and controls. RESULTS: The mean fecal elastase level was 335.3 ± 181.4 µg/g in the PHPT group and 317.4 ± 157.3 µg/g in the control group. There was no significant difference in fecal elastase levels between the two groups (p = 0.5). CONCLUSIONS: Chronic hypercalcemia in primary hyperparathyroidism did not decrease the fecal elastase level, which is an indirect indicator of chronic pancreatitis; therefore, chronic hypercalcemia in PHPT may not cause chronic pancreatitis.

Is primary hyperparathyroidism a cause of endothelial dysfunction?

OBJECTIVE: Symptomatic primary hyperparathyroidism (PHPT) is thought to be related to increased cardiovascular morbidity and mortality. In our study, we aimed to investigate endothelial dysfunction and markers of subclinical atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of vitamin D supplementation on these parameters. MATERIALS AND METHODS: Twenty-nine patients followed by medical treatment (A), 25 preoperative (B) and 23 postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were included. Groups were assessed by measurements of flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25-hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and 3 months after vitamin D replacement. RESULTS: The median FMD was 5% in group A, 5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in group A was significantly lower than groups C and D (P=.02) and was similar to the FMD measurement in group B. FMD measurements of group B were not significantly lower than groups C and D. In 13 patients with low 25OHD in group A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement (P=.02). CONCLUSION: Flow-mediated dilation was impaired in patients with PHPT, particularly in the medically observed group. Vitamin D supplementation seems to provide improvements in FMD in medically observed PHPT patients with low 25OHD levels, and this was the novel observation of our study.

Skeletal effects of vitamin D deficiency among patients with primary hyperparathyroidism.

Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent. INTRODUCTION: Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients. METHODS: We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015. RESULTS: We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm2; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm2; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men. CONCLUSION: Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.

Surgery Significantly Improves Neurocognition, Sleep, and Blood Pressure in Primary Hyperparathyroidism: A 3-Year Prospective Follow-Up Study.

Surgery for primary hyperparathyroidism (PHPT) improves health-related quality of life (HRQoL), but it is unclear whether the effects are sustained after medium-term (>2 years) follow-up, and whether the results on some or all dimensions of HRQoL will reach that of the general population. We performed a follow-up of HRQoL on average 3.3 years after surgery for PHPT using the 15D in our patient cohort (n=124) and compared the results to those of an age- and gender-standardized general population (n=1099). We studied self-reported blood pressure and current medications; new comorbidities were retrieved from electronic patient records. A total of 104 (83%) patients [eight with serum calcium (1.34-1.46 mmol/l)] returned the questionnaires. After a follow-up of 3.3 years (range 23 to 55 months), systolic and diastolic blood pressure had decreased significantly compared to baseline (the situation before surgery, p<0.001). Thirty-four (33%) had acquired a new diagnosis (range 1-7), the most common being cardiovascular disease and cancer. Mean 15D score was significantly better compared to baseline (p<0.001), the dimensions of sleeping, mental function, discomfort and symptoms, and depression had further improved (p<0.01), and no longer differed from that of the general population. In PHPT, after >2 years follow-up, surgery improves blood pressure and restores neurocognitive function and sleep to the level of the general population. The improvements observed in overall HRQoL at one year after surgery are sustained, but overall HRQoL does not reach that of the general population.

Evaluation of biomechanical properties of the cornea in patients with primary hyperparathyroidism.

The purpose of this study is to compare the corneal biomechanical properties in primary hyperparathyroid patients and healthy control subjects. The study consisted of 31 patients with primary hyperparathyroidism (study group) and 31 healthy subjects (control group). Corneal biomechanical properties, including corneal hysteresis (CH), corneal resistance factor (CRF), and intraocular pressure (IOP) were measured with an ocular response analyzer (ORA). IOP was also measured using Goldmann applanation tonometry (GAT), and central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The differences in ORA parameters and CCT between study and control group participants were analyzed. The mean CH in study and control groups was 8.7 ± 1.9 mmHg (5.3-13.7 mmHg) and 9.8 ± 1.5 mmHg (7.7-14.3 mmHg), respectively (p = 0.018). The mean CRF was 9.5 ± 1.8 (5.5-13.7) in the study group compared with 9.8 ± 1.5 (6.2-12.8) in the control group. The difference for CRF was not statistically significant (p = 0.41). In study and control group, corneal-compensated IOP (IOPcc) values were 18.2 ± 4.2 and 16.9 ± 2.7 mmHg, respectively (p = 0.12). Mean IOP measurement values with GAT were 16.3 ± 3.4 mmHg for study group and 16.5 ± 2.7 mmHg for control group (p = 0.71). The mean differences of IOPcc and IOPGAT in the study group eyes were higher than that of control group eyes (1.9 vs. 0.4 mmHg). CCT was 536.5 ± 25.4 µm (490-593 µm) in study group eyes compared with 534.2 ± 31.4 µm (472-602 µm) in control eyes (p = 0.75). Hyperparathyroidism could be associated with a decrease of CH. The differences between IOPcc and IOPGAT in these patients were higher than normal subjects. Underestimation of IOP readings with GAT may be a consequence of the lower CH in patients with hyperparathyroididsm.

Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness.

OBJECTIVE: Although an International Workshop has suggested that cardiovascular assessment in asymptomatic primary hyperparathyroidism (PHPT) patients is not necessary, improvements in risk factors of subclinical atherosclerosis have been shown following parathyroidectomy. The objectives of this study were to determine whether parathyroidectomy in asymptomatic PHPT patients causes any change in carotid intima-media thickness (CIMT), arterial stiffness [pulse wave velocity (PWV)] and soluble CD40 ligand (sCD40L) levels. DESIGN: Prospective study evaluating female patients diagnosed with asymptomatic PHPT in a single centre over a 6-month period. PATIENTS: A total of 48 subjects were included: 17 hypercalcaemic (HC, mean age: 51 ± 8 years, Ca: 2·73 ± 0·17 mmol/l) and 16 normocalcaemic (NC, mean age: 58 ± 7 years, Ca: 2·30 ± 0·10 mmol/l) PHPT patients, and 15 healthy controls (mean age: 52 ± 4 years, Ca: 2·27 ± 0·07 mmol/l). MEASUREMENTS: Biochemical tests, CIMT, PWV and sCD40L levels were compared at baseline and 6 months after parathyroidectomy (PTx). RESULTS: At baseline, CIMT and PWV values in the HC and NC patients were higher than in the control group. While there was a significant reduction in CIMT (601 ± 91 µm vs 541 ± 65 µm, P = 0·006) and PWV (9·6 ± 1·8 vs 8·4 ± 1·5 m/s, P = 0·000) in the hypercalcaemic group at the end of the 6th month after PTx, no change was observed in normocalcaemic group (P = 0·686 and P = 0·196 respectively). No differences were observed in sCD40L levels between patient and control groups or between baseline and 6 months in patients undergoing parathyroidectomy. CONCLUSION: Parathyroidectomy leads to an improvement in the structural and functional impairment associated with atherosclerosis in the vascular wall in asymptomatic hypercalcaemic PHPT patients.

Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism.

UNLABELLED: Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS). INTRODUCTION: The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT. METHODS: This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively. RESULTS: In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p = 0.05), were less likely to use vitamin D supplementation (p < 0.01), and had better renal function (p = 0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20-29 ng/ml (p = 0.002) and 25OHD ≥30 ng/ml (p < 0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20-29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p < 0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status. CONCLUSION: In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.

[Pathophysiology of primary hyperparathyroidism].

Primary hyperparathyroidism is a disease with increased cell proliferation and enhanced PTH secretion due to the escape from negative feedback by calcium ion in parathyroid cells for their tumorization. Involvements of several gene abnormalities have been demonstrated in the pathogenesis of parathyroid tumor. First, an activation of cyclin D1 gene by the translocation of 11 chromosome was found as one of the cause of parathyroid tumorigenesis. Moreover, mutation of multiple endocrine type 1 gene is the most frequent as a genetic cause of sporadic parathyroid tumor. Its related tumor is developed by an inactivation mutation of tumor suppressor gene. Parafibromin, calcium-sensing receptor, vitamin D receptor, Klotho and RET might be related to the tumorigeneis of parathyroid tumor.