Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

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.

Adenoma paratiroideo mediastínico gigante. Abordaje cervical y toracoscópico. Caso clínico / Gigant Mediastinal Parathyroid Adenoma. Cervical and Thoracoscopic Approach. Case Report

El hiperparatiroidismo primario es el tercer trastorno endocrino más común, alrededor del 85% de los casos se debe a adenomas paratiroideos. El tratamiento definitivo es la paratiroidectomía, siendo la causa más común de fracaso la resección inadecuada y la localización de tejido ectópico, representando un desafío para el cirujano. En el presente trabajo se presenta el caso de un paciente con diagnóstico de adenoma paratiroideo mediastínico gigante, siendo este el de mayor longitud descrito en la literatura en los últimos 10 años. Caso clínico: Paciente masculino de 70 años de edad quien consulta por presentar convulsiones, polidipsia y poliuria. Se determinan niveles elevados de PTH, hipercalcemia e hipofosfatemia. Estudios de imagen describen lesión alargada localizada en espacio paratraqueal derecho extendiéndose hasta el polo inferior de lóbulo tiroideo derecho. Se decide resolución quirúrgica, mediante la realización de cervicotomía y toracoscopia con evolución satisfactoria del paciente. Conclusión: Los adenomas paratiroideos ectópicos constituyen una causa común de falla quirúrgica e hiperparatiroidismo persistente, su sospecha es de gran importancia. El tratamiento definitivo es la cirugía. La localización preoperatoria por pruebas de imagen es fundamental para seleccionar correctamente la técnica quirúrgica y garantizar el éxito de la cirugía. El abordaje cervical y toracoscópico es una alternativa segura y eficaz(AU)

Primary hyperparathyroidism is the third most common endocrine disorder, about 85% of cases are due to parathyroid adenomas. The definitive treatment is parathyroidectomy, being the most frequent cause of failure the inadequate resection and the location of ectopic tissue. The ectopic parathyroid adenomas represent a challenge for the surgeon. In this paper a case of a patient diagnosed with giant mediastinal parathyroid adenoma is presented, and is the largest reported in the literature in the last 10 years. Clinical case: 70-year-old male patient presented with seizures, polydipsia and polyuria, reason for which he consults. Elevated PTH levels, hypercalcemia, and hypophosphatemia are determined. Imaging studies report an elongated lesion located in the right paratracheal space that extends to the lower pole of the right thyroid lobe. Surgical resolution was decided, by performing cervicotomy and thoracoscopy with satisfactory recovery of the patient. Conclusion: Ectopic parathyroid adenomas are a common cause of surgical failure and persistent hyperparathyroidism; their suspicion is of great importance. The definitive treatment is surgery. Preoperative localization through imaging tests is essential to correctly select the surgical technique and guarantee the success of the surgery, the cervical and thoracoscopic approach is a safe and effective alternative(AU)

Evaluation and Management of Elevated Parathyroid Hormone Levels in Normocalcemic Patients.

Primary hyperparathyroidism is a common endocrine disorder. It used to present as a highly symptomatic disease before the advent of the multichannel autoanalyzer, now usually presenting as mild asymptomatic hypercalcemia. A newer presentation has been increasingly identified in the past two decades, normocalcemic primary hyperparathyroidism, presenting with elevated parathyroid hormone concentrations and consistently normal serum calcium. These patients are usually symptomatic, with parathyroid hormone levels measured in the evaluation for kidney stones or osteoporosis. It is important to exclude causes of secondary hyperparathyroidism. This review will focus on the evaluation and management of elevated parathyroid hormone levels in normocalcemic patients.

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism.

CONTEXT: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well. OBJECTIVE: To evaluate bone material properties using impact microindentation (IMI) in PHPT patients. METHODS: In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status. RESULTS: Mean age of PHPT patients and controls was 61.8 ±â€…13.3 and 61.0 ±â€…11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ±â€…0.15 vs 0.89 ±â€…0.11, P = .37) and the femoral neck (0.70 ±â€…0.11 vs 0.67 ±â€…0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ±â€…5.7 vs 82.8 ±â€…4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ±â€…6.0 vs 79.6 ±â€…5.0, P = .015). CONCLUSION: Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness.

CONTEXT: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. OBJECTIVE: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. METHODS: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022). CONCLUSION: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

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.

FGF23 and primary hyperparathyroidism: is there a link?

INTRODUCTION: Data regarding the role of fibroblast growth factor 23 (FGF23) in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed to evaluate the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT. MATERIAL AND METHODS: Forty-two patients with ages between 30 and 80 years, diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma, and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium (Ca), phosphate (P), total procollagen type 1 N-terminal propeptide, and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), one day after surgery, and in 13 patients also prospectively at three, six, and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13 followed up patients. RESULTS: In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2 ± 1.5 ng/mL), preoperatory serum FGF23 concentration was within the normal range (75.55 ± 3.39 pg/mL) and remained unchanged one day post operation (81.69 ± 4.67 pg/mL, p = non-significant). The 13 patients followed prospectively for up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/mL, p = non-significant), despite PTH and Ca normalisation and vitamin D replenishment. Preoperatory FGF23 negatively correlated with PTH (r = -0.37, p = 0.038), but not with 25(OH)D3, Ca, P, bone mass, or metabolism markers. CONCLUSIONS: In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we think that FGF23 evaluation and dynamics are not informative regarding PHPT severity. (Endokrynol Pol 2020; 71 (4): 306-312).

Measurement of the AST to LD Ratio in Parathyroid Tissue Suspension Can Precisely Differentiate a Hyperfunctioning Parathyroid.

BACKGROUND: Frozen section of excised tissue is used to confirm removal of the etiology of primary hyperparathyroidism in the current era of intraoperative parathyroid hormone measurement and provides safeguards for surgeons. We recently reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LD) ratio in tissue suspension can accurately distinguish normal parathyroid tissue from other tissues. Therefore, we hypothesized that this ratio may also be applied to distinguish hyperfunctioning parathyroid tissue (HPT) from other tissues. METHODS: We prospectively analyzed 22 patients who underwent parathyroidectomy for primary hyperparathyroidism (benign, 21; malignant, 1) from July 2018 to October 2019. In total, 27 specimens were examined. Approximately 1 mm3 of minced HPT as confirmed by frozen sections was suspended in 1 mL of normal saline and AST and LD levels were measured. The AST/LD ratios of other tissues (normal parathyroid tissue, thyroid gland, adipose tissue, and others; n = 94) were obtained from our previous report. RESULTS: The AST/LD ratio of benign HPT was consistently higher than that of other tissues (P < 0.001). The optimal cut-off value was 0.36 according to the receiver operating characteristic curve, with 100% sensitivity and specificity. The AST/LD ratio in malignant HPT was also markedly lower than that in benign HPT. CONCLUSION: This method might be a new adjunct for intraoperative differentiation of HPT with an accuracy and turnaround time comparable with those of frozen sections, minimal cost, and no need for dedicated pathological staff. Additionally, this method might increase the treatment success rate in settings with limited medical resources.

Functional magnetic resonance imaging in primary hyperparathyroidism.

OBJECTIVE: The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). DESIGN: This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. RESULTS: There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. CONCLUSIONS: PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT.

Diferencias en el metabolismo mineral óseo hiperparatiroidismo primario normocalcémico respecto al hiperparatiroidismo primario clásico / Differences in bone mineral metabolism normocalcemicprimary hyperparathyroidism with respect to classicalprimary hyperparathyroidism

OBJETIVO: El hiperparatiroidismo primario normocalcémico es una variedad menos conocida del hiperparatiroidismo primario clásico. Presentamos en este estudio sus manifestaciones clínicas y los datos relacionados con el metabolismo mineral óseo, tanto desde el punto de vista analítico como densitométrico, comparando los mismos con un grupo de pacientes afectos de hiperparatiroidismo primario clásico, con hipercalcemia. MATERIAL Y MÉTODOS: Estudio de casos y controles donde consideramos caso a pacientes afectos de hiperparatiroidismo primario normocalcémico (n=25) y control (n=25) a pacientes con hiperpartiroidismo primario con hipercalcemia (hiperparatiroidismo primario clásico). Se les efectuó una evaluación clínica completa con recogida de datos clínicos y realizándose determinaciones analíticas en sangre y orina de 24h, así como la estimación de la densidad mineral ósea y el trabecular bone score por densitometría (absorciometría radiológica dual, DXA) y los parámetros ultrasonográficos en el calcáneo. RESULTADOS: En el estudio clínico, los pacientes afectos de hiperparatiroidismo primario clásico solo muestran una mayor prevalencia de urolitiasis (OR: 9,333; IC 95%: 1,50-82,7) en comparación con los pacientes que sufren un hiperparatiroidismo primario normocalcémico. En todos los demás parámetros clínicos, analíticos, densitométricos y ultrasonográficos, no se aprecian diferencias estadísticamente significativas entre ambos grupos. CONCLUSIONES: Con la excepción de los niveles séricos de calcio y la prevalencia de urolitiasis, el hiperparatiroidismo normocalcémico cursa de manera indistinguible del hiperparatiroidismo clásico

OBJECTIVE: Normocalcemic primary hyperparathyroidism is a less known variety of classical primary hyperparathyroidism. In this paper, we present its clinical expression and data related to bone mineral metabolism, both analytically and densitometrically, comparing them with a group of patients with classic primary hyperparathyroidism, with hypercalcemia. MATERIAL AND METHODS: Study of cases and controls where we consider case of patients with normocalcemic primary hyperparathyroidism (n=25) and control (n=25) of patients with primary hyperpartyroidism with hypercalcemia (classical primary hyperparathyroidism). A complete clinical assessment was carried out with clinical data collection and24h blood and urine analytical determinations were performed, as well as estimating bone mineral density and trabecular bone score by densitometry (dual x‐ray absorptiometry, DXA) and ultrasound parameters in the calcaneus. RESULTS: In this clinical study, patients with classic primary hyperparathyroidism only show a higher prevalence of urolithiasis (OR: 9.333; 95% CI: 1.50‐82.7) compared to patients suffering from a normocalcemic primary hyperparathy‐roidism. In all other clinical, analytical, densitometric and ultrasonographic parameters, there are no statistically significant differences between the two groups. CONCLUSIONS: Apart from serum calcium levels and the prevalence of urolithiasis, normocalcemic hyperparathyroidism is indistinguishable from classical hyperparathyroidism

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.

18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%-56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%-34% (44% combined). Conclusion:18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Persistence of "non-dipping" pattern in blood pressure after curative parathyroidectomy in apparently normotensive patients with symptomatic primary hyperparathyroidism.

BACKGROUND: The prevalence of hypertension in primary hyperparathyroidism (PHPT) varies from 20-80% with data being based on office-based blood pressure measurements. Little is known about ambulatory monitoring of blood pressure (AMBP) in PHPT and changes in blood pressure (BP) variables post-curative parathyroidectomy. Hence, we conducted a prospective study wherein we performed AMBP in apparently normotensive patients with PHPT and reevaluated them 3 months post-curative parathyroidectomy. METHODS: Consecutive patients with symptomatic PHPT aged 20 years and above underwent 24 hours AMBP at enrollment and at 3 months after successful parathyroidectomy. Pre- and postoperative BP variables were compared and correlated with serum calcium, creatinine and intact parathyroid hormone (iPTH) levels. RESULTS: After exclusion, 17 symptomatic PHPT patients were enrolled in the study. AMBP detected hypertension in 4 (23.5%) patients. There was a significant reduction in the average nighttime systolic (P=0.007) and diastolic BP (P=0.034) after parathyroidectomy. However, the average 24 hours systolic/diastolic BP, daytime systolic/diastolic BP and average 24 hours mean arterial pressure did not differ before and after surgery. Non-dipping blood pressure pattern was seen in 53% of patients at presentation and persisted in 50% of cases after successful surgery. None of the biochemical parameters significantly correlated with any BP variable. CONCLUSIONS: AMBP can help detect hypertension in patients with PHPT that remains unrecognized with routine office-based blood pressure measurement. In addition, AMBP detects loss of normal dipping pattern in BP that persists in almost half of the patients even after successful parathyroidectomy, perhaps because of permanent vascular damage induced by PHPT.

[HYPERPARATHYROIDISM AND PARATHYROID LESIONS IN THE ChNPP ACCIDENT SURVIVORS]. / GIPERPARATYREOZ TA URAZhENNIa PRYShchYTOPODIBNYKh ZALOZ U OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: Study of the status of parathyroid glands in individuals exposed to ionizing radiation as a result of the ChNPP accident and comparison with the general population of Ukraine. MATERIALS AND METHODS: Subjects exposed as a result of the ChNPP accident (n = 1,348) and people from the general population of Ukraine (n=655) were examined. Diagnostic ultrasound scan of thyroid and parathyroid glands (PTG) was conducted in all study subjects. The technique of parathyroid ultrasound screening was developed, which led to an increase in the efficiency of their imaging. Additionally, the 25-hydroxyvitamin D (25(OH)D), parathyroid hor- mone, ionized calcium and some other parameters were selectively assayed in serum. RESULTS: High incidence of parathyroid hyperplasia was detected 27-32 years after the irradiation in persons ex- posed as a result of the ChNPP accident, especially in evacuees from the 30-km exclusion zone (71.4%; χ2Yates' = 24.1; р = 0) and residents of radilogically contaminated territories (41.7%; χ2Yates' = 6.45; p < 0.01) having no primary hyperparathyroidism. High prevalence of vitamin D insufficiency and deficiency was revealed in all study subgroups, namely in 83.1 % of the general population of Ukraine along with a bit better vitamin D status in the ChNPP acci- dent survivors i.e. the vitamin insufficiency and deficiency was found in 78.7 % of them. Incidence of hyperparathy- roidism, predominantly of the secondary (normocalcemic) one, was 33.8 % among persons exposed as a result of the ChNPP accident (p > 0.3) being somewhat higher than in the general population of Ukraine (26.1%), despite above- mentioned better supply of vitamin D. CONCLUSIONS: There is a widespread insufficiency or deficiency of vitamin D (over 78.7%) in the population of Ukraine in general providing an unfavorable background for the higher prevalence of health disorders associated with calcium and phosphorus metabolism. The latter features parathyroid hyperplasia and musculosceletal, immune, cardiovascular, and endocrine system comorbidities. Such disorders should exacerbate with a secondary increase in parathyroid hormone secretion (26.1 %). Higher incidence of normocalcemic hyperparathyroidism (33.8% versus 26.1%) against a background of better vitamin D status among irradiated individuals indicates the existence of other factors, where the past combined effects of Chornobyl radioactive fallout and external parathyroid exposure are most likely to be involved. This could explain the greater number of cases of parathyroid hyperplasia and hyper- parathyroidism among the exposed subjects. However the additional precise studies are required here with clarifi- cation of the personal data in population groups of the ChNPP accident survivors. Participants of the ChNPP acci- dent clean-up work in the «iodine period¼ of 1986 are of especial concern here. Besides that, the study population should be expanded with inclusion of subjects exposed in prenatal period.

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.

Effect of Parathyroidectomy on Cardiovascular Risk Factors in Primary Hyperparathyroidism: A Randomized Clinical Trial.

CONTEXT: It remains unclear whether risk of cardiovascular diseases is increased in patients with mild (<1.45 mmol/L) to moderate (≥1.45 to 1.60 mmol/L) primary hyperparathyroidism (PHPT). OBJECTIVE: We aimed to determine the short-term effect of parathyroidectomy (PTX) on arterial stiffness, cholesterol levels, and blood pressure (BP). DESIGN: This study was a clinical trial randomly allocating patients to either PTX or a control group (no surgery). Follow-up was performed 3 months after surgery in the PTX group and 3 months after baseline in the control group. SETTING: University hospital. PARTICIPANTS: We recruited 79 patients with PHPT; 69 participants completed the study. MAIN OUTCOMES: Office and ambulatory 24-hour BP, pulse wave velocity (PWV), augmentation index, and fasting plasma cholesterol levels. RESULTS: At baseline, participants had a median level of ionized calcium of 1.41 mmol/L (range, 1.33 to 1.60 mmol/L) and PTH of 10.4 pmol/L (4.5 to 30.4 pmol/L). Median age was 64 years (range, 18 to 81) and 72% were females. Following PTX, plasma total cholesterol levels decreased significantly compared with the controls (P = 0.04). Changes in PWV, augmentation index, and ambulatory 24-hour BP did not differ between groups, except for an increase in ambulatory diastolic BP following PTX. However, in patients with baseline levels of ionized calcium ≥1.45 mmol/L, PWV decreased significantly in response to PTX compared with the control group (P = 0.03). CONCLUSION: PTX may decrease risk of cardiovascular diseases in PHPT by lowering total cholesterol levels, although ambulatory diastolic BP increases in response to surgery. Patients with moderate to severe hypercalcemia may benefit from PTX by a decrease in PWV.

Evaluation of endothelial function and diastolic function in patients with primary hyperparathyroidism before and after parathyroidectomy.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is the leading cause of outpatient hypercalcemia associated with increased cardiovascular risk. The flow-mediated vasodilation (FMV) has been proposed as a non-invasive method for assessing endothelial function. OBJECTIVE: To compare the endothelial dysfunction measured by FMV and diastolic dysfunction in patients with PHPT before and after parathyroidectomy. METHOD: We performed a quasi-experimental (before-after) study to evaluate diastolic function and FMV in patients with PHPT before and six months after parathyroidectomy. RESULTS: Fifteen patients completed study: 12 women and 3 men; 73% presented lithiasis, 27% osteoporosis and 53% metabolic syndrome; 73% presented diastolic dysfunction before the surgery and 60% after the surgery (p = 0.09). Post-isquemia brachial diameter improved from 41 mm (before surgery) to 46 mm (after surgery; p = 0.020). After surgery, we also observed an increase in the brachial diameter pre vs. post-ischemia from 41 to 46 mm (p = 0.005). Before surgery, the change in the delta of brachial diameter pre and post-ischemia was 1 mm and up to 4 mm after surgery (p = 0.03). CONCLUSIONS: There is a minor endothelial dysfunction measured by FMV in patients who underwent surgery for PHPT at 6 months after surgery, as well as a trend towards improvement in diastolic dysfunction. Echocardiography can be useful in the preoperative evaluation in patients with asymptomatic PHPT.

INTRODUCCIÓN: El hiperparatiroidismo primario (HPTP) es la principal causa de hipercalcemia ambulatoria y se ha asociado con un riesgo cardiovascular elevado. La vasodilatación mediada por flujo (VMF) es un método no invasivo que evalúa la función endotelial. OBJETIVO: Comparar la disfunción endotelial mediante VMF y la disfunción diastólica en pacientes con HPTP antes y después de la paratiroidectomía. MÉTODO: Mediante un estudio cuasiexperimental (antes-después) se evaluaron la función diastólica y la VMF antes y 6 meses después de realizar una paratiroidectomía. RESULTADOS: Se incluyeron 15 pacientes con HPTP: 12 mujeres (80%) y 3 hombres (20%); el 73% presentaron litiasis, el 27% osteoporosis y el 53% síndrome metabólico; el 73% tenían disfunción diastólica antes de la cirugía y el 60% después de la cirugía (p = 0.09). Los diámetros braquiales post-isquemia mejoraron de 41 mm antes de la cirugía a 46 mm tras la cirugía (p = 0.020). Así mismo, los diámetros braquiales preisquemia vs. post-isquemia después de la cirugía mejoraron de 41 a 46 mm (p = 0.005). Antes de la cirugía, el cambio en la delta del diámetro braquial preisquemia y post-isquemia fue de 1 mm, y subió a 4 mm después de la cirugía (p = 0.03). CONCLUSIONES: Existe una menor disfunción endotelial medida por VMF en pacientes posoperados por HPTP a los 6 meses de la cirugía. El estudio ecocardiográfico puede ser de utilidad en la evaluación preoperatoria de los pacientes con HPTP asintomáticos.