Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy

OBJECTIVE: The endothelium is a newly recognised target tissue of parathyroid hormone (PTH). It is not clear whether hyperparathyroidism affects endothelial function and whether parathyroidectomy (Ptx) has an influence on arterial vessel wall properties. We studied brachial flow-mediated vasodilation (FMD) and brachial and carotid intima-media thickness (IMT) in patients with primary hyperparathyroidism (pHPT) before and after Ptx and in healthy controls. METHODS: 19 patients with pHPT (mean+SEM, age 45+/-4.7 years, PTH 238+/-52 ng/l) were studied. Diabetes, hypertension and vascular disease were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. Enddiastolic diameter, FMD and nitroglycerine-induced (NMD) dilation of the brachial artery were measured by a multigate pulsed doppler system (echo-tracking), IMT was determined using automatic analysis of the M-line signal. Healthy volunteers where studied on one occasion, patients were studied at baseline and 6 months after Ptx. RESULTS: Six months after Ptx PTH had decreased to normal, blood pressure levels remained unchanged. Endothelium dependent FMD at baseline was impaired in patients compared to controls (4.7+/-1.2 vs. 18.2+/-3.7%, P<0.01), however, FMD improved significantly after Ptx (16.7+/-3.0%, P<0.01). Nitroglycerine-induced dilation, IMT and artery diameter were not different between groups and did not change after Ptx. CONCLUSIONS: Impaired endothelium dependent vasodilation in patients with primary hyperparathyroidism improves after successful parathyroidectomy. Endothelial dysfunction associated with primary hyperparathyroidism occurs without detectable structural wall alterations of the brachial artery and appears therefore to be an early and reversible arterial alteration.     

Prediction of bone mass change after parathyroidectomy in patients with primary hyperparathyroidism

A major challenge in the management of primary hyperparathyroidism (pHPT) is the decision regarding which patients should undergo parathyroidectomy (PTX), although the Consensus Development Conference of the NIH has proposed guidelines for the indication of surgery. In the present study, changes in bone mineral density (BMD) after PTX were compared between pHPT patients who did and did not meet the NIH criteria, and we further tried to predict the BMD change after PTX from preoperative parameters. The subjects were 44 pHPT patients (30 women and 14 men) who had had successful PTX. Lumbar and radial BMD were measured before and 1 yr after PTX by dual energy x-ray absorptiometry and single photon absorptiometry, respectively. Average annual percent increases in lumbar and radial BMD after PTX were 12.2 +/- 1.4% and 11.6 +/- 1.6% (mean +/- SEM), respectively, and those net increases were 0.0803 +/- 0.0008 and 0.0484 +/- 0.0006 g/cm2, respectively. There were no significant differences in percent or net changes in either radial or lumbar BMD after PTX between the groups divided according to each of the NIH criteria, such as age (> or =50 and <50 yr), serum calcium level (> or =12 and <12 mg/dL) or the existence of urinary stones (presence and absence). On the other hand, when the subjects were divided on the basis of radial BMD (above and below a z-score of -2), the annual percent and net increases in lumbar BMD and percent increase in radial BMD after PTX were significantly higher in the group with the lower z-score. Next, patients were divided into two groups with and without the indication of PTX based on NIH guidelines. Twenty-nine patients had the surgical indication by meeting one or more of these criteria and 15 patients had no indication without meeting any of the criteria. There were no significant differences between the two groups in annual percent or net changes in radial or lumbar BMD after PTX. A stepwise multiple regression analysis revealed that serum alkaline phosphatase level and the severity of cortical bone mass reduction were the best predictors of both percentage and net changes in lumbar BMD, with high determination coefficients (r2 > 0.7). In conclusion, a considerable increase in BMD could be obtained after PTX even in patients without surgical indication from the NIH. Alkaline phosphatase and the severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after PTX. The present findings provide a useful clue for the indication of surgery in pHPT.     

Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years

OBJECTIVE: Postmenopausal women are at increased risk of primary hyperparathyroidism (pHPT). Secondary dyslipidaemia in pHPT has attracted little attention, although morbidity and mortality associated with cardiovascular diseases have been reported to be increased in these patients. DESIGN: A population-based screening programme was used to recruit postmenopausal women with mild, asymptomatic pHPT (mean serum calcium 2.57 +/- 0.12 mmol/l) and matched controls. MEASUREMENTS AND PATIENTS: Serum lipids, lipoprotein fractions and influences of treatment for the parathyroid disease were studied in 87 case-control pairs (mean age 67 years), 69 of whom completed a 5-year follow-up period. RESULTS: pHPT was characterized by decreased serum high-density lipoprotein (HDL)-cholesterol, increased total triglycerides, very-low-density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol levels and an elevated atherogenic index. The differences were more pronounced in the cases with serum parathyroid hormone levels in the normal range and were inversely correlated to the serum parathyroid hormone level. Parathyroidectomy, with or without additive hormone replacement therapy, normalized the dyslipidaemia. Five-year surveillance of pHPT without treatment was associated with a maintained increase in total triglycerides and the atherogenic index and a decrease in HDL-cholesterol levels. CONCLUSION: Proatherosclerotic dyslipidaemia characterizes mild pHPT and is effectively reversed by parathyroidectomy. As dyslipidaemia might contribute to the increased risk of cardiovascular diseases and death observed in pHPT, the findings favour operative intervention rather than conservative surveillance in mild, asymptomatic pHPT in postmenopausal females.     

Left ventricular structure and function in primary hyperparathyroidism before and after parathyroidectomy

OBJECTIVE: Our aim was to study the effect of primary hyperparathyroidism (PHPT) and parathyroidectomy (PTX) on left ventricular (LV) wall thicknesses and systolic and diastolic function. METHODS: Fifteen patients with untreated PHPT were evaluated by applying Doppler and digitized M-mode echocardiography before and 2-3 months after PTX. Fifteen age- and sex-matched healthy controls were also examined echocardiographically. RESULTS: Prior to PTX, interventricular septal thickness (IVST), LV mass (LVM), aortic root dimension and left atrium dimension were greater and LV fractional shortening was slightly decreased in patients as compared to controls. Significantly increased LV peak late diastolic velocity (A(max)) and isovolumic relaxation time, and a slightly decreased ratio of peak early to peak late diastolic velocities (E/A(max)) in the patients indicated impairment of LV diastolic function in hyperparathyroidism. PTX reduced serum total Ca from 2. 79 +/- 0.13 to 2.39 +/- 0.09 mmol/l (p < 0.001) and tended to reduce IVST [10.6 +/- 2.1 vs. 10.4 +/- 2.0 mm; not significant (n.s.)], LV posterior wall thickness (9.6 +/- 2.0 vs. 9.2 +/- 1.0 mm, n.s.) and LVM (250 +/- 102 vs. 213 +/- 42 g; n.s.). Before PTX, there was a significant correlation between serum total Ca and LVM (r = 0.63, p < 0.05), and the PTX-induced change in serum total calcium correlated with the change in LVM (r = 0.59, p < 0.05). PTX induced no significant changes in LV systolic or diastolic function during the follow-up of 2-3 months. CONCLUSIONS: The present findings indicate that PHPT induces LV hypertrophy, slight impairment of LV systolic function and significant impairment of LV diastolic function, which are not substantially improved after TX and 2-3 months of normocalcemia.     

Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy

Objective  To determine the relationship between anaemia and myelofibrosis in patients with symptomatic primary hyperparathyroidism (PHPT) and to assess the effect of curative parathyroidectomy on anaemia and marrow fibrosis.
Design and methods  In this prospective follow-up study of 28 consecutive patients with symptomatic PHPT from January 2005 to June 2006, 15 patients were diagnosed with anaemia (haemoglobin < 130 g/l in males and < 120 g/l in females), eight (53%) of whom were finally recruited for the study. Complete blood cell count, serum calcium, phosphorus, alkaline phosphatase, intact PTH and 25-hydroxyvitamin D and bone marrow examination were performed both before and after parathyroidectomy in all ( n  = 8) patients, but bone marrow examination after surgery was performed only in those who had marrow fibrosis at baseline ( n  = 6).
Results  Anaemia was observed in 15 (53·3%) of the 28 patients with symptomatic PHPT. Normocytic normochromic anaemia that is characteristic of PHPT was found in 14 (50%) patients. Eight of the 15 patients with anaemia had a bone marrow examination and marrow fibrosis was observed in six (75%). Both anaemia and marrow fibrosis improved after successful parathyroidectomy, but improvement in anaemia was significant ( P =  0·02) only in those with marrow fibrosis at baseline. Marrow fibrosis did not correlate with duration of the disease ( P =  0·17), degree of hypercalcaemia ( P =  0·53) or serum levels of intact PTH ( P =  0·60).
Conclusions  Anaemia is common in patients with symptomatic PHPT, and was associated with marrow fibrosis in the majority of the patients who underwent bone biopsy. Both anaemia and marrow fibrosis improved after curative parathyroidectomy, but improvement in anaemia was noticeable only in those who had marrow fibrosis at presentation.     

Acute and one-year effects of cinacalcet in patients with persistent primary hyperparathyroidism after unsuccessful parathyroidectomy

OBJECTIVE: We report the acute effects of cinacalcet on calcium and parathyroid hormone (PTH) levels and the effects of 1 year of therapy on calcium and phosphorus metabolism in 4 patients with persistent primary hyperparathyroidism (PHPT) after unsuccessful parathyroidectomy. PATIENTS: Four patients (3 women; age, 24 to 71 years) were studied after 1 to 3 parathyroid operative procedures. All of them had elevated serum total and ionized calcium levels, decreased serum phosphorus, and increased concentrations of intact PTH. METHODS: Calcium and PTH responses to an acute dose of oral cinacalcet (30 mg) were studied at baseline. Effects of cinacalcet (30 mg b.i.d.) on serum calcium, phosphorus, and PTH, and urinary calcium and phosphorus were studied at 1, 3, 6, and 12 months of therapy. RESULTS: PTH concentrations were reduced by 13.0% to 86.7% after acute cinacalcet administration. Chronic therapy with cinacalcet was followed by a decrement in serum total calcium (10.2% at 12 months) and ionized calcium (10.1%) and an increase in serum phosphorus (20.8%), with only a modest decrement in PTH levels (5.1%). All patients had normal serum total and ionized calcium levels at 3 to 12 months of therapy. Urinary calcium decreased by 20.0% at 12 months. CONCLUSIONS: Cinacalcet was effective in normalizing calcium and phosphorus concentrations in patients with persistent PHPT after unsuccessful parathyroidectomy.     

维持性血液透析患者继发甲状旁腺功能亢进甲状旁腺切除后左心室功能的变化

目的了解维持性血液透析患者甲状旁腺切除后左心室收缩与舒张功能的变化。 方法选择2013年3月至2016年9月在济南军区总医院维持性血液透析继发甲状旁腺功能亢进行甲状旁腺切除术的患者33例,采用自身对照,将患者治疗前定为对照组、手术后定为观察组。分别于术前1个月内、术后6个月检测甲状旁腺激素(intact parathyroid hormone,iPTH)、血钙、血磷、钙磷乘积等生化指标,左心室舒张末期室间隔厚度、左心室后壁厚度、左心室射血分数(left ventricular ejection fraction,LVEF)、左心室舒张末期容积(left ventricular end-diastolic volume,LVdV)、二尖瓣E/A值、组织多普勒获得的二尖瓣环舒张早期峰值(Ea)与舒张晚期峰值(Aa)比值,左心室整体应变率(strain rate,SR,SR)。采用配对样本t检验。 结果观察组iPTH、血钙、血磷、钙磷乘积以及LVEF、LVdV、二尖瓣E/A值、Ea/Aa、SR较对照组均明显下降(P值分别为0.000、0.037、0.008、0.000、0.037、0.021、0.026、0.017、0.033,P均<0.05),生化指标变化幅度以iPTH下降最为明显,依次为钙磷乘积、血钙、血磷(P>0.05),反映左心室舒张功能的二尖瓣E/A值、Ea/Aa变化幅度(23.88±10.24、0.43±13.17)明显大于反映左心室收缩功能的LVEF、SR变化幅度(16.48±3.76、16.79±4.32)(P<0.05),LVEF与SR的变化幅度两者之间无明显差异(P>0.05),E/A与Ea/Aa的变化幅度两者之间有明显差异(P＝0.020)。 结论维持性血液透析患者继发甲状旁腺功能亢进甲状旁腺切除后左心室舒张功能的改善程度高于收缩功能。     

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism

OBJECTIVES: Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. DESIGN, SUBJECTS AND INTERVENTION: A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. RESULTS: At study entry, BMD was 5-6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort). CONCLUSION: In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.     

Spectrum of renal dysfunction after curative parathyroidectomy in symptomatic primary hyperparathyroidism

ObjectiveThe long-term renal consequences of curative parathyroidectomy (PTX) in symptomatic primary hyperparathyroidism (sPHPT) are not well characterized. We aimed to assess renal glomerular and tubular functions in an sPHPT cohort at ≥ 1 year's follow-up.DesignRetrospective-prospective study.MethodssPHPT patients with preoperative eGFR ≥ 60 mL/min/1.73m² and in remission (normocalcemic) for ≥ 1 year after PTX underwent clinical and biochemical assessment (calcium profile, renal parameters). Ammonium chloride and bicarbonate loading tests were performed in patients with renal tubular dysfunction (RTD).ResultsForty-eight patients (31 females) with median plasma PTH 1,029 (338–1604) pg/mL and mean eGFR 109.2 ± 26.0 mL/min/1.73m² at diagnosis were evaluated at 5.62 ± 3.66 years after curative PTX. At follow-up, eGFR was < 60 mL/min/m² in 5 patients (10.4%). Patients with > 10% drop in eGFR (n = 31) had significantly higher pre-PTX plasma PTH (1,137 vs. 687 pg/mL), and longer time to post-PTX evaluation (6.8 vs. 3.4 years). RTD was seen in 11 patients (22.9%): urinary low molecular weight proteinuria (14.6%), distal renal tubular acidosis (12.5%), hypophosphatemia (8.3%), and hypokalemia (8.3%); RTD was associated with significantly lower post-PTX eGFR (72.7 vs. 95.4 mL/min/m²). Five of the 7 RTD patients undergoing loading test had impaired urinary acidification, whereas none had impaired bicarbonate resorption.ConclusionsReduction in eGFR and subclinical RTD were prevalent at long-term follow-up in the present Asian-Indian cohort with cured sPHPT. Further studies are warranted to understand the clinical implications of these various renal abnormalities.     

Cortical bone mineral content in primary hyperparathyroidism. Changes after parathyroidectomy

The bone mineral content (BMC) of 35 patients with primary hyperparathyroidism (PHPT) was measured at the mid radius (95% cortical bone) by photon absorptiometry of a 241Am source. The majority of the patients had an overt disease of moderate to severe degree. Average serum calcium of the group was 12.3 mg/100 ml (range 10.6 to 18.0 mg/100 ml). The percentage of normality of the BMC was (Av +/- 1 SD) 75.1 +/- 13.0% for the whole group. The average increment of BMC in 14 patients 9 to 26 months after parathyroidectomy was 9.9%, with a wide dispersion. However a highly significant negative correlation (r: 0.83; P less than 0.01) was found between the initial bone mass and the percentage increment per month after surgery. No further gain was observed 2 years after parathyroidectomy except in one patient with an extremely severe bone loss. In spite of the gain obtained after surgery the bone mass remained markedly diminished in most patients showing that the cortical bone loss caused by PHPT is mainly irreversible.     

Marked improvement of psychiatric symptoms after parathyroidectomy in elderly primary hyperparathyroidism

Psychosomatic symptoms in primary hyperparathyroidism (PHPT) are various and include such conditions as obsessive-compulsive disorder, depression, anxiety, and paranoia. In the elderly the clinical features of the disease are often non-specific and difficult to diagnose. To quantify subjective symptoms of patients with hyperparathyroidism in the elderly, we determined whether these clinical manifestations resolved after surgical parathyroidectomy (PTX) in three PHPT patients over eighty years old. They were diagnosed with hypercalcemia, hypophosphatemia, high PTH concentrations, and osteoporosis. A single parathyroid adenoma was confirmed in each patient by Tc-MIBI scintigram, neck ultrasonography and computed tomographic scanning. PTX was performed in these three patients. Assessments of psychologic symptoms, using the Hamilton Rating Scale for Depression (HAM-D), serum calcium, and intact PTH were obtained before and after PTX. Mean weight of the resected adenomas was 438 +/- 138 mg (mean +/- SD). After PTX, serum calcium decreased from 11.1 +/- 0.5 to 9.2 +/- 0.5 mg/dl and intact PTH from 160.0 +/- 25.2 to 45.3 +/- 22.2 pg/ml. Total HAM-D scores in each patient decreased from 45 to 9, 17 to 1 and 15 to 5, respectively. Especially, there were marked improvements in depressive mood, psychomotor inhibition, anxiety and somatic symptoms after PTX. The quality of life in those patients was also improved by PTX. We propose here that PTX in elderly PHPT patients with psychiatric symptoms should be considered instead of oral administration, such as anti-depressants or bisphosphonates.     

Impaired endothelial function in patients with ankylosing spondylitis

OBJECTIVE: In recent years, accelerated atherosclerosis and increased risk of cardiovascular events have been described in patients with rheumatic disease, particularly for rheumatoid arthritis and systemic lupus erythematosus. However, the link between inflammation, atherosclerosis and ankylosing spondylitis is controversial. We evaluated the degree of atherosclerosis and endothelial function of ankylosing spondylitis patients ultrasonographically. METHODS: Fifty-four patients with ankylosing spondylitis (37 +/- 11 yr, 29 males, 25 females) and 31 healthy controls (35 +/- 9 yr, 16 males, 15 females) were consecutively enrolled in the study. Serum lipids, creatinine, glucose, and acute-phase proteins were assessed. The Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also evaluated. Flow-mediated dilatation and endothelium-independent dilatation of the brachial artery and intima-media thickness of the common carotid artery were measured sonographically. RESULTS: Left, right and averaged intima-media thickness of the common carotid artery did not show a statistically significant difference between the ankylosing spondylitis and control groups. However, flow-mediated dilatation was significantly lower in the ankylosing spondylitis patients (14.1 +/- 6.7 vs 17.6 +/- 8%; P = 0.03). Likewise, nitroglycerin-induced dilatation was lower in the patient group, but the difference was not significant (16.4 +/- 6.8 vs 19.8 +/- 10%; P = 0.07). No correlation was detected between flow-mediated dilatation and age, sex, serum lipids, CRP, ESR, smoking habits and disease activity scores. Intima-media thickness of the common carotid artery was positively correlated with age and BASMI score (r = 0.55, P = 0.00; r = 0.22, P = 0.04, respectively). CONCLUSION: This study demonstrates impairment of endothelial function in ankylosing spondylitis.     

Increased leukotriene B4 synthesis in patients with primary hyperparathyroidism is normalized after parathyroidectomy: a study comparing parathyroidectomy to thyroid adenomectomy

Synthesis of leukotriene B4 (LTB4) upon stimulation of peripheral blood samples with the calcium ionophore A 23187 was studied in patients with primary hyperparathyroidism who underwent parathyroidectomy. Preoperatively, an increased LTB4 concentration of 1.76 +/- 0.19 ng/ml plasma was found, vs. 0.95 +/- 0.28 ng/ml in healthy individuals. On the fourth day after operation, the LTB4 concentration was almost normalized, reaching 1.25 +/- 0.23 ng/ml plasma. At the same time, mean serum calcium levels were reduced from 6.1 +/- 0.6 meq/liter before operation to 4.53 +/- 0.28 meq/liter after operation. In a control group, euthyroid patients with thyroid adenomas who underwent adenomectomy had normal LTB4 levels before operation (0.84 +/- 0.11 ng/ml) and did not show significant changes in LTB4-synthesizing capacity. The results indicate that synthesis of LTB4 in vivo may depend in part on factors related to serum calcium concentration or calcium metabolism.