Cardiovascular disease,hypertension and renal function in primary hyperparathyroidism

OBJECTIVES: Patients with primary hyperparathyroidism run an increased risk of death in cardiovascular disease. Long ago, hypertension was found to frequently occur in these patients. The aim of this study was to compare the death risk after surgery for hyperparathyroidism of hypertensive patients with that of normotensive ones, and to investigate relations between variables of cardiovascular disease and variables of hyperparathyroidism and renal function. METHODS: A series of 845 patients with primary hyperparathyroidism and serum creatinine 相似文献   

A slight decrease in renal function further impairs bone mineral density in primary hyperparathyroidism

BACKGROUND: The impairment of renal function can affect the clinical presentation of primary hyperparathyroidism (PHPT), increasing cardiovascular morbidity, fracture rate, and the risk of mortality. AIM: The aim of the study was to assess the differences in bone status in a series of consecutive patients affected by PHPT without overt renal failure at diagnosis grouped according to creatinine clearance (Ccr). METHODS: A total of 161 consecutive patients with PHPT were studied. They were divided into two groups based on Ccr. Group A had Ccr 70 ml/min or less (n = 49), and group B had Ccr greater than 70 ml/min (n = 112). PTH, total and ionized serum calcium; urinary calcium and phosphate; serum 25-hydroxyvitamin D3; serum and urinary bone markers; lumbar, forearm, and femoral bone mineral density (BMD) were evaluated. RESULTS: Patients in group A were older than those in group B (P < 0.0001). PTH levels did not differ in the two groups, whereas both urinary calcium and phosphorus were lower in group A than group B (P < 0.01). Lower BMD was evident in group A at lumbar spine (P < 0.002), forearm (P < 0.0001), and femur (P < 0.01). In asymptomatic PHPT, those with Ccr 70 ml/min or less had lower forearm BMD than patients with higher Ccr (P < 0.00001). When adjusting for age and body mass index in PHPT, BMD at each site persisted being lower (P < 0.05) in group A than group B. In all PHPT subjects, Ccr (beta = 0.29, P < 0.0005), age (beta = -0.27, P < 0.00001), and PTH levels (beta = -0.27, P < 0.0005) were all independently associated with forearm BMD. CONCLUSIONS: In PHPT a slight decrease in renal function is associated with more severe BMD decrease, independent of age, body mass index, and PTH levels. This association is also present in asymptomatic PHPT and strengthens the National Institutes of Health recommendations for surgery in patients with mild PHPT.     

Ultrasonographic features of intrathyroidal parathyroid adenoma causing primary hyperparathyroidism

Preoperative localization study is difficult in patients with primary hyperparathyroidism (PHPT) caused by intrathyroidal parathyroid adenoma. The objective of this study was to evaluate the usefulness of ultrasonography (US) in the diagnosis of intrathyroidal parathyroid adenoma. Between January 2004 and December 2009, seven of 373 patients who underwent parathyroidectomy because of PHPT in our hospital were found to have intrathyroidal parathyroid adenoma. The ultrasonographic features of intrathyroidal parathyroid adenoma were examined retrospectively. The most characteristic feature of intrathyroidal parathyroid adenoma was a hyperechoic line on the ventral surface of the parathyroid gland. A hyperechoic line was clearly detected even in small adenomas in which feeding vessels could not be detected on color Doppler sonography. In comparison with feeding vessels, a hyperechoic line was frequently detected in normally located parathyroid adenoma. (99m)Tc-sestamibi (MIBI) scintigraphy and computed tomography (CT) could show parathyroid adenoma in the intrathyroidal position in only three of five and in only one of three patients examined, respectively. Since a hyperechoic line is characteristic of parathyroid adenoma, an intrathyroidal parathyroid adenoma could be suspected by only non-invasive US.     

Pre- and postoperative evaluation of renal function with five different tests in patients with primary hyperparathyroidism

Renal function was investigated immediately before and 1 year following parathyroidectomy in 19 patients with moderate hypercalcaemia. On both occasions, all patients underwent five different tests of glomerular and tubular function: plasma creatinine, creatinine clearance, 51Cr-EDTA-clearance, beta 2-microglobulin excretion and the desmopressin test. Glomerular filtration rate, as assessed by plasma creatinine and clearance of both creatinine and 51Cr-EDTA, was normal in most patients, and was little affected by restoration of normocalcaemia. Renal concentrating capacity, as determined by the desmopressin test, was abnormally low in 14 of 19 patients, but increased significantly after surgery. It is concluded that serious renal damage is seldom encountered in present-day HPT patients, but that a treatable decrease in renal concentrating capacity often exists.     

Effect of surgery on cardiac structure and function in mild primary hyperparathyroidism

Context The cardiovascular (CV) risk profile is worsened in primary hyperparathyroidism (PHPT), and CV mortality is related to serum calcium levels. It is unknown whether CV mortality is increased in the most common form of PHPT and whether the increased CV risk is reversible after surgery. Objective To investigate reversibility of echocardiographic variables in patients with mild PHPT who were randomized to observation without surgery or operation, and followed for 2 years. Design/Setting/Patients Forty‐nine patients (mean age 63 ± 7 years, 8 men) who had performed the 2‐year visit in a randomized study on mild PHPT (serum calcium at baseline 2·65 ± 0·09 mm ) (observation) vs 2·67 ± 0·06 mm (surgery) and where echocardiography had been performed, participated in the study. Results Calcium and parathyroid hormone (PTH) levels were normalized following surgery and were stable in the observation group. PTH levels at baseline were highly correlated with ventricular mass. Detailed echocardiography revealed a minor and borderline significant treatment effect of surgery on left ventricular mass index (LVMI) compared to observation (P = 0·066) and a significant 11% reduction in diastolic dimension of the interventricular septum (IVSd‐mean) in the surgery group (P < 0·01), with no alterations in the observation group. Conclusions Based on detailed echocardiographic measures over a 2‐year observation period, we found only minor differences between the two groups. However, the potential treatment effect on LVMI and the within‐group differences in IVSd‐mean suggest that longer follow‐up may yield larger and clinically important differences.     

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.     

Low basal thyrotropin with normal thyroid function in primary hyperparathyroidism

TSH serum levels and thyroid function in 32 patients with primary hyperparathyroidism and hypercalcemia were compared to those of 30 age and sex-matched normal subjects. Serum T3 and T4 concentrations in hyperparathyroidism were not different from normal. However, basal serum TSH concentrations measured with an ultrasensitive immunoradiometric assay were significantly lower than normal (1.09 +/- 0.49 vs 2.06 +/- 0.85 mU/l, p less than 0.001). In hyperparathyroidism, TSH, but not T4 or T3, was negatively correlated with serum calcium, not with iPTH. The increase in TSH (delta TSH) 30 min after the iv injection of TRH was also significantly blunted in patients with primary hyperparathyroidism; delta TSH was highly correlated with basal TSH in hypercalcemic patients. The basal TSH concentration was higher and no longer different from normal (1.70 +/- 1.2 mU/l) 2 to 12 months after removal of the parathyroid adenoma, when serum calcium was normalized, whereas T3 and T4 did not change. A low basal TSH with normal T4 and low T3 was found in 13 patients with hypercalcemia of malignancy. In these patients, TSH increased after treatment of hypercalcemia with 3-amino-l,hydroxypropylidene-1, 1-bisphosphonate, whereas T4 did not change. The results suggest that the set point of pituitary thyroid feedback control could be decreased in chronic hypercalcemia and that hypercalcemia could render the thyroid more sensitive to TSH.     

Asymptomatic primary hyperparathyroidism

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. In adults with the disease, a single, benign adenoma is seen approximately 80 percent of the time, with multiple gland involvement comprising most of the remaining patients. Very rarely, a parathyroid cancer is responsible but it is seen in less than 0.5 percent of patients with primary hyperparathyroidism. In this article, we will review important clinical and diagnostic features of asymptomatic primary hyperparathyroidism as well as considerations for surgical or medical management of the disease.     

Acute primary hyperparathyroidism

Acute primary hyperparathyroidism is an unusual form of primary hyperparathyroidism characterized by life-threatening hypercalcemia. Forty-three cases reported in the literature since 1974 are reviewed, along with five new cases. The average age of the patients was 55 (27 to 82), with an even distribution between men and women. Marked hypercalcemia (17.5 +/- 2.1 mg/dl) was accompanied by parathyroid hormone levels 20 times normal. Virtually all patients had symptoms. Hyperparathyroid bone disease occurred in 53 percent of patients; even more (69 percent) had nephrolithiasis or nephrocalcinosis. Combined renal and skeletal involvement was seen in 50 percent. Only three deaths were recorded. The pathophysiology of the acute hyperparathyroid state is unknown but appears to consist of uncontrolled parathyroid hormone secretion followed by cycles of hypercalcemia, polyuria, dehydration, reduced renal function, and worsening hypercalcemia. These features of acute primary hyperparathyroidism are compared with the features reported in the literature antedating multichannel screening, and with the features of the common form of primary hyperparathyroidism. Clinical guidelines by which the diagnosis may be suspected are also reviewed.     

Plasma 1,25-dihydroxyvitamin D levels in primary hyperparathyroidism depend on sex, body mass index, plasma phosphate and renal function

BACKGROUND: Primary hyperparathyroidism (PHPT) is characterized by elevated plasma levels of PTH and calcium with reduced plasma phosphate. Physiologically, renal 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D] production is stimulated by PTH and phosphate deprivation, and inhibited by 1,25(OH)(2)D itself and calcium. AIM: To investigate relations between circulating levels of 1,25(OH)(2)D, 25-dihydroxyvitamin D (25OHD), PTH, calcium, phosphate, renal function and skeletal complications in patients with PHPT. DESIGN: Cross-sectional study. MATERIAL: Two hundred and fifty-two consecutive hypercalcaemic Caucasian patients aged 24-91 (median 65.9) years (85.3% females) with PHPT. RESULTS: In patients with PHPT, plasma 1,25(OH)(2)D was increased by 27%[107 (9-250) pmol/l, median (range)] compared to controls [84 (18-172) pmol/l, P < 0.001]. In univariate models, plasma 1,25(OH)(2)D depended inversely on age (r = -0.23, P < 0.001) and plasma phosphate (r = -0.23, P < 0.001) and positively on plasma calcium (r = 0.14, P < 0.05), plasma 25OHD (r = 0,15, P < 0.05) and creatinine clearance rate (r = 0.32, P < 0.001). In the final multiple regression model, plasma 1,25(OH)(2)D depended positively on renal function (r(p) = 0.43, P < 0.001) and female sex (r(p) = 0.15, P < 0.05) but inversely on body mass index (BMI; r(p) = -0.23, P < 0.005) and plasma phosphate (r(p) = -0.18, P < 0.05). Plasma 1,25(OH)(2)D correlated positively with renal calcium excretion and inversely with lumbar spine bone mineral density (BMD) but was not associated with risk of fractures or renal stones. CONCLUSION: Patients with PHPT have elevated plasma 1,25(OH)(2)D levels but, to a large extent, individual values overlap controls. The increase in plasma 1,25(OH)(2)D depends on renal function, hypophosphataemia and the female sex and is attenuated by high BMI. High plasma 1,25(OH)(2)D is associated with higher plasma calcium levels.     

Cyanamide hepatotoxicity. Incidence and clinico-pathological features

Ground-glass hepatocytes resembling those seen in HBsAg carriers on hematoxylin and eosin and on trichrome stained sections, but giving a negative reaction to orcein and a positive one to PAS, were found in liver biopsy specimens from nine asymptomatic former alcoholics who were on treatment with cyanamide, in one of four who had been treated with cyanamide several months before the liver biopsy procedure, in none of 15 treated with disulfiram, and in one of eight who had apparently not received aversive drugs. Portal and periportal inflammatory changes and fibrosis were more frequently observed in biopsy specimens containing PAS-positive ground-glass hepatocytes than in those without, but cirrhosis was found with a similar frequency. It is concluded that periportal PAS-positive ground-glass hepatocytes are a histological marker of cyanamide treatment.     

Chondrocalcinosis in primary hyperparathyroidism. Influence of parathyroid activity and age

Chondrocalcinosis was detected in 10 of 32 patients with hyperparathyroidism. Those with chondrocalcinosis had greater parathyroid activity than those with no chondrocalcinosis. They were also older. These findings suggest that chondrocalcinosis is caused by the combined effects of sustained hypercalcaemia and age-related changes in articular cartilage.     

Treatment of primary hyperparathyroidism

We present four treatment categories for patients with primary hyperparathyroidism and describe the results of studies of patients in each category. These categories are primary surgical, secondary surgical, “biochemical” hyperparathyroidism and medical management with oral administration of neutral phosphate. The importance of the parathyroid surgeon as a diagnostician during parathyroid exploration is stressed from the point of view of the detection and aggressive surgical treatment of parathyroid chief cell hyperplasia. Short-term (1 to 2 weeks) and long-term (5 to 29 months) studies of the state of parathyroid function in relation to calcium homeostasis after successful resection of hyperfunctioning parathyroid tissue are described.Although incomplete, our 5 year prospective study of “biochemical” hyperparathyroidism shows that in approximately 20 per cent of these patients the disease progresses to where our criteria for surgical intervention are met and that no one criterion or combination of criteria has been identified as being of predictive value in determining which patients will ultimately require surgical intervention. In patients with persistent or recurrent hyperparathyroidism, chronic oral treatment with neutral phosphate was successful in decreasing serum calcium from more than 12.0 mg/dl to less than 11.0 mg/dl in four of seven patients, but significant increases in serum creatinine occurred in three of these seven patients. Significant decreases in serum calcium did not occur in patients with serum calcium values less than 11.0 mg/dl, and there were no changes in serum creatinine in this group. Nephrolithiasis was controlled in seven of eight patients, but the specific effectiveness of neutral phosphate treatment in all these patients could not be assessed because only two had metabolically active disease at the start of treatment.