Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated serum concentrations of 1-84 parathyroid hormone (PTH) after operation for sporadic parathyroid adenoma have been reported in previous studies, years after operation for primary hyperparathyroidism (pHPT). The cause and significance of this finding have not been elucidated. Primary hyperparathyroidism was diagnosed in 195 patients from January 1987 to December 1998. Operation for pHPT was performed in 124 patients. To evaluate long-term effects of elevated serum 1-84 PTH, biochemical variables and pre- and postoperative diseases were investigated from hospital case records. Of the 124 patients operated on, 103 had a solitary adenoma. Among these patients, 60 had normal serum concentrations of 1-84 PTH and calcium postoperatively, 38 patients had follow-up for more than 12 months (range 12-207 months-group A). Persistent elevated serum concentrations of 1-84 PTH and normocalcemia were found in 23 patients. Fourteen patients had follow-up for more than 12 months (range 15-76 months-group B). Two patients had persistent pHPT, and 18 were normocalcemic, but in this retrospective study data on serum 1-84 PTH were not available. No significant differences were found between groups A and B at the time of diagnosis concerning clinical characteristics. More that 12 months after operation for pHPT, the patients in group B, with persistent elevated serum concentrations of 1-84 PTH, had a significantly (c2 = 11, p = 0.005, and power of test 0.66) higher frequency of cardiovascular diseases from ischemic heart disease and hypertension. Persistent elevated serum concentrations of 1-84 PTH after operation for sporadic parathyroid adenoma may be associated with development of cardiovascular disease. This group of patients therefore needs lifelong control and, possibly, medical intervention.
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PMID:Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease. 1205 14

Primary hyperparathyroidism (pHPT) is associated with an increased fracture risk, and decreased bone density thus has been considered an indication for surgery. However, many pHPT patients have a multifactorial risk profile for osteoporosis and bone fractures. The aim of the present study was to evaluate variables associated with fracture risk within the group of pHPT patients. A series of 203 consecutive patients operated for pHPT were investigated with bone mineral content and biochemical and clinical risk factors for bone fracture. Seventeen patients (8%) had a history of at least one bone fracture up to 5 years before pHPT surgery. Twenty-six patients (13%) had a history of at least one fracture during the 10-year period prior to surgery. In the univariate analyses corticosteroid treatment, serum levels of alkaline phosphatase, 25-hydroxyvitamin D3, type I collagen telopeptide, and bone mineral content were found to be associated with a history of bone fractures up to 10 years before surgery. Additionally, age and menopausal status were of importance for fractures during the 10-year-period, whereas a history of cardiovascular disease was important for fractures during the 5-year-period prior to surgery. Multivariate analyses showed that serum level of PTH was independently associated with bone fractures during the 5-year period prior to pHPT surgery and further that serum level of 25-hydroxyvitamin D3 was associated with fractures up to 10 years before surgery. In conclusion, serum levels of 25-hydroxyvitamin D3 and PTH were independently associated with a history of bone fractures in pHPT. These variables should be considered when evaluating patients for parathyroid surgery.
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PMID:Multifactorial risk profile for bone fractures in primary hyperparathyroidism. 1229 14

Primary hyperparathyroidism (PHPT) in developing countries is characterized by severe skeletal and renal complications and apparent mortality. This is in contrast with the Western hemisphere where research interests, rather than characteristics of PHPT, seem to differ between regions. In Europe, the "nontraditional" aspects of mild-to-moderate PHPT have attracted particular attention. These symptoms and signs include risk factors for cardiovascular disease such as hypertension, phenotype IV lipoproteinemia, insulin resistance, cardiac and vascular dysfunction, and morbidity in cardiovascular diseases. Mortality in cardiovascular diseases has been found to be increased in studies that include over 6500 European patients; this risk could not be verified in North American patients. By use of the nationwide Cancer Registry and Causes-of-Death Registry, mortality was analyzed in 10,995 Swedish patients (> 20 years of age) subjected to extirpation of single parathyroid adenoma of PHPT during 1958-1997. The Swedish population standardized for age, sex, and calendar year was used as control. The first postoperative year was excluded from the analysis. In total, the study included 102,515 observed person-years in the patients. Results verify an increased risk of dying after operation for PHPT (standard mortality ratio, 1.2; 95% CI, 1.19-1.27). The increased risk persisted far beyond 15 years postoperatively and occurred in both sexes and in all investigated age groups. Principal causes of excess mortality were cardiovascular diseases, diabetes mellitus, and urogenital diseases in all age groups. However, in patients operated on between 1985 and 1997 (n = 6386), overall mortality did not differ from that of the normal population, although there was maintained excess death in stroke, diabetes mellitus, and urogenital diseases. These findings infer that modern paradigms of surgical treatment normalize the risk of dying from PHPT. This improvement may be a late consequence of liberalized calcium screenings that were introduced about 30 years ago and indicate that operation at early disease stages may offer a survival advantage. An association between diabetes mellitus and PHPT is substantiated.
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PMID:Clinical presentation of primary hyperparathyroidism in Europe--nationwide cohort analysis on mortality from nonmalignant causes. 1241 80

Cardiovascular disease [atherosclerosis and subsequent myocardial infarction (MI)] has been associated with primary hyperparathyroidism. We aimed at studying cardiovascular events before and after surgery and mortality after surgery for primary hyperparathyroidism using a historical follow-up design. A total of 674 patients who underwent surgery at three Danish centers between January 1, 1979 and December 31, 1997 were compared with 2021 age- and gender-matched controls. There was an increased incidence of acute MI up to 10 years prior to surgery [relative risk (RR) 2.5, 95% confidence interval (95% CI) 1.5-4.2] and within the first year following surgery (RR 3.6, 95% CI 1.7-7.6). The risk of MI subsequently declined to a normal level more than 1 year after surgery. Patients with MI prior to diagnosis also had a higher postoperative risk of new infarction than did patients without [odds ratio (OR) 6.0, 95% CI 1.2-30.0]. The risk of hypertension, stroke, congestive heart failure, and diabetes was increased before surgery. More than 1 year after surgery only hypertension and congestive heart failure were more frequent in patients than controls. Preoperative cardiovascular disease was associated with an increased risk of death (RR 1.8, 95% CI 1.1-2.8). Mortality following surgery was higher than in the general population between 1979 and 1990 but not between 1991 and 1997. We concluded that there was an increase in acute MI up to 10 years prior to surgery. The risk of MI decreased to a normal level after surgery, which may be important for preventing cardiovascular disease in patients with primary hyperparathyroidism.
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PMID:Cardiovascular events before and after surgery for primary hyperparathyroidism. 1261 40

In recent decades, primary hyperparathyroidism (pHPT) has changed its clinical presentation from a disease with bone and renal involvement to a frequently asymptomatic disorder detected on routine biochemistry. Nevertheless, it remains unclear whether patients with untreated mild asymptomatic hyperparathyroidism are at risk for other complications such as increased morbidity and mortality from cardiovascular diseases. There are limited data on the incidence of cardiovascular abnormalities in mild pHPT. However, pHPT has been associated with increased risk of death from cardiovascular disease, hypertension, left ventricular hypertrophy (LVH), valvular and myocardial calcifications, impaired vascular reactivity, alterations in cardiac conduction, impaired glucose metabolism, dyslipidaemia, and alterations in body composition. The nature of some of these associations is in question, because cure of pHPT does not lead to improvement of the cardiovascular disorder e.g. hypertension. In contrast, currently available data suggest that LVH, impaired glucose metabolism and dyslipidaemia may improve after surgery and that successful parathyroidectomy could decrease the excess mortality in patients with pHPT due to cardiovascular disease.
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PMID:Parathyroid adenomas and cardiovascular risk. 1279 Jul 92

The management of oestrogen deficiency bone loss needs to include general measures to protect against osteoporosis, the identification and treatment of other reversible causes of bone loss, and the use of proven agents for the treatment of osteoporosis. The general measures include improved physical activity, adequate diet (paying particular attention to calcium and vitamin D), and avoidance of behaviours that promote bone loss, such as smoking and alcohol abuse. The diseases that should be identified, other than estrogen-deficiency, include primary hyperparathyroidism, thyrotoxicosis and celiac disease. The treatments that are proven to prevent fractures in women with estrogen deficiency, include hormone replacement therapy, raloxifene, nasal calcitonin, bisphosphonates, (alendronate and risedronate) and parathyroid hormone. The most appropriate therapy in the younger woman is HRT, although the trial-based evidence that HRT prevents fractures is not strong. There is a wide choice of preparations and the use of continuous combined preparations avoids regular menstrual periods, one of the limitations to the use of HRT. Raloxifene has less effect on bone mineral density than HRT, but a similar effect on vertebral fractures and does not result in menstrual bleeding or increased risk of breast cancer. There is recent evidence suggesting that the beneficial effects on lipids translate into reduced risk of cardiovascular disease. Bisphosphonates are the standard treatment for the older woman with osteoporosis. Alendronate has been found to reduce the risk of spine, hip, and wrist fractures and has approval for a once weekly regimen, an approach that appears to prevent GI side effects. Risedronate reduces the risk of spine and non-vertebral fractures within the first year of treatment and has been shown to reduce the risk of hip fracture. It has not been associated with an excess of GI side effects. Parathyroid hormone therapy results in increases in BMD that are even greater than estrogen and the bisphosphonates and to an even greater reduction in the risk of fractures, particularly non-vertebral fractures. It works by stimulation of bone formation rather than by inhibition of bone resorption. However, it has to be given by daily injection. Thus, we have a wide choice of therapies for the woman with osteoporosis due to ovarian failure.
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PMID:Management of osteoporosis due to ovarian failure. 1286 23

The aim of the present study was to determine whether patients with the incident hospital diagnosis of primary hyperparathyroidism (PHPT) in Denmark during the period 1977-1993 had an increased mortality from cardiovascular disease and cancer compared to the rest of the Danish population. In a random sample of half of the Danish population, all patients with an incident hospital diagnosis of PHPT were identified in the National Hospital Patients Register. The mortality in the cohort was analyzed and compared with the background population. A cohort of 1578 patients was identified. Follow-up of 1179 women and 376 men, who did not die in the same month as the incident PHPT diagnosis, was made through 1993. Of these, 312 (20%) died within the follow-up period. The standard mortality ratio (SMR) for women was 1.7 (95% confidence interval [95% CI]: 1.5-1.9). SMR for men was 1.6 (95% CI: 1.3-2.0). In women an increased mortality from ischemic heart disease, cerebrovascular disease, and cancer was found. In men an increased mortality from cerebrovascular disease and cancer was found.
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PMID:Increased mortality in patients hospitalized with primary hyperparathyroidism during the period 1977-1993 in Denmark. 1464 50

The most important step in calcium homeostasis is the regulation of parathyroid hormone (PTH) secretion. The discovery and characterization of the calcium sensing receptor (CaR) of the parathyroid cell has led to a better understanding not only of the physiology of the parathyroid glands, but also of the development of hyperparathyroidism. Drugs acting on CaR can now be designed to treat hyperparathyroidism and osteoporosis. The workshop on primary hyperparathyroidism held at the National Institutes of Health in 2002 has recommended new guidelines for the treatment of asymptomatic hyperparathyroidism. Controversy still exists regarding the treatment of patients with non-classical symptoms, such as weakness, fatigue and depression. Primary hyperparathyroidism as a risk factor for cardiovascular disease and mortality is also debated. Improved techniques for the preoperative localization of pathological parathyroid glands have led to a shift in surgical strategy: surgeons abandon the traditional bilateral neck exploration in favor of a more limited approach. This change of strategy has not been based on the results of prospective randomized studies and the long term results are not known.
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PMID:Primary hyperparathyroidism. Update on pathophysiology, clinical presentation and surgical treatment. 1565 69

Patients with primary hyperparathyroidism (PHPT) have increased risk of cardiovascular disease. For patients undergoing preoperative parathyroid imaging with 99mTc-sestamibi single photon emission computed tomography (SPECT), we combined cervical SPECT and gated cardiac SPECT to achieve information about the localization of parathyroid adenomas, myocardial perfusion, and the left ventricular ejection fraction (LVEF) at rest. A series of 22 patients with PHPT and no history of myocardial infarction or angina pectoris were recruited consecutively. At 60 minutes after injection of 700 MBq 99mTc-sestamibi, SPECT of the neck and gated myocardial perfusion SPECT were performed at the same time. All of the patients who underwent parathyroidectomy had the parathyroid adenoma localized as predicted from the SPECT. Five patients (23%) had myocardial perfusion defects extending more than 15% (range 15-25%), and they had higher plasma parathyroid hormone levels (p = 0.03), and lower LVEF (p = 0.007) than patients without perfusion defects. We suggest that patients with hyperparathyroidism and suspected cardiovascular disease can undergo 99mTc-sestamibi parathyroid SPECT simultaneously with gated myocardial perfusion SPECT to obtain information about the resting perfusion status and cardiac systolic function. The results from myocardial perfusion SPECT can lead to initiation of cardiovascular treatment and eventually perioperative precautions.
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PMID:Myocardial perfusion defects and the left ventricular ejection fraction disclosed by scintigraphy in patients with primary hyperparathyroidism. 1595 36

Circulating levels of calcium ion (Ca2+) are maintained within a narrow physiological range mainly by the action of parathyroid hormone (PTH) secreted from parathyroid gland (PTG) cells. PTG cells can sense small fluctuations in plasma Ca2+ levels by virtue of a cell surface Ca2+ receptor (CaR) that belongs to the superfamily of G protein-coupled receptors (GPCR). Compounds that activate the CaR and inhibit PTH secretion are termed 'calcimimetics' because they mimic or potentiate the effects of extracellular Ca2+ on PTG cell function. Preclinical studies with NPS R-568, a first generation calcimimetic compound that acts as a positive allosteric modulator of the CaR, have demonstrated that oral administration decreases serum levels of PTH and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion in normal rats. NPS R-568 also suppresses the elevation of serum PTH levels and PTG hyperplasia and can improve bone mineral density (BMD) and strength in rats with chronic renal insufficiency (CRI). Clinical trials with cinacalcet hydrochloride (cinacalcet), a compound with an improved metabolic profile, have shown that long-term treatment continues to suppress the elevation of serum levels of calcium and PTH in patients with primary hyperparathyroidism (1HPT). Furthermore, clinical trials in patients with uncontrolled secondary hyperparathyroidism (2HPT) have demonstrated that cinacalcet not only lowers serum PTH levels, but also the serum phosphorus and calcium x phosphorus product; these are a hallmark of an increased risk of cardiovascular disease and mortality in dialysis patients with end-stage renal disease. Indeed, cinacalcet has already been approved for marketing in several countries. Calcimimetic compounds like cinacalcet have great potential as an innovative medical approach to manage 1HPT and 2HPT.
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PMID:Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism. 1610 39


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