A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A Pilot Study in Vietnam.

AIMS: Moderate to severe hyperparathyroidism (parathyroid hormone [PTH] concentrations ≥600 pg/mL) may increase the risk of cardiovascular problems and bone disease. We assume that a combination of hemodialysis with hemoperfusion may reduce the cardiovascular-related mortality rate in maintenance hemodialysis. SUBJECTS AND METHODS: From 625 maintenance hemodialysis patients, 93 people met with our inclusion criteria. Based on the level of serum PTH, the patients were divided into 2 groups: 46 patients who underwent a combination of hemodialysis and hemoperfusion (HD + HP group) for consecutive 3 years and 47 patients who used hemodialysis only (HD group). RESULTS: During 3 years of follow-up, the ratio of mortality was 4.3% in the HD + HP group which was significantly lower than in the HD group (17%), p = 0.049. Based on Kaplan-Meier analysis of cardiovascular-related mortality, patients in the HD group (red line) exhibited a significantly higher death rate compared to the HD + HP group (violet line) (log-rank test, p = 0.049). CONCLUSION: We demonstrated that a combination of hemodialysis and hemoperfusion for 3 years helped to reduce the cardiovascular-related mortality rate.

Hyperparathyroidism in men - morbidity and mortality during 21 years' follow-up.

Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ≥ 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up.A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age.Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.

Advantage of tacrolimus/mycophenolate mofetil regimen for cytotoxic T cell-mediated defence and its inhibition by additive steroid administration in high-risk liver transplant recipients.

Our previous work revealed that the recipients with the highest pre-existing numbers of CD8(+) effector T cells (TE ) [hyperparathyroidism (HPT)E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre-existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty-one HPTE recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow-up until post-operative day 2000. Regarding the immunological mechanism, in type 1 TE perforin and interferon (IFN)-γ were generated through the self-renewal of CD8(+) central memory T cells (TCM ), but decreased in the early post-transplant period due to marked down-regulation of interleukin (IL)-12 receptor beta-1 of TCM. In type 2, the self-renewal TCM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL-12Rß1(+) TCM levels, and increased at the highest level around the pre-transplant levels of IL-12Rß1(+) TCM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.

Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden.

OBJECTIVE: There is limited knowledge about the natural history of normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity. DESIGN: Cross-sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: A random population of 608 men and women, age 25-64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient). MEASUREMENTS: A serum intact parathyroid hormone (S-PTH) ≥60 ng/l was considered as HPT, S-calcium 2·15-2·49 mmol/l as normocalcaemia and S-25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17-year follow-up. RESULTS: The prevalence of nHPT was 2·0% in 1995 (age 25-64) and 11·0% in 2008 (age 38-79). S-PTH was positively correlated with age and BMI. After adjustment for these variables, a high S-PTH level (≥60 ng/l) at follow-up was associated with previously low S-25(OH)D, high osteocalcin, S-PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow-up. CONCLUSIONS: This small random population study showed that nHPT was common, 11% at follow-up. Only one individual developed mild hypercalcaemia in 13 years. Previous S-PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end-points was seen over a 17-year period.

Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography.

AIMS: Elevated parathyroid hormone (PTH) levels have been associated with increased cardiovascular risk in the general population. We aimed to elucidate whether PTH levels are associated with mortality and fatal cardiovascular events in patients referred for coronary angiography. METHODS AND RESULTS: Intact PTH was measured in 3232 Caucasian patients from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, who underwent coronary angiography at baseline (1997-2000). During a median follow-up time of 7.7 years, 742 patients died including 467 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (HRs) (with 95% confidence intervals) in the fourth when compared to the first PTH quartile were 2.13 (1.75-2.60) for all-cause and 2.47 (1.92-3.17) for cardiovascular mortality. After adjustments for common cardiovascular risk factors, these HRs remained significant with 1.71 (1.39-2.10) for all-cause and 2.02 (1.55-2.63) for cardiovascular mortality. Among specific cardiovascular events we observed a particularly strong association of PTH with sudden cardiac death (SCD). The adjusted HR for SCD in the first vs. the fourth PTH quartile was 2.68 (1.71-4.22). CONCLUSION: Our results among patients undergoing coronary angiography show that PTH levels are an independent risk factor for mortality and cardiovascular events warranting further studies to evaluate whether PTH modifying treatments reduce cardiovascular risk.

Parathyroidectomy for the treatment of hyperparathyroidism: Thirty-day morbidity and mortality.

OBJECTIVES/HYPOTHESIS: Evaluate morbidity and mortality rates for patients with different levels of hyperparathyroidism (HPT) undergoing parathyroidectomy (PTX), specifically comparing primary hyperparathyroidism to secondary and tertiary hyperparathyroidism. Assess predictive factors of increased morbidity and mortality. STUDY DESIGN: Retrospective national database review. METHODS: Patients undergoing PTX, defined by Current Procedural Terminology codes 60500, 60502, 60505, for the treatment of HPT, were identified in the American College of Surgeons National Surgical Quality Improvement Program database between 2006 and 2014. Incidence of morbidity and mortality was calculated for primary, secondary, and tertiary HPT. A t test, analysis of variance, and χ2 analyses were used to assess preoperative characteristics among the three groups. RESULTS: A total of 21,267 patients were included in the analysis. There was an overall 7.2% morbidity and mortality rate, including 45 (0.21%) deaths, a 1.8% readmission rate, and a 1.9% reoperation rate, but morbidity and mortality rates were widely divergent when comparing primary to secondary and tertiary HPT. PTX resulted in a 4.9% morbidity and mortality rate for primary HPT (n = 14,500), 26.8% morbidity and mortality rate for secondary HPT (n = 1661), and 21.8% morbidity and mortality rate for tertiary HPT (n = 588). The primary reason for readmission was hypocalcemia (18.3%). Hematoma (7.2%) and postoperative hemorrhage (3.3%) were the two most common causes of reoperation. Elevated preoperative serum creatinine, alkaline phosphatase, and hypertension resulted in a higher rate of complications after PTX (P < .0001). CONCLUSIONS: Although surgery for primary HPT is an extremely common and safe procedure with minimal morbidity and mortality rates, PTX for secondary and tertiary HPT has significantly higher rates of morbidity and mortality, requiring special attention in the postoperative period. Predictive factors of poor outcomes include hypertension, elevated creatinine, and elevated alkaline phosphatase. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:528-533, 2018.

Surgical treatment of primary hyperparathyroidism.

BACKGROUND: With the use of routine calcium evaluation, the incidence of primary hyperparathyroidism (pHPT) has considerably increased. The aim of our study was the assessment of the morbidity and the outcome of surgically treated patients with pHPT. METHODS: The charts of 279 patients (204 female, 75 male, median age: 58 years) who underwent surgery for pHPT between 1989 and 1999 were retrospectively reviewed. A follow-up was carried out on 235 patients after a mean period of 3.6 years (0.2-10 years). RESULTS: In 148 patients a unilateral, and in 130 patients a bilateral approach was taken. Transplanted parathyroid tissue was removed from the left forearm of one patient. At follow-up persistent hypocalcemia was seen in 30 patients (20 after bilateral, 10 after unilateral exploration). 6 patients (1 after bilateral, 5 after unilateral exploration) revealed a newly developed persistent paresis of the recurrent laryngeal nerve. In 5 patients persistent (1 after unilateral, 4 after bilateral exploration) and in 5 patients recurrent (2 after unilateral, 3 after bilateral exploration) pHPT could be observed. CONCLUSION: Both unilateral and bilateral cervical exploration for pHPT have a high rate of success with a low morbidity. Therefore, patients with assumed asymptomatic pHPT with unspecific neuropsychological abnormalities should also be evaluated for surgical intervention.

Primary hyperparathyroidism. A review of the long-term surgical and nonsurgical morbidities as a basis for a rational approach to treatment.

We studied long-term morbidity after parathyroid surgery for primary hyperparathyroidism in 100 patients and compared it with the long-term morbidity of medical follow-up from the literature. The surgical treatment of primary hyperparathyroidism was associated with negative results of neck explorations, persistent hypercalcemia, recurrent hypercalcemia, permanent hypoparathyroidism, or recurrent laryngeal nerve damage in 13 (19%) of 68 patients followed up for five years postoperatively. A review of medical follow-up as reported in the literature showed progression of disease in 8% to 22% of patients followed up for five to ten years. There was no convincing evidence that mild primary hyperparathyroidism resulted in progressive osteoporosis or renal failure. Furthermore, no significant improvement in hypertension, peptic ulcer disease, or renal function followed successful parathyroid surgery. Unless future studies demonstrate progressive osteoporosis or renal damage in untreated, mild primary hyperparathyroidism, medical follow-up is a reasonable alternative to surgery in the compliant patient over 50 years of age.

Clinical outcomes after parathyroidectomy in a nationwide cohort of patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged ≥18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods. RESULTS: Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Cause-specific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to 1.1). CONCLUSIONS: Parathyroidectomy is associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure. Awareness of clinical events will assist in developing evidence-based risk/benefit determinations for the indication for parathyroidectomy.

Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism.

BACKGROUND: Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. METHODS: We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. RESULTS: Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; P<0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P=0.006) higher risk of death and an 85% higher risk of graft loss (P<0.001) compared with low/normal values. CONCLUSIONS: Hyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

Epidemiology of primary hyperparathyroidism.

The impact of primary hyperparathyroidism (HPT) on the population has not been well documented, and even less information is available for asymptomatic HPT. Only 57 deaths were attributed to the condition in the United States in 1986, for a reported HPT death rate of 0.24 per million per year. Many more patients were affected, however, and the incidence of hospitalization for HPT was 6.6 per 100,000 in 1986, counting all listed diagnoses, and 2.9 per 100,000 counting only first-listed diagnoses. Surgery was performed on approximately 10,000 hospitalized patients in the United States in 1986, for a parathyroidectomy rate of about 4.2 per 100,000 per year. When nonhospitalized cases are included, the rates are even higher. The estimated annual incidence of HPT was 42.1 per 100,000 in Rochester, Minnesota in 1974-1976; the prevalence of HPT was 4.3 per 1000 in a population survey in Sweden. By any of these measures, HPT is more common in women than men and increases with aging in both sexes. The potential cost of HPT could be as high as $420 million/year in the United States, but no formal estimates have been made. Disability related to HPT or its treatment has not been quantified; randomized clinical trials to determine the utility of parathyroidectomy have not been performed; and no assessment of cost benefit or cost effectiveness of any therapeutic modality has been carried out. Until patient management and cost issues are resolved, it is premature to consider an aggressive program to screen the general population for HPT.

Clinical presentation of primary hyperparathyroidism in Europe--nationwide cohort analysis on mortality from nonmalignant causes.

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.

Longitudinal studies of mild primary hyperparathyroidism.

In 1969, a health survey was offered to all inhabitants of a town district in Sweden. A clinical examination was carried out, and among other variables, a measurement was made of serum calcium. The same procedure was repeated in 1971. From these two investigations a cohort of 176 individuals (1.1%) with sustained hypercalcemia was identified who could be followed during the subsequent 15 years. Comparisons were made with an age- and sex-matched control group from the same health survey. Survival was significantly lower in the hypercalcemic cohort than in the control group. This reduction was related to the degree of hypercalcemia and apparently mainly due to diseases of the circulatory organs. There was no marked deterioration of renal function, and although there was in some patients a moderate progression of the hypercalcemia, none developed a hypercalcemic crisis during 15 years of follow-up. In consecutively referred patients with primary hyperparathyroidism, psychiatric disturbances of mainly a depressive character were found upon detailed analysis within a majority of the patients, and parathyroid surgery resulted in a clear improvement in mental health.

Therapeutic controversies in primary hyperparathyroidism.

There is little debate about the primacy of surgery in the management of classical PHPT. Rather, the question has been what to do about the many patients with nonclassical disease. A 1990 NIH consensus conference (55) clearly recommended surgery for patients with significant adverse effects of PHPT, for patients with complicating coexistent illnesses, for younger patients, and for those in whom consistent long-term follow-up could not be assured. It allowed that conscientious surveillance may be justified in patients with minimal hypercalcemia and no adverse effects, but it recognized that for many patients, the time and expense involved in rigorous follow-up would outweigh the burden of surgery. Nine years later, the demonstrated prevalence of nonclassical symptoms and their reversibility, the evidence of "asymptomatic" but harmful effects reversible by surgery, and the accumulating evidence for surgical reduction of increased long-term mortality risk substantially strengthen the argument for surgery in such patients. For these reasons, parathyroidectomy should generally be recommended for patients with a secure diagnosis of PHPT, even in the absence of classical symptoms.

Survival after the diagnosis of hyperparathyroidism: a population-based study.

BACKGROUND: Reports of increased mortality from cardiovascular disease and malignancy in primary hyperparathyroidism have been based primarily on patients who have undergone parathyroidectomy. In order to assess the true impact of primary hyperthyroidism on mortality in the general population, we assessed survival in a large inception cohort of Rochester, Minnesota residents with primary hyperparathyroidism initially diagnosed over a 28-year span, the majority of whom were followed with uncomplicated disease. METHODS: All Rochester residents with primary hyperparathyroidism first recognized in 1965 to 1992 were identified through the Rochester Epidemiology Project medical records linkage system. Included as cases were patients with pathologic confirmation of hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia for more than a year with no other cause. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. RESULTS: During the study period, 435 cases of primary hyperparathyroidism were identified. Altogether, parathyroid surgery was performed on 126 patients (29%), with a mean delay between the initial elevated serum calcium level and surgery of 3.3 years. Patients who underwent surgery had higher maximum serum calcium levels than the patients who were observed (mean+/-SD, 11.3+/-0.7 versus 10.7+/-0.4 mg/dL, P <0.00 1), but their mean ages were similar (54+/-16 versus 56+/-17 years). Overall survival in the patients with primary hyperthyroidism was better than expected (P=0.02), but by age-adjusted multivariate analysis, higher maximal serum calcium level was an independent predictor of mortality (RR=1.3 per mg/dL; 95% CI: 1.1-1.6; P <0.02). CONCLUSION: Overall survival is not adversely affected among unselected patients with mild primary HPT in the community, although patients with more severe disease, as manifested by higher serum calcium levels, may have an increased risk of death.

Recurrence of hyperparathyroidism; a long-term follow-up after surgery for primary hyperparathyroidism.

OBJECTIVE: In general it is thought that recurrence of primary hyperparathyroidism is a rare event. To our knowledge, however, only one large patient series has been reported with a mean of more than 7 years of follow-up. The aim of the present study was to determine the long-term recurrence rate in 785 out of 886 patients operated on for primary hyperparathyroidism and followed-up for a mean of 10.03 years after surgery. DESIGN: Medical records were scrutinised. The patients who were still alive answered a questionnaire and had laboratory tests. METHODS: Follow-up data concerning the state of health, medical treatment, other diagnoses, renal function, and serum calcium and creatinine levels were found in the medical records of 203 patients, and were registered at the start of investigation of 582 patients. Intact parathyroid hormone values were determined in 252 patients. Recurrence rate and 95% confidence interval (C.I.) were calculated. RESULTS: Recurrence rate of hyperparathyroidism with constant or intermittent hypercalcaemia (n=39) was 4.97% (95% C.I.=3.45-6.74%) during a mean of 10 years of follow-up. Nine out of 39 had elevated serum creatinine levels. Recurrence rate of hyperparathyroidism with normal serum creatinine levels, including patients with normocalcaemia, intermittent hypercalcaemia, and constant hypercalcaemia was estimated to be 7-8% during a mean of 10 years of follow-up. CONCLUSIONS: Recurrence rate was determined with reasonable precision in this large patient series, and recurrence of hyperparathyroidism cannot be considered to be extremely rare, but it may occur more than 20 years after treatment in both single and multiple gland disease.

Survival after surgical treatment for primary hyperparathyroidism.

BACKGROUND: Reports have suggested that patients with primary hyperparathyroidism (pHPT) are at increased risk for premature death, even when they reach normocalcemia. This study addresses factors that may be of relevance for long-term outcome. METHODS: Between 1980 and 1984, 1052 patients (27% men and 73% women; median age, 59 years) underwent initial cervical exploration for pHPT. Long-term follow-up was obtained with regard to overall survival and cause of death. By using univariate and multivariate (Cox) survival analysis, subgroups of patients were compared. RESULTS: Median follow-up was 12 years (range, 0 to 15 years). Overall, survival was not decreased compared with the expected survival of a gender- and age-matched midwest population. Survival was better in patients with a history of kidney stones (p = 0.044), without osteoporosis (p = 0.004), and without muscle weakness (p = 0.013). CONCLUSIONS: Decreased long-term survival was not evident in this study. Age at the time of initial surgical treatment and the degree of endocrine activity of the diseased glands appear to be the most important independent prognostic factors for survival. Comparison of these data to prior Scandinavian data is not justified, principally because of the less advanced stage of disease in this study.

Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease.

BACKGROUND: The risk of dying from primary hyperparathyroidism (pHPT) is controversial and has been explored mainly in single parathyroid gland disease. The present study investigates mortality in pHPT due to multiple parathyroid gland disease. METHODS: We used the nationwide Swedish In-patient Register and Cause-of-Death Registry to compare the mortality in 3485 Swedish patients subjected to parathyroidectomy during 1964 to 1999 with that of the Swedish population (standardized for age, gender, and calendar year). The patient cohort includes 36,596 person years. RESULTS: Increased risk of death beyond the first postoperative year (standardized mortality ratio, 1.4; 95% CI, 1.37-1.52) was found in both sexes and for all age intervals below 80 years. The increased risk persisted more than 15 years postoperatively and related to cardiovascular diseases, diabetes mellitus, urogenital diseases, and malignant disorders. The increased risk of dying in cardiovascular diseases normalized during 1990 to 1999. CONCLUSIONS: pHPT caused by multiple parathyroid gland enlargement is associated with an excessive mortality similar to pHPT of single parathyroid adenoma. The findings substantiate that modern modes of surgical treatment for pHPT normalize the risk of dying from cardiovascular complications and that the hyperpararthyroid state per se is the possible cause of the premature death.

Mortality after surgery for primary hyperparathyroidism: a follow-up of 441 patients operated on from 1956 to 1979.

Four hundred forty-one patients who were operated on for primary hyperparathyroidism were observed for up to 22 years. Mortality was significantly higher than expected during the first postoperative years, for both men and women. This was predominantly due to a higher than expected incidence of diseases of the circulatory organs. The greater risk of death--compared with the expected mortality in the general patient population--appeared to decrease after the initial 5 to 8 postoperative years. However, for the entire follow-up period, the cumulative survival ratio (i.e., the ratio between the expected and the observed rates) was less than 1 for both sexes. The preoperative concentration of serum calcium did not influence the survival rates. The findings are consistent with the hypothesis that untreated hyperparathyroidism carries an increased risk of death, particularly from cardiovascular diseases but that this risk is gradually reduced after surgery.

Observations on the course of untreated primary hyperparathyroidism.

Controversy has arisen regarding the indications for elective surgical intervention in asymptomatic primary hyperparathyroidism (HPT). The present study was designed to answer two questions: Is untreated primary HPT a progressive disease over time? If not, are the risks attendant on long-term conservative management comparable to those obtained from surgery? Forty-seven patients with primary HPT, established by a persistently elevated serum calcium level and an inappropriately elevated parathormone value, who were managed conservatively and followed for a minimum of 5 years were identified. Serial data collection included calcium, phosphorus, albumin, creatinine, alkaline phosphatase, parathormone levels, skeletal x-ray films, and complications known to result from primary HPT. For each patient the collected data were divided into three equal periods of time (minimum of 20 months per period). In addition, the patients were classified into three groups based on their average serum calcium levels during the first observation period. No patient in any of the three groups experienced a significant progressive increase in serum calcium levels during the periods of observation. Sixteen of the 47 untreated patients (34%) experienced a complication usually associated with primary HPT: peptic ulcer disease (eight patients), decrease in renal function (five patients), renal calculus (one patient), hypercalcemic crisis (one patient), and ventricular conduction defect (one patient). Four deaths were attributed to these complications. In conclusion, the course of primary HPT and attendant complicating features are not accompanied by worsening of the hypercalcemia initially observed. None of the parameters studied offered an accurate prediction of likelihood, progression, or severity of complications. The risks associated with long-term nonoperative management of asymptomatic primary HPT are nevertheless considerable and exceed the morbidity and mortality rates resulting from neck exploration.