Incidence, detection and outcome of differentiated thyroid cancer in Western Sweden.

BACKGROUND: It is unclear whether the increasing incidence of thyroid cancer (TC) due to increased diagnosis of small and indolent tumours might mask a real increase of clinically significant cancers. The aim of this study was to correlate surgery, pathology and outcome data of individual patients to the mode of primary detection (palpation, by imaging or incidental) to assess if TC incidence has increased. METHODS: The Swedish Cancer Registry identified all patients with TC in Västra Götaland County representing approximately 1.6 million inhabitants. Clinical information was retrieved from medical records of patient cohorts from three study intervals (2001-2002, 2006-2007 and 2011-2014) comprising 60 per cent of all TC patients. Data were also obtained from the NORDCAN registry to compare of TC incidence with other Nordic countries. RESULTS: Between 2001 and 2014, the annualized standard incidence rate/100 000 population (ASR) of TC increased from 3.14 to 10.71 in women and from 1.12 to 3.77 in men. This was higher than the mean incidence for Sweden but similar to that in Norway and Finland. Differentiated TC (DTC) increased more than threefold. The majority of tumours (64 per cent) were detected by palpation. Larger tumours (10-20, 21-40 and greater than 40 mm) increased as much as microcarcinomas (less than 10 mm). Only 5 per cent of the tumours were detected by imaging. All disease-specific deaths (8.5 per cent of DTC in the first two cohorts) and most patients with recurrent or persistent disease (6.6 per cent of DTC cases) were diagnosed due to tumour-related symptoms. CONCLUSION: DTC in Western Sweden gradually increased between 2001 and 2014. The majority of tumours were detected by palpation suggesting a real increase in the incidence of clinically significant thyroid malignancies.

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

The epidemiology of infantile hypertrophic pyloric stenosis in Sweden 1987-96.

AIMS: To find out whether the incidence of infantile hypertrophic pyloric stenosis (IHPS) has changed over the past decade, and if so, to investigate possible contributory factors. METHODS: All infants undergoing pyloromyotomy for IHPS in Sweden between 1987 and 1996 were studied. Using the national patient registers the yearly incidence was determined and evaluated in relation to sex, latitude, urbanisation, and type of surroundings by use of a Poisson model. RESULTS: There was a substantial decline from 2.7/1000 to 0.85/1000 over the time period. The incidence in the south was almost three times greater than in the north. CONCLUSION: The declining incidence and geographical difference suggest that environmental factors are of importance in this disorder.

The improvement of renal concentration capacity after surgery for primary hyperparathyroidism.

BACKGROUND: Improvement of renal concentration capacity was long ago shown to occur after surgery for primary hyperparathyroidism (pHPT). Study of concentration capacity is of interest, as it was also shown to be a predictive factor for the risk of death in patients with pHPT, and it affected the risk of death independently of 33 other variables in multivariate analysis. METHODS: There were 98 patients with verified pHPT operated on in the years 1958-81, who had urine osmolality determinations performed both before and after surgery: 63 immediately after, and 35 with mean 3.9 years delay (SD = 1.8). Another seven patients with pHPT had urine osmolality determinations performed preoperatively only. Non-parametric sign tests, regression analysis, and correlation tests were performed. RESULTS: Both patients with severe or moderate, and mild pHPT showed a substantial change of renal concentration capacity, with mean increase of 28.3% (SD = 28.4). The increase generally occurred soon after surgery. In eight out of 98 patients, there was no improvement. A relationship was found between improvement and preoperative peak serum calcium level. In seven out of seven patients followed, untreated for mean 5.3 years (SD = 3.2), there was a mean 15% (SD = 8.0) deterioration of renal concentration capacity. CONCLUSIONS: The findings of this study add cause for surgery in patients with pHPT and give no reason for different treatment of severe, moderate or mild disease.

[Forming of opinion in medical decision making and primary hyperparathyroidism]. / Asiktsbildning vid medicinska beslut och primr hyperparatyreoidism.

A recent symposium regarding primary hyperparathyroidism, pHPT, dealt with the issue of surgical treatment versus conservative monitoring. Studies from the past decade showed an increase in mortality for patients with both mild and symptomatic pHPT. There is a direct relationship between risk of death and severity of pHPT, and surgery favorably affects mortality. Patients with untreated mild pHPT show a slow increase in mortality over time. Cardiovascular and neuropsychiatric morbidity were also shown to be ameliorated after surgery. Generally, patients with pHPT benefit from surgery. Some disagreed in spite of substantial data, and advocated a less aggressive approach, yet management must be based on strictly medical reasoning and well-performed studies. Economics may influence what we might accomplish, but must not influence the decision as to what the medical objective should be.

Increased risk of death from primary hyperparathyroidism--an update.

BACKGROUND: The aim of this study was to investigate the risk of death among patients treated for primary hyperparathyroidism during the past decade. METHODS: Using the national patient register, all patients operated on for primary hyperparathyroidism in Sweden during 1987-94 were identified and then searched for in the national register of deaths and causes of death during the same period. The control group was the whole Swedish population, matched for age, sex and calendar year. RESULTS: We found that patients treated for primary hyperparathyroidism run an increased risk of death. The risk ratios for death from cardiovascular disease were 1.71 for male and 1.85 for female patients. These estimations are of high precision because of the large patient series (n = 4461), with 95% confidence limits of 1.34-2.15 and 1.62-2.11 for men and women respectively. CONCLUSION: This finding, together with previous findings that parathyroid adenoma weight, serum calcium level and parathyroid hormone level are predictive of the risk of death, suggests the possibility that surgery in patients with primary hyperparathyroidism may offer not only relief from signs and symptoms but also improved prognosis.

Death risk factor analysis in primary hyperparathyroidism.

BACKGROUND: Patients treated for primary hyperparathyroidism run an increased risk of death. The aim of this study was to analyse several factors that may influence their risk of death. METHODS: General, laboratory, physical and clinical variables, altogether 34 variables, were defined as possible risk factors for death and were studied in a patient series of 845 patients operated on during the period 1953-82. Mean follow-up time was 10.5 years (SD 5.9); 253 patients were deceased at follow-up. Cox's proportional hazard model was used. RESULTS: We found seven variables with independent influence on the risk of death: age, sex, diabetes, cardiovascular disease, glomerular filtration rate, renal tubular concentration capacity and amount of diseased parathyroid tissue. The remaining 27 variables were separately tested, one at a time, using the same method and with the influence of age and sex eliminated. In this test situation, the year of surgery, peak serum calcium, serum creatinine level, body mass index, hypertension, psychiatric symptoms and a history of crisis were all significantly related to the risk of death. The analyses also gave information on the direction and magnitude of the effect of the variables on the risk of death. CONCLUSION: Primary hyperparathyroidism itself is a risk factor for death, but it was concluded that well-preserved renal function at surgery seems to have a protective role. We also found that the greater the amount of diseased parathyroid tissue the lesser the renal function and, furthermore, that hyperparathyroidism of substantial degree or long duration may bring about renal impairment that is not necessarily disclosed by the creatinine value alone.

Parathyroid adenoma weight and the risk of death after treatment for primary hyperparathyroidism.

BACKGROUND: Patients operated on for primary hyperparathyroidism run an increased risk of death, as was found in a previous long-term follow-up of 896 patients. METHODS: In the present study the adenoma weight was determined in 713 patients with single parathyroid gland disease operated on between 1956 and 1982 and followed up in 1986. The adenoma weight was investigated for its usefulness as a prognostic factor. RESULTS: The analysis showed that the adenoma weight was significantly related to the risk of death (p < 0.001). Also a relationship was noted between glandular weight and preoperative serum calcium level (p < 0.001), although the serum calcium level had no predictive value in relation to the risk of death beyond that of the adenoma weight. The risk increase was also estimated as a function of adenoma weight. A moderate adenoma weight increase in a patient with primary hyperparathyroidism was found to imply an increased risk of death, corresponding to the increased risk of smokers as compared with nonsmokers. CONCLUSIONS: The results of this study support surgical treatment at an early stage of primary hyperparathyroidism.

Clinical evaluation of total serum calcium in primary hyperparathyroidism and the risk of death after surgery.

This study aims to understand the behaviour and clinical value of total serum calcium in untreated primary hyperparathyroidism, to identify the significant relationship between pre-operative total serum calcium and the risk of death after surgery, and to consider the issue of when to operate. The risk of death after surgery was studied as dependent on pre-operative serum calcium levels in a series of 896 patients followed up for mean 12.9 years (SD 6.1) after surgery. The predictive power of pre-operative peak calcium levels was stronger than that of mean calcium levels. It was found that an increase of peak serum calcium from 2.60 mmolL-1 to 2.90 in one patient meant a death risk increase, with 38% still 5 years after surgery. The marginal risk increase per mmol L-1 was found to be higher below the peak serum calcium level of 2.90 mmol L-1 than above that level. The variation of total serum calcium before surgery was found to be substantial and the occurrence of transient high serum calcium levels was not unusual. Therefore, conservative surveillance with yearly total serum calcium estimations seems insufficient. Rather, early surgery, when serum calcium levels are not more than moderately increased, appears to be the most favourable alternative.

Parathyroid water clear cell hyperplasia, an O-allele associated condition.

This is an investigation into the finding that patients with primary hyperparathyroidism caused by Water Clear Cell Hyperplasia (WCCH) frequently belong to blood group O. Two control groups were defined from the same time period as 32 cases of WCCH treated at our clinic: one was a consecutive patient series with other forms of primary hyperparathyroidism (n = 864) and the other was the population in a geographically defined area in Sweden (n = 59,862). The blood group distribution of the patients with WCCH differed from the distribution of the patients with other forms of primary hyperparathyroidism with high significance (P = 0.00040). The blood group distribution did not differ between the two control groups. Strong associations between disease and HL-A type have previously been described, while associations found between disease and ABO blood groups were weaker. The association between WCCH and blood group O described here is by far the strongest association with the ABO system demonstrated to date. It is possible that the presence of an O-allele is a prerequisite for the development of WCCH.

Management of hyperparathyroid patients with grave hypercalcemia.

During recent years the total number of patients undergoing surgery for hyperparathyroidism has markedly increased, but the annual number of cases with substantial hypercalcemia has remained unchanged. Parathyroid carcinoma and water clear cell hyperplasia cause more severe hypercalcemia than other kinds of hyperparathyroidism. Grave hypercalcemia due to hyperparathyroidism is more common among the elderly, but can occur during pregnancy and also among children. Occasionally, a patient with hyperparathyroidism can also have another cause of the hypercalcemia and does not become normocalcemic until adequately treated for both. The suspicion of grave hypercalcemia should arise due to its clinical features. Determination of serum calcium and intact parathyroid hormone concentrations establishes the diagnosis. The basic treatment of grave hypercalcemia is to rehydrate the patient and to restore the sodium losses. To further lower the serum calcium value we have found bisphosphonates to be very effective. The definitive treatment of grave hypercalcemia due to hyperparathyroidism is surgery. As a last resort, frail patients with grave hyperparathyroidism can undergo surgery under local anesthesia. Repeat operations can improve the prognosis of patients with metastatic parathyroid carcinoma. Selective venous catheterization with blood sampling for determination of intact parathyroid hormone can be helpful in localizing recurrent disease.

The influence of surgery on the risk of death in patients with primary hyperparathyroidism.

The previous finding of an increased risk of premature death in a consecutive series of 896 patients operated on for primary hyperparathyroidism between 1953 and 1982 [1] raised the question of the role that surgery plays in relation to the risk of death. In the present study, undertaken to examine that issue, 3 factors--age, calendar year of surgery, and time passed after surgery--have been found to be significantly related to the risk of death (p less than 0.001), each factor contributing independently. A correlation was found between a late calendar year of surgery and a low degree of hyperparathyroidism as evaluated by serum calcium and creatinine levels. There was an increased risk of premature death in all age groups. The risk was less among patients operated on in later years. The observed normalization of the increased risk of death with time after surgery also took place sooner in patients operated on in later years. Our findings of improved survival following surgical intervention contrasts favorably with the findings of others in studies of subjects with untreated mild hyperparathyroidism. We have also found that preoperative serum calcium levels affect the risk of death, and that there is an additional factor related to the calendar year of surgery affecting the risk of death. Circumstantial evidence indicates that the duration of hyperparathyroidism contributes to this factor. Our results also show that early surgery decreases the risk of premature death in mild cases of the disease.

Premature death in patients operated on for primary hyperparathyroidism.

To investigate long-term survival after operation for primary hyperparathyroidism, a follow-up study was performed on 896 consecutive patients in whom this diagnosis had been clinically and microscopically verified. These patients were operated on in the years 1953-1982. Their mean age at operation was 57.3 years [standard deviation (SD) 13.1], overall cure rate was 97.0%, and postoperative mortality was 0.89%. Follow-up was 99.8% complete by the end of 1986. Mean follow-up time was 12.9 years (SD: 6.1). Two-hundred ninety-four patients were deceased, which was 118 more than in a control group (p less than 0.001). The latter was based on Swedish population statistics, matched for age, sex, and calendar year. Each year, the control group was the same size as the hyperparathyroid population. The risk of premature death remained increased (p less than 0.001) even after exclusion of poor-risk patients having their hyperparathyroidism diagnosed when being treated or followed because of other serious diseases. The main causes of premature death for the hyperparathyroid patients were cardiovascular and malignant diseases. Both occurred more often than in the control group (p less than 0.001). The results demonstrate that primary hyperparathyroidism causes damage that is not reversed by surgery.