Mortality after Surgery for Primary Hyperparathyroidism

Three Scandinavian studies examined long-term mortality after surgery for PHPT. Basic data from the three Scandinavian series are given in Table 43-1. The first two series included patients who had been treated during the same 24-year period.910 The third series included more patients than the other two together and covered a 30-year period. This series also had the longest follow-up.11"13 In the Helsinki study, for the first time, the long-term mortality after surgery for PHPT was compared with that in contemporary control subjects matched for gender and age.9

Surgical Complications and Cure of Primary Hyperparathyroidism

None of the series provided information regarding recurrent nerve palsy. Postoperative hypoparathyroidism occurred in 3.4% of the patients in the Uppsala series.14 In the Göteborg series, hypoparathyroidism occurred in 2.45%. After exclusion of patients who underwent reoperation, patients with multiple parathyroid gland disease, and patients with concomitant thyroidectomy for thyroid tumor, only three patients who experienced hypoparathyroidism remained in the Göteborg series. This shows that hypoparathyroidism is a rare complication in patients with a single parathyroid adenoma.11 The cure rate of PHPT among the survivors at the time of follow-up was 94% in the Helsinki series15 and 91% in the Uppsala series.10 In the Göteborg series, the cure rate was 97%, defined as a stable serum calcium concentration of less than 2.55 mmol/L during the first postoperative year."

Postoperative Mortality

Two of the series supplied information about the mortality within 1 month after surgery (Table 43-2). In the Göteborg study, the mortality for the first half of the series was 1.56%. During the last half of the series, only 1 of 448 patients (0.22%) died postoperatively.11

Long-Term Mortality

In the Helsinki series, patients undergoing surgery for appendicitis, varicose veins, or hemorrhoids and matched for age and gender were used as control subjects.9 In the Uppsala and Göteborg studies, patients were assigned to control groups on the basis of Swedish population statistics and were

TABLE 43-1. Three Scandinavian Studies on Long-Term Mortality After Surgery for Primary Hyperparathyroidism

Follow-up

City of No. of F/M Age at Study average range

Study Patients Ratio Surgery (yr) Period year duration (yh) (to)

Helsinki 334 3.0:1 53 1956-1979 1980 5.0 1-24

Uppsala 441 3.0:1 57.8 ± 12.8 1956-1979 1983 7.7 4-27

Göteborg 896 2.7:1 57.3 ± 13.1 1953-1982 1986 12.9 4-33*

'For patients who underwent reoperation, follow-up time was calculated from the last operation. F = female; M = male.

matched for gender, age, and calendar year of surgery.10"12 During 5 years of observation, the increased mortality in the Helsinki study was 3.9% of the PHPT population (see Table 43-2). The relative risk (RR) of death compared with control subjects was 1.62, with a 95% confidence interval (CI) of 0.91 to 2.94 (Table 43-3). The increased mortality among the PHPT patients was significant (P < .05) (Table 43-4).9 In the Göteborg study, the observed mortality was increased by 13.2% in the PHPT population compared with the expected mortality after a follow-up period of 12.9 ± 6.1 years. The RR was 1.67 and the CI was 1.49 to 1.87. The increase in mortality was highly significant (P < .001)." In the Uppsala study, the relative cumulative survival ratio between observed survival for the PHPT patients and the expected survival was below 1 throughout the follow-up period. The decrease in survival after surgery for PHPT was statistically significant only for females between 4 and 12 years after surgery. The survival rate was reduced by 4% after 14 years. The approximate RR in the Uppsala study was 1.45 (see Table 43-3) as calculated on the basis of available data from Palmer and coworkers.10

The RR represents the ratio between the death hazard functions of the PHPT group and those of the controls. The quotient is a function of time after surgical treatment. In the Göteborg series, it was shown that the RR decreased with time after surgery.12 In this presentation, the RR is presented as one figure for each series (see Table 43-3). This figure is the mean of the quotients in an interval of postoperative years.

The Helsinki, Uppsala, and Göteborg studies involved patients undergoing surgery for PHPT at the three hospitals during the study periods. The three studies showed increased long-term mortality after surgery for PHPT.9"11 In the largest study with the longest follow-up, the increased mortality was 13.2% of the PHPT population (118 patients).11

Risk Factors

In the Göteborg study,12 it was found that age, calendar year of surgery, and time elapsed since surgery were significantly (P < .001) and independently correlated with the risk of death (Table 43-5). The importance of calendar year of surgery and time elapsed since surgery is exemplified in Figure 43-1 by patients who were 65 years old at surgery. The RR was twice as high in 1965 as in 1980. For patients operated on in 1965, it took 12 to 14 years before the RR returned to a normal survival curve, whereas in patients operated on in 1980 it took approximately 5 years. The serum calcium concentrations were positively related to the risk of death (P < .01). Both the preoperative serum calcium and serum creatinine concentrations decreased continuously (P < .001) during the period from 1953 to 1982. Consequently, patients operated on during the early years of the study had a more severe disease. This explains in part why an early calendar year could be a risk factor for premature death. The RR of death was raised in all age groups, but patients 55 to 70 years of age at surgery had the highest RR. It was thought that young people had a better restorative capacity and that the aged had many other risk factors, making the risk of PHPT relatively less important. The increase in RR was less pronounced as time passed after surgery but was a consistent finding in all age groups.

TABLE 43-2. Mortality in Patients with Primary Hyperparathyroidism (PHPT) and Controls During Follow-up

Long-Term Mortality (%)

City of Postoperative Increased Mortality

Study Mortality (%}* phpt patients controls Among PHPT Patients (%)

Helsinki Not given 10.2 6.3 3.9

Goteborg 0.89 32.8 19.6f 13.2

"Death within 1 month postoperatively. 'Expected.

TABLE 43-3. Relative Risk of Death in Patients Who Had Undergone Surgery for Primary Hyperparathyroidism (PHPT)

TABLE 43-5. Risk Factors for Mortality in Patients Who Had Undergone Surgery for Primary Hyperparathyroidism

RR of Death 95% Confidence

Series (PHPT Patients/Controls) Limits foi RR

Helsinki Uppsala Göteborg Göteborg selected5

'Number of deaths in the PHPT group in relation to the number in the control group.

'The RR approximately calculated from Palmer et al's10 Figure 1, 0 to

7 years after surgical treatment.

•Observed to expected number of deaths.

sPoor-risk patients excluded.

RR = relative risk.

TABLE 43-5. Risk Factors for Mortality in Patients Who Had Undergone Surgery for Primary Hyperparathyroidism

Helsinki

Uppsala

Göteborg

Factor

Study

Study

Study

Serum

P<.01

NS

P<.01*

calcium

Calendar

Not studied

NS

Pc.OOl

year of

surgery

Time elapsed

Higher

The reduction

P< .001

since

mortality

in cumulative

surgery

during the earliest part of the series

survival was primarily due to an increased number of deaths during the first postoperative years

Parathyroid

Higher mean

Not studied

P< .001

adenoma

weights in

weight

the patients who died

'When the influence of the calendar year of surgery had been eliminated.

NS - not significant.

'When the influence of the calendar year of surgery had been eliminated.

NS - not significant.

In the Uppsala study,10 serum calcium concentrations and year of surgery did not influence survival. In the Helsinki study,9 serum calcium concentrations were significantly higher (P < .01) in patients who died than in other patients. In this study, it was noted that the mean parathyroid adenoma weight was higher in the patients who died during follow-up.

In the Göteborg series,13 the weight of the parathyroid adenoma was found to be a predictive factor for the risk of death (P < .001). In the series of 713 patients with a single adenoma, the adenoma weights ranged from 75 to 18,100 mg. The median adenoma weight was 610 mg. The adenoma weight at the 20th percentile was 267 mg and at the 80th percentile was 1625 mg. An increase in parathyroid weight from 267 to 1625 mg implied an increase in mortality of 57%. Adenoma weight was significantly correlated with the risk of death (P < .01) even when the influence of the serum calcium concentration had been eliminated. In all other studies and analyses concerning long-term survival, the PHPT populations had been compared with control subjects. In this analysis, for the first time, an increased mortality in the PHPT population

TABLE 43-4. Results of Statistical Analysis Linking

Primary Hyperparathyroidism (PHPT) to an

| Increased Mortality

P Values

Increased

HELSINKI

UPPSALA GOTEBORG

Mortality

STUDY

STUDY STUDY

In the PHPT

<.05

The relative <.001

population

cumulative

mortality

significantly

increased in

women, 4 to 12 years

after surgery

From

<.01

NS (P = .06) <.001

cardiovascular

disease

From malignant

None

None <.001

tumors

NS = not significant.

could be shown by using a factor bound to PHPT itself. This provides strong independent support for the results of the previous studies.

Causes of Death

In all three studies,911 increased mortality from cardiovascular disease was found among the PHPT patients (Table 43-6). The increased mortality was statistically confirmed in the

Op 1965 Op 1970 Op 1975 Op 1980

Relative Risk

Op 1965 Op 1970 Op 1975 Op 1980

Relative Risk

Time after surgery, years

FIGURE 43-1. Chart showing the association between a later year of operation, a lower relative risk for death, and a more rapid postoperative return to the normal survival curve. This figure represents patients who were 65 years old at the time of surgery for primary hyperparathyroidism. (From Hedback G, Oden A, Tisell LE. The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 1991;15:400.)

Time after surgery, years

FIGURE 43-1. Chart showing the association between a later year of operation, a lower relative risk for death, and a more rapid postoperative return to the normal survival curve. This figure represents patients who were 65 years old at the time of surgery for primary hyperparathyroidism. (From Hedback G, Oden A, Tisell LE. The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 1991;15:400.)

TABLE 43-6. Main Causes of Death in Patients !

Who Had Undergone Surgery for Primary

Hyperparathyroidism

Helsinki

Uppsala

Göteborg

Cause Study (%)

Study (%)

Study (%)

Cardiovascular 68

61

53.4

Malignant 6

12

24.5

disease

Renal 12

2

8.5

disease

Helsinki (P < .05) and Göteborg (P < .001) studies. In the Göteborg series, 157 patients, or 63 more than expected, died from cardiovascular disease during the follow-up period. In the Helsinki study, 15 more patients than control subjects died from cardiovascular disease. The follow-up studies did not add any information on the mechanisms causing the increased mortality in cardiovascular disease. However, it is interesting that echocardiographic studies have shown a high incidence of left ventricular hypertrophy in patients with PHPT.1617 In one of these studies, a significant partial regression of the left ventricular hypertrophy was noted 12 months after cure of PHPT.17 Other data have suggested that the echocardiograph-ically measured left ventricular mass is a strong predictor of cardiovascular morbidity and mortality.1819

A significant increase (P < .001) in death from malignant disease was found only in the Göteborg study. In that study, 72 patients died of malignant diseases (i.e., 27 more than expected). These malignancies were of 24 different types. Adenocarcinoma of the pancreas, including the papilla of Vater region, was the only tumor that occurred in a significantly increased number (P < .05).11 Table 43-6 shows the percentages of the three main causes of death. It was found that the percentage of patients who died from malignant disease increased with the length of follow-up (see Table 43-1). In the Göteborg study, the long observation time with many deaths helped to detect the association between PHPT and death from malignant disease. The results of the other studies with shorter follow-up periods do not conflict with the observation in the Göteborg study. A link between PHPT and malignant disease had previously been found in a series of 4163 persons who had been reported to the Swedish Cancer Registry because they had surgery for parathyroid adenomas.20 It is also interesting in this connection that hypercalcemia can induce mitotic activity.21'22 Renal disease was the third most common cause of death. In the Göteborg series, 21 of the 25 deaths from renal disease occurred during the first half of the series. The decrease in mortality from renal disease is not only an effect of early surgery for PHPT but also a result of better treatment of patients with renal stones, impaired glomerular filtration rate, or renal infections.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment