paratiroidektomi 3
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INTRODUCTION
Hyperparathyroidism (HPT) is a rather frequent disease, but not fully understood.
Although most part of the cases is presented in clearly defined clinical pictures, some patients
present atypical features.
Surgical treatment is of great value for primary, secondary and tertiary HPT.
Postoperative course is also variable and it is not completely predictable. Right after the
operation, most attention is directed to hypocalcemia, avoiding severe calcium level drop.
Hypocalcemia may be caused by postoperative hypoparathyroidism, but it may be also related to
bone remineralization. Even experienced authors did not mention renal function modification in
this period and they refer that many patients are discharged on a same day or on a next day basis
1
.Some years ago, one of the authors (LEI) observed a slight increase of creatinine levels in
some renal transplant patients submitted to parathyroidectomy. In one publication, preoperative
creatinine ranged from 0.9 to 1.7 mg/dL (mean 1.15 mg/dL), while postoperative levels ranged
from 1.0 to 3.1mg/dL (mean 1.27 mg/dL).2
Besides this observation, other authors reported the
loss of residual diuresis in dialytic patients after parathyroidetomy3.
Dr. Maria Odete Ribeiro Leite, an endocrinologist, made comments on a slight edema
after parathyroidectomy for primary HPT, usually resolving in few days (personal
communication). Although uncommon, a clinically significant decrease of renal function after
parathyroidectomy has been observed in some patients with primary HPT. In those cases, blood
pressure fluctuations during anesthesia were suspected as the cause, but not conclusively, because
no report of these fluctuations could be detected in anesthesia records.
Recently, Schwarz et. al. showed a decreased renal function in kidney transplant patients
after parathyroidectomy4. Creatinine levels increase after parathyroidectomy in transplanted
patients was previously mentioned by others5,6. In primary HPT, decreased renal function was a
collateral observation in a study 20 years ago7. In another study, a non significant elevation of
creatinine, a significant increase of u rea, a significant reduction in creatinine clearance in patients
undergoing parathyroidectomy for primary HPT, but without change in glomerular filtration rate
analyzed by the clearance of51
Cr-EDTA8.
These accounts led to some questions regarding the frequency of renal changes in patients
submitted to parathyroidectomy in tertiary HPT. Would this change occur in kidney transplant
patients undergoing other operations in the head and neck? If related to parathyroidectomy, what
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would be the role of HPT? If related to HPT, what might be expected in patients with primary
HPT?
The aim of this study was to evaluate the possible fluctuation of renal function after
parathyroidectomy. By a retrospective analysis, the frequency of renal changes were compare din
different surgical treatment groups, as follows: primary HPT, tertiary HPT after renal
transplantation, non parathyroid related head and neck tumors in kidney transplant patients and
patients with normal renal function and non parathyroid related head and neck tumors (oral,
larynx, pharynx, thyroid, salivary glands cancer or goiter).
PATIENTS AND METHODRetrospective evaluation of primary HPT of different causes and HPT after successful
kidney transplantation (tertiary HPT) submitted to parathyroidectomy at the Department of Head
and Neck Surgery of the University of So Paulo Medical School, from 1997 to April, 2007.
Kidney transplant patients without HPT submitted to resection of other head and neck
tumors under general anesthesia (OKDTx) was analyzed as a control group to patients with
tertiary HPT.
A random sample of patients with normal renal function undergoing surgical treatment for
goiter, thyroid cancer or other head and neck tumors (OHN) was considered as a control group
for primary HPT patients.
Available data of preoperative creatinine and postoperative results were investigated at
the patients charts, from the surgical notes of the first author or available at the electronic system
from the laboratory database from the institution.
The most recent available preoperative creatinine result was considered in relation to
highest postoperative level observed. A subtraction of the preoperative level from the
postoperative was calculated and then, this difference was divided by the preoperative level. The
percentual variation was estimated. This probably reflects changes in renal function. A negative
result was due to a decrease in creatinine reflecting an improvement in renal function. On the
other hand, a positive result indicated an elevation of creatinine and, consequently, a decreased
renal function.
After parathyroidectomy, the change in renal function was considered if superior to 10%.
This restriction tried to avoid variations related to measurement of creatinine, according to the
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variation coefficient from previous studies, about 4%9. The change was stratified to estimate the
magnitude of variation. If a 30% increase from preoperative level was observed, this was
considered a significant change. 6
During the period of study, laboratory employed different methods. Early measurements
were reported as serum automatized colorimetric (normal range 0.6 to 1.4 mg/dl). Later, an
automatized kinetic was employed (normal ranges 0.4 to 0.9 for women and 0.7 to 1.2 form
men). Each patient comparison was done only with the same method.
STATISTICAL ANALYSIS
Descriptive statistics included mean, median, standard deviation (SD), and standard errorof the mean (SEM).
For statistical inference, parametric or non-parametric tests were employed according to
the normality test. A dichotomy of values of less or equal to 10%, or superior to 10% was
checked with the Qui-square test.
Kruskal-Wallis, Dunns Multiple comparison, Mann-Whitney and non-paired student
were employed. Calculated descriptive value (p) was considered significant if inferior to 5%.
RESULTS
In the established 10 year period, 168 primary HPT cases were operated at the institution.
Standard surgical technique was bilateral parathyroid exploration. In 105, creatinine levels could
be compared right after the operation. They were studied as primary HPT group. Data from 38
kidney transplant patients with HPT submitted to surgery were available, and also from seven
transplanted patients without HPT operated on head and neck tumors.
In 25 patients undergoing thyroidectomy, comparative creatinine was available. Of these,
three were submitted to thyroid lobectomy only and one patient with a previous thyroidectomy in
the past underwent a central neck dissection. Total thyroidectomy or completion thyroidectomy
was the operation of the remaining 21 patients. Of these, seven were associated with central neck
dissection.
Table 1 shows the count of cases with creatinine increase superior to 10%, according to
each group.
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Table1 Counts ofcreatinine increase superior to 10%, according to different groups.
CreatinineIncrease Primary HPT Tertiary HPT OK DTx L obectomy Total Thyroidectomy OHN
Negativeor 10% 77 32 1 0 11 3
Total 105 38 7 3 22 18
Comparison of the groups of Table 1 by qui-square test yielded p50% 18
(17.1%)
9
(23.7%)
0
(0%)
3
(13.6%)
0
(0%)
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Table 3 shows descriptive statistics observed in different groups.
Table3 Creatinine variation in different groups.
Tertiary HPT OK DTx Primary HPT Total thyroidectomy OHN
minimum -33.3% -28.0% -20.2% -29.6% -33.3%
maximum +172.5% +38.0% +304.5% +88.9% +43.4%
mean +39.5% -2.7% +30.8% +18.7% -6.4%
median +28.3% -6.0% +25.0% +11.25% -7.5%
SEM 6.4% 8.4% 4.1% 6.8% 4.1%SD 39.2% 22.2% 41.8% 31.7% 17.5%
Normality test passed passed failed passed passed
According to creatinine increase, multiple group comparison did show a significant
difference (p
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Graphic 3 Distribution of postoperative creatinine change in primary HPT (HPT primrio) and OHN (CEC CCP).
These observations suggested two other comparisons. The first one between patients
undergoing parathyroidectomy for primary HPT and those submitted to total thyroidectomy with
or without central neck dissection, but a demonstrated reduction of postoperative parathyroid
hormone level. No statistical difference was observed (p=0.97, Mann-Whitney test), as shown isgraphic 4.
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Graphic 4 Postoperative change of creatinine (% variao da creatinina no PO) in patients with
primary HPT (HPT p rimrio) and total thyroidectomy with hypocalcemia (hipocalcemia PO).
The second comparison tried to answer if a difference between those with presumed
hypoparathyroidism after thyroidectomy could exist when they were compared to those without
postoperative reduction in parathyroid activity. In this condition, patients submitted to thyroid
lobectomy were included in the group of those without postoperative hypoparathyroidism. When
thyroidectomy patients were stratified according to presumed hypoparathyroidism a significant
difference was noted. Mean percent creatinine increase was + 28.5% (SEM 9%) in those with
presumed hypoparathyroid and it was + 1.2% (SEM 5%) in those without evidence of
postoperative hypoparathyroidism. (p=0.02, non paired t test, Graphic 5).
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Graphic 5 Comparison after thyroidectomy with presumed hypoparathyroidism (hipocalcemia) and
without evidence of postoperative parathyroid dysfunction (sem hipocalcemia).
In most cases, creatinine levels return to basal in few days. Graphic 6 illustrates one
patient submitted to total thyroidectomy. She has received supplemental calcium after the
thyroidectomy and the medical team in charge had sampled calcium, parathyroid hormone andcreatinine in the postoperative period. This case also illustrates that creatinine variation is not
associated with serum calcium values, as many patients have received supplemental calcium.
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C r eat in i n e v ar iati on aft er t h y r oi d ect omy i n on e cas e
0,76
1,06
0,73
0,69
0,91(estimated
value)
0
0,2
0,4
0,6
0,8
1
1,2
p r e o p e r ative o p e r atio n 1P O 3P O 9P O
T im e
Creatinine
(mg/dl)P T H
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Through a clinical observation, the present study seems to demonstrate a parathyroid
hormone hemodynamic effect on the kidney as suggested by some previous animal studies where
a decline in glomerular filtration was observed after parathyroidecotmy10,11. These animals did
not have preoperative elevated levels of parathyroid hormone as some thyroid patients of the
present study.
A creatinine change as consequence of blood pressure changes in anesthesia seems not
probable to explain all cases, as patients with head and neck neoplasms undergo more extensive
operations, with more pronounced fluid loss, and in many of them creatinine levels decreased.
Evaluation of renal function by creatinine measurement is questionable, but it is still a
reality in clinical practice
12
. The possible interference of drugs, as cephalosporins or increase inbilirubin13, is apparently less probable in these cases. There is an observation that creatinine
clearance is overestimated in some patients with HPT8, suggesting that the creatinine increase is
not a real change in renal function. However, how can one explain creatinine increase in some
thyroidectomy patients, without previous HPT?
The retrospective nature of this study is associated with many doubts and caution in
interpretation of these observations is advised. Clearly, a prospective study, with other markers of
renal function, as cystatin C, would be of interest. Even measurement of bilirubin would be
justified, as parathyroid hormone affected hepatic flow in an experimental study14
.
There is evidence that renal disease is a world problem of public health, affecting 5% to
10% of population, with progressive loss of kidney function, cardiovascular disease and early
death15. The knowledge of nephrotoxic drugs (anti-inflammatory, antibiotics and radiological
contrasts) make their use selective, with protective measures, lowering their risk of renal
complications.
Recognizing that the surgical treatment of the parathyroid glands by itself may interfere
with renal function is of clinical value. Patient counseling before the operation and careful
preoperative evaluation of renal function are necessary.
Postoperative care is also recommended as the present authors observed a few patients
with a permanent or a progressive loss of renal function after the parathyroidectomy. Indeed,
Edvall showed renal alterations due to HPT16
. Some are functional and revert after excision of
hyperactive parathyroid tissue. However, in some cases, HPT seems to promote an organic
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tubular lesion that is irreversible. In advanced disease, parathyroidectomy may represent the loss
of compensatory mechanism16
.
Special attention should be directed to patients with single kidney, to those with a
previous compromise in renal function, and to those at risk groups, as diabetics and hypertensive
patients.
REFERENCES
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2. Ianhez LE. Transplante Renal. Seguimento a longo prazo. So Paulo: Lemos Editorial; 2002. p.37.
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affect residual diuresis in hemodialysis patients? Nephron. 2000;86(3):402-3.
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parathyroidectomy. Nephrol Dial Transplant. 2007;22(2):584-91.
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calcium on rat renal function. Nephron. 1999;83(1):59-65.
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13. Weber JA, van Zanten AP. Interferences in current methods for measurements of creatinine. Clin Chem.
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14. Charbon GA, Hulstaert PF. Augmentation of arterial hepatic and renal flow by extracted and syntheticparathyroid hormone. Endocrinology. 1974;96(2):621-6.
15. Moe SM, Dreke T, Lameire N, Eknoyan G. Chronic kidney disease-mineral-bone disorder: a new paradigm.
Adv Chronic Kidney Dis. 2007;14(1):3-12.
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renal clearance and renal vein catheterization. Acta Chirur Scand Suppl. 1958;114(Suppl 229):1-56.