Artigo Original
Estado funcional do autoenxerto da paratireoide
e sobrevida após paratireoidectomia
Parathyroid autograft functional status and survival
after parathyroidectomy
Resumo
Antecedentes: Níveis baixos paratormônio (PTH) podem se
correlacionar com a sobrevida de pacientes em diálise. A sobrevida
do paciente pós paratireoidectomia de acordo com a função autoenxerto foi analisada. Métodos: Estudo retrospectivo de 107
pacientes em diálise consecutivos submetidos à paratireoidectomia
total e auto-enxerto antebraço imediato entre 2006 e 2010. Os
níveis de PTH no pós-operatório foram estudados ao longo do
tempo. Os pacientes foram agrupados de acordo com os níveis
de PTH, e as curvas de sobrevida foram calculadas. Resultados:
Uma redução sustentada de PTH ocorreu após paratireoidectomia.
Os níveis médios de PTH foram reduzidos de 1904 pg/mL no préoperatório para 43, 55, 47, 63, 62,5 e 52 pg/mL, 6, 12, 24, 36, 48 e
60 meses após a operação, respectivamente. Considerando-se o
nível de PTH, houve uma taxa de sobrevivência significativamente
reduzida em doentes com níveis de PTH superior a 261 pg/mL,
em comparação com pacientes com níveis de PTH de 88- 261
pg / mL (p = 0,04, Logrank Test). Conclusão: Em pacientes de
diálise, níveis de PTH no pós-operatório maiores que 261 pg/mL
podem estar associados a uma pior sobrevida, em comparação
com pacientes com níveis intermediários de 88-261 pg/mL, após
uma paratireoidectomia total com auto-enxerto imediato.
Descritores: Hiperparatireoidismo; Paratireoidectomia; Análise
de Sobrevida.
INTRODUCTION
Early patients with secondary hyperparathyroidism
(2HPT) had their disease detected only after bone
symptoms evolved.1 Later, even in the absence of
symptoms, the impact of the mineral metabolism
disturbance in mortality was recognized.2
Fabio Montenegro 1
Stenio Roberto Castro Lima Santos 2
Marilia D’Elboux Guimaraes Brescia 2
Melani Ribeiro Custodio 2
Climerio Pereira Nascimento Junior 2
Sergio Samir Arap 2
Ledo Mazzei Massoni Neto 3
Rosa Maria Affonso Moyses 4
Vanda Jorgetti 4
Lenine Garcia Brandao 5
Abstract
Background: Low parathormone (PTH) levels may correlate with
survival in dialysis patients . The post parathyroidectomy patient
survival according to the autograft function is analyzed herein.
Methods: Retrospective study of 107 consecutive dialysis patients
submitted to total parathyroidectomy and immediate forearm
autograft from 2006 to 2010. The postoperative PTH levels
were studied over time. The patients were grouped according to
PTH levels, and the survival curves were calculated. Results: A
sustained reduction of PTH occurred after parathyroidectomy. The
median PTH levels were reduced from 1904 pg/mL preoperatively
to 43, 55, 47, 63, 62.5 and 52 pg/mL at 6, 12, 24, 36, 48 and
60 months after the operation, respectively. Considering the PTH
level, there was a significantly reduced survival rate in patients with
PTH levels greater than 261 pg/mL compared with patients with
PTH levels of 88- 261 pg/mL (p=0.04, Logrank Test). Conclusion:
In dialysis patients Postoperative PTH levels greater than 261
pg/mL may be associated with a worse survival compared with
patients with intermediate levels of 88 to 261 pg/mL after a total
parathyroidectomy with immediate autograft.
Key words: Hyperparathyroidism; Parathyroidectomy; Survival
Analysis.
Parathyroidectomy is still an important therapeutic
option in the treatment of severe 2HPT in dialysis
patients, notably in developing countries. In Brazil, 10.7%
of patients under dialysis presented parathyroid hormone
(PTH) levels greater than 1,000 pg/mL.3
The operation improves the long-term survival in
dialysis patients with advanced 2HPT.4 However, low
1)Doutor. Médico Assistente da Disciplina de Cirurgia de Cabeça e Pescoço do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.
2)Doutor em Medicina pela Faculdade de Medicina da Universidade de São Paulo .
3)Pós-graduando da Faculdade de Medicina da Universidade de São Paulo.
4)Livre-Docente pela Faculdade de Medicina da Universidade de São Paulo.
5)Professor Titular da Faculdade de Medicina da Universidade de São Paulo.
Instituição: Disciplina de Cirurgia de Cabeça e Pescoço, Departamento de Cirurgia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Laboratório de
Investigação Médica 28 e Instituto do Câncer de São Paulo (DCCP HFCMUSP-LIM 28-ICESP). E Disciplina de Nefrologia, Laboratório de Investigação Médica.
São Paulo / SP - Brasil.
Correspondência: Fabio Luiz de Menezes Montenegro - Avenida Dr. Enéas de Carvalho Aguiar, 255 Instituto Central 8o andar Sala 8174 CEP 05403-000 Telefone: (+55 11) 2661-6425 - E-mail:
[email protected]
Artigo recebido em 07/05/2015; aceito para publicação em 30/06/2015; publicado online em 15/07/2015.
Disclosure of Financial Interests and Potential Conflicts of Interest: All authors have neither financial interests nor potential conflicts of interest.
Rev. Bras. Cir. Cabeça Pescoço, v.44, nº 1, p. 7-9, Janeiro / Fevereiro / Março 2015 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
7
Estado funcional do autoenxerto da paratireoide e sobrevida após paratireoidectomia. levels of PTH after the operation were associated with
lower survival rates.5
In this retrospective analysis of a cohort of patients
with severe 2HPT in a single institution we analyzed if
different PTH levels after parathyroidectomy had an
impact on survival rates in the long-term.
PATIENTS AND METHODS
We reviewed the data of dialysis patients operated
on for 2HPT in a single institution from January 2006 to
March 2010. All operations were performed at the same
institution and the patients also had their laboratory work
up at the same facility. The Institutional Review Board
approved the study.
Reoperative cases and patients with a previous
successful kidney transplant were not included. The
indications for parathyroidectomy were those recommended
by a national kidney society.6 All patients were treated with
the intention of total parathyroidectomy and immediate
heterotopic parathyroid autograft. Parathyroid tissue was
selected macroscopically and autografted in the forearm,
with multiple or single pockets as previously described.7
The survival time after the operation was analyzed
according to the levels of PTH at 3-6 months after the
operation, when available. We tested the survival stratifying
patients according a classification employed at the institution
for autograft function as follows: functional status 1 (FS1)
- below the lower limit for the method; functional status 2
(FS2) - within the normal range for the method; functional
status 3 (FS3) - above the upper limit but not by more than
three times; and functional status 4 (FS4) – greater than
three times the upper normal limit for the method.8
The following biochemical parameters were analyzed
before the operation: total calcium (tCa, reference range
8.6-10.2 mg/dL), ionized calcium (iCa, 4.6-5.3 mg/dL),
phosphorus (P, 2.7-4.5 mg/dL), and PTH (16-87 pg/mL).
After the operation, the event of a successful kidney
transplant and the survival time since the operation were
calculated in months.
Montenegro et al.
The statistical test employed in each analysis is
indicated in the text. The survival analysis included
Kaplan-Meier survival curves, which were compared with
the Logrank Test. The analysis included the Hazard Rate
(HR) and 95% Confidence Interval (CI).
RESULTS
There were 51 male and 56 female patients submitted
to an intended total parathyroidectomy and immediate
forearm autograft during the period described. Their ages
ranged from 9 to 74 years (mean 44.6, SD 12.0). Mean
preoperative values observed were : tCa = 10.0 mg/dL
(SD 0.9) , iCa = 5.2 mg/dL (SD 0.4), P= 6.0 mg/dL (SD
1.4). The median PTH was of 1904 pg/mL (Q1-Q3 12882500).
Of these 107 cases, persistent 2HPT occurred in
six patients. Three of these patients were lost to follow
up, and the three others underwent a successful second
exploration.
In total, 21 patients underwent renal transplantation
after the parathyroidectomy at a mean time of 28.6
months (SD 18.7). One patient lost the kidney graft a
few days after receiving it, and he restarted dialysis.
Another patient died of infection two months after the
transplantation. All others are doing well.
The postoperative PTH level was significantly lower
from the preoperative values in all postoperative periods.
Table 1 shows PTH levels (Figure 1).
STATISTICAL ANALYSIS
The descriptive statistics included the analysis of
the distribution using the Kolmogorov-Smirnov Test.
Continuous data are presented as means and standard
deviations (SD). Non-parametric are described by the
median and interquartile range (Q1-Q3).
Figure 1. Shows the survival curves according to FS. A small difference
is present comparing patients with FS4 and FS3 (p = 0.04, Logrank
test; HR= 0.16 [CI 0.03 – 0.92]). No difference could be identified
when comparing FS1 with FS3 (p= 0.29 Logrank test) or FS2 with FS3
(p=0.12).
Table 1. PTH values in pg/mL before and after the parathyroidectomy. Time in months after the
operation (m).
n
median
Q1-Q3
preoperative
107
1904
1288-2500
3-6 m
97
43
20-112.5
12 m
87
55
24-105
24 m
73
47
16-113.5
36 m
61
63
25-1975
48 m
42
62.5
24-289,8
60 m
21
52
17.5-169.5
8 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Rev. Bras. Cir. Cabeça Pescoço, v.44, nº 1, p. 7-9, Janeiro / Fevereiro / Março 2015
Estado funcional do autoenxerto da paratireoide e sobrevida após paratireoidectomia. Montenegro et al.
DISCUSSION
REFERENCES
In the present study, we showed that different
levels of PTH are apparently associated with different
rates of survival in the long-run. Higher levels of PTH
were more deleterious than intermediate levels of PTH.
Levels of systemic PTH inferior to 87 pg/mL after a
parathyroidectomy had no statistically significant better
survival.
Based on bone biopsy studies, low PTH levels
correlated with low-turnover bone disease.9 There is some
concern that low-turnover may have an adverse effect on
survival. Indeed, the present study is in accordance with
previous observations of a J- or U-shaped correlation
between the PTH levels and mortality2 in persons under
regular dialysis and in some patients with low PTH levels
after parathyroidectomy.5
This study has several limitations. The small number
of patients with elevated PTH may compromise the
power of our analysis. However, we could demonstrate
that higher PTH levels appear to be related to a worse
survival. We could not clarify if low levels of PTH are
equally worse, as no statistical difference was observed
when patients with levels lower than 87 pg/mL were
compared to those with levels in the range of 88-261 pg/
mL. Perhaps, a longer time of follow up would help clear
this doubt.
The need for higher levels of PTH after the operation
may drive new recommendations to surgical treatment.
The autograft of more tissue than current standards
or subtotal parathyroidectomy are possibilities that
might be tested. Caution is necessary, as higher levels
of PTH may be in fact more harmful than lower ones.
Parathyroidectomy is a very important tool to treat severe
2HPT and total parathyroidectomy with immediate
autograft is commonly employed, with good results.10,11
Parathyroid cryopreservation is an expensive and not
universally available technique.12, 13 When available, the
use of cryopreserved parathyroid between six to 12 months
after the parathyroidectomy may be beneficial, despite
the evidence of function even after years of storage.14
However, present authors believe that parathyroid
cryopreservation is not mandatory in parathyroid surgery
for severe 2HPT, as irrespective to levels of PTH after the
operation, survival is improved in operated cases when
compared to patients not operated on.15
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Draibe SA, et al. K/DOQI-recommended intact PTH levels do not
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autotransplantation in renal patients: a prospective study of 66 patients.
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14. Leite AK, Junior CP, Arap SS, Massoni L, Lourenço DM, Brandão
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De Lima JJ. Parathyroidectomy reduces cardiovascular events and
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CONCLUSION
Post parathyroidectomy autograft function and PTH
levels may affect survival.
Rev. Bras. Cir. Cabeça Pescoço, v.44, nº 1, p. 7-9, Janeiro / Fevereiro / Março 2015 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
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