ORIGINAL ARTICLE

Thyroid Function After Unilateral Total Lobectomy

Risk Factors for Postoperative Hypothyroidism
Dorival De Carlucci Jr, MD; Marcos Roberto Tavares, MD; Marcos Takeo Obara, MD;
Leandro Augusto Liporoni Martins, MD; Flavio Carneiro Hojaij, MD; Claudio Roberto Cernea, MD

Objective: To evaluate the incidence of postoperative

hypothyroidism among patients who underwent unilateral total lobectomy and identify related factors.
Design: Retrospective medical record analysis.
Setting: Oncological center and private clinic.
Patients: From March 1996 to July 2005, 228 euthy-

roid patients underwent unilateral total lobectomy for benign diseases; 168 had all the information required for
inclusion in this study.
Main Outcome Measures: Serum levels of thyrotropin and antithyroidal antibodies were assessed, as well
as ultrasonographic evaluation of the remaining thyroid
lobe and review of all histological specimens, with emphasis on lymphocytic infiltration. Hypothyroidism was
defined as thyrotropin level greater than 5.5 mU/L.

curred in 61 cases (32.8%), during a median follow-up

period of 29 months (range, 6-108 months). Statistically related factors included higher preoperative thyrotropin levels (2.1 mU/L among hypothyroid patients vs
1.2 mU/L in euthyroid patients; P .001), smaller thyroid remnant volume (3.9 mL vs 6.0 mL, respectively;
P =.003); right vs left lobectomy (P=.006), and higher
thyroperoxidase antibody serum levels (P =.009).
Conclusions: Postoperative hypothyroidism appeared
in 32.8% of the cases in this series, especially among
patients with elevated preoperative thyrotropin and
postoperative thyroperoxidase antibody levels, after
right lobectomy and when a smaller thyroid remnant
was left. After confirmation with larger prospective
series, these results may support the indication for
early postoperative hormone supplementation in these
instances.

Results: Most patients were female (88%), with a me-

dian (range) age of 45 (16-72) years. Hypothyroidism oc-

Author Affiliations:
Department of Head and Neck
Surgery, University of Sao Paulo
Medical School,
Sao Paulo, Brazil.

Arch Otolaryngol Head Neck Surg. 2008;134(10):1076-1079

LTHOUGH SYMPTOMATIC

thyroid nodules are present in 4% to 7% of American adults, recent ultrasound studies have
revealed nodules in up to 50% of the population beyond the fifth decade of life, the
majority of them occult.1-3 Between 5% and
20% of the American population have
some thyroid abnormality; this percentage increases in some subpopulations.4
Thyroid dysfunction affects 1% to 2% of
the UK adult population.5 This glandular
malfunction is considered the second most
frequent endocrinologic disease after diabetes.6 In Brazil, abnormal thyroid glands
have been found by ultrasonography in
40% to 56% of adult women; 17% to 35%
were nodules.7,8
Large goiters have become less common since the control of the areas with io-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008
1076

dine deficiency. Today, the most common indication for surgery of nontoxic
goiter is suspicion of malignancy.9
Several studies evaluating thyroid function after hemithyroidectomy for benign
thyroid disease have been published. The
incidence of postoperative hypothyroidism depends on the functional capacity of
the thyroid remnant.10 The reported incidence of hypothyroidism ranges from 5%
to 35%, depending on the follow-up interval and how the investigators define hypothyroidism.11
At present, there is evidence to suggest that patients with glandular lymphocytic infiltration have an increased risk of
developing hypothyroidism, but this finding has not been used in the treatment of
these patients.10,12,13
A solitary thyroid nodule is a common clinical problem for which hemithyWWW.ARCHOTO.COM

Downloaded from www.archoto.com on August 11, 2011

2008 American Medical Association. All rights reserved.

roidectomy is often performed to exclude the possibility of malignancy. Although the use of needle biopsy as
a preoperative diagnostic tool has reduced the number
of operations, most solitary nodules that are removed
surgically are benign on histological section analysis.
The occurrence of hypothyroidism after hemithyroidectomy affects postoperative outcome and quality of
life.14 The objectives of this study were to verify the frequency of postoperative hypothyroidism in a series of
consecutive patients who underwent hemithyroidectomy and to identify potential clinical and surgical risk
factors.

Table. Risk Factors for Postoperative Hypothyroidism

Hypothyroid, % Euthyroid, %
P
(n = 61)
(n = 125)
Value

Factor
Women
Suspicion of malignancy
Thyrotropin level 2.0 mU/L,
preoperatively
Right lobectomy
Remnant thyroid volume
4.0 mL
Thyroperoxidase antibody
positive

91.8
55.7
79.1

85.6
65.6
37.2

.23
.19
.001

60.7
61.0

39.2
41.0

.006
.04

61.1

38.8

.009

METHODS

PATIENTS
During the 9-year period from March 1996 to July 2005, 228
patients who underwent primary surgery for nontoxic goiter
at the Brazilian Institute for Cancer Control, Sao Paulo, Brazil,
and from the authors private clinic have been retrospectively
studied. Collected data included age, sex, preoperative and postoperative serum thyrotropin and free thyroxine levels, presence of thyroid antibodies (antithyroglobulin and antithyroperoxidase), surgical indication, final pathologic results, and length
of follow-up. Forty-two patients were excluded: 18 patients were
receiving thyroid hormone therapy with levothyroxine preoperatively; 10 had subclinical preoperative hypothyroidism detected by thyrotrophin levels greater than 5.5 mU/L; and 14 patients did not have enough data available. A total of 186 patients
were included in the study; 163 (87.6%) were female, with a
median (range) age of 45 (16-72) years. This study was approved by the institutional review board of the Brazilian Institute for Cancer Control.

EXAMINATIONS
The laboratory evaluation of the thyroid function, determined
by the levels of free thyroxine, ranged from 0.7 to 1.70 ng/dL
(to convert to picomoles per liter, multiply by 12.871) by radioimmunoassay; thyrotropin ranged from 0.35 to 5.5 mU/L.
Thyroglobulin antibody and thyroperoxidase antibody levels
were considered positive when they were higher than 35 U/mL.
These tests were performed preoperatively and postoperatively, 4 to 8 weeks after surgery.
Surgical indications were laringotracheal deviation caused by
large goiters and suspicion of malignancy. All patients underwent hemithyroidectomies, which comprised total resection of
1 lobe and of the isthmus. Only cases with benign disease were
included in this study. The size of the remnant thyroid tissue was
determined by ultrasonographic examination after surgery and
was correlated with the body mass index.
Final pathologic results were divided into adenoma and adenomatous goiter. The histologic slide reports from all patients were reviewed by 3 senior pathologists (which included
M.T.O. and L.A.L.M.) to evaluate the presence of associated
focal or diffuse lymphocytic thyroiditis by a semiquantitative
analysis, as previously described.10,15 The density of lymphocytic aggregation was semiquantitatively graded (grade 0 for
the absence of aggregates of lymphocytes; grade I, 1-3 aggregates per slide; grade II, 4-8 aggregates per slide; and grade III,
8 aggregates per slide). Grade IV was reserved for Hashimoto disease. Another semiquantitative analysis was performed, considering the intensity of lymphocytic follicles, with
grades of 0 for absence, I for minor quantity, II for moderate,
and III for increased amount of lymphoid follicles.

Postoperative hypothyroidism was defined as thyrotropin

levels above 5.5 mU/L at the first postoperative evaluation, 4
to 8 weeks later.
A paired t test and Pearson 2 test were used. P.05 was
considered statistically significant. Multivariate analysis was performed, with logistic regression corrected by the HosmerLemeshow test, to determine the odds ratio for postoperative
hypothyroidism.
RESULTS

The most frequent indication for thyroidectomy was suspicion of malignancy in 116 cases (62.4%). The most common pathologic diagnosis was adenomatous goiter in
81.1% of the cases. The left side of the thyroid gland was
removed in 100 of 186 surgical procedures (53.8%).
The overall prevalence of postoperative hypothyroidism was 32.8% (61 of 186 cases),with a median follow-up period of 29 months (range, 6-108 months). No
statistical correlation was observed between hypothyroidism and sex, age, the indication of operation, or the
final pathology report.
Preoperative thyrotropin levels were statistically significantly higher in the group with postoperative hypothyroidism than in the euthyroid group. The mean thyrotropin level in the hypothyroid group was 2.1 mU/L
compared with 1.2 mU/L in the euthyroid group
(P.001). When the preoperative thyrotropin levels were
between 2.0 and 5.5 mU/L, 79.1% of the patients had laboratory evidence of postoperative hypothyroidism, whereas
among cases with preoperative levels greater than 2.0
mU/L, only 37.2% had hypothyroidism (P .001)
(Table).
Ultrasonographic examination revealed a mean volume of 3.9 mL of the remnant thyroid tissue in the hypothyroid group compared with 5.0 mL in the euthyroid group (P=.003). In the hypothyroid group, 61.0%
of the individuals had residual thyroid volume of 4.0 mL
or smaller (Table).
The overall prevalence of thyroperoxidase antibodies was 15.8%. It was higher among cases with postoperative hypothyroidism compared with the euthyroid
group (61.1% vs 38.8%, respectively; P=.009). The thyroglobulin antibody analysis showed no statistically significant difference.
Considering the side of the operation, 60.8% of the
euthyroid patients had their left thyroid lobe surgically

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008
1077

WWW.ARCHOTO.COM

Downloaded from www.archoto.com on August 11, 2011

2008 American Medical Association. All rights reserved.

Cases, %

45
40
35
30
25
20
15
10
5
0

Grade
0
I
II
III
IV

P < .001

Thyroperoxidase
Antibody Positive

Thyroperoxidase
Antibody Negative

Figure. Antithyroperoxidase antibodies and lymphocytic aggregation.

P value by Pearson 2 test.

removed. Conversely, 60.7% of hypothyroid cases underwent a right lobectomy, and the difference was statistically significant (P = .006) (Table). These findings
seem to be related to residual thyroid volume; in the
euthyroid group this volume was larger than 4.0 mL in
71.4% of the left lobectomy cases and 4.0 mL or smaller
in 58.8% of the right lobectomy cases (P = .006). This
difference was not significant in the hypothyroid group
(P=.57).
The semiquantitative analysis of the lymphocytic infiltration showed no statistically significant difference between the 2 groups of patients. In hypothyroid cases,
grades II and III lymphoid follicles were noted in 9.8%
and 11.8%, respectively, compared with 8.3% and 6.5%,
respectively, in the euthyroid group (P = .23).
There was a clear association between serum positive
thyroid antibodies and intensity of lymphocytic infiltration (P .001) (Figure).
The risk for postoperative hypothyroidism was 7.1
times higher when preoperative thyrotropin level was
higher than 2.0 mU/L (odds ratio, 7.14; 95% confidence
interval, 2.5-20.3; P .001). The influence of the laterality of the excised thyroid lobe was confirmed when all
cases with a residual volume larger than 4.0 mL were compared: right thyroid lobectomy was associated with a 7.8fold increased risk for postoperative hypothyroidism compared with left lobectomy (odds ratio, 7.8; 95% confidence
interval, 2.0-30.4; P = .003).
COMMENT

Hemithyroidectomy is considered an adequate treatment for benign nodules operated on because of suspected malignancy.10,14-18 In fact, this is presently the main
indication for thyroid surgery.9
In the present series, the prevalence of postoperative
hypothyroidism was 32.8%, which is comparable with
most international series.11,17,19 There was a significant
correlation with preoperative thyrotropin levels. It is noteworthy that, even within the normal laboratory range,
there was a direct relationship between the occurrence
of postoperative hypothyroidism and thyrotropin level
greater than 2.0 mU/L, with a 7.1 times higher risk. This
observation was confirmed by other authors11,17,19 and
might be associated with decreased functional reserve of
the thyroid gland. According to Miller et al,19 a preoperative thyrotropin level in the upper-normal reference

range should alert the surgeon to the possibility of postoperative hypothyroidism.

Previous series including only toxic goiters pointed
out the influence of the amount of remnant thyroid tissue on postoperative thyroid function. Small volume was
related with hypothyroidism, but also with no risk of recurrent thyrotoxicosis.15,16 Similarly, in nontoxic goiter,
the volume of the residual thyroid tissue seems to be relevant. In Brazil, there are some areas of iodine deficiency and, consequently, large multinodular goiters are
common. In fact, 37.6% of the operations in the present
series were indicated by compressive symptoms caused
by large goiters. This finding may explain the importance of the volume of the residual thyroid tissue in this
series: postoperative hypothyroidism was 6.3 times more
prevalent when the volume of this remnant, evaluated
by ultrasound examination, was 4.0 mL or smaller (odds
ratio, 6.3; 95% confidence interval, 1.6-24.5; P=.008).
Thyroiditis is also related to postoperative hypothyroidism. The lymphocytic infiltrate of the thyroid gland
decreases thyroid function, and a semiquantitative analysis of this infiltrate usually reflects the risk of hypothyroidism.10,13 Nevertheless, no such statistical correlation was found in the present series.
The presence of thyroid antibodies has been associated with thyroiditis.20 In this series, the majority of patients who developed postoperative hypothyroidism presented with thyroperoxidase antibodies. Interestingly, a
direct relationship between elevated thyroid antibodies
and higher degrees of lymphocytic infiltration was noted.
Curiously, in the present series, hypothyroidism was
statistically significantly related to the side of the surgery. More patients who had right hemithyroidectomy
became hypothyroid. To our knowledge, this observation has not been previously reported, and it is somewhat difficult to understand. One possible explanation
could be the difference in size of the thyroid lobes, suggested by the large series of thyroid ultrasound examinations.21
In conclusion, the incidence of postoperative hypothyroidism after hemithyroidectomy is not negligible and
should not be overlooked. Roughly one-third of hemithyroidectomy patients may have this consequence and might
need thyroxine oral supplementation. This study suggests that the following factors are associated with an increased risk: elevated preoperative thyrotropin levels, elevated levels of thyroperoxidase antibodies, operations
involving the right thyroid lobe, and residual thyroid tissue volume 4.0 mL or smaller. In these instances, a closer
follow-up or even an earlier onset of oral thyroxine administration is advised. The role of lymphocytic infiltrate was not clear.
Submitted for Publication: April 26, 2007; final revision received November 26, 2007; accepted December
11, 2007.
Correspondence: Dorival De Carlucci Jr, MD, Rua Padre Joao Manuel, 450 Room 18, Cerqueira Cesar, Sao
Paulo 01411-001, Brazil (decarlucci@uol.com.br).
Author Contributions: Dr De Carlucci had full access to
all the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analy-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008
1078

WWW.ARCHOTO.COM

Downloaded from www.archoto.com on August 11, 2011

2008 American Medical Association. All rights reserved.

sis. Study concept and design: De Carlucci and Tavares.

Acquisition of data: De Carlucci, Obara, and Hojaij. Analysis and interpretation of data: De Carlucci, Tavares, Martins, Hojaij, and Cernea. Drafting of the manuscript: De
Carlucci, Obara, Martins, and Cernea. Critical revision
of the manuscript for important intellectual content: De Carlucci, Tavares, Hojaij, and Cernea. Statistical analysis: De
Carlucci and Hojaij. Obtained funding: De Carlucci. Administrative, technical, and material support: De Carlucci, Obara, Martins, and Cernea. Study supervision: De
Carlucci, Tavares, and Cernea.
Financial Disclosure: None reported.
Previous Presentation: This study was presented at the
2007 American Head & Neck Society Annual Meeting;
April 28, 2007; San Diego, California.
REFERENCES
1. Gharib H, Mazzaferri EL. Thyroxine suppressive therapy in patients with nodular
thyroid disease. Ann Intern Med. 1998;128(5):386-394.
2. Bisi H, Fernandes VS, De Camargo RY, Koch L, Abdo AH, De Brito T. The prevalence of unsuspected thyroid pathology in 300 sequential autopsies, with special reference to the incidental carcinoma. Cancer. 1989;64(9):1888-1893.
3. Bennedbk FN, Hegeds L. Management of the solitary thyroid nodule: results
of a North American survey. J Clin Endocrinol Metab. 2000;85(7):2493-2498.
4. Dunn JT. Guarding our nations thyroid health. J Clin Endocrinol Metab. 2002;87
(2):486-488.
5. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a
community: the Whickhan survey. Clin Endocrinol (Oxf ). 1977;7(6):481-493.
6. Bartalena L, Bogazzi F, Pinchera A. Thyroid function tests and diagnostic protocols for investigation of thyroid dysfunction. Ann Ist Super Sanita. 1991;27
(3):531-540.
7. Tomimori E, Pedrinola F, Cavaliere H, Knobel M, Medeiros-Neto G. Prevalence
of incidental thyroid disease in a relatively low iodine intake area. Thyroid. 1995;
5(4):273-276.

8. Furlanetto TW, Peccini S, Schenider MAO, et al. Prevalence of thyroid nodules

in 40 years-old or old women [in Portuguese]. Rev Assoc Med Bras. 2000;
46(4):331-334.
9. Berglund J, Bondeson L, Christensen SB, Larsson AS, Tiblin S. Indications for
thyroxine therapy after surgery for nontoxic benign goiter. Acta Chir Scand. 1990;
156(6-7):433-438.
10. Berglund J, Bondeson L, Christensen SB, Tiblin S. The influence of different degrees of chronic lymphocytic thyroiditis on thyroid function after surgery for benign, non-toxic goiter. Eur J Surg. 1991;157(4):257-260.
11. Piper HG, Bugis SP, Wilkins GE, Walker BAM, Wiseman S, Balinski CR. Detecting and defining hypothyroidism after hemithyroidectomy. Am J Surg. 2005;
189(5):587-591.
12. Buchanan MA, Lee D. Thyroid auto-antibodies, lymphocytic infiltration and the
development of post-operative hypothyroidism following hemithyroidectomy for
non-toxic nodular goiter. J R Coll Surg Edinb. 2001;46(2):86-90.
13. Capezzuto E, Carlini M, Balsanelli M, Piperno G, De Santis G. Post-surgical hypothyroidism: lymphocyte infiltration and antithyroglobulin antibodies as markers in 73 cases studied by us [in Italian]. Minerva Chir. 1987;42(4):323-326.
14. Cheung P, Boey J, Wong J. Thyroid function after hemithyroidectomy for benign nodules. World J Surg. 1986;10(4):718-723.
15. Bang U, Blichert-Toft M, Petersen PH, Nielsen BB, Hage E, Diederichsen H.
Thyroid function after resection for non-toxic goitre with special reference to thyroid lymphocytic aggregation and circulating thyroid autoantibodies. Acta Endocrinol (Copenh). 1985;109(2):214-219.
16. Young HB, MacLeod N. The fate and function of the thyroid remnant: a surgical
and radioactive iodine study. Br J Surg. 1972;59(9):726-731.
17. McHenry CR, Slusarczyk SJ. Hypothyroidism following hemithyroidectomy: incidence, risk factors, and management. Surgery. 2000;128(6):994-998.
18. Blichert-Toft M, Egedorf C, Christiansen C, Axelsson CK. Function of pituitarythyroid axis after surgical treatment of non-toxic nodular goiter. Acta Med Scand.
1979;206(1-2):15-19.
19. Miller FR, Paulson D, Prihoda TJ, Otto RA. Risk factors for the development of
hypothyroidism after hemithyroidectomy. Arch Otolaryngol Head Neck Surg. 2006;
132(1):36-38.
20. Woeber KA. Subclinical thyroid disfunction. Arch Intern Med. 1997;157(10):10651068.
21. Kerr L. Atualizacao em ultra-sonografia de alta resolucaovalor do doppler colorido.
In: Rosa JC, Romao LA. Glandula Tireoide. 2nd ed. Sao Paulo, Brazil: Lemos Editorial; 2001:119-158.

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008
1079

WWW.ARCHOTO.COM

Downloaded from www.archoto.com on August 11, 2011

2008 American Medical Association. All rights reserved.