Download Hypothyroidism following hemithyroidectomy for benign nontoxic

ORIGINAL ARTICLEFOR BENIGN NONTOXIC THYROID DISEASE
HYPOTHYROIDISM FOLLOWING HEMITHYROIDECTOMY
Hypothyroidism following
hemithyroidectomy for benign
nontoxic thyroid disease
Kristin A. Seiberling, MD; Jose C. Dutra, MD; Sanija Bajaramovic, MD
Abstract
Hypothyroidism following hemithyroidectomy for benign
nontoxic thyroid disease is an underappreciated phenomenon. Up until recently, it was common practice for physicians to place post-hemithyroidectomy patients on thyroid
suppression therapy during the immediate postoperative
period. That practice began to fall out of favor as a result
of two developments: (1) the publication of data that put
into question the efficacy of levothyroxine therapy for
preventing recurrent disease or thyroid growth and (2)
a heightened awareness of the morbidity associated with
levothyroxine. We conducted a retrospective chart-review
study of 58 patients with benign nontoxic thyroid disease
who had undergone hemithyroidectomy from 1994 through
2003 at one institution. Of these 58 patients, 14 (24.1%)
had become hypothyroid after surgery, including 7 who
had been so diagnosed 1 month postoperatively and 6 at
2 months. The remaining 44 patients were euthyroid. The
mean preoperative serum thyroid-stimulating hormone
(TSH) levels in the hypothyroid and the euthyroid groups
were 2.39 and 1.07 μIU/ml, respectively—a statistically
significant difference (p < 0.0001). A tissue diagnosis
consistent with chronic inflammation (lymphocytic thyroiditis or Hashimoto’s thyroiditis) was found in 50.0%
of the hypothyroid patients, compared with only 6.8% of
the euthyroid patients—again, a significant difference (p
< 0.001). No significant difference was seen between the
two groups with respect to age, sex, or the weight of the
resected gland. We conclude that hypothyroidism after
From the Department of Otolaryngology–Head and Neck Surgery (Dr.
Seiberling and Dr. Dutra) and the Department of Endocrinology
(Dr. Bajaramovic), Northwestern University Feinberg School of
Medicine, Chicago.
Reprint requests: Kristin A. Seiberling, MD, Department of Otolaryngology–Head and Neck Surgery, Northwestern University Feinberg
School of Medicine, 303 E. Chicago Ave., Searle 12-561, Chicago,
IL 60611. Phone: (312) 503-8920; fax: (312) 503-1616; e-mail:
[email protected]
The information in this article was originally presented at the Triological
Society’s Combined Otolaryngology Spring Meeting; April 30,
2004; Scottsdale, Ariz.
Volume 86, Number 5
hemithyroidectomy is not an uncommon occurrence.
Apparent risk factors include a high mean preoperative
serum TSH level and tissue pathology consistent with
chronic inflammation. It may be wise to follow patients
with these identifiable risk factors more closely during the
postoperative period; monitoring should include scheduled
serial serum TSH draws.
Introduction
The development of hypothyroidism following hemithyroidectomy for benign nontoxic thyroid disease is an
underappreciated complication. In the past, it was common practice for physicians to place most post-hemithyroidectomy patients on prophylactic thyroid suppression
therapy with low-dose levothyroxine. The rationale for
this strategy was based on the assumption that the addition of low-dose levothyroxine would prevent recurrence
of disease in the remaining thyroid tissue by inhibiting
endogenous production of thyroid-stimulating hormone
(TSH). A consequence of this practice was that the administration of levothyroxine prevented physicians from
recognizing those patients who would have otherwise
become hypothyroid after hemithyroidectomy.
In more recent years, physicians stopped administering
thyroid suppression therapy during the immediate postoperative period. Instead, the new strategy was to follow these
patients clinically for signs of recurrence or growth. The
emergence of the new trend was based on two developments: (1) the publication of data that put into question the
efficacy of levothyroxine therapy for preventing recurrent
disease or thyroid growth and (2) a heightened awareness
of the morbidity associated with levothyroxine.1,2
One result of thyroid suppression therapy with levothyroxine is subclinical thyrotoxicosis (subclinical hyperthyroidism), defined as the presence of a low TSH level
with a normal free thyroxine (FT4) level. Some studies
have shown an association between this state and various
endocrine and cardiac abnormalities.3-10
With fewer patients being placed on levothyroxine during
the immediate postoperative period, it has become easier
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SEIBERLING, DUTRA, BAJARAMOVIC
to identify those who develop hypothyroidism. Routine
thyroid function tests obtained as early as 1 month after
surgery may identify those patients with subclinical, as
well as overt, hypothyroidism.
We conducted a study to identify certain risk factors that
may place a patient at a higher risk for developing hypothyroidism after hemithyroidectomy. These potential risk
factors include age, sex, tissue pathology characteristics,
the size of the thyroid remnant, a history of neck irradiation, and coexisting thyroid autoimmune disease.
Patients and methods
After obtaining institutional review board approval, we
conducted a retrospective chart review of all patients who
had undergone a hemithyroidectomy from 1994 through
2003 at Northwestern Memorial Hospital in Chicago. We
identified 150 such patients by searching a surgical pathology database using the search terms hemithyroidectomy
and thyroid lobectomy.
Charts were reviewed for information on age, sex, serum
TSH levels (both preoperative and postoperative), final
surgical pathology results, the weight of the resected gland,
postoperative symptoms, a history of neck irradiation,
and coexisting thyroid autoimmune disease. The indication for surgery was not used as a criterion for patient
eligibility, but we did exclude those patients who had a
preoperative diagnosis of malignancy, hyperthyroidism,
or hypothyroidism. Other exclusion criteria included age
less than 18 years or more than 90 years, the administration of postoperative thyroid suppression therapy, previous
use of any medication known to alter thyroid hormone or
serum TSH level, a completion thyroidectomy within the
previous 2 years, a lack of appropriate laboratory work,
and a lack of follow-up.
A total of 58 patients—44 women and 14 men, aged 23
to 75 years (mean 46.5)—met our eligibility requirements.
Their tissue specimens were sent for routine pathology
and analyzed for the presence of inflammation, the type
of nodular disease, the size of the nodules, and the surrounding tissue pathology.
An elevated serum TSH level was used as a marker
for hypothyroidism. All patients had at least one serum
TSH level drawn before surgery and at least one other
drawn within 6 weeks after surgery. Serum TSH levels
were measured by using the standard serum assay at our
institution (range of normal: 0.4 to 4.0 µIU/ml). Patients
who were clinically asymptomatic but who had a serum
TSH level greater than 4.0 µIU/ml with a normal FT4 level
were diagnosed as having subclinical hypothyroidism.
Overt hypothyroidism was diagnosed in those who had
an elevated serum TSH level and a low FT4 level and in
those who had symptoms attributable to hypothyroidism.
The scheduling of serum TSH measurements was based
on the known half-life of thyroxine (T4), which is 7 days,
296
and the response of serum TSH to changes in the T4 level
(TSH rises immediately after a drop in T4 levels). Although
study data vary, it is generally believed that the TSH level
should rise in 4 to 5 weeks if the remaining thyroid gland
is not producing enough T4.11
Data analysis was performed with the unpaired Student’s
t test for p value calculation, 95% confidence intervals
(CIs), means, standard deviations, and percentages.
Results
There were several reasons that only 58 of the 150 patients
in our database (38.7%) met our eligibility requirements.
First, during the first 5 years of our study’s time frame,
administration of prophylactic thyroid suppression therapy
was routine at our institution. As a result, we had to exclude
50 patients (33.3%), and therefore a good deal of our data
was obtained from surgeries performed from 1999 through
2003. Another 27 patients (18.0%) had undergone a completion thyroidectomy within the previous 2 years, and proper
follow-up was lacking in 15 others (10.0%).
Of the 58 study patients, 14 (24.1%) had become hypothyroid postoperatively, and the remaining 44 patients
(75.9%) were euthyroid.
Demographic characteristics. There were no statistically
significant differences between the hypothyroid group
and the euthyroid group with respect to age (mean: 47.8
and 46.8 yr, respectively) and sex (distribution: 3 men/11
women and 11 men/33 women, respectively).
Pre- and postoperative TSH levels. The mean preoperative serum TSH level in the 14 patients who had become
hypothyroid was 2.39 µIU/ml (range 1.17 to 3.90; 95%
CI: 1.53 to 2.94). Their mean postoperative level was
14.88 µIU/ml (range: 4.80 to 70.73; 95% CI: 4.43 to
25.28) (table 1).
A complete thyroid function panel (serum TSH, FT4, and
T4 measurements) was obtained from 8 of the 14 hypothyroid patients. Of these 8 patients, 6 had overt hypothyroidism and 2 had subclinical hypothyroidism. The patients
with subclinical hypothyroidism were asymptomatic, but
laboratory testing showed a mildly elevated TSH level
and a normal FT4 level.
Of the 14 hypothyroid patients, 7 were diagnosed as such
1 month postoperatively, 6 at 2 months, and the other at 4
months (table 1). Most of these higher TSH levels ranged
between 4.80 and 9.62 µIU/ml (table 1).
In the euthyroid group, the mean preoperative TSH
level was 1.07 μIU/ml (range: 0.39 to 2.35; 95% CI:
1.01 to 1.37). The difference in preoperative TSH levels
between the hypo- and euthyroid groups was statistically
significant (p < 0.0001).
All 44 patients in the euthyroid group had at least one
serum TSH level drawn within 6 weeks after surgery.
While 34 of them had multiple TSH levels drawn at
various times, 10 patients had only one TSH level drawn,
ENT-Ear, Nose & Throat Journal  May 2007
HYPOTHYROIDISM FOLLOWING HEMITHYROIDECTOMY FOR BENIGN NONTOXIC THYROID DISEASE
Table 1. Pathology in the 14 hypothyroid patients
Pt. Age
1
2
3
4
5
6
7
8
9
10 11 12 13 14 60
73 29 54 58 26 48 61 49 56 32 32 53 38 TSH level
Preop Postop (μIU/ml)
(μIU/ml)
1.25
1.70
1.23 3.57 2.56 2.21 2.60 3.45 2.42 1.84 3.90 3.10 2.50 1.17 14.20
9.62
5.22 70.73 4.90 6.99 5.96 16.25 6.02 5.86 4.80 5.07 18.25 34.40 Diagnosis,
months
postop*
2
1
2
1
4
2
2
2
1
1
1
2
1
1
Pathology
Multinodular goiter w/degenerative changes
Chronic lymphocytic thyroiditis w/follicular adenoma
Follicular adenoma
Hashimoto’s thyroiditis w/colloid nodules
Follicular adenoma (benign Hürthle cell adenoma)
Diffuse atrophy and scarring of the thyroid gland
Diffuse chronic inflammation w/follicular adenoma
Chronic lymphocytic thyroiditis w/follicular adenoma
Multinodular goiter
Chronic inflammation w/follicular adenoma
Follicular adenoma
Follicular adenoma
Hashimoto’s thyroiditis w/follicular adenoma
Hashimoto’s thyroiditis w/adenomatous goiter
* The number of months postoperatively that the patient was diagnosed as hypothyroid.
and all 10 of these levels had been drawn at either 5 or 6
weeks postoperatively (table 2). Fourteen of the euthyroid
patients had TSH levels drawn at 1 and 2 months after
surgery; the remaining 20 euthyroid patients had the last
of their TSH levels drawn between 4 months and 2-plus
years after surgery.
Tissue pathology. Seven of the 14 hypothyroid patients
(50.0%) had a tissue diagnosis consistent with inflammation (i.e., chronic lymphocytic thyroiditis and Hashimoto’s
thyroiditis), compared with only 3 of the 44 euthyroid
patients (6.8%). The difference was statistically significant
(p < 0.001).
Among the other 7 patients in the hypothyroid group, 4
(28.6%) had a diagnosis of follicular adenoma, 2 (14.3%)
had multinodular goiter, and 1 (7.1%) had diffuse atrophy
and scar tissue on the thyroid gland (table 1). The patient
with atrophy and scar tissue had undergone treatment
with radioactive iodine (131I) for multinodular goiter disease 2 years earlier, and she had been euthyroid prior to
hemithyroidectomy.
Table 2. TSH testing in the 44 euthyroid patients
Most recent draw 5 wk postop 6 wk postop 2 mo postop 4 mo postop 5 mo postop 6 mo postop 7 mo postop 1 yr postop > 2 yr postop Volume 86, Number 5
n
6
4
14
3
2
2
7
4
2
Most of the euthyroid patients had follicular adenoma
(table 3). Other pathologies included multinodular goiter,
adenomatous hyperplasia, and hemorrhagic cysts. Two
patients had normal thyroid tissue.
The mean weight of the resected tissue in the hypoand euthyroid groups was 27.2 and 20.6 grams, respectively. This difference was not statistically significant
(p = 0.1662).
Neck irradiation. Only 1 patient—a hypothyroid patient—had a history of neck irradiation.
Discussion
The usual indication for hemithyroidectomy is the presence of a single dominant thyroid nodule in a patient
whose fine-needle aspiration findings are suspicious or
indeterminate. Hemithyroidectomy is also performed on
patients with unilateral or bilateral thyroid enlargement,
toxic or nontoxic nodular thyroid disease, and diffuse or
multinodular goiter. Because only one lobe of the thyroid
gland is removed, hemithyroidectomy is associated with
a lower incidence of postoperative hypocalcemia and
recurrent and superior laryngeal nerve injury than is total
thyroidectomy.12 Because the remaining lobe is unharmed,
most patients retain enough thyroid function to remain
euthyroid. Therefore, hemithyroidectomy is the procedure
of choice for patients who likely have benign pathology.
Hypothyroidism. Its advantages notwithstanding,
hemithyroidectomy may result in hypothyroidism, and
patients should be made aware of this possibility. The
risk factors for hypothyroidism have not been extensively
studied. During our medline literature search, we found
that few studies of the incidence and risk factors of hypothyroidism after thyroid lobectomy have been published in
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SEIBERLING, DUTRA, BAJARAMOVIC
Table 3. Pathologic findings in the 44 euthyroid patients
Pathology Follicular adenoma
n (%)
26 (59.1) Multinodular goiter 6 (13.6) Adenomatous hyperplasia 5 (11.4)
Chronic lymphocytic thyroiditis
3 (6.8)
Hemorrhagic cyst 2 (4.5) Normal thyroid tissue 2 (4.5)
the United States; the reported incidence in those studies
ranged from 7.4 to 35%.13,14
It is standard care to treat overt hypothyroidism with
hormone replacement therapy, but treatment guidelines are
less definitive for subclinical hypothyroidism. The latter
has been reported to occur spontaneously in 10% of women
older than 60 years.10 Although patients with subclinical
hypothyroidism are clinically asymptomatic, they have an
increased risk of developing a major depressive disorder or
mood disorder, an increased left ventricular hypertrophy,
and an unfavorable lipid profile.15-17 Studies have shown
that the treatment of subclinical hypothyroidism results in
a favorable response in terms of mood affect and low-density lipoprotein levels, and many authors support thyroid
hormone replacement therapy in these patients.18
Thyrotoxicosis. While prophylactic thyroid suppression
therapy was once thought to be devoid of negative health
consequences, recent data have shown that subclinical thyrotoxicosis does in fact have some adverse health effects. It
has been shown to negatively affect calcium balance and decrease bone mineral density; increase total cholesterol and
low-density lipoprotein levels and decrease high-density
lipoprotein levels; and lower the threshold for depression
and other psychiatric disorders.5,6 Subclinical thyrotoxicosis
is also associated with a three-fold increase in the risk of
atrial fibrillation.3,4,7 Other cardiac complications include
increased heart rate, increased left ventricular mass index,
impaired cardiac contractility, diastolic dysfunction, and
the induction of ectopic atrial beats or arrythmias.8,9 Those
who are specifically at risk for adverse effects are elderly
women and patients with a known diagnosis of coronary
artery disease and/or ischemic heart disease.10 Therefore,
given the lack of substantial evidence supporting the efficacy of thyroid suppression therapy in preventing recurrent
thyroid disease, it seems prudent to forgo it as a routine
strategy after hemithyroidectomy and to observe patients
for the need for thyroid supplementation therapy.
Literature review. Our finding that 24.1% of patients
developed hypothyroidism after undergoing hemithyroidectomy for benign thyroid disease is consistent with others
298
Comment
In 2 cases, surrounding tissue contained focal areas
of chronic inflammation
Degenerative changes were seen in 2 cases
In both cases, large cysts occupied the entire lobe
reported in the literature. In fact, Buchanan and Lee reported
an identical 24.1% incidence in 2001.19 They found that
patients with nodular goiter and elevated thyroid autoantibody levels were significantly more likely to become
hypothyroid following unilateral thyroid lobectomy (p <
0.001). They also found that patients with elevated thyroid
autoantibody levels had a significantly higher incidence of
lymphocytic thyroiditis (p < 0.001). They concluded that
an elevated thyroid autoantibody level is an independent
risk factor for hypothyroidism. We recognize the role that
thyroid autoantibody levels may play in the development
of postoperative hypothyroidism, but because ours was a
retrospective study, we were limited by the type of data
we could analyze, and we therefore did not factor this
variable into our analysis.
In 1991, Berglund et al reported that the incidence of
hypothyroidism following surgery for benign nontoxic
goiter was 7.4%.13 They found a significant correlation
between the incidence of postoperative hypothyroidism
and the degree of chronic lymphocytic thyroiditis after
unilateral surgery (p = 0.016). A year later, Okamoto et
al reported a similar correlation in patients with Graves’
disease who underwent subtotal thyroidectomy.20
Regarding other potential risk factors, we did not find
any significant difference between our two groups with
respect to age, sex, and the weight of the resected gland.
However, we did find that the mean preoperative serum
TSH level was significantly higher in the hypothyroid
group (2.39 vs. 1.07 µIU/ml; p < 0.0001). That finding
supports one reported in 2000 by McHenry and Slusarczyk,
who found that the incidence of post-hemithyroidectomy
hypothyroidism was 35%.14 Like us, they found that the
incidence of postoperative hypothyroidism significantly
correlated with higher preoperative serum TSH levels,
and they found no link between postoperative hypothyroidism and age, sex, the presence of inflammation,
and the weight of the resected gland. In their study, the
mean preoperative serum TSH level was 1.94 μIU/ml in
the hypothyroid group and 1.10 μIU/ml in the euthyroid
group (p < 0.05).
ENT-Ear, Nose & Throat Journal  May 2007
HYPOTHYROIDISM FOLLOWING HEMITHYROIDECTOMY FOR BENIGN NONTOXIC THYROID DISEASE
Our study, like others, has shown that the presence of certain factors may place a patient at a higher risk of developing
hypothyroidism following hemithyroidectomy. However,
as previously mentioned, we do recognize the limitations
of our study, given its retrospective nature. One subject of
conjecture is the possibility that some of the hypothyroid
patients would have eventually become euthyroid over
time as the remaining thyroid tissue compensated for the
loss of one lobe. We were unable to determine this because
all patients who had an elevated serum TSH level postoperatively were immediately placed on thyroid replacement
therapy, regardless of whether they were symptomatic or
not. Conversely, we cannot know if the opposite would
have occurred. All but 1 of the 14 hypothyroid patients
had been so diagnosed within 2 months. However, because
serum TSH levels were not drawn from all patients at
regular intervals, we cannot know if some of the euthyroid
patients who were not followed as often eventually would
have become hypothyroid. Our postoperative follow-up
period was only 2-plus years. An argument could be made
that at least some of the patients in the euthyroid group
might have eventually become hypothyroid.
Despite these limitations, we believe that our findings
have confirmed the identity of the key risk factors for the
development of hypothyroidism during the immediate
postoperative period following hemithyroidectomy. We
intend to conduct future research in this area by means of
a prospective study.
12. Fewins J, Simpson CB, Miller FR. Complications of thyroid and
parathyroid surgery. Otolaryngol Clin North Am 2003;36:189206, x.
13. Berglund J, Bondeson L, Christensen SB, Tibblin S. The influence
of different degrees of chronic lymphocytic thyroiditis on thyroid
function after surgery for benign, non-toxic goitre. Eur J Surg 1991;
157:257-60.
14. McHenry CR, Slusarczyk SJ. Hypothyroidism following hemithyroidectomy: Incidence, risk factors, and management. Surgery 2000;
128:994-8.
15. Ineck BA, Ng TM. Effects of subclinical hypothyroidism and its
treatment on serum lipids. Ann Pharmacother 2003;37:725-30.
16. Glueck CJ, Streicher P. Cardiovascular and medical ramifications
of treatment of subclinical hypothyroidism. Curr Atheroscler Rep
2003;5:73-7.
17. Vitale G, Galderisi M, Lupoli GA, et al. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new
ultrasound tool: Pulsed tissue Doppler. J Clin Endocrinol Metab
2002;87:4350-5.
18. Vanderpump MP, Tunbridge WM. Epidemiology and prevention
of clinical and subclinical hypothyroidism. Thyroid 2002;12:
839-47.
19. Buchanan MA, Lee D. Thyroid auto-antibodies, lymphocytic
infiltration and the development of post-operative hypothyroidism
following hemithyroidectomy for non-toxic nodular goitre. J R Coll
Surg Edinb 2001;46:86-90.
20. Okamoto T, Fujimoto Y, Obara T, et al. Retrospective analysis
of prognostic factors affecting the thyroid functional status after
subtotal thyroidectomy for Graves’ disease. World J Surg 1992;16:
690-5.
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