Keywords
hypothyroidism - Iraq - lobectomy - predictors - thyroid
Introduction
Thyroid disorders can affect one or both lobes. Unilateral removal (lobectomy) can
be optimal for toxic adenoma, cytologically indeterminate nodules, and low risk differentiated
thyroid cancer (DTC).[1] Many factors affect thyroid function such as age, gender, race, time of day, season,
dietary iodine level, socioeconomic status, stress, body mass index (BMI), immune
status, phase of menstrual cycle, and overall individual wellbeing.[2] The prevalence of postoperative hypothyroidism depends on the duration of follow-up
after surgery and on the criteria used to define hypothyroidism.[3]
The reported incidence of postlobectomy hypothyroidism is quite different among studies,
with an average of 22%.[4] Varying levels of its definitions also complicate the diagnosis of hypothyroidism.
The National Health and Nutrition Examination Survey III suggested 0.4 to 4.0 mIU/L
as the thyroid-stimulating hormone (TSH) reference range. However, others have suggested
upper limits of 3.59, 5.5, 7.0, 8.0, and 10.0 mIU/L. This makes interinstitutional
and pooled data sets difficult to be interpreted or generalized.[5]
Many risk factors predict the development of hypothyroidism in patients undergoing
thyroid lobectomy. Patient age at the time of surgery is strongly correlated with
the final thyroid outcome. It is a relevant clinical predictor of future hypothyroidism
and the need for thyroid hormone replacement.[6] Higher preoperative TSH level translates into higher posthemithyroidectomy hypothyroidism.
However, a definite cutoff point has yet to be established.[5] The presence of thyroid peroxidase antibody (TPO) was the most well-studied risk
factor. The literature reviewed that hypothyroidism posthemithyroidectomy ranges from
38.9 to 59%.[7] Lymphocytic infiltration of the gland carries a higher incidence of hypothyroidism.
Furthermore, the magnitude of the lymphocytic infiltration also has some influence,
with 49% for high-grade infiltration and 10% for low-grade in cases undergoing surgery.[8] Derived weight ratio is the proportion of thyroid lobe remnant (as calculated from
ultrasonographic dimensions) to the total body weight, which is considered a predictor
of postoperative thyroid failure. A higher incidence of postoperative hypothyroidism
is associated with a derived ratio of less than 0.08 g/kg.[9] Antithyroglobulin antibody (ATA) and thyroid peroxidase antibody preoperatively
might predict subclinical thyroiditis, which is the ultimate result of an inflammatory
process by thyroid antigens and its antibodies.[10]
[11] Serial postoperative assessments for any sign or symptom of hypothyroidism are advisable.[12] Starting 1 month postoperatively, followed by subsequent evaluations depending on
the initial laboratory results.[1]
Unlike previous clinical practice, recent medical approaches are directed against
the routine use of levothyroxine after hemithyroidectomy. This will obviate the adverse
effects of replacement therapy, particularly in postmenopausal women.[10] However, levothyroxine prescription or discontinuation depends mainly on TSH levels
postoperatively.[13] The mean time from surgery to detection of hypothyroidism varies between studies
and ranges from 4 to 8 months. About 90% of patients who develop hypothyroidism are
detected within the first-year postsurgery.[14]
This study aimed to assess the predictors of hypothyroidism after thyroid lobectomy.
Patients and Methods
Setting and Design
This was a retrospective observational study that was conducted at Faiha Specialized
Diabetes, endocrine, and Metabolism Center (FDEMC) and Zain Alabdeen Teaching Hospital
during a period of 9 months from January 2022 to October 2022. The study included
documented data from medical archives of 80 patients who had thyroid lobectomy regardless
of the cause, ethnicity, age, gender, and comorbid conditions. Only preoperative euthyroid
patients were included (defined as TSH level between 0.5 and 5.5 mIU/L). We excluded
patients with preoperative hypothyroidism (defined as TSH level > 5.5 mIU/L) or taking
levothyroxine and patients with a history of radiation, and those undergone previous
thyroid surgery.
Data Collection
Information was collected regarding the patient's age, sex, occupation, residence,
history of hypertension, BMI, pathology, and surgical procedure, pre- and postlobectomy
TSH, TPO, and ATA levels.
Statistical Analysis
The data were analyzed using Statistical Package for Social Sciences (SPSS) version
26. The data are presented as mean, standard deviation, and ranges. Frequencies and
percentages present categorical data. An independent t-test (two-tailed) was used to compare TSH levels according to postlobectomy thyroid
status. The chi-squared test assessed the association between postlobectomy thyroid
status and certain risk factors. Receiver operating characteristic (ROC) curve analysis
was constructed for preoperative TSH level to predict postlobectomy hypothyroidism.
The sensitivity, specificity, and accuracy of serological markers were calculated.
A level of p-value less than 0.05 was considered significant.
Results
The total number of patients was 80. Their age ranged from 32 to 81 years, with a
mean of 46.42 ± 11.3 years. Females were predominant (72.5%) in the studied population.
In this study, only 23.8% of patients had normal BMI; the vast majority were obese
or overweight. Benign pathology was diagnosed in 67.5% of patients, and the most common
surgical approach used for lobectomy was the classical procedure (65%). We noticed
that 22.5% of study patients developed hypothyroidism after lobectomy, as shown in
[Table 1]. In this study, preoperative TSH level was substantially higher in patients who
developed postlobectomy hypothyroidism than those who did not (3.12 vs. 1.99 mIU/L).
The highest prevalence of postlobectomy hypothyroidism was seen significantly in patients
with positive thyroid peroxidase autoimmunity 44.1% and those with positive thyroglobulin
autoimmunity 38.9%. No statistically significant associations were detected (p ≥ 0.05) between the incidence of postlobectomy hypothyroidism and patient risk factors
profile except for preoperative TSH level and autoimmune thyroid antibodies markers,
as shown in [Table 2].
Table 1
General characteristics of patients undergoing thyroid lobectomy
|
Variable
|
n (%)
|
|
Gender
|
Females
|
58 (72.5)
|
|
Males
|
22 (27.5)
|
|
Body mass index (BMI)
|
Normal
|
19 (23.8)
|
|
Overweight
|
44 (55.0)
|
|
Obese
|
17 (21.2)
|
|
Hypertension
|
37 (46.3)
|
|
Malignant pathology
|
26 (32.5)
|
|
Thyroid peroxidase autoimmunity
|
34 (42.5)
|
|
Thyroglobulin autoimmunity
|
36 (45.0)
|
|
Previous surgical approach for lobectomy
|
Classical
|
52 (65.0)
|
|
Minimally invasive
|
19 (23.8)
|
|
Endoscopic
|
9 (11.2)
|
Table 2
Association between patient characteristics and postlobectomy hypothyroidism
|
General characteristics
|
Postlobectomy
|
Total (%)
n = 80
|
p-Value
|
|
Hypothyroid[a] (%)
n = 18
|
Euthyroid[b] (%)
n = 62
|
|
Age (year)
|
|
< 40
|
3 (17.6)
|
14 (82.4)
|
17 (21.3)
|
0.704
|
|
40–59
|
9 (21.4)
|
33 (78.6)
|
42 (52.5)
|
|
≥ 60
|
6 (28.6)
|
15 (71.4)
|
21 (26.3)
|
|
Sex
|
|
Male
|
6 (27.3)
|
16 (72.7)
|
22 (27.5)
|
0.528
|
|
Female
|
12 (20.7)
|
46 (79.3)
|
58 (72.5)
|
|
BMI level
|
|
Normal
|
2 (10.5)
|
17 (89.5)
|
19 (23.8)
|
0.206
|
|
Overweight
|
10 (22.7)
|
34 (77.3)
|
44 (55.0)
|
|
Obese
|
6 (35.3)
|
11 (64.7)
|
17 (21.3)
|
|
Pathology
|
|
Benign
|
10 (18.5)
|
44 (81.5)
|
54 (67.5)
|
0.219
|
|
Malignant
|
8 (30.8)
|
18 (69.2)
|
26 (32.5)
|
|
Surgical approach
|
|
Classical
|
11 (21.2)
|
41 (78.8)
|
52 (65)
|
0.898
|
|
Minimal invasive
|
5 (26.3)
|
14 (73.7)
|
19 (23.8)
|
|
Endoscopic
|
2 (22.2)
|
7 (77.8)
|
9 (11.3)
|
|
Preoperative TSH
|
3.12 ± 1.2
|
1.99 ± 0.87
|
|
0.001
|
|
Thyroid peroxidase autoimmunity
|
|
Positive
|
15 (44.1)
|
19 (55.9)
|
34 (42.5)
|
0.001
|
|
Negative
|
3 (6.5)
|
43 (93.5)
|
46 (57.5)
|
|
Thyroglobulin autoimmunity
|
|
Positive
|
14 (38.9)
|
22 (61.1)
|
36 (45.0)
|
0.001
|
|
Negative
|
4 (9.1)
|
40 (90.9)
|
44 (55.0)
|
Abbreviations: BMI, body mass index; TSH, thyroid-stimulating hormone.
a Hypothyroid: defined as TSH value > 5.5 mIU/L.
b Euthyroid: defined as TSH level between 0.5 and 5.5 mIU/L.
ROC curve analysis was constructed for preoperative TSH level to predict postlobectomy
hypothyroidism. As shown in [Fig. 1], the cutoff point of preoperative TSH level was 2.61 mIU/L. So, preoperative TSH
level more than 2.61 mIU/L predicts the risk of postlobectomy hypothyroidism (area
under the curve = 74%). Preoperative TSH level was 60% sensitive, 89.7% specific,
and 75.6% accurate for predicting future hypothyroidism (as shown in [Table 3]).
Fig. 1 Receiver operating characteristic curve for preoperative thyroid-stimulating hormone
level in predicting postlobectomy hypothyroidism.
Table 3
Diagnostic accuracy of preoperative TSH and autoimmune markers as a predictor for
risk of postlobectomy hypothyroidism
|
Marker
|
Sensitivity
|
Specificity
|
PPV
|
NPV
|
Accuracy
|
|
Preoperative TSH level (m IU/L)
|
60%
|
89.7%
|
65%
|
81.4%
|
75.6%
|
|
Thyroid peroxidase autoimmunity
|
83.3%
|
69.4%
|
44.1%
|
93.5%
|
72.5%
|
|
Thyroglobulin autoimmunity
|
77.8%
|
64.5%
|
38.9%
|
90.9%
|
67.5%
|
|
Combined thyroid peroxidase and thyroglobulin autoimmunity
|
100%
|
98.4
|
94.7%
|
100%
|
98.8%
|
Abbreviations: NPV, negative predictive value; PPV, positive predictive value; TSH,
thyroid-stimulating hormone.
Autoimmune thyroid antibodies provide additional predictive value for the development
of future hypothyroidism.
Discussion
For some thyroid problems, thyroid lobectomy has historically been considered a safe
and successful surgical treatment. Although the contralateral lobe remains intact,
there is a possibility of developing hypothyroidism after surgery. The reported incidence
ranges between 9 and 49%.[15] Compared to total thyroidectomy, lobectomy has a significantly lower rate of complications,
and most patients do not require thyroid hormone replacement.[14] This study reported a 22.5% chance of postlobectomy hypothyroidism, which agrees
with the Cho et al's study, in which, following thyroid lobectomy, 21.1% of people
developed hypothyroidism.[11] The pooled risk of hypothyroidism after lobectomy from 22 studies on meta-analysis
conducted by Verloop et al was 22%.[9] On the other hand, Lang et al's study reported a higher incidence of hypothyroidism,
as they noticed that 29.3% of participants had postoperative hypothyroidism, and one-third
of them needed thyroxine replacement.[16] The incidence of postlobectomy hypothyroidism in the Ng et al study was 13%, at
the lower end of the reported incidence quoted in the literature.[17] Hypothyroidism has a broad spectrum of presentations ranging from asymptomatic to
severely symptomatic.[18] Therefore, surgical decision should be made after judicious balance between the
primary surgical indication and the possibility of developing hypothyroidism postoperatively.
Lifelong medication and regular medical follow-up can greatly affect patients' quality
of life. Thus, predicting risk factors for developing hypothyroidism after partial
thyroid surgery is essential.[19] Some risk-scoring systems have been described to predict hypothyroidism after lobectomy.
However, most of these have only one variable or are applicable after surgery, making
them difficult to use in preoperative predictions.[20] Many studies have proposed risk factors for developing postlobectomy hypothyroidism,
like higher preoperative TSH, the presence of antithyroid antibody and lymphocytic
infiltration of the gland, higher resected lobe size, and lower remaining thyroid
volume. Nevertheless, these risk factors are not the subject of a clear consensus
in the literature.[8]
This study found no significant associations between patient age, sex, BMI level,
histopathology, and surgical approach with the development of postoperative hypothyroidism.
A recent study by Meyer et al revealed that postlobectomy hypothyroidism and thyroxine
replacement were significantly associated with older age and malignant thyroid pathology.
No correlation existed with sex, BMI, and family history (p> 0.05).[6] In the same concern, Cho et al study found that age, sex, follow-up period, and
operation type performed were not significant factors for postlobectomy hypothyroidism
development.[11]
This study observed that the mean preoperative TSH level was significantly higher
in patients who developed postlobectomy hypothyroidism (p= 0.001).
Moreover, ROC curve analysis reported that preoperative TSH level more than 2.61 mIU/L
is the best predictor for postlobectomy hypothyroidism. Preoperative TSH level was
60% sensitive and 89.7% specific for that purpose. With a cutoff value of 2.0 mIU/L,
the Cho et al study found that the proportion of postlobectomy hypothyroidism was
significant in individuals with high-normal preoperative TSH levels.[11] Similarly, Park et al reported that preoperative TSH levels differed significantly
between patients with postoperative hypothyroidism and those with postoperative euthyroidism,[20] which agreed with the results of other studies like Lang et al in which hypothyroidism
was associated with a higher preoperative TSH level and Meyer et al which report that
postlumpectomy hypothyroidism was associated with a higher preoperative TSH.[6]
[16]
Subclinical thyroiditis can be detected through increased autoantibodies preoperatively.[11] This study proves that thyroid autoimmunity is a valuable predictor of postoperative
hypothyroidism. Thyroid peroxidase has 83.3% sensitivity and 69.4% specificity, while
slightly lower values have been estimated for thyroglobulin autoantibodies sensitivity
of 77.8% and specificity of 64.5%. Furthermore, the combination of TPO and thyroglobulin
antibodies in the same patient increases the sensitivity to 100% and specificity to
98.4% to predict future thyroid failure. Similarly, Cho et al reported that the incidence
of postlobectomy hypothyroidism is significantly higher in those with two or more
positivity on preoperative thyroglobulin, ATA, and antimicrosomal antibody (p = 0.006, odds ratio = 9.492). It was significant at 67% sensitivity and 83% specificity
to predict postlobectomy hypothyroidism.[11]
The predictive value of screening tests of postoperative hypothyroidism can be enhanced
by finding multiple risk factors in the same individual as compared to either one
alone.[21] Therefore, good preoperative evaluation is very important to ensure good thyroid
outcome after surgery.
Conclusion
Higher TSH levels and thyroid autoimmunity predict a higher risk of developing hypothyroidism
after thyroid lobectomy. Good preoperative evaluation is necessary to predict postoperative
thyroid outcome. Surgical decision should be made after proper balance between surgical
indication and the possibility to develop hypothyroidism in the future.
