Hypothyroidism following hemithyroidectomy for benign nontoxic thyroid disease.

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 [micro]IU/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 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 (F[T.sub.4]) 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 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 [micro]IU/ml). Patients who were clinically asymptomatic but who had a serum TSH level greater than 4.0 [micro]IU/ml with a normal F[T.sub.4] level were diagnosed as having subclinical hypothyroidism. Overt hypothyroidism was diagnosed in those who had an elevated serum TSH level and a low [FT.sub.4] 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 ([T.sub.4]), which is 7 days, and the response of serum TSH to changes in the [T.sub.4] level (TSH rises immediately after a drop in [T.sub.4] 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 [T.sub.4]. (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 [micro]IU/ml (range 1.17 to 3.90; 95% CI: 1.53 to 2.94). Their mean postoperative level was 14.88 [micro]IU/ml (range: 4.80 to 70.73; 95% CI: 4.43 to 25.28) (table 1).

A complete thyroid function panel (serum TSH, F[T.sub.4], and [T.sub.4] 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 F[T.sub.4] 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 [micro]IU/ml (table 1).

In the euthyroid group, the mean preoperative TSH level was 1.07 [micro]IU/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, 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 ([sup.131]I) for multinodular goiter disease 2 years earlier, and she had been euthyroid prior to hemithyroidectomy.

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 hypo-and 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 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 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 auto-antibody 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 [micro]IU/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 [micro]IU/ml in the hypothyroid group and 1.10 [micro]IU/ml in the euthyroid group (p < 0.05).

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.

References

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(4.) Sawin CT. Subclinical hyperthyroidism and atrial fibrillation. Thyroid 2002;12:501-3.

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(6.) Schlote B, Nowotny B, Schaaf L, et al. Subclinical hyperthyroidism: Physical and mental state of patients. Eur Arch Psychiatry Clin Neurosci 1992;241:357-64.

(7.) Al-Abadi AC. Subclinical thyrotoxicosis. Postgrad Med J 2001; 77:29-32.

(8.) Fazio S, Biondi B, Carella C, et al. Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: Beneficial effect of beta-blockade. J Clin Endocrinol Metab 1995;80:2222-6.

(9.) Burmeister LA, Flores A. Subclinical thyrotoxicosis and the heart. Thyroid 2002;12:495-9.

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(11.)Benediktsson R, Toft AD. Management of the unexpected result: Compensated hypothyroidism. Postgrad Med J 1998;74:729-32.

(12.) Fewins J, Simpson CB, Miller FR. Complications of thyroid and parathyroid surgery. Otolaryngol Clin North Am 2003;36:189-206, 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 R Cardiovascular and medical ramifications of treatment of subclinical hypothyroidism. Curt 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.

Kristin A. Seiberling, MD; Jose C. Dutra, MD; Sanija Bajaramovic, MD

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: [phone]; fax: [phone]; e-mail: [e-mail]

The information in this article was originally presented at the Triological Society's Combined Otolaryngology Spring Meeting; April 30, 2004; Scottsdale, Ariz.

Table 1. Pathology in the 14 hypothyroid patients

                       TSH level
                                              Diagnosis,
                Preop            Postop         months
Pt.   Age   ([micro]IU/ml)   ([micro]IU/ml)    postop *

 1    60         1.25            14.20            2
 2    73         1.70             9.62            1
 3    29         1.23             5.22            2
 4    54         3.57            70.73            1
 5    58         2.56             4.90            4
 6    26         2.21             6.99            2
 7    48         2.60             5.96            2
 8    61         3.45            16.25            2
 9    49         2.42             6.02            1
10    56         1.84             5.86            1
11    32         3.90             4.80            1
12    32         3.10             5.07            2
13    53         2.50            18.25            1
14    38         1.17            34.40            1

Pt.   Pathology

 1    Multinodular goiter w/degenerative changes
 2    Chronic lymphocytic thyroiditis w/follicular adenoma
 3    Follicular adenoma
 4    Hashimoto's thyroiditis w/colloid nodules
 5    Follicular adenoma (benign Hurthle cell adenoma)
 6    Diffuse atrophy and scarring of the thyroid gland
 7    Diffuse chronic inflammation w/follicular adenoma
 8    Chronic lymphocytic thyroiditis w/follicular adenoma
 9    Multinodular goiter
10    Chronic inflammation w/follicular adenoma
11    Follicular adenoma
12    Follicular adenoma
13    Hashimoto's thyroiditis w/follicular adenoma
14    Hashimoto's thyroiditis w/adenomatous goiter

* The number of months postoperatively that the patient was
diagnosed as hypothyroid.

Table 2. TSH testing in the 44 euthyroid patients

Most recent draw         n

 5 wk postop              6
 6 wk postop              4
 2 mo postop             14
 4 mo postop              3
 5 mo postop              2
 6 mo postop              2
 7 mo postop              7
 1 yr postop              4
>2 yr postop              2

Table 3. Pathologic findings in the 44 euthyroid patients

Pathology                   n (%)     Comment

Follicular adenoma        26 (59.1)   In 2 cases, surrounding tissue
                                        contained focal areas of
                                        chronic inflammation

Multinodular goiter        6 (13.6)   Degenerative changes were seen
                                        in 2 cases

Adenomatous hyperplasia    5 (11.4)

Chronic lymphocytic        3 (6.8)
  thyroiditis

Hemorrhagic cyst           2 (4.5)    In both cases, large cysts
                                        occupied the entire lobe

Normal thyroid tissue      2 (4.5)