Original Article
Thyroid Diseases after Treatment of Hodgkin's Disease
N Engl J Med 1991; 325:599-605August 29, 1991
- Abstract
- Abstract
Background and Methods.
Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years.
Results.
A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk.
Conclusions.
High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients. (N Engl J Med 1991; 325:599–605.)
Media in This Article
Figure 1
Actuarial Risk of Hypothyroidism in 1787 Patients Treated for Hodgkin's Disease from the Time of Initial Therapy.Figure 2
Influence of Age at Irradiation on the Development of Hypothyroidism.Article Activity
- Article
A VARIETY of thyroid diseases have been found in patients treated for Hodgkin's disease; among them, hypothyroidism is the most common. Hypothyroidism was first recognized as a complication of external irradiation of the neck for Graves' disease in 1929 and was first reported in 1965 in patients who were euthyroid before neck irradiation.1 2 3 4 A high incidence of hypothyroidism was reported from our institution in 1971 among patients treated for lymphoma, a finding confirmed by other investigators.5 6 7 8 9 10 11 12 13 Iodinated radiographic contrast agents may or may not contribute to the risk of hypothyroidism, and the effect of chemotherapy has not been determined. Graves' disease and ophthalmopathy also have occurred, but their incidence and risk have not been defined.14 15 16 17 18 19 20 21 Transient thyrotoxicosis occasionally has developed in association with painless thyroiditis, and thyroid cancer has also occurred.22 23 24 25 26 27 28 29 30 However, analyses of second neoplasms in patients with Hodgkin's disease who were treated at Stanford University, were entered in the Danish Cancer Registry, or were part of an international collaborative study based on data from cancer registries identified no increased risk among these patients.31 32 33 In contrast, the risk of thyroid cancer was increased among women treated for Hodgkin's disease who were entered in the Connecticut Tumor Registry.34
We studied a large number of patients with Hodgkin's disease who were treated at Stanford University in order to obtain further information about the spectrum and incidence of benign and malignant thyroid diseases in such patients.
Methods
Between January 1961 and April 1989, 2109 patients received their primary treatment for Hodgkin's disease at Stanford University Medical Center. We reviewed the records of 1791 patients. Four patients were excluded from the analyses because they had undergone thyroidectomy before treatment for Hodgkin's disease (one patient had follicular thyroid cancer 22 years before the diagnosis of Hodgkin's disease, two had benign thyroid adenomas, and in one patient thyroidectomy established the diagnosis of Hodgkin's disease). The remaining 1787 patients either were alive at last contact (1533 patients) or had died of causes other than Hodgkin's disease (254 patients). The 318 patients who died of progressive Hodgkin's disease were not analyzed. The mean age at the time of treatment was 28 years (range, 2 to 82). There were 1047 male and 740 female patients. Virtually all patients had lymphangiography, and the majority of patients who were treated after 1974 had CT scans of the chest, abdomen, and pelvis after receiving iodinated contrast material.
The extent of radiation therapy ranged from treatment of the involved fields to total lymphoid irradiation but included the thyroid region in 1677 of the 1787 patients. The radiation doses specified are the calculated dose to the cervical lymph nodes or suprasternal notch and thus are slight overestimates of the actual dose to the thyroid region because of partial shielding by a midline cervical—spinal cord block placed in the posterior neck fields. In children treated with this blocking technique, the thyroid isthmus received a mean (±SD) of 64±13 percent and thyroid tissue 2 cm lateral to the midline received 87±8 percent of the dose prescribed to the cervical nodes.12 One hundred forty patients received a total of 15 to 30 Gy to the cervical lymph-node regions. The majority of the remaining 1537 patients received a total of 44 Gy to cervical lymph-node areas.
The treatment groups were as follows: 810 patients received radiation alone (788 of the 1677 patients with thyroid-region irradiation); 186 received only radiation initially, followed by chemotherapy after a relapse (185 of 1677); 725 received a combination of radiation therapy and chemotherapy (695 of 1677); 57 received chemotherapy alone (0 of 1677); and 9 received chemotherapy followed by radiation of the thyroid region after recurrence (9 of 1677). The initial chemotherapy regimens consisted primarily of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (omitted after mantle irradiation) in 622 patients; procarbazine, melphalan (Alkeran), and vinblastine in 166 patients; doxorubicin, bleomycin, vinblastine, and dacarbazine in 26 patients; and combinations of these or other regimens in 163 patients.
The duration of treatment ranged from 2 weeks for patients receiving 15 Gy of involved-field irradiation to as long as 14 months for those receiving total lymphoid irradiation and chemotherapy. The time to the development of thyroid disease was measured from the initiation of therapy. Generally, patients were followed bimonthly during the first year after completing therapy, every three months during the second year, every four months during the third year, twice annually during the fourth and fifth years, and annually thereafter. If two years had elapsed since the last contact, a letter and health questionnaire were mailed to the patient and the patient's local physician. Serum free thyroxine and thyrotropin were generally measured once or twice each year during the first five years of follow-up in asymptomatic patients, whenever symptoms suggested thyroid dysfunction, and annually after five years unless the patient was clinically euthyroid while receiving thyroxine therapy. Both hormones were measured with several different methods during the study period, mostly radioimmunoassays in the case of thyrotropin and calculations of the free thyroxine index or direct measurement in the case of free thyroxine. The mean duration of follow-up was 9.8 years in the 1787 study patients and 9.9 years in the subgroup of 1677 patients who underwent irradiation of the neck.
The actuarial risks of thyroid disease were calculated from the initial treatment date according to the technique of Kaplan and Meier.35 The significance of differences between groups for each comparison was assessed by the generalized Wilcoxon test of Gehan.36 The data for patients who had no specific thyroid disease were censored at the time of the last follow-up or on the date of death. Potential risk factors for thyroid disease, such as age, sex, dose of radiation, and exposure to chemotherapy, were assessed by univariate and multivariate analysis. The correlation of covariates with outcome was calculated according to the multivariate technique of Cox.37 To calculate the relative risks of thyroid cancer and Graves' disease, the total person-years of observation from the initiation of treatment for Hodgkin's disease to the last follow-up date, the date of death, or the date of diagnosis of thyroid cancer or Graves' disease were applied to annualized incidence rates matched for age and sex to generate the expected incidence. This was compared with the observed incidence, and the difference was assessed for significance according to the approach of Monson.38 Incidence rates were obtained from the Connecticut Tumor Registry for thyroid cancer and from data for Olmsted County, Minnesota, and Malmö, Sweden, for Graves' disease.39 40 41 The absolute risk per 100,000 person-years was calculated by subtracting the number of expected cases from the number of observed cases, dividing the value by the number of person-years of observation, and multiplying by 100,000. All P values are two-tailed.
Results
Of the 1787 patients at risk for thyroid disease, 573 were found to have thyroid abnormalities (Table 1Table 1
Thyroid Disease after Treatment of Hodgkin's Disease.), and all but 3 were part of the group of 1677 patients who had undergone irradiation of the thyroid region. The actuarial risk of developing a thyroid abnormality 20 years after irradiation was 52 percent, with events continuing as late as 26 years after treatment (actuarial risk at 26 years, 67 percent).Hypothyroidism
Biochemical evidence of hypothyroidism was the most common finding, affecting 512 irradiated patients and 1 patient who had not undergone thyroid irradiation. Although our usual policy was to start thyroxine treatment on the basis of an increased serum thyrotropin concentration alone (subclinical hypothyroidism), 208 of the 486 patients who received thyroid hormone—replacement therapy had abnormally low serum free thyroxine values as well as increased thyrotropin concentrations (overt hypothyroidism). Serum free thyroxine and thyrotropin measurements were not available for nine patients receiving thyroxine; they were considered to have thyrotropin elevations alone. Twenty-seven patients who had increased serum thyrotropin concentrations were not given thyroxine. Twenty had normal values during 5 to 22 years of additional follow-up (mean, 12); six remained clinically euthyroid (but were not tested) for 3 to 11 years; and no further data were available for one patient. Although many patients had more than one measurement of serum thyrotropin that was increased before thyroxine therapy was initiated, progression from increased serum thyrotropin concentrations alone to overt hypothyroidism occurred in only six patients before therapy was initiated.
The actuarial risk of having either overt or subclinical hypothyroidism was 44 percent by 25 years after therapy for Hodgkin's disease. Decreased thyroid function was most commonly identified during the second and third years after treatment (135 and 107 cases, respectively), and the incidence declined thereafter. Overt hypothyroidism developed in three patients, and subclinical hypothyroidism developed in three more than 18 years after treatment. Thirty-six percent of the 740 female patients were affected, as compared with 24 percent of the 1047 male patients. Among those with hypothyroidism, the likelihood of overt disease was similar in both sexes (43 percent of female patients vs. 39 percent of male patients). The actuarial risk of both overt and subclinical hypothyroidism at 20 years was 44 percent for patients who had received more than 30 Gy to the thyroid, 27 percent for those who had received 7.5 to 30 Gy, and 2 percent for those who had not undergone irradiation of the thyroid region (P = 0.008 for a dose of more than 30 Gy as compared with a dose of 7.5 to 30 Gy; P = 0.0001 for a dose of 7.5 to 30 Gy as compared with no irradiation) (Fig. 1Figure 1
Actuarial Risk of Hypothyroidism in 1787 Patients Treated for Hodgkin's Disease from the Time of Initial Therapy.). The actuarial risk of overt hypothyroidism was 20 percent in patients receiving more than 30 Gy to the thyroid, 5 percent in patients receiving 7.5 to 30 Gy, and 2 percent in those not undergoing irradiation (P = 0.001 for a dose of more than 30 Gy as compared with 7.5 to 30 Gy; P = 0.2 for a dose of 7.5 to 30 Gy as compared with no irradiation). The 20-year actuarial risk of overt or subclinical hypothyroidism increased from 40 percent for the 788 patients treated with radiation alone to 49 percent for the 889 patients treated with both chemotherapy and neck radiation (P = 0.008). The 704 patients who received chemotherapy as part of the initial management of Hodgkin's disease had a higher risk of hypothyroidism than the 185 patients receiving chemotherapy for recurrence after irradiation (53 percent vs. 43 percent at 20 years, P = 0.05).The relations among the radiation dose, sex, effects of chemotherapy, and age were complex. Only 3 percent of the patients treated with radiation alone received less than 40 Gy, as compared with 18 percent of the patients who received combined therapy. Because the majority of the patients treated with the lower doses were children, the average age of the patients receiving combined therapy was 26 years, as compared with 29 years for patients treated with radiation alone. The distribution of hypothyroidism according to age at irradiation generally paralleled the age distribution of the population (Fig. 2Figure 2
Influence of Age at Irradiation on the Development of Hypothyroidism.). However, the percentage of patients in whom hypothyroidism developed increased from 15 percent among the patients who were less than 5 years of age when treated for Hodgkin's disease to 39 percent among those who were 15 to 20 years of age when treated, and it gradually declined with advancing age to 17 percent among the patients over 70 years of age when treated. Since the dose of radiation tended to increase with age in children, univariate and multivariate analyses were performed separately for the 272 pediatric patients (age less than 17 years) and the 1405 adults (Table 2Table 2
Risk Factors for Hypothyroidism after Thyroid Irradiation during Treatment of Hodgkin's Disease.*). In the children, an increasing dose of radiation was the chief correlate of the risk of subsequent hypothyroidism (the relative risk increased by 1.06 per gray, P = 0.000001). Increasing age was associated with a slightly increased risk of hypothyroidism in the univariate analysis but was not a significant cofactor in the multivariate analyses. Sex was not a significant risk factor for hypothyroidism in children. In adults who underwent thyroid irradiation, however, female sex was the chief univariate risk factor for hypothyroidism, followed by exposure to chemotherapy, an increasing dose of radiation, and younger age when treatment was begun. Multivariate analysis indicated that women had a relative risk of hypothyroidism that was 1.6 times the risk in men. The relative risk of hypothyroidism increased by 1.02 per gray of radiation exposure, increased by 1.42 with the addition of chemotherapy to thyroid irradiation, and decreased by 0.99 with each additional year of age.The mantle-irradiation techniques evolved substantially during the period of this study. Most patients treated between 1961 and 1970 received 2.2 to 2.75 Gy per day, up to a total dose of 44.0 Gy. Anterior and posterior fields were treated on alternate days. The dose per fraction was reduced during the period from 1971 to 1980, and the use of chemotherapy increased. Since 1981 most patients have been treated daily with 1.5 to 2.0 Gy, with both anterior and posterior fields treated each day, an approach that substantially decreases the daily dose to the thyroid region. The risk of hypothyroidism was evaluated according to the decade during which treatment was initiated, to assess whether the intensity of radiation treatment affected the development of hypothyroidism. The actuarial risk of hypothyroidism in general paradoxically increased significantly with each advancing decade, although the cumulative probability of hypothyroidism was similar for all decades (cumulative risks of overt or subclinical hypothyroidism: 1961 to 1970, 32 percent; 1971 to 1980, 42 percent; and 1981 to 1990, 38 percent; all P values <0.0014). The actuarial risk of overt hypothyroidism did not differ significantly according to decade, although the cumulative probability of overt hypothyroidism declined slightly, but not significantly (1961 to 1970, 19 percent; 1971 to 1980, 13 percent; and 1981 to 1990, 10 percent). An increased rate of diagnosis of subclinical hypothyroidism appears to be responsible for the overall increased risk of hypothyroidism (cumulative probability of subclinical hypothyroidism: 1961 to 1970, 12 percent at 24 years of follow-up; 1971 to 1980, 28 percent at 16 years; and 1981 to 1990, 28 percent at 6 years; all P values <0.0001). These trends reflect improvements in the accuracy of laboratory tests of thyroid function, increased clinical awareness of thyroid dysfunction and more frequent testing, and increased incorporation of chemotherapy during the advancing decades.
Hyperthyroidism
Graves' hyperthyroidism (diffuse goiter, high serum free thyroxine and low serum thyrotropin concentrations, and increased thyroid uptake of radioiodine) developed in 30 patients 3 weeks to 18 years after treatment for Hodgkin's disease was begun (mean, 5.3 years). This was the first recognized sign of thyroid dysfunction in 20 patients. However, 5 patients had been found to have overt hypothyroidism and 5 subclinical hypothyroidism 10 to 94 months (mean, 41) before they were given a diagnosis of hyperthyroidism, and all 10 of these patients had received thyroxine therapy. Seventeen of the 30 patients with hyperthyroidism also had infiltrative ophthalmopathy. Four other patients in whom infiltrative ophthalmopathy developed were also given a diagnosis of Graves' disease: at the time of the diagnosis three had hypothyroidism, and one was euthyroid. On average, the 34 patients in whom Graves' disease developed were 25 years of age when they began treatment for Hodgkin's disease (range, 9 to 45). Eighteen were males, and 16 were females. The actuarial risk of Graves' disease was 3 percent in patients receiving more than 30 Gy, 1 percent in patients who received 7.5 to 30 Gy, and 2 percent among 110 patients who had not undergone irradiation of the thyroid. Annualized incidence rates of Graves' disease are not available for a clearly comparable normal population. However, estimates of the relative risk of Graves' disease after treatment for Hodgkin's disease ranged from 7.2 (95 percent confidence interval, 4.8 to 9.6; P<0.00001), on the basis of rates in Olmsted County, Minnesota,40 to 20.4 (95 percent confidence interval, 13.5 to 27.3; P<0.00001), on the basis of rates in Malmö, Sweden.41 The absolute risk ranged from 170 to 188 cases per 100,000 person-years. The higher estimates are based on incidence rates reported from Sweden, which are more current than those from Minnesota and are specified according to sex. Univariate analysis showed that age, sex, dose of radiation, and exposure to chemotherapy were not significant risk factors for Graves' disease.
Thyrotoxicosis with Low Radioiodine Uptake
Transient, mildly symptomatic thyrotoxicosis developed in six patients, with no thyroid enlargement or tenderness compatible with silent thyroiditis (Table 1). Five cases occurred 10 to 24 months after neck irradiation, and one occurred 15 years after irradiation. All had elevated serum free thyroxine and low thyrotropin concentrations and low thyroid uptake of radioiodine. Overt hypothyroidism developed in all six patients in two to three months and then was treated. Three patients had received radiation therapy alone, and three received combined therapy for their Hodgkin's disease.
Thyroid Nodular Disease
Palpable abnormalities of the thyroid gland were identified in 48 patients 1.5 to 25 years after therapy: 44 patients had nodules, and 4 patients who were euthyroid or had hypothyroidism had symmetric thyroid enlargement that was diagnosed as Hashimoto's thyroiditis. Nine patients were receiving thyroxine when the palpable abnormality was detected. Twelve patients had solitary, clinically benign nodules that concentrated radioiodine on scanning and were treated conservatively. Four nodules were identified as colloid cysts by ultrasonography and examination of aspirates. Clinical examination of the thyroid gland revealed that two patients had multinodular goiter. A malignant condition was suspected in 26 patients with nodules that showed reduced uptake of radioiodine. Twenty-five of the 48 patients with palpable abnormalities of the thyroid gland had also received chemotherapy, including 12 of the 26 patients with nodules thought to be malignant.
Thyroidectomy was performed on 26 patients 1.5 to 26 years after irradiation of the neck (median, 14) (Table 1). The actuarial risk of undergoing thyroidectomy in the 1677 irradiated patients was 7 percent 20 years after irradiation and 27 percent at 26 years. The lesions were benign adenomas in 10 patients, single adenomatous nodules in 6 patients, multinodular goiter in 4 patients, and thyroid cancers in 6 patients (3 were papillary cancers, 2 were mixed papillary and follicular, and 1 was follicular). The thyroid cancers were diagnosed 9 to 19 years after therapy for Hodgkin's disease was begun (median, 13). The age of the patients when radiation therapy was begun varied (5, 17, 23, 23, 29, and 32 years). The actuarial risk of thyroid cancer was 1.7 percent beyond 19 years after neck irradiation, as compared with an expected risk of 0.07 percent in a normal population matched for age and sex. The relative risk of thyroid cancer in the 1677 irradiated patients was 15.6, with a 95 percent confidence level of 6.3 to 32.5 (6 cases observed vs. 0.385 expected, P<0.00001). The absolute risk was 33.9 cases per 100,000 person-years. All cancers were confined to the thyroid gland, and no patient has had recurrent or metastatic thyroid cancer. None of the six patients in whom thyroid cancer developed had received thyroxine or had an increased serum thyrotropin concentration before thyroidectomy. Two of the six had received both chemotherapy and radiation. Five patients in whom benign nodules developed had received thyroxine.
Discussion
The outcome in patients with Hodgkin's disease has improved dramatically during the past 30 years, with long-term survival now expected for most patients. Although thyroid disease is not a cause of mortality in these patients, it represents the most common problem requiring evaluation and intervention during the routine follow-up of patients after therapy for Hodgkin's disease. The 47 percent cumulative probability of hypothyroidism has varied little over a period of nearly three decades.5 In children, the probability of hypothyroidism increased with increasing age, largely as a function of the increasing dose of radiation to the thyroid. Among adults, the risk in women was 1.6 times that in men. An increasing dose of radiation was a less important factor than the addition of chemotherapy to irradiation, although the majority of adult patients received similarly high doses of radiation to the gland. Advancing age slightly but progressively decreased the risk after 20 years of age.
The iodine load associated with the use of radiographic contrast agents (particularly the ethiodized oil used in lymphangiography) may or may not predispose patients to radiation injury of the thyroid.5 6 7 , 9 , 12 Lymphangiography has been independently associated with an increased risk of hypothyroidism in patients irradiated for childhood cancer.42 Since lymphangiography was performed uniformly, its potential contribution to the development of hypothyroidism cannot be assessed in our series. The iodine load from intravenous contrast agents used in CT scanning could be an additional factor, since the interval to the development of chemical hypothyroidism has decreased since the introduction of CT scanning in 1974. Nevertheless, the cumulative probability of hypothyroidism has not changed.
Whether thyroid hormone—replacement therapy is necessary in patients with subclinical hypothyroidism is difficult to assess, since we usually treated them. Twenty-seven patients had elevated serum thyrotropin concentrations that were not treated and proved to be transient. However, 41 percent of the patients treated with thyroxine had overt hypothyroidism, despite frequent screening. We think that subclinical hypothyroidism does evolve to overt hypothyroidism more often than not and should be treated, although we identified this transition in only six patients. In addition, most palpable abnormalities and all the thyroid cancers in our patients occurred in those not receiving thyroxine. Patients with subclinical hypothyroidism may be at risk for hypercholesterolemia and accelerated atherosclerosis; the latter may be a significant risk factor for cardiovascular disease after treatment of Hodgkin's disease.43 44 45
Thyroid hormone—replacement therapy clearly does not eliminate all risk of subsequent thyroid abnormalities. As indicated in previous case reports, Graves' disease may develop in patients receiving thyroxine.22 , 46 In this series 33 percent of the patients in whom Graves' hyperthyroidism developed had been receiving thyroxine before its onset. Thyroxine therapy also did not prevent the development of palpable abnormalities in the thyroid gland: 19 percent of the patients with thyroid nodular disease were receiving it. Although none of the 6 patients who had thyroid cancer had received thyroxine, among the irradiated patients there was no difference in the risk of thyroid cancer between the 486 patients who had received thyroxine and the 1191 patients who had not received thyroxine.
The risk of Graves' disease appears to be significantly increased after treatment for Hodgkin's disease, with a risk that is 7.2 to 20.4 times the expected risk and a total incidence of 170 to 188 cases per 100,000 person-years. Although the risk of Graves' disease may vary between and within countries, the total incidence was similar in Malmö, Sweden, and Olmsted County, Minnesota (17.7 vs. 19.8 cases per 100,000 person-years).40 , 41
Analysis of data from the Connecticut Tumor Registry showed a relative risk of thyroid cancer of 6.7 among 3211 patients with Hodgkin's disease, 2109 of whom had received some form of radiation.34 The risk of thyroid cancer increased 10 years after the diagnosis of Hodgkin's disease and remained increased thereafter. In our series thyroid cancer developed in two men and four women 9 to 18 years after irradiation, for an overall relative risk of 15.6 (95 percent confidence interval, 6.3 to 32.5). This higher estimate of risk may reflect the fact that the population was larger during the period of increasing risk. A previous analysis did not show an increased relative risk of thyroid cancer among patients with Hodgkin's disease who were treated at Stanford; however, the analysis was confined to 1507 patients treated between 1968 and 1985, with an average follow-up of 6.2 years.31 The overall relative risk of thyroid cancer was not significantly increased in patients with Hodgkin's disease, according to an analysis of records compiled from international cancer registries (relative risk, 2.8 in male patients and 2.2 in female patients), but the risk increased in the limited population with follow-up exceeding 10 years.33
To decrease the risk of thyroid injury, some have proposed excluding the thyroid from the fields of irradiation.47 However, given the frequent involvement of low cervical lymph nodes adjacent to the thyroid, the occasional apparent involvement of the gland itself, and the difficulty of ensuring the reproducibility of such blocking, we do not think that this is a useful approach to this problem. The administration of thyroxine before irradiation did not prevent subsequent hypothyroidism in one study.48 However, the cost of starting replacement therapy early could be less than that of monitoring thyroid function, given the high risk of hypothyroidism after treatment of Hodgkin's disease. Whatever program to minimize hypothyroidism is chosen, continued follow-up is necessary to assess the adequacy of therapy and to detect the appearance of other thyroid diseases.
Supported in part by a grant (CA-34233) from the National Institutes of Health.
We are indebted to Drs. Saul A. Rosenberg, Richard T. Hoppe, Sarah S. Donaldson, and Sandra J. Horning for their contributions to the ongoing care of these patients; and to Ms. Anna Vargese for data management and analysis.
Source Information
From the Departments of Radiation Oncology (S.L.H., R.S.C.) and Diagnostic Radiology and Nuclear Medicine (I.R.M.), Stanford University School of Medicine, Stanford, Calif. Address reprint requests to Dr. Hancock at the Department of Radiation Oncology, Stanford University Medical Center, A089, Stanford, CA 94305.
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