Hypothyroidism after radiotherapy for laryngeal cancer

doi:10.1016/S0167-8140(00)00276-0

Radiotherapy and Oncology

Volume 57, Issue 1, 1 October 2000, Pages 97-101

https://doi.org/10.1016/S0167-8140(00)00276-0 Get rights and content

Abstract

Purpose: To investigate the incidence of hypothyroidism after radiotherapy of laryngeal cancer, including the possible factors that could predict the onset of hypothyroidism.

Materials and methods: We report this study on patients treated by radiotherapy as part of the treatment for laryngeal cancer in the Department of Oncology in Eastern Finland. Sixty-five males and seven females were treated with radiotherapy between 1974–1995.

Thyroid function was determined by measuring serum thyroid stimulating hormone, and serum free thyroxine (FT4). The studied risk factors for hypothyroidism included age, treatment modalities, radiation dose and energy, height of the radiation field, and follow-up time.

Results: Hypothyroidism was detected in 17 (24%) of the 72 patients. Hypothyroidism was clinically unsuspected in all but one patient. Hypothyroidism was more common, if the height of the radiation field was ≥7 cm, or the patient had been operated. Hypothyroidism was less common if less than a half of the thyroid bed was irradiated.

Conclusion: The detection of hypothyroidism clinically is difficult, and the rate of hypothyroidism warrants routine assessment of thyroid function after irradiation of laryngeal cancer.

Introduction

In the European Union approximately 23 300 new larynx cancers were diagnosed in 1990 [1]. They are usually treated with surgery, radiotherapy or a combination. Thyroid dysfunction is a recognized side effect after radiotherapy of head and neck tumours. The risk for hypothyroidism is 14–36%, when radiotherapy alone is used in laryngeal cancer [5], [7], [9], [10]. When radiotherapy is combined with surgery, which may include hemithyroidectomy, the risk is increased to 43–66% [2], [5], [7], [9], [10]. Other potential risk factors include the dose of radiotherapy delivered to the region of the thyroid gland, chemotherapy prior to radiation therapy, gender, age, and total vs. partial irradiation of the thyroid gland.

The purpose of this study was to investigate the frequency of thyroid dysfunction following radiation therapy for laryngeal cancer either with or without other treatments. For the first time the impact of the height of the radiation field, which significantly reflects the proportion of the thyroid gland irradiated, was assessed. The impact of follow-up time, total dose, age, and surgical operation on the risk of hypothyroidism were studied, as well.

Section snippets

Subjects

Thyroid function was assessed in 72 patients (65 men, seven women) irradiated for laryngeal cancer in Eastern Finland during 1975 to 1995. The main characteristics of the patients are given in Table 1.

Patients, who had diabetes, coronary heart disease, obstructive arterial disease of the extremities, chronic obstructive pulmonary disease (COPD), dementia, and/or hypertension, were considered to have a chronic disease that could have an impact upon the outcome of radiation side effects.

Radiotherapy

Treatment

Results

Seventeen (24%) of the 72 patients had an elevated TSH-value (range 6.3–258 mU/l). FT4 was assessed simultaneously in 65 of the 72 patients. Most of the patients with an elevated TSH, also had a decreased FT4. One patient had a decreased FT4 with normal TSH.

The effects of total dose, quality of radiation, field height, patient's age, chronic diseases, time after radiotherapy, and other treatments for laryngeal cancer on hypothyroidism are shown in Table 3.

Patients with an early stage vocal cord

Discussion

The appearance of postradiation hypothyroidism has been known for a long time. The use of TSH assessment has made the diagnosis of subtle changes easy, and the hypothyroidism can be detected early. The occurrence of radiation induced hypothyroidism has been studied in both lymphoma and head and neck tumour patients. A review of thyroid abnormalities after therapeutic external radiation has been published lately [3].

The incidence of abnormal TSH level in the present study after radiotherapy

Conclusions

We suggest that the routine evaluation of thyroid function is important in patients, who have been treated with radiotherapy, and whose treatment portals have included a large part of the thyroid gland. A reduction in the thyroid function often occurs without any significant symptoms, and often remains clinically undetected. The incidence of thyroid dysfunction may be decreased by reducing the field size or the irradiated volume of the thyroid gland and by using modern radiation equipment with

Acknowledgements

We thank Pirjo Halonen, M.Sc., for reviewing the statistics. Source of financial support: none.

References (11)

R.J Black et al.
Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990
Eur J Cancer
(1997)
S.L Hancock et al.
Thyroid abnormalities after therapeutic external radiation
Int J Radiat Oncol Biol Phys
(1995)
K Nishiyama et al.
A prospective analysis of subacute thyroid dysfunction after neck irradiation
Int J Radiat Oncol Biol Phys
(1996)
R Tell et al.
Hypothyroidism after external radiotherapy for head and neck cancer
Int J Radiat Oncol Biol Phys
(1997)
M.J Donnelly et al.
Thyroid dysfunction following combined therapy for laryngeal carcinoma
Clin Otolaryngol
(1995)

There are more references available in the full text version of this article.

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Citation Excerpt :
Most previous studies on RHT focused on head and neck cancers or Hodgkin lymphoma. The incidence of RHT has been shown to be as high as 30% to 50% after RT.7-13 As a result, the National Comprehensive Cancer Network guidelines for head and neck cancers and Hodgkin lymphoma recommend routine assessment of thyroid function after RT. However, large differences exist in the RT field, RT dose, and treatment modalities between patients with head and neck cancers or lymphomas and patients with breast cancer.
Our objective was to assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiation therapy (RT) in patients with breast cancer.
Eligible patients with breast cancer who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times after RT. RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT.
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The incidence of RHT was high in patients with breast cancer. Thyroid function test should be started no later than 6 months after RT. We recommend that the Dmean of the thyroid should be kept lower than 21 Gy for hypofractionated RT.
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To investigate the rate and risk factors for developing hypothyroidism (HT) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).
A total of 135 consecutive patients treated with IMRT for NPC were prospectively evaluated during a median follow up of 34.1 months. Serum thyroid function assessments before and after IMRT were periodically monitored. To identify risk factors for HT occurrence, univariate and multivariate Cox regression analyses were performed.
Thirty-nine patients (28.9%) developed primary HT. The 2- and 3-year incidences of primary HT were 29.6% and 43.9%, respectively. The median clinical latency for primary HT was 15.1 months (3.2–33.8 months). No cases of central HT were observed. Univariate and multivariate analyses revealed that the risk increased with younger age and decreased with higher pretreatment thyroid volume. Patients with thyroid mean dose ≥45 Gy had a 4.9 times increased risk of HT than those receiving lower mean dose. Alternatively, the thyroid V45 below 0.5 and V50 below 0.35 were found to significantly lower the incidence rate of HT.
The incidence of primary HT after IMRT for NPC continued to increase with time. The thyroid mean dose constraint was approximately 45 Gy. We recommended plan optimization objectives to reduce thyroid V45 to 0.5 and V50 to 0.35.
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A glândula tiroideia é particularmente sensível aos efeitos da exposição a radiação e a disfunção tiroideia constitui uma consequência frequente e muitas vezes subestimada. As sequelas da irradiação tiroideia direta incluem: hipotiroidismo, tiroidite, doença de Graves, adenomas, bócio multinodular e carcinoma. O hipotiroidismo primário constitui a manifestação mais frequente dos efeitos da radiação sobre a tiroide. A sua irradiação determina um efeito carcinogénico importante nas crianças e aparentemente limitado nos adultos. Embora não seja consensual, muitos estudos verificaram que o risco de hipotiroidismo aumenta proporcionalmente à dose administrada, enquanto o risco de desenvolver uma neoplasia maligna é máximo com doses relativamente baixas, declinando a partir de doses mais elevadas. Atendendo ao longo período entre a RT e o aparecimento de lesões neoplásicas malignas, torna-se fundamental um follow-up a longo prazo dos sobreviventes de cancro na infância. Doentes submetidos a RT cervical por qualquer causa devem manter vigilância prolongada, uma vez que as consequências funcionais da RT cervical sobre a tiroide também se podem manifestar tardiamente. Uma vez que os doentes irradiados apresentam um risco elevado de desenvolver complicações subsequentes, deverá ser definido um plano de vigilância específico das mesmas e a instituição atempada de terapêutica, caso se justifique.
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Hypothyroidism after radiotherapy for laryngeal cancer

Abstract

Introduction

Section snippets

Subjects

Radiotherapy

Results

Discussion

Conclusions

Acknowledgements

Eur J Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Thyroid dysfunction following combined therapy for laryngeal carcinoma

Clin Otolaryngol