ﻘﺤﺗ ﻪﻟﺎﻘﻣ ﻴ
ﻘ ﻲ
ﻲﭘﺍﺮﺗﻮﻳﺩﺍﺭ ﺯﺍ ﻲﺷﺎﻧ ﻱﺪﻴﺋﻭﺮﻴﺗﻮﭙﻴﻫ ﻥﺍﺰﻴﻣ ﻲﺳﺭﺮﺑ
يرادﺮﺳ ﺮﻬﭼﻮﻨﻣ ﻲﻧﺎﺨﻤﻳﺮﻛ ﺪﻴﻌﺳ ،1
ﻲﭽﻏﻼﻛ ﺎﺗ ﻲﺑ ،1
*
ﻲﻤﺷﺎﻫ رﺎﮔزﻮﻣآ زﺎﻧﺮﻓ ،1
نﺎﻴﻤﻇﺎﻛ ﻲﻠﻋ ،1 1
هﺪﻴﻜﭼ
ا ﺪﻫ ا ف ﺘـﺴﻛا ﻲﭘاﺮﺗﻮـﻳدار ﺖـﺤﺗ ﻪﻛ ﺮﺴﻧﺎﻛ ﻪﺑ ﻼﺘﺒﻣ نارﺎﻤﻴﺑ رد ﻢﻴﺳﺪﻴﺋوﺮﻴﺗﻮﭙﻴﻫ ﺲﻧاﺪﻴﺴﻧا ناﺰﻴﻣ ﻪﻌﻟﺎﻄﻣ ﻦﻳا رد: لﺎﻧﺮ
ﺪﺷ ﻲﺑﺎﻳزرا ﺪﺷ ﻲﻣ ﻞﻣﺎﺷ ار ﺪﻴﺋوﺮﻴﺗ ﻪﻴﺣﺎﻧ ﻲﭘاﺮﺗﻮﻳدار ﺪﻠﻴﻓ و ﺪﻧدﻮﺑ .
ﺎﻬﺷور : ﻞﻳروآ هﺎﻣ زا ﻪﻛ ﺮﮕﻧ هﺪﻨﻳآ ﻪﻌﻟﺎﻄﻣ ﻦﻳا رد 2004
ﺮﺒﻣﺎﺳد ﺎﺗ 2005 ﺪـﺷ مﺎﺠﻧا
، يﺎﻫﺮـﺴﻧﺎﻛ ﻪـﺑ ﻼﺘـﺒﻣ نارﺎـﻤﻴﺑ
ﻲﭘاﺮﺗﻮﻳدار مﺎﺠﻧا ﺖﻬﺟ ﺮﺴﻧﺎﻛﻮﺘﻴﺘﺴﻧا يژﻮﻟﻮﻜﻧا ﻲﭘاﺮﺗﻮﻳدار ﺶﺨﺑ ﻪﺑ ﻪﻛ ندﺮﮔ وﺮﺳ ﺎﻳ و نﺎﺘﺴﭘ ﺎﺟرا
و ﺪـﻧدﻮﺑ هﺪﺷ ع
ﻲﭘاﺮﺗﻮﻳدار ﺪﻠﻴﻓ ﺪﻴﺋوﺮﻴﺗ ﻪﻴﺣﺎﻧ
ﺪﺷ ﻲﻣ ﻞﻣﺎﺷ ﻢﻫ ار ﺪﺷ ﻪﺘﻓﺮﮔ راﺮﻗ ﻲﺳرﺮﺑ ﺖﺤﺗ
. ـﺴﺗ نﺎـﻣز رد يﺪـﻴﺋوﺮﻴﺗ يﺎـﻫ ﺖ
و نﺎﻣرد عوﺮﺷ 3
و 6 هﺎﻣ و ﺪﺷ ﻲﺑﺎﻳزرا ﻲﭘاﺮﺗﻮﻳدار مﺎﻤﺗا زا ﺪﻌﺑ .
ﺎﻫ ﻪﺘﻓﺎﻳ 34: ﺪﻨﺘﻓﺮﮔ راﺮﻗ ﻲﺑﺎﻳزرا ﺖﺤﺗ رﺎﻤﻴﺑ ﻦﻴﮕﻧﺎﻴﻣ ﻦﺳ ﻪﻛ
53 لﺎﺳ ) 83 - 22 لﺎﺳ ( دﻮﺑ . 18 و نز رﺎﻤﻴﺑ 16 رﺎـﻤﻴﺑ
ﺪﻧدﻮﺑ دﺮﻣ . ا ﻲﺘﻓﺎﻳرد زود ز
) 7400CGY - 5000 ( ﻦﻴﮕﻧﺎﻴﻣ ﺎﺑ 6000CGY
دﻮﺑ . رد ﺪﻴﺋوﺮﻴﺗ ﻲﻨﻴﻟﺎﺑ ﻪﻨﻳﺎﻌﻣ ﺮﺷ نﺎﻣز
عو
ﻳ نارﺎﻤﻴﺑ مﺎﻤﺗ و لﺎﻣﺮﻧ نﺎﻣرد ﺪﻧدﻮﺑ ﺪﻴﺋوﺮﻴﺗ ﻮ
. ﺖﺴﺗ زا ﺪـﻌﺑ ﻪﻛ ﺪﺷ يﺮﻴﮔ هزاﺪﻧا نﺎﻣرد ياﺪﺘﺑا ردTSH
3 و 6 هﺎـﻣ
ﺖﺷاد يا ﻪﻈﺣﻼﻣ ﻞﺑﺎﻗ توﺎﻔﺗ .
ﻧ ﻪﺠﻴﺘ يﺮﻴﮔ ﺞﻳﺎﺘﻧ سﺎﺳا ﺮﺑ: هﺪﻣا ﺖﺳد ﻪﺑ
ﻢﺋﻼﻋ نارﺎﻤﻴﺑ زا ماﺪﻛ ﭻﻴﻫ ﻮﭙﻴﻫ
ﺪـﻌﺑ هﺎـﻣ ﺶﺷ تﺪﻣ لﻮﻃ رد يﺪﻴﺋوﺮﻴﺗ
زا مﺎﻤﺗا نﺎﻣز تﺪﻣ ﻪﻛ ﺪﺳر ﻲﻣ ﺮﻈﻧ ﻪﺑ و ﺪﻧدﺮﻜﻧ اﺪﻴﭘ نﺎﻣرد 6
نارﺎـﻤﻴﺑ رد يﺪﻴﺋوﺮﻴﺗﻮﭙﻴﻫ ﺖﻴﻌﺿو ﻲﺑﺎﻳزرا ﺖﻬﺟ هﺎﻣ
ﻧ و ﺪﺷﺎﺑ دوز يﺮﻴﮕﻴﭘ ﻪﺑ زﺎﻴ
ﻞﻗاﺪﺣ 12 ﺎﺠﻧآ زا و دراد هﺎﻣ ﻲﮔﺪﻧز يا ﻪﻈﺣﻼﻣ ﻞﺑﺎﻗ رﻮﻄﺑ ﻦﻴﺴﻛوﺮﻴﺗ ندﺮﻛ ﻪﻓﺎﺿا ﻪﻛ
تﺎﻌﻟﺎﻄﻣ مﺎﺠﻧا داد ﺪﻫاﻮﺧ ﺮﻴﻴﻐﺗ ار يﺪﻴﺋوﺮﻴﺗﻮﭙﻴﻫ نارﺎﻤﻴﺑ ﻲﻠﻴﻤﻜﺗ ﻲﻨﻴﻟﺎﺑ
ﺪﺷﺎﺑ ﻲﻣ يروﺮﺿ .
تﺎﻤﻠﻛ ﺪﻴﻠﻛ :ي ﻢﻴﺳﺪﻴﺋوﺮﻴﺗﻮﭙﻴﻫ ،
ﺪﻴﻳوﺮﻴﺗ يدﺮﻛ رﺎﻛ يﺎﻫ ﺖﺴﺗ ،
ﻲﭘاﺮﺗﻮﻳدار
1 . ،يژﻮﻟﻮﻜﻧا ﻲﭘاﺮﺗﻮﻳدار ﺶﺨﺑ
مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﺮﺴﻧﺎﻛ ﻮﺘﻴﺘﺴﻧا ناﺮﻬﺗ ﻲﻜﺷﺰﭘ
* لﻮﺌﺴﻣ هﺪﻨﺴﻳﻮﻧ :
ﻲﭽﻏﻼﻛ ﺎﺗ ﻲﺑ ﺮﺘﻛد
ﻮﺘﻴﺘﺴﻧا ،يژﻮﻟﻮﻜﻧا ﻲﭘاﺮﺗﻮﻳدار ﺶﺨﺑ ناﺮﻬﺗ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﺮﺴﻧﺎﻛ
ﻦﻔﻠﺗ : 02166581633
ﻲﻜﻴﻧوﺮﺘﻜﻟا ﺖﺴﭘ :
30
BCCR
Basic &Clinical Cancer Research
ORIGINAL ARTICLE
Incide Incide Incide
Incidence of nce of nce of nce of Hypothyroidism Hypothyroidism Hypothyroidism a Hypothyroidism a after a fter fter fter External Radiation t
External Radiation t External Radiation t
External Radiation to Thyroid Region o Thyroid Region o Thyroid Region o Thyroid Region
M. Sardari M.D1,S.Karimkhani M.D1, B. kalaghchi M.D*1 F. Amouzegar hashemi M.D1, A.Kazemian M.D1
A B S T R A C T
Background: In this study we evaluated the incidence of hypothyroidism in patients who received external beam radiation due to cancer, when radiation portals included thyroid gland.
Methods: This prospective study was conducted from April 2004 to December 2005 among patients with head and neck or breast malignancies who referred to Radiation Oncology Department of Cancer Institute, Imam Khomeini hospital, treated with external beam radiotherapy. All patients received radiation to the thyroid gland. Thyroid function was tested at the beginning of treatment, 3 months and 6 months after the completion of radiotherapy.
Results: In all 34 patients were included in the study. The median age of patients was 53 years. Eighteen patients were female and 16 were male. All patients received external radiotherapy. They received radiation ranging from 5000 cGY (14 patients 41.2%) to 7400 cGY (1 patient 2.9%) with median of 6000 cGY. Physical examination of thyroid at the beginning of treatment was normal and all of the patients were euthyroid . The results from TSH test showed significant difference at baseline, after 3 and 6 months follow-up (P
= 0.001)
Conclusion: The findings indicated that none of the patients developed hypothyroidism in a period of six months after completion of radiotherapy.
However, it seems that 6 months fallow-up is early for judgment about evaluation of patients for hypothyroidism state and it needs further follow up for minimum of 12 months.
Keywords :Hypothyroidism, Thyroid Function Test, Radiotherapy
1. Radiation Oncology Department, Cancer Institute, Tehran University of Medical Sciences
*Corresponding author:
Radiation Oncology Department , Cancer Research Center, Cancer institute, Tehran University of medical sciences
Tel: +98 21 66581633 Email: [email protected]
Date Receive: 07.01.2010 Date Acceptance: 07.03.2010
31
BCCR
INTRODUCTION
arcinoma of head and neck is the 5th most common malignancy worldwide (1) probably because of increased consumption of alcohol and smoking.
Surgery, radiotherapy with or without chemotherapy is the mainstream of management
of such malignancies, used either alone or in combination.
In treatment of head and neck cancers target volume of irradiation always includes whole volume of thyroid gland and in breast cancer supraclavicular field always contains a part of thyroid gland.
Thyroid gland is one of the major human’s endocrine glands with the average weight of 12- 20 grams (2). Although adult thyroid cells are relatively radio-resistant due to their low
proliferative index, hypo function of thyroid is a known side effect of radiotherapy to the head and neck malignancies over 40 years(3).
After external beam radiotherapy to the neck the documented incidence of sub-clinical hypothyroidism varies widely from 0.3% to 44%
(4). Addition of surgery to the neck region vastly increases the incidence of hypothyroidism, but addition of chemotherapy probably has little or no effect (5).
Hypothyroidism has a significant impact on the quality of life. Thus, assessment of thyroid gland function should be included as part of routine follow-up of patients who undergo radiation of thyroid gland region, prior to expression of frank clinical hypothyroidism, especially in children and senile cases due to their greater morbidity.
This study assessed the risk of developing hypothyroidism in head and neck and breast malignancies, where radiation portals included thyroid gland.
This prospective study was conducted from April 2004 to December 2005 among a sample of head and neck or breast malignancies with confirmed histopathological diagnosis. Patients referred to Radiation Oncology Department of Cancer Institute, Imam Khomeini hospital and treated with external beam radiotherapy. Before the initiation of the radiotherapy all patients underwent detailed history and physical examination including thyroid gland examination and measurement of T3RU, T4 and TSH. All tests were carried out in the same laboratory. Patients
with thyroid metastasis, positive history of thyroid disease and thyroid surgery were excluded.
All patients treated with CO 60 with radiation to the primary site and neck including the thyroid gland. Total dose of radiotherapy ranged from 5000 cGY to 7400 cGY in 20 to 37 fractions which was delivered by parallel opposed, mantel , anterior and posterior fields. Those patients who had TSH serum level higher than 4.5 m U/I were considered as sub-clinical hypothyroidism state.
Thyroid function tests were repeated at 3 and 6 months follow-up.
RESULTS
In all 34 patients were included in the study. The median age of patients was 53 years, ranging from 22 to 83. Eighteen patients were female and 16 were male.
Patients histopathological characteristics were:
adenoid cystic carcinoma (n = 2, 5.8%), adenocarcinoma (n = 5, 14.7%), basal cell carcinoma (n = 1, 2.9%), invasive ductal carcinoma (n = 7, 20.6%), mucinus carcinoma (n
= 1, 2.9%%), poorly differentiated carcinoma (n = 1, 2.9%), sarcoma (n =1, 2.9%), squamous cell carcinoma (n = 12, 35.3%) and un differentiated carcinoma (n =4, 11.8%).
Sites of primary tumor were: breast (n = 13, 38.2%), hypo pharynx (n = 2, 5.9%), larynx (n = 8, 23.5%), nasopharynx (n = 2, 5.9%), neck (n = 4, 11.8%), parotid (n = 1, 2.9%), skin (n = 2, 5.9%), sub mandibular gland (n = 1, 2.9%) and tongue (n = 1, 2.9%).
All of patients received external radiotherapy.
C
METHODS
They received radiation ranging from 5000 cGY (14 patients 41.2%) to 7400 cGY (1patient 2.9%) with median of 6000 cGY. The number of fractions was from 20 to 37 fractions with median of 29. Dose per fraction was 200 cGY in 23 patients (67.6%) and 250 CGY in 8 patients (23.5%) with median of 200 CGY. They treated with different fields such as: Mantel in 3 patients (8.8%), anteroposterior in 3 patients (8.8%), anterior in 9 patients (26.5%), bilateral in 9 patients (26.5%), and lateral in 16 patients(47.1%).
Physical examination of thyroid at the beginning of treatment was normal and all of the patients were euthyroid. According to our data: T3RUP test which was done at the beginning of radiotherapy , after 3 and 6 months did not show any significant difference ( P = 0.37).
Also T4 test which was done at the beginning of radiotherapy, after 3 and 6 months did not show any significant difference(P = 0.50). However, the results from TSH test at the beginning of radiotherapy (0.5912) , after 3 months (0.7481) and 6 months (0.7908) follow-up showed significant difference (P = 0.001). There was no sign of hypothyroid state because TSH in none of patients was higher than 4.5 (cutting edge).
DISCUSSION
In addition to surgical intervention, radiotherapy is the only known curative management of patients with head and neck malignancies. It may be used either alone or in combination with surgery and /or radiotherapy.
In 1961 Felix et al. (3) first reported a case of hypothyroidism six year after treatment with external radiotherapy in a patient with laryngeal carcinoma. Since then, several other investigators have reported the occurrence of hypothyroidism in patients who have received radiotherapy in the neck region. Despite these reports, tests for thyroid functions are not yet included in the follow up protocols of patients with head and neck malignancies(6).
There is a general agreement that hypothyroidism
is a much more common complication following radio therapeutic management of head and neck cancers with a frequency ranging from 43 to 66%
and sometimes up to 80% and more often depending upon duration of the follow-up(5,6,7).
Since radiation-induced hypothyroidism is a late effect, it is expected that as time passes the incidence will increase and some patients with sub-clinical hypothyroidism will progress to clinical hypothyroidism.
Dose of radiation required for producing hypothyroidism is also confusing. Degrot (8) and Hancock et al. (9) suggested that radiation doses in range of 3000 to 8000 rad are required to produce hypothyroidism. At the same time Hancock et al. reviewed 1787 patients of Hodgkin’s disease treated with Mantle field irradiation at the dose of 3500-4500 cGY and estimated a 43% actuarial risk of developing hypothyroidism in more than 50% of cases at a long time follow-up.
The way in which radiotherapy produces hypothyroidism is also incompletely understood.
This may be due to direct follicular destruction or prevention of cell division or vascular damage to the thyroid gland or immunologically mediated damage to the thyroid gland or a various combinations of factors. Histological examination of thyroid gland after external irradiation has documented follicular cell damage following doses as low as 225 cGY (10). Most common signs and symptoms of hypothyroidism e.g.
depression, lethargy, skin changes, constipation, weight gain (> 10% of original body weight) etc.
are ill defined and can be easily overlooked in cancer patients. Since there is a high rate of co- morbidity in these patients and the disease and its treatment may have nutritional, physical and psychological consequences, there is always a risk for masking the clinical features of hypothyroidism. Thus, clinical examination of the cancer patients for hypothyroidism alone is not enough.
We have found no effect of age, gender, cancer site, neck node status or radiation dose on the incidence of hypothyroidism. Similar findings were reported by other investigators (11, 12).
In conclusion, the findings from this study indicated that none of the patients developed
33
hypothyroidism in a period of six months after completion of radiotherapy. However, it seems that 6 months fallow-up is early for judgment about evaluation of patients for hypothyroidism state and it needs further follow up for minimum of 12 months.
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