Effects of Antitumor Chemotherapy and Radiation Therapy on Thyroid Gland in Hodgkin’s Lymphoma Patients during Follow-up Observations

S.V. Shakhtarina, A.A. Danilenko, V.V. Pavlov, V.S. Parshin, O.V. Timokhina, G.A. Simakova

Medical Radiological Research Center under the Ministry of Health of the Russian Federation, 4 Koroleva str., Obninsk, Kaluga Oblast, Russian Federation, 249036

For correspondence: A.A. Danilenko, PhD, Senior scientific worker 4 Koroleva str., Obninsk, Kaluga Oblast, Russian Federation, 249036; Tel: +7(48439)9-31-01; e-mail: danilenko@mrrc.obninsk.ru

For citation: Shakhtarina S.V., Danilenko A.A., Pavlov V.V., Parshin V.S., Timokhina O.V., Simakova G.A. Effects of Antitumor Chemotherapy and Radiation Therapy on Thyroid Gland in Hodgkin’s Lymphoma Patients during Follow-up Observations. Klin. Onkogematol. 2014; 7(4): 533–539 (In Russ.).


This paper presents data on Hodgkin’s lymphoma (HL) patients who developed a second tumor — thyroid cancer — after therapy. The cohort includes 1789 patients (1177 women and 612 men) who were treated between 1968 and 1997 in the Medical Radiological Research Center, Obninsk (Russia) with radiotherapy alone or chemo-radiotherapy involving irradiation of supradiaphragmatic nodal areas (including cervico-supraclavicular lymph nodes) and spleen with the total tumor dose (TTD) up to 40 Gy. The total observation period was 18949 person/years. Thyroid cancer was registered in 9 women and 1 man. The expected (standardized) incidence of thyroid cancer was calculated with regard for gender, age, and in accordance with incidence rates for Russian population. For the cohort of 1177 women treated for HL (with 13 032 person/year follow up) the expected incidence was 1.15, while the actual incidence was 9 cases. The relative risk was 7.81 (95% CI: 3.47–13.9). For the cohort of 612 men (with 5917 person/year follow up) the expected incidence of thyroid cancer was 0.11, while the actual one was 1 case. The relative risk was 9.09 (95% CI: 0–0.44). Structural (sonographic, morphological) and functional changes in thyroid gland were studied in 335 HL patients treated with radiotherapy alone or chemo-radiotherapy (including irradiation of cervico-supraclavicular lymph nodes) at TTD of 40, 30, 20 Gy who received therapy between 1970 and 2010 and remained in continuous remission throughout the follow-up period. Nodular masses were found in thyroids of 72 (21.5 %) patients; decreased echogenity of thyroid tissue in 36 (10.7 %) patients; cysts in 21 (6.2 %); and thyroid cancer in 3 (0.9 %) patients. Functional changes were only seen in thyroids of patients (n = 316) who were given cervico-supraclavicular irradiation. Subclinical hypotheriosis was found in 72 (22.8 %), and the clinical one in 5 (1.6 %) patients; elevated antibody levels were found in 80 (25.3 %) patients. Decreased incidence of structural and functional thyroid changes was seen (p < 0.05) with decreased TTD during irradiation of the cervico-supraclavicular area.

Keywords: Hodgkin’s lymphoma, thyroid gland, hypothyroidism, thyroid cancer.

Accepted: September 10, 2014

Read in PDF (RUS)pdficon


  1. Atahan I.L., Yildiz F., Ozyar E., Uzal D. Thyroid dysfunction in children receiving neck irradiation for Hodgkin’s disease. Radiat. Med. 1998; 16(5): 359–61.
  2. Hancock S.L., McDougall I.R., Constine L.S. Thyroid abnormalities after therapeutic external radiation. Int. J. Radiat. Oncol. Biol. Phys. 1995; 31: 1165–70.
  3. Healy J.C., Shafford E.A., Reznek R.H. et al. Sonographic abnormalities of the thyroid gland following radiotherapy in survivors of childhood Hodgkin’s disease. Br. J. Radiol. 1996; 69: 617–23.
  4. Шахтарина С.В., Павлов В.В., Даниленко А.А., Афанасова Н.В. Лечение больных лимфомой Ходжкина с локальными стадиями I, II, IE, IIE: опыт Медицинского радиологического научного центра. Онкогематология. 2007; 4: 36–46.  [Shakhtarina S.V., Pavlov V.V., Danilenko A.A., Afanasova N.V. Management of patients with Hodgkin’s lymphoma with local stages I, II, IE, IIE: experience of the Medical radiological scientific center. Onkogematologiya. 2007; 4: 36–46. (In Russ.)]
  5. Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразо- ваний в России и странах СНГ в 2008. Вестник РОНЦ им. Н.Н. Блохина РАМН. 2010; 21(2, прил. 1): 60–1. [Davydov M.I., Aksel’ E.M. Statistics of malignancies in Russia and CIS countries in 2008. Vestnik RONTs im. N.N. Blokhina RAMN. 2010; 21(2, suppl. 1): 60–1. (In Russ.)]
  6. Vandenbroucke J.P. A shortcut method for calculating the 95 per cent confidence interval of the standardized mortality ratio. Am. J. Epidemiol. 1982; 115: 303–4.
  7. Hancock S.L., Hoppe R.T. Complications of treatment and causes of mortality after Hodgkin’s disease. Semin. Radiat. Oncol. 1996: 6(3): 225–42.
  8. Tucker M.A., Jones P.H., Boice J.D. Jr. et al. Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group. Cancer Res. 1991; 51: 2885–8.
  9. Sklar C., Whitton J., Mertens A. et al. Abnormalities of the thyroid in survivals of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab. 2000; 85: 3227–32.
  10. Bethge W., Guggenberger D., Bamberg M. et al. Thyroid toxicity of treatment for Hodgkin’s disease. Ann. Hematol. 2000; 79(3): 114–8.
  11. Балашов А.Т., Мясников А.А. Заболевания щитовидной железы при комплексном лечении лимфогранулематоза. Проблемы эндокринологии. 1998; 2: 19–21. [Balashov A.T., Myasnikov A.A. Diseases of the thyroid gland in complex treatment of lymphogranulomatosis. Problemy endokrinologii. 1998; 2: 19–21. (In Russ.)]
  12. Van Santen H.M., Vulsma T., Dijkgraaf M.G. et al. No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adults survivors of childhood cancer. J. Clin. Endocrinol. Metabol. 2003; 88: 3657–63.
  13. Hancock S.L., Cox R.S., McDougall I.R. Thyroid diseases after treatment of Hodgkin’s disease. N. Engl. J. Med. 1991; 325: 559–605.
  14. Loeffler M.L., Tarbell N.J., Garber J.R., Mauch P. The development of Grave’s disease following radiation therapy in Hodgkin’s disease. Int. J. Radiat. Oncol. Biol. Phys. 1988; 14: 175–8.
  15. Mortimer R.H., Hill G.E., Galligan J.P. et al. Hypothyroidism and Grave’s disease after mantle irradiation: a follow-up study. Aust. N. Z. J. Med. 1986; 16: 347–51.