BACKGROUND
External beam radiation therapy (EBR) is an effective treatment for several types of cancer. In particular, two cancers that often present in children, Hodgkin’s lymphoma and medulloblastoma/primitive neuroectodermal tumors (PNET), respond very well to EBR. The field of EBR in these cases includes the front of the neck where the thyroid gland is located. Because of this, the thyroid is frequently in the field of radiation and the EBR can damage the thyroid and cause it to fail, causing hypothyroidism. Indeed, hypothyroidism is a potential long-term complication of EBR therapy for certain cancers in children, adolescent, and young adults, specifically head, neck, brain, or spinal radiation.

While hypothyroidism can be treated with thyroid hormone replacement, prevention of thyroid damage during EBR would be a better option. Turning off the thyroid by treating with thyroid hormone to suppress the level of thyroid stimulating hormone (TSH) may be one way to prevent long-term damage to the thyroid by EBR. This study examined whether high dose thyroid hormone therpay taken before and during radiation could be protective in reducing the subsequent risk of hypothyroidism in such patients.

THE FULL ARTICLE TITLE
Massimino et al Long-term results of suppressing thyroidstimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study. Front. Med. 15, 101–107 (2021). https://doi.org/10.1007/ s11684-020-0752-2

SUMMARY OF THE STUDY
The study patients were children, adolescents, and young adults (age 1 to 21 years) that were treated with EBR involving the head or neck in a children’s cancer cancer in Milan, Italy, between January, 1998 and February, 2001.

The cancer diagnosis of patients was medulloblastoma/ PNET or Hodgkin’s lymphoma. Starting 14 days before EBR, all patients were prescribed levothyroxine 1 to 2 μg/kg daily in the morning on an empty stomach (1 or more hours before breakfast) and the dose was adjusted every three days with the goal of achieving a TSH level < 0.3 μIU/L (below normal). The levothyroxine was continued during the entire course of radiation treatment.

A total of 37 patients with medulloblastoma/PNET and 14 patients with Hodgkins lymphoma were treated with thyroid hormone during their EBR. The target TSH levels of < 0.3 μIU/L during EBR were achieved in 32% (7/22) of the medulloblastoma/PNET patients and 57% (8/14) of the Hodgkin’s lymphoma patients. At last reported follow-up, the percentage of patients with TSH values at target during radiotherapy who were diagnosed with hypothyroidism was 14% (1/7) of the medulloblastoma/ PNET patients and 25% (2/8) Hodgkin’s lymphoma patients. The percentage of patients with TSH values that were not at target during radiotherapy who were diagnosed with hypothyroidism at follow up was: 60% (9/15) of the medulloblastoma/PNET patients and 100% (6/6) Hodgkin’s lymphoma patients.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study suggested that suppressing TSH levels with thyroid hormone treatment in children during EBR may decrease the risk of developing hypothyroidism. Importantly, thyroid hormone treatment that failed to suppress TSH levels did not appear to be protective. While promising, further research is needed to definitively determine whether thyroid hormone treatment before and during radiotherapy may be beneficial in reducing subsequent development of underactive thyroid.

— Anna M. Sawka, MD, PhD

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