ESPE Yearbook of Paediatric Endocrinology

Brief summary: This study used a Delphi approach to generate consensus guidelines for screening of asymptomatic childhood cancer survivors for thyroid dysfunction and recommendations for the management of abnormal thyroid screening results.

A Delphi panel of 40 clinical experts (oncologists, endocrinologists, and primary care physicians) participated in three rounds of anonymous questionnaires, formatted as clinical scenarios. Consensus was defined by agreement by at least 90% of the panelists. Disagreement was defined as <70% panelist agreement.

Panelists reached consensus that childhood cancer survivors treated with radiation, including neck, total body, whole brain or hypothalamic–pituitary axis (HPA), and therapeutic meta-iodobenzylguanidine (MIBG), should undergo lifelong screening by annual TSH and free T4 measurements, starting within one year after the completion of treatment (98% agreement). Panelists disagreed on long-term screening for thyroid dysfunction in childhood cancer survivors with acute thyroid injury after immunotherapy (31%–50%). There was also disagreement on indications for brain (17%–43%) or thyroid (50%–65%) imaging, laboratory tests to assess HPA function (29%–75%), and the appropriate TSH cut-off to start treatment for subclinical hypothyroidism. Lack of evidence was the most frequent reason for not recommending additional testing or medication. Panelists’ opinions did not vary by geographic area, specialty, or specific clinical experience.

Thyroid function abnormalities, such as primary or central hypothyroidism and thyroid nodules, are common sequelae of childhood cancer treatment. Evidence is still scarce for the management of thyroid dysfunction among asymptomatic childhood cancer survivors. As expected, panelists agreed that thyroid dysfunction is most associated with the different modalities of radiotherapy involving irradiation of the neck and/or HPA. Conversely, the use of traditional cytotoxic chemotherapy only should not prompt screening for thyroid dysfunction, even if alkylating agents and bleomycin have been associated with hypothyroidism. As this study demonstrates, thyroid ultrasound is still controversial as a screening measure in asymptomatic childhood cancer survivors without suggestive clinical findings (e.g. a thyroid lump on neck palpation). On the other hand, ultrasound is a noninvasive diagnostic tool commonly used to evaluate survivors with biochemical thyroid abnormalities or those with a high risk of thyroid nodules (i.e. patients treated with neck or total body irradiation).

Interestingly, this study, which assessed expert physicians, found that consensus was lacking for the screening of individuals treated with immunomodulatory agents. Growing evidence links immunomodulatory agents to acute thyroiditis during therapy, which can clinically manifest as hyper or hypothyroidism (1). Both tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors have been reported to cause acute thyroid toxicity. TKI cause thyroid disruption related to vascular damage and disruption of the transport and metabolism of thyroid hormones. Early autoantibody positivity and elevated serum cytokines are associated with immune-related thyroid dysfunction during treatment with immune-checkpoint inhibitors. There is recent data that TKI-induced hypothyroidism persists after treatment. However, there is little evidence on the clinical course of thyroiditis induced by immune-checkpoint inhibitors.

Reference: 1. Jannin A, Penel N, Ladsous M, et al. Tyrosine kinase inhibitors and immune checkpoint inhibitors-induced thyroid disorders. Crit Rev Oncol Hematol. 2019; 141:23–35.