Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism?

Background:After exposure to cranial radiotherapy (cRT), hypothalamic-pituitary (HP) disorders are frequently observed in childhood brain tumor survivors (CBTS). It has been reported that the time to develop HP disorders varies, with a short lag time for GH deficiency (GHD) especially when compared to central hypothyroidism (CeH). (1, 2) In clinical practice, however, a decline in FT4 concentration in CBTS is frequently observed prior to or shortly after the diagnosis GHD. Declining FT4 concentrations with (inadequate) normallow TSH concentrations in CBTS may indicate radiation damage to TSH secreting cells. Hypothesis: The decline in FT4 concentration, often observed prior to or shortly after the diagnosis of GHD in CBTS who received cRT, can be validated in a large nationwide cohort. Methods: Inclusion criteria for the nationwide cohort study were: patients with a brain tumor diagnosed between 2002 and 2012, surviving >2 years after diagnosis and treated with cRT. All CBTS who developed GHD were included and CBTS with primary hypothyroidism were excluded. GHD was defined as an abnormal peak value of GH in one or two GH stimulation tests. The paired sample T-test was used to compare median FT4 concentrations at start of tumor treatment versus the median FT4 concentrations at diagnosis of GHD versus the median first FT4 concentrations after starting GH treatment. Results:Seventy-three CBTS had been diagnosed with GHD and were included for this study. Twenty-one CBTS (28.8%) were diagnosed with CeH prior to the diagnosis of GHD and therefore received treatment with thyroxine (T4). In 52 of the 73 CBTS (71.2%) FT4 concentrations were longitudinally analysed. GHD was diagnosed after a median follow-up time of 2.4yr after tumor diagnosis. The total median dose of cRT was 54Gy (range 15-72Gy). Median FT4 concentrations declined from 15.4 pmol/l after the start of tumor treatment to 14.0 pmol/l (P