Changes in thyroid function in survivors of brain tumours followed longitudinally
HK Gleeson, L Smethurst & SM Shalet
The hypothalamic-pituitary-thyroid axis can be affected following therapy for brain tumours. Primary thyroid damage is frequent following craniospinal irradiation(CSI). Central hypothyroidism is less commonly reported following cranial irradiation(CI), however, some investigators have argued it is underdiagnosed and may be more prevalent than growth hormone deficiency(GHD). Utilising thyroid function tests(TFT) for the diagnosis of central hypothyroidism is notoriously difficult with most clinicians relying on basal TSH and T4 measurements. The diagnosis is 'made' if T4 falls or is below or in the lower third of the normal range. To investigate whether in a cohort of brain tumour survivors with radiation-induced GHD the T4 falls with time following irradiation we have examined serial TFT.
68 patients (30CI,38CSI) were identified with two serial TFT (TSH(mU/L),total T4(tT4)(nmol/L)) results at different time points, 26 of these patients had three serial TFT results. All TFT were estimated with the patient off thyroxine replacement. TFT from a median of 5(2-7)(range)years (n=68), 9(4-10)years (n=58) and 20(11-33)years (n=36) after irradiation were recorded.
5vs9years- In all, CI and CSI patients TSH and tT4 were unchanged between these two time points- All:2.1vs2.0mU/L;98vs97nmol/L,respectively; CI:1.9vs1.9mU/L,95vs89nmol/L; CSI:2.2vs2.3mU/L,99vs101nmol/L.
5vs20years- In all patients TSH and tT4 fell, however, after CI alone TSH and tT4 were unchanged but after CSI TSH was unchanged but tT4 fell between these two time points- All:3.0vs2.5mU/L(p=0.05),101vs93nmol/L(p=0.02); CI:2.4vs2.2mU/L,98vs94nmol/L; CSI:3.1vs2.7mU/L,109vs90nmol/L(p=0.01).
5vs9vs20years- In all patients and after CI alone TSH and tT4 was unchanged however after CSI TSH was unchanged but tT4 fell between these three time points- All:2.9vs2.3vs2.5mU/L,101vs101vs94.5nmol/L; CI:2.6vs2.1vs2.5mU/L,95vs101vs94nmol/L; CSI:2.9vs2.5vs2.5mU/L,102vs105vs93nmol/L(p=0.04).
In conclusion there are no significant changes in thyroid function between 5 and 9 years, however many years later a fall is seen in patients treated with CSI but not after CI only. This confirms that progressive central hypothyroidism is infrequent certainly within the first 10 years of irradiation. The fall in tT4 levels over many years although significant for the group study is of minor significance at the level of the individual patient and his/her management.