TY - JOUR
T1 - Declining free thyroxine levels over time in irradiated childhood brain tumor survivors
AU - van Iersel, Laura
AU - Clement, Sarah C
AU - Schouten-van Meeteren, Antoinette Y N
AU - Boot, Annemieke M
AU - Claahsen-van der Grinten, Hedi L
AU - Granzen, Bernd
AU - Sen Han, K
AU - Janssens, Geert O
AU - Michiels, Erna M
AU - van Trotsenburg, A S Paul
AU - Vandertop, W Peter
AU - van Vuurden, Dannis G
AU - Caron, Hubert N
AU - Kremer, Leontien C M
AU - van Santen, Hanneke M
N1 - Publisher Copyright:
© 2018 The authors Published by Bioscientifica Ltd.
PY - 2018/12
Y1 - 2018/12
N2 - OBJECTIVE: The incidence of cranial radiotherapy (cRT)-induced central hypothyroidism (TSHD) in childhood brain tumor survivors (CBTS) is reported to be low. However, TSHD may be more frequent than currently suspected, as its diagnosis is challenging due to broad reference ranges for free thyroxine (FT4) concentrations. TSHD is more likely to be present when FT4 levels progressively decline over time. Therefore, we determined the incidence and latency time of TSHD and changes of FT4 levels over time in irradiated CBTS.DESIGN: Nationwide, 10-year retrospective study of irradiated CBTS.METHODS: TSHD was defined as 'diagnosed' when FT4 concentrations were below the reference range with low, normal or mildly elevated thyrotropin levels, and as 'presumed' when FT4 declined ≥ 20% within the reference range. Longitudinal FT4 concentrations over time were determined in growth hormone deficient (GHD) CBTS with and without diagnosed TSHD from cRT to last follow-up (paired t-test).RESULTS: Of 207 included CBTS, the 5-year cumulative incidence of diagnosed TSHD was 20.3%, which occurred in 50% (25/50) of CBTS with GHD by 3.4 years (range, 0.9-9.7) after cRT. Presumed TSHD was present in 20 additional CBTS. The median FT4 decline in GH-deficient CBTS was 41.3% (P < 0.01) to diagnosis of TSHD and 12.4% (P = 0.02) in GH-deficient CBTS without diagnosed TSHD.CONCLUSIONS: FT4 concentrations in CBTS significantly decline over time after cRT, also in those not diagnosed with TSHD, suggesting that TSHD occurs more frequently and earlier than currently reported. The clinical relevance of cRT-induced FT4 decline over time should be investigated in future studies.
AB - OBJECTIVE: The incidence of cranial radiotherapy (cRT)-induced central hypothyroidism (TSHD) in childhood brain tumor survivors (CBTS) is reported to be low. However, TSHD may be more frequent than currently suspected, as its diagnosis is challenging due to broad reference ranges for free thyroxine (FT4) concentrations. TSHD is more likely to be present when FT4 levels progressively decline over time. Therefore, we determined the incidence and latency time of TSHD and changes of FT4 levels over time in irradiated CBTS.DESIGN: Nationwide, 10-year retrospective study of irradiated CBTS.METHODS: TSHD was defined as 'diagnosed' when FT4 concentrations were below the reference range with low, normal or mildly elevated thyrotropin levels, and as 'presumed' when FT4 declined ≥ 20% within the reference range. Longitudinal FT4 concentrations over time were determined in growth hormone deficient (GHD) CBTS with and without diagnosed TSHD from cRT to last follow-up (paired t-test).RESULTS: Of 207 included CBTS, the 5-year cumulative incidence of diagnosed TSHD was 20.3%, which occurred in 50% (25/50) of CBTS with GHD by 3.4 years (range, 0.9-9.7) after cRT. Presumed TSHD was present in 20 additional CBTS. The median FT4 decline in GH-deficient CBTS was 41.3% (P < 0.01) to diagnosis of TSHD and 12.4% (P = 0.02) in GH-deficient CBTS without diagnosed TSHD.CONCLUSIONS: FT4 concentrations in CBTS significantly decline over time after cRT, also in those not diagnosed with TSHD, suggesting that TSHD occurs more frequently and earlier than currently reported. The clinical relevance of cRT-induced FT4 decline over time should be investigated in future studies.
KW - Central nervous system neoplasms
KW - Growth hormone deficiency
KW - Hypothyroidism
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85065059019&partnerID=8YFLogxK
U2 - 10.1530/EC-18-0311
DO - 10.1530/EC-18-0311
M3 - Article
C2 - 30400062
SN - 2049-3614
VL - 7
SP - 1322
EP - 1332
JO - Endocrine connections
JF - Endocrine connections
IS - 12
ER -