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

L Van Lersel, S C Clement, A Y N Schouten-Van Meeteren, A M Boot, H L Claahsen-Van Der Grinten, B Granzen, K S Han, G O Janssens, E M Michiels, A S P Van Trotsenburg, W P Vandertop, D G Van Vuurden, H N Caron, L C M Kremer, H M Van Santen

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Abstract

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
Original languageEnglish
Title of host publicationEndocrine Reviews
Publication statusPublished - 2017

Publication series

NameEndocrine Reviews
Volume38

Cite this

Van Lersel, L., Clement, S. C., Schouten-Van Meeteren, A. Y. N., Boot, A. M., Claahsen-Van Der Grinten, H. L., Granzen, B., ... Van Santen, H. M. (2017). Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism? In Endocrine Reviews (Endocrine Reviews; Vol. 38).
Van Lersel, L ; Clement, S C ; Schouten-Van Meeteren, A Y N ; Boot, A M ; Claahsen-Van Der Grinten, H L ; Granzen, B ; Han, K S ; Janssens, G O ; Michiels, E M ; Van Trotsenburg, A S P ; Vandertop, W P ; Van Vuurden, D G ; Caron, H N ; Kremer, L C M ; Van Santen, H M. / Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism?. Endocrine Reviews. 2017. (Endocrine Reviews).
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title = "Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism?",
abstract = "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",
keywords = "Student t test, TSH secreting cell, acute lymphoblastic leukemia, brain tumor, cancer epidemiology, child, childhood, clinical practice, clinical study, clinical trial, cohort analysis, controlled study, diagnosis, endogenous compound, female, follow up, growth hormone deficiency, human, hypothalamus, hypothyroidism, male, provocation test, radiation injury, radiosensitivity, radiotherapy, skull irradiation, survivor, thyrotropin, thyroxine",
author = "{Van Lersel}, L and Clement, {S C} and {Schouten-Van Meeteren}, {A Y N} and Boot, {A M} and {Claahsen-Van Der Grinten}, {H L} and B Granzen and Han, {K S} and Janssens, {G O} and Michiels, {E M} and {Van Trotsenburg}, {A S P} and Vandertop, {W P} and {Van Vuurden}, {D G} and Caron, {H N} and Kremer, {L C M} and {Van Santen}, {H M}",
year = "2017",
language = "English",
isbn = "0163-769X",
series = "Endocrine Reviews",
booktitle = "Endocrine Reviews",

}

Van Lersel, L, Clement, SC, Schouten-Van Meeteren, AYN, Boot, AM, Claahsen-Van Der Grinten, HL, Granzen, B, Han, KS, Janssens, GO, Michiels, EM, Van Trotsenburg, ASP, Vandertop, WP, Van Vuurden, DG, Caron, HN, Kremer, LCM & Van Santen, HM 2017, Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism? in Endocrine Reviews. Endocrine Reviews, vol. 38.

Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism? / Van Lersel, L; Clement, S C; Schouten-Van Meeteren, A Y N; Boot, A M; Claahsen-Van Der Grinten, H L; Granzen, B; Han, K S; Janssens, G O; Michiels, E M; Van Trotsenburg, A S P; Vandertop, W P; Van Vuurden, D G; Caron, H N; Kremer, L C M; Van Santen, H M.

Endocrine Reviews. 2017. (Endocrine Reviews; Vol. 38).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

TY - CHAP

T1 - Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism?

AU - Van Lersel, L

AU - Clement, S C

AU - Schouten-Van Meeteren, A Y N

AU - Boot, A M

AU - Claahsen-Van Der Grinten, H L

AU - Granzen, B

AU - Han, K S

AU - Janssens, G O

AU - Michiels, E M

AU - Van Trotsenburg, A S P

AU - Vandertop, W P

AU - Van Vuurden, D G

AU - Caron, H N

AU - Kremer, L C M

AU - Van Santen, H M

PY - 2017

Y1 - 2017

N2 - 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

AB - 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

KW - Student t test

KW - TSH secreting cell

KW - acute lymphoblastic leukemia

KW - brain tumor

KW - cancer epidemiology

KW - child

KW - childhood

KW - clinical practice

KW - clinical study

KW - clinical trial

KW - cohort analysis

KW - controlled study

KW - diagnosis

KW - endogenous compound

KW - female

KW - follow up

KW - growth hormone deficiency

KW - human

KW - hypothalamus

KW - hypothyroidism

KW - male

KW - provocation test

KW - radiation injury

KW - radiosensitivity

KW - radiotherapy

KW - skull irradiation

KW - survivor

KW - thyrotropin

KW - thyroxine

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UR - http://www.mendeley.com/research/declining-ft4-concentrations-following-cranial-irradiation-indications-early-development-mild-centra

M3 - Chapter

SN - 0163-769X

T3 - Endocrine Reviews

BT - Endocrine Reviews

ER -

Van Lersel L, Clement SC, Schouten-Van Meeteren AYN, Boot AM, Claahsen-Van Der Grinten HL, Granzen B et al. Declining FT4 concentrations following cranial irradiation: Indications for early development of mild central hypothyroidism? In Endocrine Reviews. 2017. (Endocrine Reviews).