Thyroid-stimulating hormone suppression for protection against hypothyroidism due to craniospinal irradiation for childhood medulloblastoma/primitive neuroectodermal tumor.
OBJECTIVE
Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor.


METHODS
From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered l-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 mum/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed.


RESULTS
Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the "adequately TSH-suppressed" group and 20% for the "inadequately TSH-suppressed" group (p = 0.02).


CONCLUSIONS
Thyroid-stimulating hormone suppression with l-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.
Massimino
Maura
M
Department of Pediatrics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. maura.massimino@istitutotumori.mi.it
Gandola
Lorenza
L
Collini
Paola
P
Seregni
Ettore
E
Marchianò
Alfonso
A
Serra
Annalisa
A
Pignoli
Emanuele
E
Spreafico
Filippo
F
Pallotti
Federica
F
Terenziani
Monica
M
Biassoni
Veronica
V
Bombardieri
Emilio
E
Fossati-Bellani
Franca
F
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000517:prevention & control*; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D018242:Neuroectodermal Tumors, Primitive / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D013972:Thyrotropin / Q000037:antagonists & inhibitors* / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D015415:Biomarkers; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine