Iodine Prophylaxis Following Nuclear Accidents. Proceedings of a Joint WHO/CEC Workshop, July 1988

170 Pages·1990·3.46 MB·English

by  Eileen Rubery and E. Smales (Eds.)

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IODINE PROPHYLAXIS
FOLLOWING NUCLEAR ACCIDENTS
Proceedings of a joint WHO/CEC Workshop
July 1988
Edited by
Eileen Rubery and Elizabeth Smales
Department of Health London, United Kingdom
Published on behalf of the
World Health Organization
Regional Office for Europe
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First edition 1990
Library of Congress Cataloging-in-Publication Data
Iodine prophylaxis following nuclear accidents: proceed-
ings of a joint WHO/CEC workshop, July 1988 / edited by
Eileen Rubery & Elizabeth Smales.
p. cm.
"Published on behalf of the World Health Organization
Regional Office for Europe."
"Papers presented provided the basis for the development
of guidelines . . . issued by the WHO Regional Office for
Europe (Guidelines for iodine prophylaxis, Environmental
health series, no. 35, 1989)"—Pref.
1. Thyroid gland—Diseases—Prevention—Congresses.
2. Iodine—Therapeutic use—Congresses. 3. Nuclear
power plants—Accidents—Health aspects—Congresses.
4. Iodine—Isotopes—Toxicology—Congresses. I. Rubery,
Eileen. II. Smales, Elizabeth. III. World Health Organization.
IV. Commission of the European Communities. V. World
Health Organization. Regional Office for Europe. Guide-
lines for iodine prophylaxis.
[DNLM: 1. Iodine—therapeutic use—congresses. 2. Radi-
ation Injuries—prevention & control—congresses. 3. Thy-
roid gland—physiology—congresses. WN 650 I697 1988]
RC655.I67 1990 614.5'944-dc20 89-72197
British Library Cataloguing in Publication Data
Iodine prophylaxis following nuclear accidents
1. Man. Thyroid. Drug therapy. Iodine
I. Rubery, Eileen II. Smales, Elizabeth III. World Health
Organization, Regional Office for Europe 616.44061
ISBN 0-08-037496-4
The views expressed in this publication are those of the
authors and do not necessarily represent the decisions or
the stated policy of the World Health Organization
Printed in Great Britain by BPCC Wheatons Ltd., Exeter
Foreword
For many years, as part of its overall programme of technical cooperation with
Member States, the WHO Regional Office for Europe has assisted in the
development of contingency planning for, and response to, different types of
accident. In addition to the natural disasters that from time to time strike our
region, such as earthquakes and floods, the number of technological accidents,
some of which have had serious public health consequences, has been increas-
ing.
Following the accident to a nuclear plant at Chernobyl, USSR, the Regional
Office set up an emergency centre that provided information to Member States
on a systematic basis and responded to large numbers of ad hoc requests.
Many queries were received about the appropriate application of iodine
prophylaxis and whether side effects were likely to occur. On the basis of
experience gained after Chernobyl, it was deemed necessary to develop guide-
lines giving both a scientific rationale and practical information on formu-
lation, storage, and application. Several countries have already indicated that
they will build the guidelines into their national contingency plans for nuclear
emergencies.
As an important milestone in the preparation of the guidelines, a scientific
workshop was held in Brussels in July 1988, jointly organized with the Com-
mission of the European Communities. This meeting brought together a group
of eminent experts in the fields of endocrinology, radiology, and public health.
I am confident that this volume, containing the papers presented at the work-
shop, will form an important reference work in relation to further research
efforts and as background to the iodine prophylaxis guidelines, which have
now been issued in the Environmental Health Series of the WHO Regional
Office for Europe.
J.E. ASVALL
Regional Director for Europe
World Health Organization
vn
Preface
Following the nuclear accident at Chernobyl in April 1986, many European
countries considered the possible value of iodine prophylaxis to protect the
population from the possible adverse health effects on the thyroid from uptake
of radioiodine. After evaluating the predicted levels of contamination and its
probable timing, only a few countries officially recommended the adminis-
tration of stable iodine. In some others, members of the public took iodine
tablets without or against the advice of the authorities. Enquiries at national
and local levels by the World Health Organization revealed considerable con-
fusion about the criteria that should be adopted for making decisions on
prophylaxis.
The WHO Regional Office for Europe was therefore requested to develop
guidelines on iodine prophylaxis as part of a special project on the public
health dimensions of nuclear accidents, funded by the Governments of Switz-
erland and the United Kingdom. A survey was carried out on the use of iodine
prophylaxis following the Chernobyl accident and a subsequent consultation,
held in Copenhagen in September 1987, developed an outline for the proposed
guidelines. A joint WHO/CEC workshop was thereafter organized in Brussels
in July 1988, which was attended by 22 experts in public health, endocrinology
and radiation protection, to review the scientific basis for iodine prophylaxis
and to identify gaps in knowledge. The list of participants is given at the end
of section 5.
The papers presented at the joint WHO/CEC workshop form sections 1-4
of this book. At the end of this meeting, there was a discussion of the con-
clusions that could be drawn from the data presented and preliminary recom-
mendations were drafted. These were subsequently developed into the
conclusions and recommendations of the workshop, in consultation with those
present at the meeting. These are contained in the report of this meeting,
which provides the rationale for the use of stable iodine prophylaxis following
a nuclear accident and which forms section 5 of this book. The conclusion and
recommendations of the workshop provided the basis for the development of
guidelines on iodine prophylaxis that have now been issued by the WHO
Regional Office for Europe (Guidelines for iodine prophylaxis, Environmental
Health Series, No. 35,1989). Although it was considered important for WHO
to issue guidelines to the responsible authorities as quickly as possible, consid-
erable gaps in knowledge were acknowledged and several important areas for
future work were identified.
We hope that this volume will provide a stimulus to further work on the
IX
X PREFACE
relevant aspects of the problems involved in iodine prophylaxis. The support
of Dr G. Gerber of the Commission of the European Communities in organiz-
ing the Brussels workshop is gratefully acknowledged, and all those who have
given their time, experience, and efforts to this volume are cordially thanked.
EILEEN RUBERY
ELIZABETH SMALES
Thyroid Physiology in Utero and
Neonatally
G. MORREALE DE ESCOBAR and
F. ESCOBAR DEL REY
Unidad de Endocrinologia Experimental, Instituto de Investigaciones
Biomedicas, Consejo Superior de Investigaciones Cientificas y Facultad
de Medicina de la Universidad Autonome, Madrid, Spain
The topic can be considered in three parts:
(1) The fetus.
(2) The mother.
(3) The neonate.
Within each area, information pertaining to the human fetus and neonate,
and its mother, is considered where this exists. Findings from animal experi-
ments are also discussed when inadequate information is available for man.
1. The fetus
1.1. Development of the gland
Most human endocrine systems appear very early in life and are functionally
well developed by birth. The thyroid is among the earliest to appear1.,2 It is
first visualized at 16-17 days of gestation (dg), when it is in contact with the
developing heart. At 3-4 weeks (wks) it appears as a flasklike vesicle with a
narrow neck attached to the buccal cavity. It becomes bilobed and by 5V2-6
wks it is composed of a solid mass of tissue expanding laterally as it descends
caudally. By 6-7 wks after rupture of the stalk, it reaches its final position in
the anterior lower neck. It then weighs 1-2 mg. The gland continues to
increase in weight to approximately 5 mg by the end of the 1st trimester (12
wks), after which the rate of increase becomes very rapid, to about 50 mg by
13 weeks, 100-300 mg by 20 wks (mid-gestation), 200-600 mg by 24 wks
(end of 2nd trimester) and 1-3 g at term3."6 In all studies, individual data for
fetuses of comparable age show marked variability.
Histologically, three main stages are observed:7 the pre-colloid, the begin-
ning colloid, and the follicular growth. The pre-colloid stage extends between
6V2-10 wks (47-72 dg), followed by the beginning colloid stage at IO-IIV2
wks (73-80 dg), after which follicular growth occurs. The dating of these
3
4 G. MORREALE DE ESCOBAR AND F. ESCOBAR DEL REY
events is only approximate, as large individual variations are found in most
studies. Between the 3rd and 6th month, follicles are formed throughout the
gland, and near term follicles are well formed and filled with colloid.4
Although anti-thyroglobulin (Tg) antibody linked to an immunofluorescent
label will bind to material in glands which still are afollicular, mature 19 S Tg,
the specific marker of normal thyroid epithelial cells, is not found until follicles
form and colloid appears.3'4'7'8 As the thyroid follicles and colloid increase, so
does the total Tg content. From the mean concentration values reported by
radioimmunoassay (RIA)6 and the changes in thyroid weight, the Tg content
increases from about 1.2 mg at mid-gestation to 12 mg at birth. These are
tentative figures, as individual variability in Tg concentrations is also quite
marked.
7.2. Onset of iodide concentrating capacity
The capacity to concentrate iodide, as measured by determining the uptake
of radioiodide in the fetal gland when radioiodide is administered to the
mother, does not start to appear until 12-14 wks gestation.4'5'9'10 It coincides
with the appearance of definite colloid-containing spaces. The study per-
formed by Evans et al.4 showed that uptake of radioiodide by the fetal thyroid
is very low (0.003-0.4%/gland) up to 18-22 wks, after which it starts increasing
(0.18-0.8%/fetal thyroid). There is a rapid increase at 23-24 wks to about
0.6-3%/fetal thyroid, as illustrated in Fig. 1. There is a gap in the data between
24 wks (end of 2nd trimester) and term (40 wks), the few reported in vivo
uptake data during this period being from anencephalic fetuses, with uptakes
of 1.3 and 3.0% dose/thyroid gland. As calculated per gram of thyroid tissue,
the uptake appears to be higher at mid-gestation than at term, but obviously
lower throughout fetal life as compared to the first days after birth and in
infancy (Fig. 2). The fetal data indicate a higher uptake as compared to adult
thyroid glands. The results reported by Costa et al.5 were in general agreement
(Fig. 2). These authors also found a tenfold increase in total fetal thyroid
uptake between the 3rd and 6th month of intrauterine development, and
uptakes which were ten times those of the mothers, on a weight for weight
basis.
Such results were obtained after maternal exposure to a single dose of
radioiodide. Beierwaltes et al.n studied the concentrations in fetal thyroids of
radioisotopes from fall-out, obtained within a 10-mile radius of Ann Arbor,
Michigan, between 12 November 1958 and 1 August 1959, when atomic blasts
from the USA, UK and USSR were frequent. Data were obtained for 27
fetuses from 25 pregnancies, from 5 months gestation to term. A very great
variability in the concentration of radioactivity (the major radioactive compon-
ent being 131I) was found for fetuses of the same age, even among twins. Despite
this great variability, the average concentrations in the fetal thyroids were
more than 10 times those in adults (Fig. 3). It is also interesting that the
THYROID PHYSIOLOGY IN UTERO AND NEONATALLY
THYROID UPTAKE OF RADIOIODINE, % THYROID WEIGHT, grams
3.0F= 1.5 P"-
X
I
I
A /·
FETAL AGE in months
FIG. 1. Changes in weight (Hght-hand panel) and in 131I uptake (left-hand panel)
found for human thyroid fetuses at different stages of gestation. Taken from Evans
et al.4 Results from Costa et al.5 are superimposed as triangles. The 131I uptake data
are given as % of the dose given to the mother, and are not corrected for the amount
of the isotope sequestered by the material thyroid.
THYROIDAL UPTAKE OF I-I3I, % per qrom
40.0r
30.0 h
10.0
5 0 h
0 5 10 15 20 25 30 35 40 | | CHILD f
FETAL AGE , in weeks AT BIRTH INFANT ADULT
FIG. 2. Changes in thyroidal 131I uptake, referred to the weight of the gland, at
different stages of development. Taken from Evans et al.,4 with data from Costa et
al.5 superimposed as triangles. Fetal data do not take into account the proportion
of the dose sequestered by the maternal thyroid.
5 G. MORREALE DE ESCOBAR AND F. ESCOBAR DEL REY
100 ■ύϊ. I ·*«"
E 10
o
■ ' ; \
V
i 1 I I I i i I I i_
Nov Dec Jan Feb Mar Apr May June July
FIG. 3. Radioactivity, mainly due to radioisotopes of iodine, found in fetal and
adult human thyroid glands obtained within a 10-mile radius of Ann Arbor, Michi-
gan (USA), between November 1958 and August 1959 when atomic blasts from
the USA, UK and USSR were frequent. Drawn from data by Beierwalte set a/.11.
radioiodine concentrations were low in the thyroids of fetuses from a few
mothers on desiccated thyroid medication, or receiving high doses of organic
or inorganic iodine, even if the glands had been collected when fall-out was
high. The authors calculated that the maximum total radiation delivered by
fall-out to any fetal thyroid gland was 0.47 rads, an amount unlikely to result
in hypothyroidism or to induce carcinoma.
As a result of the capacity to concentrate iodine, the total iodine content of
the fetal thyroid gland increases with thyroid weight, and with gestational age.
The total iodine concentration is fairly constant, and not significantly different
at 22-25 wks (37.5 ± 22.4 μg I/g) as compared to term (59.9 ± 42.3 μgI/g).6
As the weight is increasing, the total I content increases from 14 μg I/gland at
the end of the 2nd trimester to 49 μg I/gland at 30-34 wks, and 44 μg I/gland
at term.6 These values are approximate, as both the total I concentration and
the thyroid weight are highly variable for fetuses of the same age.
It is important to realize that during this stage of development there is a
continuous accumulation of iodine by the fetal gland. It is therefore likely that
in case of contamination of the environment with radioisotopes of iodine, the
fetal thyroid will continue to accumulate the isotope, even when the gland of
adults has reached a stage of isotopic equilibrium with the environmental
radioiodine. This situation of positive iodine balance continues after birth; the
total iodine content of an adult thyroid is of the order of 10 mg, that is, about
200 times that of the newborn.
1.3. Onset of thyroid hormone synthesis
Chromatographie studies on fetal thyroid glands labeled in vivo do not
reveal organically bound radioiodide until the 19th wk,12 despite the
appearance of radioiodine uptake at earlier ages. Labeled T4 and T3 were