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VOLUME 40 DECEMBER 1967 NUMBER 6
COMMENTARIES
GOITER
‘DEMIC GOITER remains one of the most
widespread nutritional diseases in the
world today. The major cause is iodine
deficiency. The World Health Organization reports a high incidence of goiter in
Thai-land (where a program of iodine
supple-mentation was instituted), in the mountains of Western Pakistan, Lebanon, Basutoland,
and Kenya.1 The incidence of goiter in
io-dine-deficient regions may be as high as
50%. Of three goitrous zones in the
Hima-layas, two were selected for iodine
supple-mentation and one was reserved as a
con-trol. There was a striking reduction of
goi-ter in the zones provided with the iodine
supplement but not in the third.2 Many
similar studies have been pursued with
equally rewarding results. Substantiation of
iodine deficiency as the major cause has
been provided in many studies: (1) high
thyroidal uptake of isotopic iodine, (2) low levels of urinary iodine, (3) elevated
thyro-tropin in the serum, and (4) regression
upon the administration of iodine or
thy-roid hormone.36 Goiter due to iodine
deficiency is also to be found in New Guin-ea, Italy, Greece, and, perhaps surprising to
some, in the United States. It is 50 years
since Marine and Kimball described the
high incidence of goiter in the school
chil-dren of Akron, Ohio, and recognized the
basis of the problem. In Tecumseh,
Michi-gan, where the incidence of goiter in
ani-mals and man was very high, it diminished
after 1924 with the introduction of iodine
supplementation, principally as iodized
table salt. However, in a survey of this
re-gion in 1959-1960, goiter was found in 2.9%
of males and 10.2% of females.8 In
Tecum-seh, the iodine content of drinking water is
low and the use of iodized salt is not
uni-form-only 62% of the salt purchased in
that community was iodized during that
period. Although iodine supplementation of
table salt is obligatory in some countries, this is not so in the United States.
While this “old” problem appears to be
still with us and the role of iodine
de-ficiency is vel1 supported, the picture is
not entirely clear. Females in a community
with endemic goiter show a much higher
incidence than males. In central Italy the
sex ratio is 3:1, and, despite the evidence for low iodine intake in some regions, only
14% of the population have goiters. There
is evidence that nontasters of
phenylthio-urea (PTC) are more susceptible. It is to
be recalled fiat PTC nontasters are also
more susceptible to athyrotic cretinism and
adenomatous goiters.9 Furthermore, in low
lying regions of Greece,6 near the sea, in
Cali, Colombia,’#{176} and the Northern Islands
of Japan,” endemic goiter of unknown
etiology, clearly not related to low iodine intake, has been described in recent years. Indeed, the intake of iodine in the Northern Japanese islands is very high and the inci-dence of goiter decreases upon withdrawal
of kelp from the diet. Excessive iodine
in-take itself has been known”” to produce
goiter and many sporadic cases due to this
factor have been described in man. The
936 GOITER fetal thyroid gland seems to be especially
sensitive to enlargement upon exposure to
excessive iodine, and neonatal goiter is
common when the mother has taken large
amoun ts. Within iodine-deficient areas the
iresetice of many without goiters raises
qestiotis. Several hypotheses have been
advanced to explain this: (1) the severity of
iodine deficiency may vary among
individ-uals within one locality, (2) the excretion of iodine (which is renal) may vary greatly
so that sonie better conserve their small
stores, (3) subtle degress of thyroidal
(lvshormonogenesis may exist within a
pop-ulation so that some are more likely to
de-velop goiter on a given low intake of iodine than others, and (4) ingestion of a
goitro-genic substance superimposed on a
low-io-dine intake may occur in a part of the
pop-ulation. The ingestion of goitrogenic
sub-stances as the basis of endemic goiter has
rarely been reported.
Within the North American continent,
particularly along the coastal regions where
so large a proportion of our population
lives, it is unlikely that iodine deficiency
plays any but a small and peculiar role in
causing goiters. And, although goiter is not
frequent in these areas, it nonetheless
oc-curs. The exact incidence is unknown. On
occasion, ingestion of a goitrogenic drug
(generally iatrogenic) is incriminated. However, in these regions there is now sub-stantial evidence that chronic lymphocytic
thyroiclitis explains many, if not most, of
the instances. In Boston, Philadelphia, and
Houston the majority of children with
goi-ter have been shown to have chronic
lym-phocytic thyroiditis.1416 In GOteborg, 30%
and in Glasgow 33% of goiters in all ages
are the result of chronic lymphocytic
thyroiditis’7’8 As yet the etiology and
pathogenesis of this condition is unknown. It has been often suggested that a viral in-fection is the cause, but many believe that
an unknown immunologic peculiarity of the
subject is an additional and important
fac-tor. Recent studies suggest that this
condi-tion may bring about juvenile acquired
hypothyroidism.’9 Thyroid hormone and/or
steroids have been variously employed in
its treatment, but neither has as yet been
shown to be of ultimate benefit.
Goiter continues to present a problem in
man throughout the world. Geographical
conditions must be taken into account in
designing the differential diagnosis. In
many regions nutritional deficiency
(io-dine) is the cause, but, even so, the incon-stancy of goiter under these circumstances is tantalizing. Nor is it to be supposed that
so-called “advanced nations” are free from
this fault. In some areas where adequate
iodine intake is beyond doubt, chronic
lym-phocytic thyroiditis seems to explain many
goiters. Sporadic cases must be given care-ful consideration, as should unusual
endem-ic outbreaks, with an eye to exposure to
goitrogens, hereditable disorders of thyroid
hormone synthesis, and other possible
causes. Factors affecting the thyroid gland
may compromise its function and thus
in-terfere with normal development.
Further-more, carcinoma of the thyroid occurs more
frequently in regions of endemic goiter.
Certainly those environmental causes of
thyroid disorders which may easily be
rem-edied deserve attention.
ALFRED M. B0NGI0vANNI, M.D. Children’s Hospital of Philadelphia University of Pennsylvania
1740 Bainbridge Street
Philadelphia, Pennsylvania
REFERENCES
1. The WHO programme in nutrition. WHO Chron., 19:429, 1965.
2. Sooch, S. S., and Ramalingaswami, V.:
Pre-liniinary report of an experiment in the
Kangra Valley for the prevention of
Hima-layan endemic goitre with iodized salt. Bull. WHO, 32:299, 1965.
3. Stanbury, J. B., Brownell, C. L., Riggs, D. S., Perinetti, H., Itoiz, J., and DelCastillo, E. B.: Endemic Goiter. Cambridge, Massachusetts: Harvard University Press, 1954.
4. Black, M. L., Hoffman, M. j.,Mason, E. K.,
and Hetzel, B. S.: Correction of iodine de-ficiency in New Guinea natives by iodized
oil injection. Lancet, 2:767, 1965.
5. DeLuca, F., Cramarossa, L., Tonelli, S. A.,
L., and Cassano, C.: Iodine deficiency in
two endemic goiter areas of central and southern Italy. J. Clin. Endocr., 26:393, 1966.
6. Malamos, B., Miras, K., Koutras, D. A., Kos-tamis, B., Benopoulos, P., Matzos,
J.,
Levis, C., Rigopoulos, C., Zerifos, N., and Tas-sopoulus, C. N.: Endemic goiter in Greece: Metabolic studies. J. Clin. Endocr., 26:696, 1966.7. Marine, D. M., and Kimball, 0. P.: The pre-vention of simple goiter in man. J. Lab. Cliii. Med., 3:40, 1917.
8. \latavinovic, J., Hayner, N. S., Epstein, F. H., Kyelsberg, M. 0.: Goiter and other thyroid diseases in Tecumseh, Michigan. J.A.M.A., 192:234, 1965.
9. Fraser, C. R.: Cretinism and taste sensitivity to phenylthiocarbanlide. Lancet, 1:964, 1961.
10. Wahnier, H. W., Gaitan, E., and Correa, P.:
Studies of iodine metabolism in endemic
nodular goiter. J. Clin. Endocr., 26:279, 1966.
11. Suzuki, H., Higuchi, T., Sawa, K., Ohtaki, S., and Horiuchi, Y.: Endemic coast goitre in Hokkaido, Japan. Acta Endocr., 50:161, 1965.
12. Wheeler, R. S., and Hoffmann, E.: Goiterous chicks from iodine-injected eggs. Endocrin-ology, 45:208, 1949.
13. Morgans, M. E., and Trotter, W. R.; Two cases of myxoedemo attributed to iodine
admin-istration. Lancet, 2:1335, 1953.
14. Gribetz, D., Talbot, N. B., and Crawford, ). D.: Goiter due to lymphocvtic thvroiditis
(Hashimoto’s struma). New Eng. J. Med.,
250:555, 1954.
15. Leboeuf, G., and Bongiovanni, A. M.: Thy-roiditis in childhood. Advances Pediat., 13:
183, 1964.
16. Clayton, C. W., and Johnson, C. M.: Strunia
lvmphomatosa in children. J. Pediat., 57:
410, 1960.
17. Heimann, P., and Schn#{252}rer, L. B.: Needle bi-opsy of the thyroid gland. A report of 117
cases, with special references to the diag-nostic accuracy of the method in benign thyroid disorders. Acta Chir. Scand., 128:85, 1964.
18. Buchanan, W. W., McG.Harden, R., and Clark, D. H.: Hashimoto’s thvroiditis. Brit. J. Surg., 52:430, 1965.
19. Winter, J., Eberlein, \V. R., Botigiovanni, A. M.: Thvroiditis in childhood. J. Pediat., 69: 709, 1966.
PULMONARY
FUNCTION,
DEDUCED
FROM
URINARY
NITROGEN
TENSIONS
T
HE elegant studies reported byLed-better, Homma, and Farhi in this issue
are entitled “Readjustment in Distribution of Alveolar Ventilation and Lung Perfusion in the Newborn.” It must come as a great surprise to the reader to discover that the
only measurement actually made was the
partial pressure of nitrogen in the infants’
urine. How could one conclude that there
were significant imbalances between the
distribution of alveolar ventilation and
pul-monary blood flow (VA/Q) in the first days
of life in normal infants from a urine
sam-ple? It is all the more astounding in the
light of previous (and seemingly more
di-rect) studies of alveolar-arterial oxygen and carbon dioxide differences which led others
to consider the differences largely
ex-plained by anatomical right-to-left shunts. The reader is urged to follow the
careful-ly outlined arguments in the discussion of
this paper for the analysis of the assump-tions made, technical problems, and, finally,
the physiological principles which make the
argument so compelling. It is perhaps not
surprising that the theoretical basis for this
analysis was first worked out by one of the
authors, Dr. Farhi, and Dr. Hermann Rahn.
The method depends on the following
physiological events. Normally, about 80%
nitrogen is inspired with each breath. Since
the lung behaves as a tonometer to bring
gases into equilibrium with the blood
