Excerpts from:
ENDEMIC GOITRE in the
UNION of SOUTH AFRICA and SOME NEIGHBOURING TERRITORIES.
Union of South Africa, Department
of Nutrition.
March 1955.
By
Douw G. Steyn, B.Sc., Dr. Med. Vet. (Vienna),
D.V.Sc., Professor of Pharmacology, Medical Faculty, University
of Pretoria;
J. Kieser, Artseksamen (M.D.), former Chief Medical Inspector
of Schools, Transvaal Provincial Administration;
W.A. Odendaal, D.Sc., Research Officer in Nutrition, Union Department
of Nutrition, Pretoria;
H. Malherbe, M.A., M.B.Ch.B., Senior Medical Officer, Poliomyelitis
Research Foundation, South African Institute for Medical Research,
Johannesburg;
H.W. Snyman, M.B.Ch.B. (W.W. Rand), M.D. (Groningen), Professor
of Medicine, Medical Faculty, University of Pretoria;
W. Sunkel, B.Sc., Division of Chemical Services;
C.P. Naude, D.Sc., Division of Chemical Services;
H. Klintworth, M.Sc., Division of Chemical Services; and
E. Fisher, M.Sc., Division of Chemical Services, Union Department
of Agriculture, Pretoria.
I. INTRODUCTION
The information supplied in this publication
is intended to serve two purposes, namely: (1) As a report on
the investigations made by the South African Goitre Research Committee
appointed, some six years ago, under the auspices of the Medical
Faculty of the University of Pretoria, and (2) to give a short
account of our present knowledge of the main features and causes
of endemic goitre. Further, it is hoped that the information contained
herein will serve as a source of knowledge and guidance to those
who are interested in endemic goitre. An attempt has been made
to give a fairly full list of references pertaining to the various
aspects of the problem. All the members of the Committee were
employed full-time in their respective professions, consequently
progress with the investigations was much slower than we had hoped.
It is with deep appreciation that we acknowledge the financial
assistance given us by the South African Council for Scientific
and Industrial Research for this investigation...
III. CAUSES OF SIMPLE OR ENDEMIC GOITRE
G. GOITROGENIC AGENTS
Fluorine
Goldenberg was the first to introduce fluorine
therapy in hyperthyroidism and Basedow's disease on the assumption
that simple goitre and cretinism were caused not by iodine deficiency
but by a superabundance of fluorine in the air, food and water
[Steyn (126)]. In 1938 one of us [D.G.S. (126)] discussed the
literature dealing with the effects of fluorine on man and animal,
including its effects on the thyroid and parathyroid glands. The
consensus of opinion is that iodine and fluorine have antagonistic
effects on the thyroid gland. Successful use has been made of
the antagonistic effect of these two halogens in the treatment
of cases of hyperthyroidism. (126) While investigating poisoning
with highly mineralized subterranean waters in the North-Western
Cape Province in 1936, one of us (D.G.S.) (126, 127, 128, 129)
saw several cases of endemic goitre in European women on farms
in the districts of Kenhardt and Upington. As that area was known
to be iodine-rich, the presence of some goitrogenic agent in the
drinking water was immediately suspected. That area is a known
endemic fluorine area and this halogen was immediately suspected.
For further details concerning fluorine as a goitrogenic agent
in the North-Western Cape Province, see VI B (3).
The results of Goldenberg's researches inspired
May (124) to go deeper into iodine-fluorine antagonism. He, like
Goldenberg, Todd and Orlowski, confirmed the beneficial effects
of fluorine administration in cases of hyperthyroidism and Basedow's
disease. Schittelhelm, Eisler, and Sturm, and May (124) and his
collaborators found that the elevated blood iodine present in
all cases of hyperthyroidism, was reduced by fluorine administration.
Also the increased glycolysis and elevated blood calcium in hyperthyroidism
was counteracted by fluorine.
According to Kraft and May [Iodine Facts (Fact
318) (4)] the fluorine content of drinking-water in goitrous areas
in Germany ranges from 220 to 290 ug. per litre compared with
140 ug. per litre in non-goitrous areas. However, according to
our investigations in South Africa, it appears that such low concentrations
of fluorine in drinking water do not constitute a significant
factor in the causation of endemic goitre. Nevertheless, if the
iodine content of the water is already very low, such low concentrations
of fluorine in the drinking water may conceivably aggravate the
effects of iodine deficiency on the thyroid.
Boyer and his co-workers (131) found that 3-fluorotyrosine,
3-fluorophenylalanine, 3-fluoro-5-iodotyrosine, and 3, 5-difluorotyrosine
had no marked effect on the BMR of the rat when given by injection
or in the ration.
Held (133) studied the metabolism of human beings
receiving 1.5 to 2.5 mg. fluorine for two to eight weeks. He found
no perceptible influence on the function of the thyroid gland.
Also Evans and Phillips (125) failed to find a correlation between
the fluorine content of the thyroid gland and the BMR of the patient.
Further, the data collected by them "gave no definite evidence
that fluorine in any way played a part in human hyperthyroidism
by its action on the thyroid gland." According to Wilson
(130) "the distribution of endemic goitre in the Punjab and
in England is related to the geological distribution of fluorine
and the distribution of human dental fluorosis (mottled enamel)".
Linnell and Greere (32) state "One of us
is intimately acquainted with the formerly highly goitrous area
where Buckinghamshire borders on Northamptonshire and Bedfordshire,
where recent surveys have shown a high incidence of fluorosis".
In experiments with fluorine on rats Spira (134)
recorded advanced lesions in the kidneys and thyroid glands. In
chronic poisoning changes in these glands are often present.
McClure (132) supplies details of the amounts
of fluorine in foods. It is interesting to note that the fluorine
values for tea are very high (3.2 to 122.6 ppm) in comparison
with foods and other beverages.
In a private communication Professor R. De Josselin
De Jong of Holland informed one of us (D.G.S.) that according
to his knowledge of the fluorine content of the food and water
supplies in Holland it is highly improbable that this halogen
plays a role in the causation of endemic goitre in that country.
Wespi (247) reviews the literature on iodine-fluorine
antagonism very fully. He states that it is possible that fluorine
may attack iodine metabolism at different points and that basically
it can be accepted that there is a certain degree of iodine-fluorine
antagonism.
VI. ENDEMIC GOITRE IN THE UNION OF SOUTH AFRICA
AND NEIGHBOURING TERRITORIES
North-western Cape. - In 1936 while
on an investigation into poisoning of man and animal by subterranean
waters in the North-Western Cape Province, one of us [D.G.S. (126-129)]
encountered several cases of goitre in European women living on
farms. Enquiries made revealed that a fair percentage of people,
especially women, settling in this part of the country developed
enlargement of the thyroid gland within 10 to 15 years after having
entered the area. This was a puzzling phenomenon as the North
Western Cape Province is known to be rich in iodine. It was realized
that endemic goitre in this area could not possibly be the result
of primary iodine deficiency in the soil, food and water. It was
thought that the cause must be sought in the drinking water. The
area is semi-arid and all drinking water, except that of towns
and farms situated on the Orange River, is drawn from wells and
boreholes. It was also known that the subterranean waters in the
North-Western Cape Province generally contain harmful quantities
of fluorine. It was considered that there was a possibility that
fluorine has an antithyroid (goitrogenic) action. After having
consulted the literature and conducting some experiments upon
rats, it was realized that fluorine is a goitrogenic agent and
that endemic goitre in the North-Western Cape Province is
due not to an inherent primary iodine deficiency but chiefly to
the general presence of harmful quantities of fluorine in the
drinking-water (italics in original).
It is possible that the large quantities of calcium generally
present in the subterranean waters in that area, enhances the
goitrogenic effect of fluorine. Generally speaking the diet of
the people is very satisfactory as it included a good percentage
of meat with vegetables, fruit and bread. A large percentage of
the vegetables and fruit is imported.
Table C presents a summary of the results of
our investigations into the incidence of endemic goitre in the
North-Western Cape Province. Some 200 adults and 4,813 scholars
were examined. The incidence of simple goitre in adults, especially
women, in that area is by no means low. Several men and women
informed us that after treatment with large doses of iodine,
usually Lugol's solution, their goitres disappeared. Also the
incidence of thyrotoxicosis, including exophthalmic goitre, is
fairly high. We gained the impression that the incidence of nodular
goitre in adolescents and adults is higher in fluorine-induced
goitre areas than in areas where goitre is due to a primary iodine
deficiency. Of all goitre areas investigated the percentage of
thyrotoxicosis and thyroid operations was by far the highest in
the North-Western Cape Province. The fairly general use of large
amounts of iodine in the form of Lugol's solution in the treatment
of simple goitre probably is, in a certain measure at least, responsible
for the high incidence of thyrotoxicosis in this area.
A few explanatory remarks should be made about
certain points in the table. The Kenhardt water supply analysed
by us has been in use for a few years only. This supply is seepage
water pumped from the beds of very sandy rivers. Flooded rivers
are rare occurrences in the North-Western Cape Province and many
people living close to rivers with deep sand beds draw their water
supplies from wells sunk in these beds. As a rule such water is
wholesome, fairly rich in iodine and low in fluorine as is evidenced
by the present municipal water supply of Kenhardt, which contains
220 ug of iodine per litre and only 0.05 parts of fluorine per
million parts. Prior to this supply, Kenhardt used borehole water
which contained from 2.8 to 3.4 parts of fluorine per million
parts. Unfortunately its iodine content is unknown. Undoubtedly,
the fairly high percentage of goitre in the scholars at the Kenhardt
schools is: (1) the result of drinking the previous municipal
water supply up to some years ago; and (2) due to the fact that
a large percentage of the scholars hail from farms where the water
contains harmful quantities of fluorine. With the present iodine-rich
and fluorine-low municipal water supply, the goitre and mottled
teeth problem should disappear from Kenhardt residents in the
near future. It is intended to re-visit all the known goitre areas
after a few years in order to ascertain what the result of fresh
and more wholesome water supplies and/or the iodization of salt
has been. Iodized salt will shortly be provided to all endemic
goitre areas in the Union of South Africa except those areas in
the North-Western Cape Province where fluorine is the cause of
the malady.
Needless to say, the North-Western Cape Province
is known as an endemic fluorosis area where the teeth are very
badly mottled and caries very prevalent. In 1936 one of us (D.G.S.)
saw a case of "poker back" (osteosclerosis of the spine)
in a male of 40 years on a farm north of Upington where the borehole
water contained 2.8 parts of fluorine per million parts. We were
fortunate in that we had a number of cases where entire families,
who drank only borehole water, were affected by goitre. The diets
of the families concerned could in no way be regarded iodine-deficient
and we could to no conclusion other than that the fluorine in
the water, in spite of the presence of large quantities of iodine,
was the cause of goitre. As examples two cases could be quoted:
The drinking-water of two goitrous families contained 820 ug.
of iodine and 5.5 mg. of fluorine per litre, and 380 ug. of iodine
and 3.2 mg. of fluorine per litre respectively. It is generally
accepted that the fluorine content of drinking-water should not
exceed 0.8 to 1 part per million parts. It will be recollected
that the Netherlands Goitre Commission suggested that for the
prevention of goitre, drinking water should contain approximately
50 ug. of iodine per litre. Calculated on this basis, the water
from the two above boreholes contained approximately 7 to 16 times
more iodine that is necessary for the prevention of Goitre.
Although the highly fluorinated subterranean
waters are the major cause of endemic goitre in the North-Western
Cape Province, there are certain areas in the northern and north-western
parts where goitre is due, in a measure at least, to primary iodine
deficiency, as for example at Upington, Karos, Sultana, Oord,
Askham, Van Zylsrust, Seodin and Kuruman. From the table it is
clear that the fluorine content of these water supplies is so
low that it is of no toxicological significance. However, it should
be explained that a large percentage of the children attending
these schools hail from farms in the vicinity or situated long
distances away. It is known that water from many of the boreholes
on these farms contain harmful quantities of fluorine. The incidence
of goitre in scholars at Port Nolloth and Vryburg is fairly high
in spite of very satisfactory concentration of iodine and a minimal
amount of fluorine in the municipal water supply. Also in this
case the majority of scholars hail from farms where the water
of many of the boreholes probably contains harmful quantities
of fluorine, or may be deficient in iodine. A clear picture of
the whole position will be gained only after very extensive and
intensive investigations, including analyses of water, soil, and
food, in the entire area have been made...
RECOMMENDATIONS MADE TO THE UNION DEPARTMENT
OF HEALTH AND DEPARTMENT OF NUTRITION
Some two years ago the Goitre Research Committee,
as a result of its investigations, recommended to the Minister
of Health that iodized salt be supplied to all endemic goitre
areas in the Union of South Africa and to the entire Caprivi Strip
and Swaziland. It was strongly recommended that iodized salt be
not supplied to the fluorine-induced endemic goitre areas
(italics in original) for reasons previously
explained. The only solution of this type of goitre is the removal
of fluorine from the water supplies...
VIII. DISCUSSION
Prophylaxis and Treatment of Simple Goitre. -
It is generally accepted that man's physiological requirements
of iodine is approximately 2.0 ug. per kilogram per day, i.e.
if man daily ingests this amount of iodine there should be no
significant enlargement of the thyroid gland. However, recent
researches into the problem of thyroid enlargement have revealed
to us various interesting and important factors upon which the
normal function and size of this gland depend. These factors have
been discussed under III and VIII B. It has become obvious that
we cannot lay down a single definite figure for man's
daily iodine requirement as it depends upon various factors, e.g.
goitrogenic foods, goitrogens in the drinking water, goitrogenic
medicines, bacterial infections, and vitamin deficiencies. Fortunately,
as a general rule simple goitre, irrespective of the cause, can
be very, or fairly, satisfactorily combated by an adequate increase
in man's daily iodine intake, except when the enlargement of the
gland is due to the ingestion of excessive amounts of fluorine,
as happens in areas where the subterranean waters are heavily
contaminated with this halogen. The only correct solution to fluorine-induced
endemic goitre is the removal of this element from the drinking
water. Also from the point of view of general health this is the
correct procedure...
In the Union of South Africa we have the complicating
fact that in the endemic fluorine area (North-Western Cape Province)
there are certain localities where endemic goitre is due, not
to the presence of excessive quantities of fluorine in the water,
but to a deficiency of iodine in the water supplies. Such localities
are Upington, Karos, and other townships and farms drawing their
water supplies from the Orange River. On the other hand, there
are endemic goitre areas where the major cause of the disease
is primary iodine-deficiency and where there are odd cases where
the disease is fluorine-induced. A few such cases we found in
the vicinity of Polela, Natal, where the subterranean drinking-water
contained 2.4 parts of fluorine per million parts...
It is recommended that the use of iodized salt
be not made compulsory throughout the Union of South Africa but
that propaganda be made for its use only in endemic goitre areas
where the disease is due to a primary iodine deficiency, i.e.
in all the known endemic goitre areas except in that part of the
North-western Cape Province where goitre is fluorine-induced.
As stated before, the only solution to the latter type of goitre
is the removal of fluorine from the drinking water.
XI. REFERENCES (for above excerpts)
4. Iodine Facts, Vol. I (1-380) (1940-1946).
32. LINNELL, J.W. and R. GREENE (1947). - Thyrotoxicosis. The
Overseas Post Graduate Med. Jour., Vol. 2, pp. 29-37.
124. MAY, W. (1935). - Antagonismus zwischen Jod und Fluor im
Organismus. Klin. Wschr., 14 Jrg., pp. 790-792.
125. EVANS, R.J. and P.H. PHILLIPS (1938). - The Fluorine Content
of the Thyroid Gland in Cases of Hyperthyroidism. J.A.M.A., Vol.
III, No. 1, p. 300.
126. STEYN, D.G. (1938). - Fluorine Poisoning in Man and Animal.
Printed by Cape Times, Ltd., Cape Town (47 pages).
127. STEYN, D.G. and N. REINACH (1939). - Water Poisoning in Man
and Animal, together with a Discussion on Urinary Calculi. Onderstepoort
J. of Vet. Sc. & An. Ind., Vol. 12, No. 1, pp. 167-230.
128. STEYN, D.G. (1948). - Fluorine and Endemic Goitre. S.A. Med.
Jour., Vol. 22, No. 16, 28 Aug., pp. 525-526.
129. STEYN, D.G. (1948). - Vergiftiging van Mens en Dier Deur
Drinkwater. Tydskr. vir Wetenskap en Kuns, Okt. 1948, bl. 105-116.
130. WILSON, D.C. (1941). - Fluorine in the Aetiology of Endemic
Goitre. Lancet, Febr. 8, pp. 211-212.
131. BOYER, P.D. et al. (1941). - The Toxicity of 3-Fluorotyrosine,
3-Fluorophenylalanine, 3-Fluoro-5-Iodotyrosine, and 3,5-Difluorotyrosine
and Their Effect upon the Basal Metabolic Rate of the Rat. (From
the Department of Biochemistry, University of Wisconsin, Madison),
Jour. of Biol. Chem., Vol. 140, xx.
132. McCLURE, F.J. (1949). - Fluorine in Foods. Publ. Heallth
Rep. Vol. 64, No. 34, pp. 1061-1074.
133. HELD, A.J. (1953). - Fluorine and the Thyroid Gland. Chem.
Abstr., Vol. 47, p. 12661.
134. SPIRA, L. (1953). - Pathological Findings in Fluorine Intoxication.
A.M.A. Arch, Indust. Hyg. & Occup. Med., Vol. 7, No. 3, p.
262.
247. WESPI, H.J. (1954). - Besteht ein Antagonismus zwischen Fluor
und Jod. Schweiz. Rundschau f. Med., 43 Jrg., pp. 616-623.