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.
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
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…
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).
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128. STEYN, D.G. (1948). – Fluorine and Endemic Goitre. S.A. Med. Jour., Vol. 22, No. 16, 28 Aug., pp. 525-526.
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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.