Pathophysiology of Himalayan endemic goitre.

The mountain slopes of the Himalayas, Alps, Pyrenees, and Andes have been the world’s most notorious foci of endemic goiter (1). The northern frontiers of India extending from Kashmir in the west to Assam in the east form an extensive Himalayan goiter belt (2). Forty million persons are believed to be exposed to the risk ofgoiter in this belt and approximately nine million are afflicted with it. The pioneering work of the late Sir Robert McCarrison in the early part of this century focused attention not only on the extent of the Himalayan endemic goiter but also on its cause and on the reaction of the thyroid to various noxious influences, i.e., nutritional, toxic, and infective (3). Despite all that has been written about the etiology and pathogenesis of endemic goiter, many problems still remain unresolved. The study by Stanbury and his co-workers (4), the first of its kind, of the metabolism of iodine in people with endemic goiter in western Argentina, employing radioactive iodine and modern chemical methods of assay of stable iodine, indicated that lack of iodine in the diet was the most probable cause in that area. Similar observations confirming the primary role of iodine deficiency have been made in other parts of the world such as Venezuela, Holland, Finland, Greece, Eastern and Western New Guinea, and the Congo. Studies in Tasmania, Scandinavia, Central Europe, and Colombia suggest the operation of other goitrogenic factors of dietary origin in the development of the disease (5). It has been suggested that the iodide deficiency hypothesis cannot explain endemic goiter in every area and that other factors may be significant. A naturally occurring goitrogenic substance was isolated from human foods (6). Clements (7) felt that endemic goiter among the children in Tasmania was probably due to ingestion of a goitrogenic substance capable of interfering with the iodide trapping mechanism. There are other scattered observations that incriminate factors other tha i iodide deficiency (8-10), but to this date no naturally occurring goitrogen has been shown conclusively to be responsible for endemic goiter in any community, although it may be playing an adjunct role in some areas (1 1). Even in Tasmania where there seemed to be a definite possibility of a goitrogen playing a role, recent studies indicate that iodine administration can effectively reduce goiter prevalence there(ll, 12). The etiological factors of Himalayan and sub-Himalayan endemic goiter have been under investigation for the past 16 years in our laboratory and the results of some of these studies have been reported (13-16). The studies carried out so far in various areas in the Himalayan goiter belt included field surveys of prevalence, clinical evaluation, and biochemical investigations. In recent years, our studies have been extended to include Nepal (which is in the Himalayan goiter belt), Ceylon, and further studies were made in the Indian goiter belt itself. This paper presents the results of these more recent studies. The areas where studies of endemic goiter have been made by our group in India, Nepal, and Ceylon are indicated in Fig. 1. The studies made in Ceylon have been published (17), and are not discussed in detail here again; only the results obtained are given in relation to those obtained in the Himalayan goiter belt in India and Nepal. The results of studies made in goats living in the endemic area and in rats under an experimental iodine-deficient regimen in our laboratories are also presented in brief as they throw considerable light on the findings obtained in human studies.