Derbyshire Neck and Iodine Deficiency

Goitre and the associated neurological deficits of cretinism and deaf mutism due to iodine deficiency were common in Derbyshire, giving rise to the term Derbyshire Neck. These diseases were most prevalent in the 19th century and earlier, when they had devastating effects in the rural population. Since then they have declined in frequency. However, iodine deficiency disorders are still prevalent worldwide, and iodine deficiency is the single most common cause of mental retardation and brain damage. Globally, 2.2 billion people, ~38% of the world population, live in risk areas of iodine deficiency. Dietary iodine deficiency and environmental goitrogens block the synthesis of thyroid hormones. Iodine deficiency disorders are common in areas of low environmental iodine. But the iodine geochemical cycle is complex, and iodine deficiency disorders may develop in areas where iodine is present in the environment but is not bioavailable; this is because it is chemically bound in the soils, or because other dietary components inhibit the synthesis of thyroid hormones. In 19th century Derbyshire iodine deficiency diseases were likely to have been multifactorial. Goitres occurred principally in limestone areas and were due to the binding of iodine in the alkaline soils, with impaired uptake into local farm produce. Supplementary mechanisms may have included genetic susceptibility and dietary goitrogens. The decline of iodine deficiency diseases began with the increased standard of living and a wider range of dietary products from areas outside Derbyshire. Figure 1. Diffuse enlargement of thyroid producing “Derbyshire Neck” in a female (from the archives of Derbyshire County Council). years; and often the last half year of this time it grows more than it had for a year or two before. It generally occupies the whole front of the neck, as the whole thyroid gland is here generally enlarged, .... but is rather in the pendulous form, not unlike, as Albucasis says, the flap or dew-cap of a turkey-cocks neck, the bottom being generally the bigger part of the tumor and going gradually less upwards.... By the situation and nature of the complaint it occasions a difficult breathing, and very much so upon the patient`s taking cold, or attempting to run or walk fast. In some the tumor is so large , and so much affects their breathing as to occasion a loud wheezing.... .It is very common in many counties in England, Derbyshire especially, where from its frequency, it has the name Derby-neck .... .I have been informed by a gentleman of the faculty, from Duffield in Derbyshire, that there were near fifty poor girls afflicted with it in that small village. Erasmus Darwin (1796), working as a medical practitioner in Lichfield, drew attention to water supplies as a possible cause of goitre: Bronchocele. Swelled throat. An enlargement of the thyroid gland said to be frequent in mountainous countries, where river water is drank, which has its source from dissolving snows. This idea is a very ancient one ...The inferior people of Derby are much subject to this disease, but whether more so than other populous towns I can not determine; certain it is that they chiefly drink the water of the Derwent, which arises in a mountainous country, and is very frequently blackened as it passes through the morasses near its source; and is generally of a darker colour, and attended with whiter foam, than the Trent. A more vivid and compelling account of the disease and its disastrous social effects on affected families is given by Rev. D. Vawdrey, Rector of Darley Dale and vice-chairman of Bakewell Union in evidence to Parliament (British Parliamentary Papers 1968) and he made the important link between goitre and neurological deficits. Goitre is an evil incident to this locality, so extensive and so mischievous that no report of the districts of Derbyshire would be complete without some reference to it. There is a great deal of it in this parish. In one family six daughters were deaf and dumb, one son a maniac, and another imbecile. In another family four daughters were deaf and dumb. There are many other cases of imbecility and imperfect development either of bodily or mental power or both, all in this parish. Yet this parish is well drained, has admirable water all flowing from gritstone and is spread over a wide and very open valley. Goitre chiefly prevails among the aboriginal inhabitants. I know but of one instance where any strangers coming to live here (and there are many) have shown any symptoms of it. Among the aborigines the system of intermarrying has been carried on for generations to an extent which I have never met with out of Derbyshire and to this fact more than any other, I attribute the prevalence of this disease (in fact the western half of the parish is underlain by limestone, and much more has calcareous soils on the limestonerich till). At the same hearing, Mr C. Evans (British Parliamentary Papers 1968) noted significantly that Cases of 'Derbyshire neck' are diminishing though still hanging about the districts in which it used to prevail. Dr William Webb (1886), a physician and surgeon of Wirksworth for thirty years, emphasized the association of goitre and cretinism (Fig. 2), but gave further insight into the changing frequency of the disease and into life for working women then. He had an eye for the rocks and water sources as possible aetiological factors: goitre is a true hypertrophy of the thyroid gland from the excessive performance of functional duty. This theory explains to some extent the occurrence of bronchocele when the girl is approaching womanhood; and also those cases which happen in women who get their bread as workers in the cotton mills of Derbyshire and who have frequently to walk two, three or even four miles, over steep hills to their work before six-o-clock in the morning; then to live in a flocculent atmosphere, working all the time, for ten hours a day and afterwards to tramp over the same ground at night. .... Enlargement of the thyroid gland is for the most part seen in women belonging to the working classes, although not altogether confined to them. It is also common in those whose ancestors have intermarried. .... It is found equally amongst the Yoredale rocks and limestone formations, and does not appear to be confined to those who drink any special character of water. .... It is much less prevalent now than it was thirty years ago and yet women drink the same waters. They get better wages, which means better and more nutritious food. The railway communication which did not then connect the goitrous districts with the county town has now given the people opportunities and means to pay visits to other parts of which they constantly avail themselves; GERARD SLAVIN MERCIAN GEOLOGIST 2005 16 (2) 80 Figure 2. Two 19th century cretins from Derbyshire. “I have a family in my recollection at this moment, consisting of a man and his wife (since dead) having a large fibrous goitre. Both are of average mental capacity. They have some sharp children and also two cretin women their offspring. These latter, in age between 20 and 35, are stunted in growth and have but limited powers of understanding or even of going to and fro, except in the shuffling gait of the paralytic. They sit from morning till night, nursing a doll, or other toy and comporting themselves as very little children do, but with only a fractional part of their intelligence”. (from Webb, 1886). DERBYSHIRE NECK AND IODINE DEFICIENCY MERCIAN GEOLOGIST 2005 16 (2) 81 consequently there has been less intermarriage and less breeding in-and-in; and I am decidedly of the opinion that, if the decrease of bronchocele take place in the same ratio as it has done in the last generation, ere another has passed away, endemic goiter will, so far as Derbyshire is concerned, have almost disappeared. Goitre was, thus, widely recognized in Derbyshire in the 18th and 19th centuries in anecdotal accounts, but the wider pattern of associated diseases was also seen as a problem by physicians and politicians alike. Towards an understanding The first systematic study of goitre in England and Wales (Berry, 1891) delineated a high frequency goitre belt extending from Cornwall, through Somerset, Oxfordshire and the Midlands to Derbyshire and the northern Pennines, with offshoots into North and South Wales (Fig. 3). Berry described the Carboniferous limestone areas of England as the very hot bed of goitre, and recorded particularly numerous sufferers in Cromford, Matlock, Youlgreave, Bakewell, Baslow and Stoney Middleton. Stocks (1927) surveyed the prevalence of goitre in 375,000 schoolchildren throughout England and Wales, confirming the distribution of goitre and the high rates in limestone areas. Turton (1933) studied the prevalence of goitre in Derbyshire, and noted that it was not confined to but was much more prevalent in limestone areas. Significantly, he noted that by then cretins had become a rarity. The Goitre Subcommittee of the Medical Research Council (1944) estimated that in England and Wales there were 500,000 cases of thyroid enlargement in persons between the ages of 5 and 20 years. Kelly and Snedden (1958, 1960) commented that there was no reason to suppose any lessening of the figure in the intervening years. However, a survey by general practitioners of thyroid abnormalities in the Peak District (West Derbyshire Medical Society, 1966) showed a large decrease in thyroid abnormalities in younger people but without a comparable decrease in adults; this provoked them to write that the time had not yet come to forecast the imminent passing of Derbyshire neck and led to the increased recommendation of iodised salt to younger families in their care. Nevertheless they observed: a lower consumption of locally grown produce began with the railway penetration of the Derbyshire valleys near the turn of the last century and one of the older practitioners used to say this coincided with a fall in the local prevalence of goitre even then. In conclusion, the natural history of goitre and its associated disorders in Derbyshire was that its prevalence in the 19th was severe, affecting whole communities, but that it slowly declined in severity. This decline preceded any specific treatment for iodine deficiency, with the opening of rural areas to the wider world by better communications, importation of dietary products from outside Derbyshire and improved living standards. Goitre persisted until the middle years of the 20th century, despite the introduction of iodine prophylaxis. A similar progression in other limestone districts has been observed, as at Hooke Norton in Oxfordshire (on Jurassic limestone), where iodine deficiency persisted in school children until the 1950s (Hughes et al, 1959). Iodine deficiency in goitre Numerous ancient treatments for goitre included seaweed extracts, and iodine was discovered in burnt seaweed residues by the French chemist Courtois in 1811. Coindet, an Edinburgh-trained physician, gave potassium iodide to goitrous patients in Geneva in 1820 with great success. However, others gave iodide in a grossly high dosage; the induced side effect of thyrotoxicosis caused fatalities, and the treatment largely fell into disrepute (Langer, 1960). At the end of the 19th century, fried sheep thyroid or dried thyroid extract was used successfully in the therapy of hypothyroidism, and in the search for the active principal, iodine was found in the gland. The active hormone thyroxin was identified and named by Kendall in 1919. It was synthetised by Harrington and renamed thyroxine (T4), a more chemically correct name, for it is an amino-acid derivative with four iodine atoms rather than an indole structure as Kendall believed. Subsequently a second hormone triiodothyronine (T3) was found. Marine (1920) re-established the therapeutic and prophylactic use of iodine in a report on the prevention Figure 3. Goitre distribution in Great Britain, recognized by Berry (1891), with much of the main goitre belt (shaded), underlain by carbonates. of simple goitre in schoolgirls in Akron, Ohio. However, his view of endemic goitre as an iodine deficiency disease was not without opposition. The long-established view was that endemic goitre was due to something in the water supplies toxins, bacteria or parasites (McCarrison, 1906; Berry, 1891) rather than iodine deficiency; this view prevailed for some time and with contention. Turton (1933), working in Derbyshire, produced experimental evidence purporting to show that endemic goitre was not related to iodine deficiency and concluded there was no case for the promiscuous administration of iodine amongst either the children or adults of this county. Nevertheless, opinion changed, and following Stocks` survey (1927), a recommendation was made for the prophylactic administration of iodine to girls in endemic areas of England and Wales, but was never implemented. During the 1939-45 war, concern at the prevalence of goitre in women munitions workers prompted the Medical Research Council to appoint a Goitre Subcommittee (1944). They recommended the general adoption of iodised salt throughout the country, but no government action followed, except that iodide was added to the vitamin tablets issued to expectant and nursing mothers. Iodised salt became commercially available in Britain in the immediate post-war years through the initiative of Cerebos. Iodised salt was custom-packed for various Cooperative Society stores, but the last supplied were in the Derbyshire area. Sources of iodine in the diet The recommended adult daily intake of iodine is about 100-150 μg/day (Hetzl, 2000). Fish and seafood is a major source of dietary iodine, and is forty times richer than most other foodstuffs (Johnson et al, 2003). Arable crops and vegetables are not rich in iodine, and inland areas far from the marine source may provide only low amounts of iodine. Leafy vegetables and grass concentrate iodine by adsorption on the leaves from the atmosphere. Iodine may then enter the diet through animal products, especially those of grazing animals; these secondarily concentrate iodine, by ingesting not only grass and leaves but also soil, which includes soil-bound iodine not bioavailable through plants. In today's developed countries, a major source of iodine lies in dairy products because of the addition of iodine to cattle feed and the use of iodine containing disinfectants in cattle sheds. Iodised salt is a potentially important source, but its use is not mandatory and much on our shops is not iodinated. In the past, surface water supplies were emphasized as an important source of dietary iodine, but water sources are likely to supply less than 10% of daily dietary requirements. Inhalation of atmospheric iodine is possible but with a minor input of only 0.5 μg/day. Pathophysiology of the thyroid The thyroid gland lies in front of the trachea in the neck. Its principal function is to secrete iodinecontaining hormones. This depends on an adequate iodine supply and uptake by the thyroid, on hormone synthesis and release from the gland. Geochemical or dietary agents may interfere at different stages, producing a primary lack of iodine in the diet, inhibition of hormone synthesis or alterations in hormone usage. • Iodine concentration in the thyroid. Iodide is absorbed from the gut and circulates by the blood to the thyroid where it is concentrated to maintain an iodine gradient of 100:1 between the thyroid cell and the blood. In iodine deficient conditions the gradient may rise to > 400:1 to keep the required daily intake. • Synthesis and release of thyroid hormones. Iodide is oxidized to either nascent iodine or I3 which combine rapidly with tyrosine, to form monoand diiodotyrosine and these are coupled to form the thyroid hormones, thyroxine containing 4 iodine atoms (T4) and tri-iodothyronine containing 3 iodine atoms (T3). • Peripheral action of thyroid hormones. T4 and T3 are released into the blood and carried to the tissues. There they maintain cellular metabolism at a basal rate. In addition to these actions, the hormones have important effects on the growth and development of the brain in the foetus and new-born. Therein lies the major importance of iodine deficiency disorders. Foetal and neonatal brain development is characterized by two main periods of growth. The first is between the third and fifth months of pregnancy when there is nerve cell proliferation and initial organization of the nervous system. The second occurs in the third trimester and continues into the second and third years of post-natal life. Thyroid hormones coordinate and regulate growth through binding of T3 to nerve cells in different parts of the brain. During the initial phase of growth the supply of thyroid hormones to the foetus is almost entirely maternal. T3 bound to foetal nerve cells is produced by the foetus from circulating maternal T4. Foetal synthesis of T3 from maternal T4 is of particular importance in those areas where there is a combined deficiency of selenium and iodine (see below), when it is a factor in determining the clinical type of cretinism (Delange, 2000). Control of thyroid function The activity of the thyroid gland is controlled by a feedback mechanism: low levels of thyroid hormones induce secretion of thyroid stimulating hormone (TSH) from the pituitary gland. There is then an increase in the number, size and functional capacity of thyroid cells with increased synthesis and release of thyroid hormones from an enlarged thyroid a goitre. Enhanced physiological TSH secretion occurs at particular times of need such as adolescence, in girls at the menarche and in pregnancy. In these groups, even on an adequate diet, slight thyroid enlargement may be seen. In some cultures, mild thyroid enlargement and enhanced delicate curve of the neck in young women is seen as a sign of beauty. During the Renaissance, goitre was a common feature in Italian paintings of the GERARD SLAVIN MERCIAN GEOLOGIST 2005 16 (2) 82 Madonna. In the context of endemic goitre, any environmental factor interfering with thyroid hormone synthesis or function results in thyroid stimulation from the pituitary and pathological enlargement. Clinical effects of iodine lack Thyroid enlargement in an individual may cause symptoms (Fig. 1), but this is rarely a major public health problem. However, endemic goitre is a marker for important associated syndromes arising from maternal thyroid hormone deficiency in pregnancy, including infertility, abortions and stillbirths, endemic cretinism and impaired mental capacities in children and adults. The whole spectrum of disorders is better termed iodine deficiency disorders (IDD). There are two polar forms of endemic cretinism the neurological and the myxoedematous types (McCarrison, 1908) though many are intermediate in presentation. These forms relate to the timing of the maximal hormonal deficiency insult to the child`s development, whether early in pregnancy or in the neonatal period (Stewart & Pharoah, 1996). Neurologic cretinism is characterized by severe mental deficiency, deaf mutism and spastic paralysis. The myxoedematous form shows mental deficiency with short stature and markedly delayed sexual and bone maturation. The skin and other tissues may be thickened by a mucinous deposit which gives rise to the term “myxoedematous” An associated deficiency of selenium in a geographical area is a factor in the predominance of myxoedematous cretinism in that location (Delange, 2000). Importantly, studies in at-risk populations indicate that cretinism is not an all-or-none phenomenon and that iodine deficiency has wider neural effects than the classical forms. Associated with endemic cretinism, increased numbers in the “normal” population have motor and cognitive deficits. Any neural damage to the brain is permanent, and eradication of iodine deficiency is therefore a critical public health matter.