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The present status of endemic goitre and endemic cretinism in China

Ma Tai, Lu Tizhang, Tan Yubin, Chen Bingzhong, and Zhu Xianyi (H.l. Chu)
Institute of Clinical Endocrinology, Tianjin Medical College, Tianjin, China

DISTRIBUTION AND PROPHYLAXIS

China is a vast country, having a territory of 9,600,000 km², divided into 22 provinces, 3 municipalities, and 5 autonomous regions; the total population is about one billion. Endemic goitre and endemic cretinism have been common and widely distributed throughout this country. Endemic goitre has been reported from all provinces and cities except Shanghai. Endemic cretinism has been variously reported from most of the endemias of goitre, with the incidence ranging from zero to as high as over 10 per cent; Jiangsu, Zhejiang, Jiangxi, Taiwan, and Shanghai have no official reports on endemic cretinism.

The prevalence of endemic goitre and endemic cretinism is closely related to geological conditions. The geological features and natural landscapes of China are highly variable. As a rule, endemicity is prominent in mountainous areas, but serious endemic foci have also been found on sedimentary plains. Goitre is usually prevalent in places far away from the sea, but endemias have occasionally been found in coastal provinces of this country (fig. 1).

FIG. 1. Several Significant Endemias of Goitre and Cretinism in China

Surveys of several significant endemias scattered over many provinces of China are shown in table 1 (1-13). All these surveys were done before the beginning of regular salt iodization programmes in the areas studied.

The criteria used for grading endemic goitre were in accordance with the document published in 1978 (14) by the Scientific Committee of the Endemic Disease Control Bureau of North China. They are similar to the criteria given by Stanbury et al. in 1974 (15). Individuals with grade I goitre or larger are considered to be endemic goitre patients.

TABLE 1. Incidence of Endemic Goitre and Cretinism in Several Significant Endemias in China

* Of adolescents.
** Of schoolgirls.

TABLE 2. Prophylaxis of Endemic Goitre

* Male. ** Female

The criteria used for diagnosis of endemic cretinism were established during the scientific conference on endemic goitre and endemic cretinism in 1980 at Hueixian (16) and are quite similar to the definition given by Querido and coworkers in 1974 (17). The main criterion is: "Any individual born in an endemic goitre area, who has mental deficiency in various degrees, together with either neurological defect or hypothyroidism."

Ever since the establishment of the People's Republic of China in 1949, the Chinese Government and its Ministry of Health have given full attention to the use of iodized salt for goitre prevention. It is a co-operative enterprise under the direction of the Chinese Central Government, with members of the Ministry of Health, Ministry of Chemical Industry, and Ministry of Commerce, with the National Co-operative Head Office as executive committee. With the help of health technical experts, satisfactory results have been achieved with the close collaboration of the above-mentioned ministries and provincial governments.

It has been reported that up to the end of 1979, in the 16 provinces and autonomous regions in greater North China, including north-eastern as well as north-western provinces, iodized salt has been supplied free of additional cost to 70 per cent of the areas where goitre is known to be endemic. The number of goitre patients decreased from 15 million in 1973 to 7.5 million in 1979. No new cases have been discovered in 20 per cent of these areas, and the disease has come under control in several provinces. For example, Shaanxi Province used to be a heavily endemic area, where there were 576,000 goitre patients in 1972. The number decreased to 158,000 in 1979 as a result of persistent use of iodized salt during these years. Also, a salt iodization programme has been carried out regularly in Hebei Province, where there were 1,560,000 goitre patients in 1972. By 1979, the number had dropped to 390,000.

Some examples of the results of iodized salt prophylaxis appear in table 2 (18-25). In most provinces the concentration of potassium iodide in salt is 1: 20,000 (the concentration of iodine is 1: 26,000). In some provinces where the concentration of potassium iodide in salt is 1: 50,000, satisfactory results have also been obtained.

In addition to iodized salt prophylaxis, iodized oil has been used in some areas of China. People living in the Tarim Basin of Xinjiang Autonomous Region and Nei-Monggol Autonomous Region can get raw rock salt at no cost from the numerous salt deposits in the desert. The ordinary salt iodization programme is not applicable there. Under such circumstances, iodized oil injection is the method of choice. In China, instead of the more expensive ethiodol, lipoidal or iodized soybean oil has been used for intramuscular injection and has given satisfactory results without significant unfavourable side effects. Oral administration of iodized oil is also under trial.

However, there are still certain endemic areas, especially in the south-eastern and south-western parts of the country and in Xinjiang Autonomous Region, where iodine prophylaxis has not yet been practiced or enforced for various reasons.

In addition to endemic goitre caused by iodine deficiency, we discovered it in the coastal areas where the inhabitants had an excessive iodide intake, either fishermen cultivating and consuming kelp and other seaweeds, or people drinking iodine-rich, deep well water in and around the oil field. This finding is in accord with those of Suzuki (26), who has found endemic goitre in kelp-eating fishermen of Hokkaido, Japan. The extremely high intake of iodine and the high plasma levels of iodide block hormone synthesis and release by the thyroid in susceptible individuals, and this results in goitre. The physiological rationale for this occasional susceptibility to chronic high intake of iodine is not entirely clear at present.

CLINICAL MANIFESTATIONS OF ENDEMIC CRETINISM

The clinical picture of endemic cretinism in China is quite variable. The common type is neurological cretinism, but typical myxoedematous cretinism can also be seen in some endemias of this country. A number of mixed forms characterized by either predominant neurological defects or predominant hypothyroidism have been found in other parts of the country. The classification of the two types of cretins is based on the following criteria:

1. Mental retardation is the common criterion in both types.
2. Neurological cretins have predominantly neurological manifestations, such as abnormalities in hearing and speech, congenital diplegia, strabismus, and only occasionally myxoedema.
3. Myxoedematous cretins have predominantly hypothyroid manifestations, such as stunted growth, sexual underdevelopment, myxoedema, and other clinical symptoms and signs of hypothyroidism, and only occasionally upper motor neuron defects.

The endemic cretinism in the suburb of Chengde City, Hebei Province, was of the neurological type. During the first survey in 1961 (27, 28) the morbidity rate was 2.4 per cent; the youngest patient was 5 years of age, and the oldest was 55. Most were under 12. They all showed mental retardation, and some were profoundly retarded. Hearing and speech defects were also striking; 26.2 per cent were completely deaf, and 46.3 per cent were completely mute. Upper motor neuron defects were also quite common; 76.2 per cent had an abnormal gait, 8.6 per cent scissor gait, 27.5 per cent an exaggerated knee jerk, and 3.8 per cent had severe spastic paralysis. Pneumoencephalographic examination of four cases of cretinism showed two with widening of the subarachnoid space, indicating atrophic changes in the brain. EEG examination showed low frequency and irregular rhythm; 53.9 per cent had no alpha waves, while 92.3 per cent had paroxysmal bilateral synchronic theta waves.

Physically they showed definite developmental retardation. Their heights were 3.1 to 13.0 cm lower than normal. The ratio of the upper and lower body measurements was greater than 1. Roentgenological examination of the wrists showed delayed bone age in 76.5 per cent, but 32.7 per cent of the normal children of the same age in the same locality showed slightly delayed bone age, considered to be the result of malnutrition.

Sexual development was usually delayed in both male and female cretins. Menarche usually delayed by one to five years, yet some of these women eventually attained full maturation and gave birth normally. Only two cretins had definite myxoedema, with no other obvious signs of hypothyroidism and no enlargement of the sella turcica on radiological examination.

The thyroid gland was not palpable in 63.7 per cent, palpable but not visible in 23.8 per cent, and only 12.5 per cent had a definite goitre. Average 24-hour thyroid uptake was 69.0 ± 12.1 per cent in seven goitrous cretins and 82.7 ± 12.4 per cent in 10 non-goitrous cretins. Protein-bound iodine was 2.86 ± 1.92m g% in 19 goitrous cretins and 3.05 + 1.30,ug% in 27 non-goitrous cretins. The thyroids of the latter were shown to be slightly decreased in size by scanning.

Endemic cretinism has been thoroughly studied in Guizhou Province. The rates of endemic cretinism in Heba (29), Pingliang, and Shilong communes in this province in 1979 were 3.1,2.8, and 2.5 per cent, respectively. Among 407 cases carefully observed, 180 were male and 227 were female. The youngest was six months old and the oldest 19 years of age. This was taken to imply that endemicity in these regions was of only recent origin. Mental retardation was marked in all of the patients; 42.9 per cent were classified as idiots, 37.7 per cent as imbeciles, and 9.4 per cent as morons. Among the patients, 92.8 per cent had speech defects, and 82.9 per cent had hearing defects of varying degrees. Vestibular function was sluggish in 96 per cent; gait was abnormal in 77.8 per cent, 46.1 per cent had a positive Babinski sign; 35.2 per cent had upper motor neuron paralysis; and many showed severe deformity of the extremities. Cranial nerve defects were present in 23.5 per cent, largely manifested in squinting. X-ray examination showed delayed bone age. The appearance of the ossification centres of the femoral head was usually much delayed and sometimes fragmented. Sometimes metacarpal bones, metatarsal bones, and patellae showed mottling. Thyroid enlargement was found in 15.3 per cent.

Heba Commune was also an untreated endemia. Urinary iodine excretion in cretinous children averaged 21.4 ± 3.1 m g/g creatinine; 24-hour thyroid uptake was 76.0 ± 10.4 per cent; serum T4 was 4.1 ± 2.6, m g/dl, serum T3 was 122.0 ± 37.7 ng/dl, and serum TSH was 36.3 ± 2.2 , m U/ml. There was no apparent clinical sign of myxoedema among the cretins, but the presence of hormonal hypothyroidism could not be disputed. We could not, therefore, consider that this was a pure neurological type of cretinism.

Both neurological and myxoedmatous types of endemic cretinism can be seen in Hetian and Luofu counties of Xinjiang Autonomous Region (30). A survey conducted in 1980 revealed that goitre incidences were 55.7 per cent and 46.5 per cent, respectively, and the incidence of cretinism was 2.08 and 1.83 per cent, respectively. Seventy-two cretins were examined, 38 male and 34 female. The oldest was 68 years of age, and the youngest was only 3. Judging by the incidence in older persons, this endemia has very likely been present for some time.

All 72 cretins were divided into three clinical types. Twenty-four were neurologic, 20 were mixed, and 31 were myxoedematous. Since these 72 cretins were not taken at random, these figures hardly represent the real incidence of the different clinical types. A comparison of the neurological and myxoedematous patients showed significant differences according to various categories.

The myxoedematous patients showed less mental retardation than those with the neurological type. They could react to the environment in an ordinary manner, but locomotion was sluggish. Sometimes they were capable of performing simple manual tasks. Their facial expressions were apathetic, but with fewer silly laughs than observed in neurologic cretins.

Hearing and speech defects were less marked in typical myxoedematous cretins. Among the 26 cases of myxoedematous cretinism examined, only 4 showed impairment of hearing, and neither complete deafness nor deaf-mutism was found. Vestibular function tests usually elicited normal responses. Most of the patients could speak logically and clearly, but not fluently. In contrast, among 15 cases of neurological cretinism, 9 had impairment of hearing, and 6 were severely deaf. Vestibular tests evoked no response. There was no marked sign of upper motor neuron paralysis in the myxoedematous type, except that some showed slightly increased patellar reflexes. The upper motor neuron defects were less marked in the neurological cretins of Hetian than in the cretins in Chengde or Guizhou. No marked deformity of the extremities was observed.

The myxoedematous cretins showed marked dwarfism, the average height of the 19 typical adults patients being 121.9 cm, which was similar to the average height of children nine to ten years old in the same locality. The height of neurological cretins was close to that of normal inhabitants. Body proportions were infantile, and the legs were short in proportion to height in the myxoedematous cretins. Most of them had characteristic facial features: the eyes were far apart, nose bridges were flattened, and the nose wings were wide. The neck, fingers, and toes were usually short, with thin, fragile fingernails. The most impressive sign in some severe cases was softness of the ear wings and nose tip, as though there was no cartilage.

X-ray examination showed marked retardation in bone maturation. The bone age of the carpus and metacarpus was delayed. There was epiphyseal and metaphyseal dysgenesis of the radius and ulna. The femoral head was usually mottled in appearance and sometimes fragmented.

Sexual development was much retarded. Eight out of the 12 adult male myxoedematous cretins had infantile external genitalia or undescended testes. Some had gynecomastia. Nine of the 13 adult females had infantile external genitalia and underdeveloped breasts. Secondary sexual characteristics such as pubic hair, axillary hair, and beard were usually lacking. Amenorrhoea or scanty menstrual flow was present in most adult female patients. Both males and females were usually infertile.

Myxoedema was, as a rule, clearly manifest in the myxoedematous cretins, and also could be found in the neurological cretins in mild degrees. It was marked in the buttock, loin, and shoulder regions, and in severe cases it was present all over the body. The skin was cold, dry, and coarse without hair growth. The patients usually had a sense of cold, decreased sweating, and constipation. Achilles reflex times showed prolongation of VP interval, while it was within normal limits in neurological cretins. Owing to general weakness of the skeletal muscles, patients had difficulty in performing heavy physical work. There was usually lumbar lordosis and protuberant abdomen, sometimes accompanied by either umbilical or inguinal hernia.

Goitre was comparatively rare in the myxoedematous cretins. Eight goitres were found in 14 neurological cretins, but only two were found in 27 myxoedematous cretins. Enlargement of the sella turcica on X-ray examination was present in some of the latter patients.

Laboratory examination showed that serum T₄ was 4.5 ± 1.4 m g/dl T₃ was 41.0 ± 29.3 ng/dl; and TSH was 118.5 ± 114.4, m U/ml (normal value 8 m U/ml) in myxoedematous cretins. T₄ was 7.9 ± 2.3, m g/dl, T3 was 91.5 ± 32.4 m g/dl, and TSH was 49.6 ± 71.6,m U/ml in neurological cretins. All of these figures show significant statistical differences.

Another extensive study of myxoedematous cretinism has been conducted in Chang Han Ying Commune of Liang Chen County of Nei-Monggol Autonomous Region (31). The goitre rate was 28.31 per cent, and the rate of cretinism was 0.37 per cent. Forty-one cretins were studied; 87.8 per cent were of the myxoedematous type, and 12.2 per cent were mixed type. No pure neurological cretin was found here.

TABLE 3. Prevalence of the Principal Clinical and Metabolic Characteristics of Endemic Cretinism in China

The youngest was 6 years of age and the oldest was 28, indicating that this endemia is a relatively new one. Mental examination showed that there were 2 idiots, 16 imbeciles, and 23 morons. Hearing examination revealed that six patients had slight impairment (hearing loss about 40 to 50 db), and three had severe impairment (hearing loss about 70 to 90 db). Two had severely impaired hearing combined with feeblemindedness, and five were complete deaf-mutes. Most of these cretins could speak intelligible sentences but with a slight deviation in pronunciation. The motor neuron defect sign was rarely seen. Body growth was stunted, sexual development was retarded, and myxoedema was present in all cases. Softness of ear wings and nose tips was also noticed in this group of patients. The thyroid was not enlarged in 85 per cent of them (table 3).

Thus, a comparative study of the different types of cretin in China showed that the chief manifestions of neurological cretinism were irreversible feeble-mindedness, impaired hearing and speech, congenital diplegia, and strabismus. The hypothyroidism was either of slight degree or subclinical.

On the other hand, stunted growth, sexual underdevelopment, manifest hypothyroidism, and mental retardation were the main features of the myxoedematous cretin. Hearing and speech defects were comparatively slight, and upper motor neuron signs were only occasionally seen. Most cases of endemic cretinism fell between these two extremes of a wide spectrum. We are uncertain whether neurological and myxoedematous cretinism are distinctly different disease entities, but certainly there are pathogenetic discrepancies between the two. Evidently neurological cretinism is chiefly the result of iodine deficiency and hypothyroidism during gestation, while the myxoedematous type is somewhat similar to sporadic cases of cretinism.

Prophylaxis of endemic cretinism by an iodized salt programme has been successful in all parts of the country. In the suburb of Chengde City (unpublished data), no new cretin has been found since initiation of salt iodization 21 years ago. All four children of two cretinous mothers were cretins before iodine prophylaxis, but after having iodized salt, each mother gave birth to an intelligent child.

References

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