Goitre Due to Dyshormonogenesis with Particular Reference to Sporadic Goitrous Cretinism and Sporadic Familial Goitre in Young Patients

Evidence for inherited disturbances of hormone synthesis in selected cases of sporadic goitre as well as in sporadic goitrous cretinism has been presented and discussed. Such defects in synthesis are considered to be the cause of the goitres, and of the hypothyroidism in these cases. The findings encourage further research to establish the truth or falsity of the hypothesis that inherited defects in hormone synthesis have a significant role in the pathogenesis of goitre. Implicit in the hypothesis which seeks to explain the pathogenesis of goitre on the basis of a defect in hormone synthesis is the belief that the goitre is the result of a compensatory effort mediated through the anterior pituitary and increased production of thyrotrophin (TSH) (Table XIX). The thyroid becomes hyperplastic and enlarges, and with less or more success makes good the difficulties in hormone production. If the goitre fails to produce enough hormone hypothyroidism as well as goitre results, as in sporadic goitrous cretinism. Alternatively, the hyperplastic gland, though perhaps still inefficient per unit mass of tissue, may, by its increase in size, compensate for its intrinsic inadequacy and produce enough hormone to keep the patient euthyroid. Defects at various levels of synthesis occur in varying degrees of severity, from the more or less complete which produces goitrous cretinism recognizable in infancy to the minimal, which only comes to light when special tests, such as the MIT excretion test, are used to detect it. It is not difficult to imagine that minor defects may occur and account for goitres which develop later in life. Depending on their severity they may operate alone or they may require additional factors to augment their effects. The belief that inherited defects in hormone synthesis may lead to goitre does not conflict with other theories of goitro genesis. Indeed) it complements them and helps to explain the rather uncertain role of some of the traditional factors in the causation of sporadic goitre. Ho doubt iodine deficiency and goitrogens may act alone, but they probably do so rarely in this country. It appears reasonable to expect that increased metabolic demands, for example at puberty and during pregnancy, iodine deficiency, and even at times exogenous goitrogens, should contribute to the evolution of goitre more readily in the gland that already has to overcome an inherited defect in hormone synthesis. Sporadic goitre, as it is usually met with in practice, shows a marked predominance in females who usually out-number males by approximately 8 to 1. By contrast, amongst the special cases of goitrous cretinism and sporadic goitre discussed in this thesis there were 17 females and 9 males giving a much lower relative incidence in females. The cause of the marked predominance of sporadic goitre, as it is usually met with, in the female sex is uncertain. Perhaps it is due, in part at least, to the altered metabolic demands and the other endocrine changes which occur at puberty, during reproductive life including during pregnancy, and at the menopause. Such factors presumably exert a relatively more important influence in patients with minor enzyme defects than in those with more severe defects, and so lead to the different sex ratios in the two groups