Thyroglobulin-rich colloid goitres: a result of the combined action of lithium and methimazole on the rat thyroid.
Naturally occurring euthyroid goitres in man and goitres produced in experimental animals by iodine deficiency or goitrogen feeding both have in common a thyroglobulin of low iodine content. The latter experimental goitres are always depleted of colloid and thyroglobulin. In contrast, natural goitres often contain excessive amounts of colloid which may accumulate because of endocytosis becoming refractory to TSH. We tested the hypothesis that minute doses of goitrogens could lower the iodine content of thyroglobulin without colloid depletion. We then examined whether such a low-dose 'classical' goitrogen could induce excessive colloid storage rather than depletion if acting in concert with lithium, a cation which blocks endocytosis. Rats on an adequate iodine intake were fed minimal doses of methimazole either alone or combined with lithium chloride. Chronic minimal-dose methimazole treatment lowered the iodine content of thyroglobulin without changing thyroglobulin content and thyroid weight. In contrast, addition of lithium to methimazole, produced goitres containing supranormal amounts of poorly iodinated thyroglobulin. We conclude that borderline doses of goitrogens can lower iodination of thyroglobulin without causing hyperplasia and colloid depletion. Thyroglobulin-rich goitres can be obtained by adding a second goitrogen which inhibits endocytosis. As an alternative to Marine's hypothesis of colloid goitre formation we suggest that inhibition of endocytosis, e g by goitrogens of the lithium type, could cause colloid and thyroglobulin accumulation in human iodine deficiency goitre.
D000818:Animals; D003102:Colloids / Q000032:analysis*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006042:Goiter / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood
D003102:Colloids; D008713:Methimazole; D013972:Thyrotropin; D013954:Thyroglobulin; D007455:Iodine; D008094:Lithium