The clinical chemistry and pathologic physiology of thyroid tissue.

THE RAPIDLY GROWING list of inborii errors of metabolism has largely defied satisfactory classification (1). Some of these disorders fall into neat biochemical analogues with no unifying clinical theme, whereas others can be grouped into anatomic pigeonholes or into schemes related to organ systems although there is not the slightest biochemical relationship. There are a few instances where order has emerged and an agreeable coherence can be discerned. For example, there are now at least 7 biochemically distinct disorders in the biosynthesis, structuring, and dismantling of glycogen. These have clinical features in common, and each is the result of a unique biochemical lesion at a specific single step along the route of glycogen metabolism. There are at least 3 separate diseases of the sulfur-containing amino acids-methionine, cystathionine, homocystine, and cysteine-and man himself may be thought of as a methionineless mutant since he is unable to synthesize this amino acid. There are at least 3 biochemically distinct disorders of tile urea cycle, all with overlapping clinical manifestations. Perhaps as we learn more of the nature of inherited disease and of biochemical pathways, it will be possible to arrange these diseases into rational groupings; and if this serves no other purpose, it will at least make the learning process easier. The familial diseases of thyroid function characterized by the paradox of goiter and hypothyroidism are an interesting group in which sepa-