John B. Stanbury

The syndrome of congenital goiter with butanol-insoluble serum iodine

Abstract Clinical and laboratory data on five patients suffering from one variety of congenital hypothyroidism with goiter are reported, and similar cases from the literature are reviewed. In these patients hypothyroidism and goiter develop early in life. They may suffer permanent physical and mental retardation unless the disorder is detected and adequate replacement therapy is given. There is increased RaI 131 uptake by the thyroid and no release of I 131 upon administration of potassium thiocyanate. The deiodinase activity is normal. An abnormal iodinated polypeptide or protein is secreted by the thyroid. It is detected by its failure to extract into n-butanol from acidified serum. A similar complex is present in the urine. Abnormalities in the distribution of I 131 in the thyroid subcellular particulate fractions and in the thyroidal proteins have been detected in the two glands which have been available for analysis. This syndrome may be the expression of a congenital defect in thyroglobulin synthesis. Similar observations in certain patients with adenomatous colloid goiter suggest that this type of congenital goiter and a type of adenomatous colloid goiter may represent different levels of expression of a common genetic defect.

DEIODINATION OF THE IODINATED AMINO ACIDS

When iodotyrosines or iodothyronines labeled with are administered intravenously to normal man, most of the labeled iodine appears in the course of time in the urine as free inorganic iodide. Only negligible amounts of the undegraded parent substances pass the renal barrier intact. Evidently, there are mechanisms in the body that can remove iodine from the aromatic rings of these physiologically important substances and in the process reduce i t to its ionic form. Much effort has attended the study of these processes of deiodinization, for it has become apparent that they may be critical in ordering the metabolic impact of these compounds. Indeed, deficiencies of deiodination may underlie profound disturbances of growth and development.’ p 2 The problem of deiodination has been approached in many laboratories from many different points of view. Seemingly discordant results may be attributed to differences in technique and, perhaps more significantly, to differences in the events being measured. This review will survey the pathways and mechanisms of deiodination of the aromatic amino acids and their chemical relatives, as indicated by information obtained from both in vivo and in vitro studies.

Sulfur amino acids as precursors of β-mercaptolactate-cysteine disulfide in human subjects☆

Abstract Reduction of protein in the diet, addition of pyridoxine or of neomycin did not affect the urinary excretion of β-mercaptolactate-cysteine disulfide of a mentally defective patient who was excreting this mixed disulfide. Addition of cysteine to the diet did increase the excretion of this disulfide and the phenomenon was also observed to a lesser degree in normal control subjects. No additional mixed disulfide was formed when methionine was administered either to the patient or to normal controls. Excretion of taurine, sulfate, and thiosulfate was also measured. It was concluded that the response of the patient to a cysteine load was abnormal compared with the normal controls, and it is suggested that the mixed disulfide might have been derived from an enlarged intracellular pool of β-mercaptolactate in the patient with a subsequent block in metabolism, which became more significant after cysteine loading but not after methionine loading.

Metabolism of sulfur-containing amino acids in a patient excreting β-mercaptolactate-cysteine disulfide

Abstract l -[ 14 C]cystine and, 3 months later, l -[ 35 S]methionine were injected intravenously into a mentally retarded patient excreting β-mercaptolactate-cysteine disulfide. The rate of decrease of radioactivity in the plasma was measured, and the rate of appearance of radioactive amino acids in the urine was determined by fractionation of the urinary amino acids on the amino acid analyzer. Radioactive mixed disulfide rapidly appeared in the urine after [ 14 C]cystine injection. At least 60% of the radioactivity was present in the cysteine half of the molecule. No mixed radioactive disulfide was found in the urine after administration of [ 35 S]methionine but there was a rapid conversion to radioactive taurine.

The diagnostic use of radionuclides in the thyroid disorders of childhood

The radioisotopes of iodine have proven useful in the differential diagnosis of thyroid disorders in infancy and childhood. Their use has been somewhat limited for technical reasons and because of concern that radiation from any source is particularly hazardous in this age group. The introduction of 99 m Tc-labeled pertechnetate and of radioisotopes of iodine that are free of beta emission or that have a short half-life, or both, and instrumentation that permits measurement in the nanocurie range are advances that promise to extend into the pediatric group the full range of diagnostic techniques employing these agents. Although exact measurements of thyrotropin and circulating thyroid hormones have reduced substantially the need for diagnostic procedures employing radionuclides, there are still occasions when the added information provided by these tests is invaluable. Included in this list are measurements of thyroid function for the diagnosis of hyper- or hypothyroidism, thyroid scanning for the activity of discrete nodules or of metastatic disease in areas remote from the thyroid, definition of the nature of certain rare inborn metabolic errors that impair thyroid function, studies on thyroiditis, and differential diagnosis of certain hypothyroid states due to defective embryological development.

Double-isotope derivative assay of serum iodothyronines: I. Preparation of acetyl derivatives of thyroxine and triiodothyronine☆

Abstract In order to apply the double-isotope derivative method to assay of total serum thyroxine or triiodothyronine, the stable mono- and diacetyl derivatives of these compounds were prepared and examined for use in an assay procedure. The monoacetyl derivatives were found to be best for this purpose since they show greater stability, are more soluble in polar solvents, and are easier to purify by chemical or chromatographic means. Therefore the N -acetyl- 3 H derivatives of thyroxine and triiodothyronine were used to develop an assay procedure.

Double-isotope derivative assay of serum iodothyronines: III. Triiodothyronine

Abstract A new highly selective and specific assay of serum triiodothyronine has been developed using the double-isotope derivative principle. The assay results are not impaired by artifactual conversion of T4 to T3. Digestion of the serum sample with papain prior to extraction resulted in a shortened purification of the acetylated derivative and improved the final recovery. The double-isotope derivative T3 assay may prove useful in thyroid research.

DOUBLE-ISOTOPE DERIVATIVE ASSAY OF SERUM IODOTHYRONINES. II. THYROXINE.

Abstract An improved method has been developed for double-isotope derivative assay of total serum T4. In the double-isotope derivative assay, tritiumlabeled acetic anhydride is used to make a derivative of the unknown T4, which is purified and counted. The new procedure includes greatly shortened and simplified acetylation and purification steps. Also a resin column method has proved superior to butanol for extracting T4 from serum prior to acetylation. The precision of T4 assay by the double-isotope derivative approach compares favorably with that of other methods and may prove useful in thyroid research.

The Metabolic Basis for Certain Disorders of the Thyroid Gland

3-5-3’-triiodothyronine. In order to accomJ)hish this end, the gland must synthesize, store and secrete these two ahniflo acids. This is accomplished by means of a complex sequence of biochemical steps which are only partially understood at the present time. It may he accepted as a generality that any impairliient in any of these steps will inevitably he niet by an attempt at colnpensatory hyperplasia of the gland through the well known feed-back control system involving the anterior pituitary gland. Compensation may be sue