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Biomedical subjects

J R Stockigt

Publications and source records attributed to J R Stockigt.

At least 91 records · Page 5Linked to original sources
PubMed1982

Familial euthyroid thyroxine excess: characterization of abnormal intermediate affinity thyroxine binding to albumin.

The abnormal high capacity T4 binding site of familial euthyroid T4 excess was separable from prealbumin and T4-binding globulin but not from albumin. We therefore compared T4 binding by albumin preparations isolated from the sera of normal and affected subjects. By equilibrium dialysis, albumin from affected subjects showed an extra T4 binding site (Kd approximately 50 nM) in addition to the T4 binding sites of normal albumin (Kd approximately 4 microM). Comparison of the estimated capacity of the additional site (200 microM) with the molar concentration of albumin suggested that only about one third of albumin molecules from affected subjects contained the extra binding site. Estimates of affinity and capacity were used to derive combining powers for the diverse classes of serum T4 binding sites. From these estimates, it appears that the presence of the abnormal site accounts for the approximate doubling of normal mean total T4 (from approximately 100 nM or 7.7 micrograms/dl to approximately 200 nM or 15.5 micrograms/dl), in order to maintain a normal free T4 in the face of the increased T4 association with albumin. Studies of [125I]T4 displacement from albumin of affected subjects showed low T3 affinity and competition by barbitone. Relative molar concentrations to give equivalent displacement of [125I]T4 were: 3,3',5,5'-tetraiodothyroacetic acid, 0.4; T4, 1.0; rT3, 4; 8-anilinonaphthalene sulfonic acid, 10; T3, 80; salicylate, 200; and barbitone, 40,000. Studies with dithiothreitol suggested that disulfide bonds were critical in maintaining the T4-albumin association. These findings indicate that familial T4 excess is due to abnormal intermediate affinity, sulfhydryl-sensitive T4 binding sites that are inseparable from the albumin found in affected subjects.

Barbital↗
PubMed1981

Limitations of a new free thyroxine assay (Amerlex free T4).

We have assessed a new method of free T4 measurement (Amerlex) which uses a novel unidentified T4-labelled analogue, said to be unreactive with T4 binding proteins in serum, together with an antibody that binds both analogue and T4. Free T4 is assessed by competition with analogue for antibody binding-sites. The test method has been compared with free T4 measured by equilibrium dialysis and with a technique using an immobilized T4 antibody. All methods gave the expected free T4 levels in normal, hyperthyroid and hypothyroid subjects and normal free T4 levels with high or low levels of T4 binding globulin. However, in autosomal dominant familial euthyroid T4-excess, where T4 is abnormally bound to albumin, the test method gave apparent high free T4 levels suggestive of hyperthyroidism. In a selected group of severely-ill euthyroid patients the new method gave apparent low free T4 levels. In view of these discrepancies, binding of labelled analogue was evaluated by dextran-charcoal separation of 4 degraees C. Familial euthyroid T4-excess sera showed greater analogue binding and samples with low prealbumin concentration showed less binding than did normal sera. Despite its validity with variations in TBG, it appears that Amerlex Free T4 is influenced by lower-affinity, high-capacity T4 binding sites in serum, so that apparent free T4 concentration may vary with changes in the concentration of such sites.

Diagnostic Errors↗
PubMed1981

Atrial fibrillation and arterial embolism in hyperthyroidism.

Atrial fibrillation or flutter was present in 70 of 381 patients with uncontrolled hyperthyroidism; return to stable sinus rhythm occurred in 39 with antithyroid and antiarrhythmic treatment. One third of the patients who reverted did so in the first week of treatment while still hyperthyroid. As expected, reversion was more likely in younger patients, and in those with arrhythmia of recent onset, without evidence of other heart disease. Eight patients with arrhythmia had proven (five) or probable (three) major arterial embolic episodes. Four of these eight patients died. Embolism tended to occur at an early stage, during uncontrolled hyperthyroidism, in patients with both atrial fibrillation and cardiac failure. These findings suggest that prophylactic anticoagulation may be appropriate in this high risk group, although more extensive studies are necessary before effective prevention of embolism can be claimed.

Adolescent↗
PubMed1981

The effect of triamterene and sodium intake on renin, aldosterone, and erythrocyte sodium transport in Liddle's syndrome.

Liddle's syndrome was diagnosed in a 23-yr-old Chinese girl with hypertension and hypokalemia by the presence of suppressed renin and negligible plasma and urinary aldosterone secretion. Adrenal corticosteroids, including aldosterone, were suppressed by dexamethasone and stimulated by ACTH. While spironolactone was ineffective, triamterene (2,4,7-triamino-6-phenyl-pteridine) treatment corrected the hypertension and hypokalemia and restored PRA to normal provided that sodium intake was not excessive. During long term treatment with triamterene, blood pressure was extremely sensitive to salt intake, increasing promptly with high intake and decreasing with low salt intake. As a result of the chronic hypervolemia and sodium retention consequent upon the patient's persistent high salt intake and increased renal tubular sodium reabsorption, plasma renin and aldosterone remained low. Erythrocyte sodium concentration and membrane permeability were increased. Triamterene with salt restriction was able to lower the intracellular sodium concentration but did not correct the increased sodium permeability. This suggests that there is an abnormality of sodium transport in Liddle's syndrome which affects the erythrocytes as well as the renal tubular cells.

Adrenocorticotropic Hormone↗
PubMed1981

Familial euthyroid thyroxine excess: an appropriate response to abnormal thyroxine binding associated with albumin.

Responses of the pituitary-thyroid axis and T4 binding to plasma proteins were studied in three kindreds with familial euthyroid T4 excess, an autosomal dominant condition in which affected subjects have high concentrations of plasma T4 with a high free T4 index, but normal free T4 by equilibrium dialysis. Treatment of affected subjects with exogenous T4 or T3 led to gradual suppression of TSH secretion when the free level of T4 or T3 increased above normal. When total T4 was reduced toward normal by potassium iodide treatment or previous subtotal thyroidectomy, the findings suggested mild hormone deficiency. In affected subjects from all three families, equilibrium dialysis showed increased [125I]T4 binding, with evidence of abnormal high capacity binding when an excess of unlabeled T4 was added. In contrast, T3 binding showed no major abnormality. Serum concentrations of T4-binding globulin, prealbumin, and albumin were normal, but gel electrophoresis and immunoprecipitation of binding proteins indicated that 25-30% of tracer [125I]T4 was albumin bound (normal, 10-12%). Abnormal binding, studied by an adsorption separation system in the presence of T4 excess, was inhibited by increments of barbitone. These findings suggest that T4 excess is an appropriate response to abnormal T4 binding so as to maintain normal free T4. The excess bound T4 is associated with a normal quantity of albumin. The basis for increased T4-albumin binding remains to be determined.

Adolescent↗
PubMed1980

19-nor analogs of adrenal steroids: mineralocorticoid and glucocorticoid receptor activity.

The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19-norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19-noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3-fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis à vis their parent compounds (19-norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR.

Aldosterone↗
PubMed1979

The course of untreated mild T3 toxicosis.

A selected group of 12 patients with mild T3 toxicosis, has been assessed without treatment during a period of from seven to 38 months. Progression to typical hyperthyroidism with combined T4 and T3 excess occurred in one case of solitary toxic adenoma, while a spontaneous remission with return of the thyrotropin response to thyrotropin-releasing hormone occurred in one patient with a diffuse goitre. The other 10 patients showed persistence of isolated high levels of T3 without clinical or biochemical progression. These findings suggest that progression to typical hyperthyroidism is infrequent in mild T3 toxicosis. Because of the possible adverse effects of therapy it may be appropriate to observe, rather than treat, some patients with mild clinical and biochemical features of hyperthyroidism.

Humans↗