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We report a case of a male patient thyroidectomized for follicular thyroid carcinoma and presenting extremely elevated serum thyrotropin levels under L-T4suppressive therapy. Administration of L-T3in increasing amounts resulted in a significant decrease of serum TSH levels. The nature of the possible molecular defects underlying this unusual condition and pitfalls arising from the failure of L-T4therapy to inhibit TSH secretion in a patient in postsurgical follow-up for follicular carcinoma are discussed.

A 30-yr-old woman with allergie rhinitis and multinodular goiter developed atopic manifestations on different desiccated thyroid extract treatment. U rticaria was observed when the patient was on L-T4treatment; no atopy was experienced during L-T3regimen. Serum total immunoglobulin E (IgE) concentration was 390 ± 7kU/liter (mean ± SD) prior to any treatment and rose to 850 ± 7.5 kU/liter when the patient developed urticaria, but declined to baseline figures while she was on L-T3. Intracutaneous testing was positive for desiccated pork thyroid powder, L-T4and D-T4, but negative for L-T3, DIT and L-tyrosine. I mmunoradioligand analyses of mixtures of patient’s serum or precipitated immunoglobulin fraction and of 125I-T4or of 125I-T3revealed binding of radiolabeled thyroxine to the patient’s serum IgE, in turn bound to anti-human-lgE serum covalently coupled to paper discs. This binding was completely inhibited by the preincubation of immunoglobulin fraction with excess unlabeled L-T4and D-T4, but not with excess nonradioactive L-T3, thus proving the specificity of the binding. Preadsorption experiments performed with desiccated pork thyroid powder solution mixed with the patient’s immunoglobulin fraction suggested binding of some unknown component(s) of desiccated thyroid which was apparently not thyroglobulin. This study provides evidence of IgE antibodies to L-T4cross reacting with D-T4and capable of binding 125I-T4in serum. It also suggests a model for the detection of circulating IgE antibodies to thyroid hormones.

This paper describes the identification of circulating autoantibodies to thyroid hormones in 5 patients with Graves’ disease (n = 2), Hashimoto’s thyroiditis (n = 1), primary myxedema (n = 1) and Sjögren syndrome (n = 1) out of 351 individuals. The 351 patients suffered from different autoimmune thyroid disorders, thyroid cancer or lymphoreticular system disorders as well as autoimmune non thyroid illnesses. Immunoglobulin G (IgG) binding of one or both tracer thyroid hormones and in one case also of reverse triiodothyronine, was demonstrated by radioimmunoprecipitation experiments and by reverse flow zone electrophoresis or cellulose acetate electrophoresis and autoradiography. In all cases the binding of radiolabeled thyroid hormones to IgG was displaced by an excess of the respective non radioactive thyroid hormone. Thyroglobulin displaced the binding in 2 cases but preadsorption with human thyroglobulin was ineffective in other 2 cases. Radioimmunoelectrophoresis and autoradiography of the Immunoelectrophoresis plates indicated that in 2 cases the light chains involved in the binding were k chains of the G3 subclass and to a lesser extent of the G1 subclass, in another case they were λ chains and therefore of restricted heterogeneity. In a case of myxedema coma IgG were polyclonal (k and λ chains of the G1 > G2 > G3 subclasses). The thyroxine (T4) or triiodothyronine (T3) antibodies interfere with the hormone measurement in unextracted serum by falsely lowering their concentrations when non specific separation methods are used and raising their concentrations when double antibody radioimmunoassays are used.In one serum containing anti-T4antibodies, the association constant (Ka) was 0.63 × 106l/M and absolute binding (Ab0) was1.54 x10-7l/M. In another serum with anti-T3IgG, Ka was 4.44 × 107l/M and Abo 6.22 × 10-9l/M. In the case of myxedema coma Ka ranged between 3.1 and 4.3 × 108l/M.

Thyroid hormones (TH) have been shown to exert a direct stimulatory effect on the Ca++-dependent ATPase from human and other mammalian erythrdcytes. In this in vitrosystem, T4has been shown to be more effective than T3. In the present study, TH effects on Ca++-dependent ATPase were investigated, using rabbit and human erythrocyte membranes, after preincubation with 10−10M T4, in the presence or in the absence of exogenous calmodulin (CaM) (5.10−12M to 5.10−9M). Ca++-dependent ATPase activity was measured as inorganic phosphate (Pi) release from 1 mM ATP. The results showed that basal Ca++-dependent ATPase activity in rabbits was moderately increased by T4(1.44 ± 0.05 vs 1.32 ± 0.04 μmol Pi/mg protein/90 min, mean ± SE; p<0.05). The time course of Pi release did not show any stimulatory effect of T4during the first hour of incubation. The effect of T4became apparent, however, 1 h after the addition of ATP (ΔT4: 15%). With human membranes, T4induced a relative stimulation of the Ca++-dependent ATPase of 8–10% (p<0.05) in experimental conditions where the enzyme was not maximally stimulated by CaM (A CaM over basal activity: 5–40%). In conditions of high CaM stimulation (Δ CaM: 50–320%), T4had no effect. These results confirm that Ca++-dependent ATPase activity is increased by T4. The effect of T4is small, and appears as a late event during incubation with ATP. Stimulation by T4is expressed in states of low enzyme activation by CaM. In conclusion our results do not favor a direct stimulation of Ca++-dependent ATPase by T4, but suggest an indirect effect on the red blood cell membrane.