Klaus W. Wenzel

Pharmacological interference with in vitro tests of thyroid function

Numerous drugs may cause changes in the serum concentrations of T4 and of T3. If such alterations are not recognized an incorrect diagnosis may result. In moderate degrees of hypo- and hyperthyroidism thyroid hormone levels may be spuriously normal, or the influence of pharmacological substances may lead to false diagnosis of thyroid disease in euthyroid patients. Since prediction of such alterations remains uncertain, it may be necessary to perform additional investigations when a potential artefact is recognized. On the other hand many pharmacological agents, especially those which interact with neurotransmitters, may influence TSH secretion, too. The TRH-test may show an increase or decreased TSH response, although complete suppression is only rarely seen during high-dose glucocorticoid treatment when low TRH doses are applied. Because of TRH-test gives such wide separation between different clinical states false interpretations are generally less likely than with drug-induced changes in T4 and T3 values.

Aspects of the absorption of oral L-thyroxine in normal man

Using a double isotope method, the optimal conditions for the absorption of an L-thyroxine (L-T4) preparation were examined. In particular, the influence of food intake on L-T4 absorption was examined. As distinct from the unfavorable results hitherto obtained with L-T4 lactase mixtures, a tablet similar to a commercial 100 mug L-T4 lactose preparation showed good absorptionof 70.6% +/- 12.9% SD. In the fasting state, the L-T4 absorption of both preparations was significantly better (p less than 0.001) than with simultaneous food intake: 79.3% +/- 7.2% SD versus 63.9% +/- 10.5% SD. The calculated absorption of a 3-mg L-T4 dose in a lactose preparation used in testing thyroid suppressibility was significantly lower (p less than 0.001) than the absorption of a smaller L-T4 dose, and the absorption in the fasting state was again signifiantly (; less than 0.01) higher compared to that with simultaneous food intake: 52.6% +/- 4.3% SD versus 43.9% +/- 5.4% SD. The possibility of retention in the liver in the case of a large 3-mg L-T4 dose is indicated. The data suggest that with L-thyroxine medication simultaneous food intake should be avoided.

Relations between serum levels of TSH, TBG, T4, T3, rT3 and various histologically classified chronic liver diseases

Serum levels of TSH, thyroxine-binding globulin (TBG), T4, T3 and reverse T3 (rT3) were measured in 36 patients with fatty liver disease, 11 patients with chronic persistent hepatitis, 17 patients with chronic active hepatitis, and 29 patients with liver cirrhosis. TBG was significantly above normal levels in both groups of chronic hepatitis, the slight concomitant T4 and T3 increase was significant only for Tt in chronic persistent hepatitis. A significant decrease in T4 and T3 concentration was found in fatty liver disease and in hepatic cirrhosis. A shift in T4 conversion to rT3 could exclusively be demonstrated for the group of hepatic cirrhosis, reflected by a significant increase in rT3. As our findings indicate normal TSH levels and a lack of clinical signs of hypothyroidism in chronic liver disease, the possibility of diverse regulating changes must be considered.

Syndrome of persisting thyroid stimulating immunoglobulins and growth promotion of goiter combined with low thyroxine and high triiodothyronine serum levels in drug treated Graves’ disease

Among 48 Graves’ patients treated with antithyroid drugs there were 8 patients with a further growth of an already enlarged goiter and a persistence of thyroid stimulating immunoglob-ulins (TSI). TSI activity did not persist in a comparison group of patients with less severe initial symptomes and an uncomplicated course during a similar regimen of drug treatment. Thyrotoxi-cosis was difficult to control in this subgroup of patients as low serum T4 was accompanied by borderline high T3 levels although TSH in serum remained undetectable. In spite of comparable low doses of antithyroid drugs serum T4 in the complicated group remained significantly lower (58±15 nmol/l SD vs. 97±19 nmol/l SD, p<0,001) and serum T3 stayed significantly higher (3,66 ± 0,49 nmol/l SD vs. 2,15 ± 0,50 nmol/l SD, p < 0,001) than in the group with uncomplicated treatment. It is discussed that the promotion of goiter growth could be due to growth stimulating antibodies, and that a local intrathyroidal iodide depletion during antithyroid drug treatment might cause the shift from T4 to T3 production in this entity of Graves’ patients.

Binding of solubilized human TSH-receptor protein by peripheral blood lymphocytes of patients with Graves’ disease

Peripheral blood lymphocytes (PBL) from patients with hyperthyroidism due to Graves’ disease (GD) were investigated for the ability to bind radioiodinated TSH receptor protein as hypothetical autoantigen (ABL). Thyrotropin-displacing antibody (TDA)-positive patients, who relapsed and were investigated shortly after starting antithyroid drug therapy, as well as TDA-positive patients with a first diagnosis of GD, who were investigated before starting therapy, showed significantly increased numbers of ABLs (0.2 ±0.17%, p<0.01 and 0.15 ± 0.08%, p<0.001, respectively) when compared to controls (0.018 ± 0.016%). In contrast, TDA — negative patients had no significant increase of ABLs (0.08 ± 0.09%). Preincubation of PBLs with excess unlabelled antigen and nylon wool filtration of PBLs, reduced the number of ABLs markedly. Blocking of the binding sites on the lymphocytes with anti-lg serum and blocking of the antigen itself by TSH depleted PBLs almost totally from ABLs. The present data indicate that: i) there are lymphocytes of B-cell characteristics capable of binding TSH-receptor; ii) there is a correlation between the appearance of ABLs in hyperthyroid GD patients and the detection of TDA in patients’ sera; iii) in Hashimoto, toxic nodular goiter and in some normals, a small amount of TSH receptor binding ABLs are detectable.