monensin and Hyperthyroidism

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

Topics: Animals; Cells, Cultured; Culture Media; Disease; Humans; Hyperthyroidism; Hypothyroidism; Liver; Male; Monensin; Ouabain; Propylthiouracil; Rats; Rats, Wistar; Reference Values; Regression Analysis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The effects of monensin on subcellular structure, release of thyroglobulin (TG) and peroxidase (PO) activity were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). TG concentration in the culture medium was measured by a sandwich enzyme immunoassay and the amount of TG in cultured cells was measured with an identical sandwich enzyme immunoassay after lysis of the cells with Triton X-100. PO activity of cultured cells was measured by a biochemical method. Addition of TSH (10 mU/ml/day) to the culture medium increased the synthesis and release of TG. When monensin (1 micron/l) was added to the medium on the last day of a 3-day incubation with TSH, the Golgi complex showed vacuolative change ultrastructurally, and the amount of intracellular TG was increased, whereas the amount of TG in the culture medium and PO activity became lower than those in the control group. These results suggest that in cultured Basedow's cells, TG is secreted through the Golgi complex, and that the activity of PO is elevated after processing in the Golgi complex.

Topics: Cells, Cultured; Humans; Hyperthyroidism; Microscopy, Electron; Monensin; Peroxidases; Thyroglobulin; Thyroid Gland; Thyrotropin