The effect of iodine deficiency on thyroid function in the infant rat

We have studied rats born to severely iodine-deficient mothers and subsequently maintained on a low-iodine diet (LID) from birth to 41 days. They were compared with controls born to mothers fed a high-iodine diet (HID). LID babies from birth on had large goiters, high thyroid labeled MIT/DIT ratios and radioiodine uptakes, high plasma TSH and low plasma T4 in comparison to HID controls. Thyroid labeled T3/T4 ratios were low in all babies at birth but were higher in the LID than HID babies from day 5 on and were greater than 1 after day 10, approximating the T3/T4 of the mothers. Coupling efficiency, as indicated by thyroid labeled (T3 + T4)/(MIT + DIT), was relatively low for the first 4 postnatal days for both the HID and LID babies and was associated with a lower plasma T4 than at later intervals. Injection of 0.05 mug 127I- simultaneously with 131I- caused an acute increase in labeled T4 and decrease in MIT formation in LID babies of all ages, but did not affect T3 synthesis. Doses of 127I- 20 times as large had no effect on labeled iodoamino acid synthesis in HID babies. Thyroid organic radioiodine content in newborn LID rats was 65% lower at 24 hr than at 4 hr after 131I injection, indicating that thyroid secretion was occurring. A few of the LID pups were "runts" approximately 60% the size of HID babies the same age. However, the overwhelming majority of LID babies maintained the same weight as HID controls from birth until weaning. After weaning, the LID babies grew at a slower rate than the HID controls. Relative thyroid weight, radioiodine metabolism and plasma TSH were no different in runts of various ages or in their mothers than in the "normal" LID controls. Adaptation was apparently adequate in the LID babies to maintain a nearly euthyroid state. We suggest that the low labeled T3/T4 ratio in the first few days of life in the LID babies may be due to a coupling deficiency in newborn rats resulting in a proportionately greater formation of iodotyrosines than of iodothyronines compared to older animals. This results in a greater intrathyroidal retention of iodine during intracellular thyroglobulin proteolysis and a more highly iodinated thyroglobulin in the LID babies than after normal coupling is achieved.     

阿伦膦酸钠在大鼠动脉钙化中的作用

目的研究阿伦膦酸钠(AL)对在体和离体大鼠动脉钙化的影响。方法4周龄SD雄性大鼠18只随机分为AL组、钙化组和正常组,前2组分别给予皮下注射华法林15mg.100g-1.12h-1,4d;维生素D3300000U.kg-1.24h-1,3d,以制备大鼠动脉钙化。AL组在钙化模型制备之前4d给予AL1mg.kg-1.24h-1皮下注射。细胞分为AL10-9、10-7和10-5mol/L组,钙化组和正常组。结果AL组大鼠主动脉vonKossa染色黑色深染结构减少。AL治疗的各组茜素红S染色发现钙结节计数较钙化组减少[(6.8±2.7,6.2±4.2,5.3±2.4)%比(7.4±3.8)%],细胞钙沉积含量减少[(5.2±1.2,4.8±1.7,3.5±1.8)%比(5.6±1.6)%],ALP活力和细胞增殖均降低,并呈剂量依赖性。结论AL能抑制大鼠动脉钙化。     

The effect of fenclofenac on thyroid function

The non-steroidal anti-inflammatory agent fenclofenac competitively inhibits the binding of thyroxine(T4) and triiodothyronine (T3) by thyroxine-binding globulin(TBG). Eight male volunteers completed a 4-week study during which they took fenclofenac 600 mg twice daily. The concentration of fenclofenac in serum reached a plateau after 1 week of therapy after which the mean concentration(+/SEM) of the drug in serum was 78.6 o.2 mg/1.During the steady state period on treatment there were reductions of the mean serum concentrations of total T4 to 35% (P less than 0.001), total T3 to 55% (P less than 0.001), free T4 to 69% (P less than 0.001) and free T3 to 90% (NS) of the respective pretreatment values. There were also significant changes in the concentrations of thyrotropin and reverse T3 in serum. After starting treatment with fenclofenac serum concentrations of thyrotrophin fell to a nadir after 2-4 days at which time the mean concentration was 34% (P less than 0.01) of the pretreatment value, whilst reverse T3 values increased to a maximum of 136% (P less than 0.001) of the pretreatment values over 1-2 days. There was subsequently an increase of the thyrotrophin and a reduction in reverse T3 concentrations to normal by 2 weeks of pretreatment. Transient pituitary suppression was also suggested by the response to to thryotrophin-releasing hormone (TRH): 7 days after starting fenclofenac the mean thyrotrophin response was 62% (P less than 9.001) of the pretreatment value. After 4 weeks of fenclofenac the response of TRH had returned to normal. After discontinuing fenclofenac there was a transient increase in the mean concentration of thyrotrophin in serum, to 129% of the pretreatment value (P less than 0.001), with a subsequent return to normal. Four weeks after discontinuing fenclofenac the serum concentrations of thyroid hormones and thyrotrophin were normal.     

The effect of amiodarone on thyroid gland function

Plasma concentrations of T4, FT4, T3, rT3 and TBG, as well as of TSH before and after stimulation with TRH were studied in 25 patients, who had been treated with amiodarone for up to nine years. At the beginning of therapy, all the parameters mentioned above were found to be in the normal range in all patients. After two months of therapy, T4 had increased from 100 nmol/l +/- 24 nmol/l to 155 nmol/l +/- 32 nmol/l (p less than 0.01), and FT4 from 22 pmol/l +/- 10.5 pmol/l to 32 pmol/l +/- 8 pmol/l (p less than 0.01). T3 had decreased to the lower normal range (n.s.). TBG showed no significant changes. The TRH-tests had been normal in the beginning, but they remained positive in only 20% of the cases. At the end of the study, rT3 exceeded the normal range in all 25 patients. Two patients developed definite hyperthyroidism with elevations of T3 up to 4.7 nmol/l and 7.5 nmol/l, respectively. In one of them, we decided to discontinue amiodarone. Testing of thyroid function under antithyroid drug therapy revealed a hyperfunctioning autonomous adenoma, which was successfully eliminated by radioactive iodine therapy. In the other patient, it was not possible to withdraw amiodarone, so we initiated long-term treatment with antithyroid drugs. Our data support the assumption that amiodarone causes an impairment of the peripheral conversion of T4 to T3. As a result, one finds elevated serum concentrations of T4, which, in combination with the mainly negative TRH-test, must not be interpreted as proof of a hyperthyroid metabolic state being present. Hyperthyroidism is confirmed only if serum concentrations of T3 are also elevated.