Thyroid gland, dose

Both drugs, MMI and PTU, are actively concentrated by the thyroid gland. Intrathyroidal concentrations of MMI are in the range of 5 x 105 M. There is no difference in intrathyroidal concentrations of MMI 3-6 and 17-20 h after ingestion of 10 mg of carbimazole. Little is known about intrathyroidal concentrations of PTU. Eight hours after a single dose of 10 mg of MMI or 100 mg of PTU inhibition of intrathyroidal organification of iodide is about 90% and 60%,... 

Patients with mild or subclinical hypothyroidism do not need to be started on the full replacement dose because they still have some endogenous hormone production. Start these patients on 25 to 50 meg/day, and titrate every 6 to 8 weeks based on TSH levels. Over time, it is likely that the LT4 dose will need to be increased slowly as the patient s thyroid gland loses residual function. 

Studies of low-dose perchlorate exposure in healthy human subjects A small number of studies have been published investigating the effects of low doses of perchlorate in thyroid function in healthy adults (without thyroid disease). One study was conducted in healthy male volunteers, involving the administration of 10 mg of perchlorate in drinking water for 14 days. A significant decrease in the uptake of iodine by the thyroid was observed at this dose, but there was no evidence of adverse effects on thyroid hormones or TSH concentrations [262]. Another recent study was conducted in healthy adults to determine the highest dose of perchlorate at which there is no effect on the uptake of iodine by the thyroid gland [263]. 

Special precautions Store this radioisotope behind 3 mm thick lead shielding. The effective biological half-life in humans is around 140 days. The thyroid gland is the critical organ in terms of dose, and one would be well... 

Small doses of disulfiram reportedly can cause effects on thyroid iodine uptake and thyroid gland hypertrophy. It may also produce dermatitis and acneform rashes. 

In addition, the metabohsm of OCAs results in the release of large amounts of E into the circulation. As described for KI, I released from OCAs may have effects at the thyroid gland and if used alone to treat hyperthyroidism, OCAs carry the same potential to induce increased secretion of thyroid hormone and exacerbation of thyrotoxicosis. When an OCA is used in the treatment of hyperthyroidism, large doses of antithyroid agents are usually administered concomitantly. However, the combination of OCAs and antithyroid drugs may cause resistance to the antithyroid drugs with time, presumably because of the elevation in intrathyroidal 1 content. Thus, it is recommended that the use of OCAs be reserved for short-term treatment of patients with severe thyrotoxicosis and significant comorbidity (e.g., myocardial infarction, sepsis, stroke) for rapid control of plasma Tj concentrations. 

In rats exposed to 2,3-benzofuran for 103 weeks, the occurrence of cystic follicles in the thyroid glands was increased in males at doses of 30 and 60 mg/kg/day but decreased in females at doses of 60 and 120 mg/kg/day (NTP 1989). Parathyroid hyperplasia was increased in male rats exposed for 103 weeks to a dose of 30 mg/kg/day, secondary to increased severity of nephropathy (NTP 1989). ... 

Holm, L.E., Eklund, G., and Limdell, G. (1980a). Incidence of malignant thyroid tumors in humans after exposure to diagnostic doses of iodine-131 II. Estimation of thyroid gland size, thyroid radiation dose, and predicted versus observed number of malignant thyroid tumors, J. Natl. Cancer Inst. 65,1221. 

The thyroid gland also regulates its uptake of iodide and thyroid hormone synthesis by intrathyroidal mechanisms that are independent of TSH. These mechanisms are primarily related to the level of iodine in the blood. Large doses of iodine inhibit iodide organification (Wolff-Chaikoff block, see Figure 38-1). In certain disease states (eg, Hashimoto s thyroiditis), this can inhibit thyroid hormone synthesis and result in hypothyroidism. Hyperthyroidism can result from the loss of the Wolff-Chaikoff block in susceptible individuals (eg, multinodular goiter). 

Propylthiouracil is rapidly absorbed, reaching peak serum levels after 1 hour. The bioavailability of 50-80% may be due to incomplete absorption or a large first-pass effect in the liver. The volume of distribution approximates total body water with accumulation in the thyroid gland. Most of an ingested dose of propylthiouracil is excreted by the kidney as the inactive glucuronide within 24 hours. 

In contrast, methimazole is completely absorbed but at variable rates. It is readily accumulated by the thyroid gland and has a volume of distribution similar to that of propylthiouracil. Excretion is slower than with propylthiouracil 65-70% of a dose is recovered in the urine in 48 hours. 

Laboratory animals fed PBBs had body weight loss, skin disorders, and nervous system effects, and their livers, kidneys, thyroid glands, and immune systems were seriously injured. Some animals fed high amounts died. PBBs also caused birth defects in animals, but it is not known for sure whether PBBs make males or females infertile. Most of the effects in animals occurred after they ate large amounts of PBBs for short periods or smaller amounts for several weeks or months. In a lifetime study in rats and mice treated orally with PBBs at doses higher than those expected from environmental exposure, body weight loss and effects on the livers, kidneys, and thyroid glands were observed. A few studies tested animals exposed to PBBs by skin contact. These... 

Reported estimated doses in the mice were 3,200 and 6,650 mg/kg/day in males and 3,760 and 7,780 mg/kg/day in females (NTP 1986). Hepatocellular adenoma or carcinoma (combined) occurred at significantly increased incidences in low-dose male mice (22/50, p=0.002) and high-dose male mice (18/50, p=0.019) in comparison to controls (8/50) and showed a positive dose-related trend (p=0.021). Incidences of hepatocellular carcinoma alone were not significantly increased in either the low- or high-dose male mice. Slightly elevated incidences of thyroid gland follicular cell adenoma or carcinoma (combined) were... 

Neoplastic effects in the NTP (1986) bioassay included increased incidences of neoplastic nodules in the liver in the male and female rats and hepatocellular adenoma or carcinoma (combined) in the male mice. Slightly elevated incidences of thyroid gland follicular cell tumors were additionally observed in exposed male mice, although the increases were equivocal. No exposure-related neoplastic changes were found in the chronic study of the 77.4% decaBDE mixture (Kociba et al. 1975 Norris et al. 1975a), but the power of this study to detect carcinogenic effects is limited by the very low dose levels in comparison to those tested in the NTP bioassay. 

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