The effect of perchlorate, thiocyanate, and nitrate on thyroid function in workers exposed to perchlorate long-term

Perchlorate (ClO(4)(-)) and thiocyanate (SCN(-)) are potent and nitrate (NO(3)(-)) a weak competitive inhibitor of the thyroid sodium-iodide symporter. To determine the effects of long-term, high ClO(4)(-) exposure on thyroid function, we conducted a study of 29 workers employed for at least 1.7 yr (50% over 5.9 yr) in an ammonium ClO(4)(-) production plant in Utah. Serum ClO(4)(-), SCN(-), and NO(3)(-); serum T(4), free T(4) index, total T(3), thyroglobulin (Tg), and TSH; 14-h thyroid radioactive iodine uptake (RAIU); and urine iodine (I) and ClO(4)(-) were assessed after 3 d off (Pre) and during the last of three 12-h night shifts in the plant (During) and in 12 volunteers (C) not working in the plant. Serum and urine ClO(4)(-) were not detected in C; urine ClO(4)(-) was not detected in 12 of 29 and was 272 microg/liter in 17 Pre workers; serum ClO(4)(-) was not detected in 27 of 29 Pre; and serum and urine ClO(4)(-) were markedly elevated during ClO(4)(-) exposure to 868 microg/liter and 43 mg/g creatinine, respectively. Serum SCN(-) and NO(3)(-) concentrations were similar in all groups. Thyroid RAIUs were markedly decreased in During compared with Pre (13.5 vs. 21.5%; P < 0.01, paired t) and were associated with an increase in urine I excretion (230 vs. 148 microg I/g Cr; P = 0.02, paired t) but were similar to those in the C group (14.4%). Serum TSH and Tg concentrations were normal and similar in the three groups. Serum T(4) (8.3 vs. 7.7 microg/dl), free T(4) index (2.4 vs. 2.2), and total T(3) (147 vs. 134 ng/dl) were slightly but significantly increased in the During vs. Pre workers (P < 0.01, paired t). Thyroid volumes and patterns by ultrasound were similar in the 29 workers and 12 community volunteers. In conclusion, high ClO(4)(-) absorption during three nights work exposure decreased the 14-h thyroid RAIU by 38% in ClO(4)(-) production workers compared with the RAIU after 3 d off. However, serum TSH and Tg concentrations and thyroid volume by ultrasound were not affected by ClO(4)(-), suggesting that long-term, intermittent, high exposure to ClO(4)(-) does not induce hypothyroidism or goiter in adults.     

Skin manifestations of internal malignancy

This article concentrates on the major signs and syndromes that are associated with internal malignancies in the geriatric population. Included are cutaneous metastases, ectopic adrenocorticotropic hormone-producing syndromes, and disorders arising from APUD cell tumors. The major paraneoplastic disorders of dermatomyositis, generalized pruritus, Bazex's syndrome, and acanthosis nigricans also are discussed. Also included are Bowen's disease of skin; arsenical toxicity; and the Peutz-Jeghers', Gardner's, and Torre's syndromes, which are indicative of systemic or organ-related carcinogens.     

Human platelets exert cytotoxic effects on tumor cells

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.     

The effect of iodine on lymphocytic thyroiditis in the thymectomized buffalo rat

Excess iodine has been associated with an increased incidence of lymphocytic thyroiditis (LT) in the BB/W rat, obese strain chicken, and hamster. The spontaneous incidence of LT in the Buffalo (Buf) rat is increased by neonatal thymectomy. In the present study, the effect of combined thymectomy and excess iodine ingestion on the incidence of LT in Buf rats has been examined. Buf rats were thymectomized at 1 day of age and randomized at 4 weeks of age to receive either standard rat chow with tap water (controls), or standard rat chow with 0.05% iodine in the drinking water (iodine group) for 12 weeks. The serum was assayed for TSH, antithyroglobulin antibodies, and iodine. The thyroids were fixed in Bouin's solution and stained with hematoxylin and eosin, and the presence of thyroiditis was determined. Iodine increased the incidence of LT from 31% in the control group to 73% in the iodine-treated group (P less than 0.05). Serum TSH concentrations and levels of thyroglobulin antibodies were significantly higher in the iodine-treated rats, primarily due to the increased incidence of LT and subsequent iodine-induced hypothyroidism. These data suggest that iodine enhances the effect of neonatal thymectomy on LT in Buf rats and support the concept that iodine may play an important role in the expression of LT in predisposed animals.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Effect of biological alterations of type I 5'deiodinase activity on affinity labeled membrane proteins in rat liver and kidney

Type I iodothyronine 5'deiodinase (5'D-I) is a membrane-bound enzyme catalyzing the deiodination of T4 to T3. The affinity label, N-bromoacetyl-thyroxine (BrAcT4), has previously been used to characterize a 27 kilodalton protein (p27) from rat liver and kidney microsomes with characteristics of the catalytic subunit of the 5'D-I. We examined the effect of physiological conditions, known to alter 5'D-I activity, on affinity-labeled proteins in rat liver and kidney microsomes. To confirm that the affinity labeled protein was associated with the deiodinase, we treated rats with the active site directed enzyme inhibitor, propylthiouracil (PTU), in the absence and presence of 100-fold excess methimazole (MMI), an antithyroid drug which blocks PTU inhibition of 5'D-I in vivo. In addition, we used the affinity label as a probe to measure 5'D-I levels in membrane preparations from short and long term fasted rats. Rats were treated ip with PTU (50 micrograms/100 g BW) or MMI (5 mg/100 g BW); in a second experiment, groups of rats were fasted for 4 days (4 D), 1 day (1 D), or fed ad lib (C) and hepatic and kidney microsomes were prepared. 5'D-I activity and 5'D-I content, as judged by specific incorporation of the affinity label into p27, were determined. PTU decreased both 5'D-I activity and BrACT incorporation into p27 by 60-65%. Coadministration of MMI attenuated the effect of PTU on 5'D-I activity and p27 affinity labeling. No other affinity labeled proteins were affected. In fasting experiments, the changes in affinity labeling of p27 paralleled the changes in 5'D-I activity. 5'D-I activity was significantly decreased in hepatic microsomes obtained from 4 D-fasted rats as compared to C rats, but was unchanged in hepatic microsomes from 1 D-fasted rats or in kidney microsomes from 1 D or 4 D-fasted rats as compared to C. Maximal BrAcT4 incorporation into p27 decreased by 45% in hepatic microsomes from 4 D-starved rats as compared to C (6.7 +/- 0.9 vs. 11.9 +/- 1.5 pmol BrAcT4 incorporated/mg microsomal protein, respectively). There was no change in p27 content in hepatic microsomes from 1 D-starved rats (11.2 +/- 1.1). Starvation failed to alter the BrAcT4 labeling of kidney microsomes (16.7 +/- 4.4, 16.2 +/- 6.6, and 14.8 +/- 3.2 pmol BrAcT4 in 4 D, 1 D, and C rats, respectively). In this study, we have demonstrated that alterations in biological activity of 5'D-I correspond to alterations in affinity labeling of p27.     

The effects of gonadal steroids on the content of substance P in the rat anterior pituitary

The effects of gonadectomy and of the administration of gonadal steroids on the content of substance P in the anterior pituitary (AP-SP) were studied in adult rats. The effect of gonadal status on the AP-SP content of thyroidectomized (TX) rats was also studied. We have confirmed that the AP-SP content in adult males is higher than that in adult females. Ovariectomy (OVX) caused an increase in AP-SP content which was apparent 6 days after surgery. Estradiol (E2; 2 micrograms/rat daily) administered for 13 days beginning the day after OVX prevented the increase in AP-SP content induced by OVX. Orchiectomy of adult rats had no effect on AP-SP content 14 and 45 days after surgery. E2 administered to adult female rats for 13 days caused a reduction in the AP-SP content, whereas dihydrotestosterone (0.2 mg/rat daily for 13 days) caused an increase that was even more pronounced in TX rats. E2 administration to TX adult female rats caused a significant decrease in the AP-SP content both when treatment was begun on the day after surgery or 2 weeks later. Administration of T4 (1.5 and 25 micrograms/100 g BW daily for 7 days) to rats made hypothyroid by thyroidectomy 2 weeks earlier abolished the increase in AP-SP content seen in TX animals. Neither E2 nor dihydrotestosterone had an effect on the substance P content of any of the brain regions examined. The AP-SP content of pregnant or lactating rats was not different from that of age-matched controls. The content of substance P in the AP and median eminence did not vary significantly throughout the estrous cycle. The data indicate that AP-SP content is dependent on the gonadal status of the animal and that gonadal steroids interact with thyroid hormones in the regulation of substance P turnover in the AP.     

The differential effects of thyroid and gonadal hormones on substance P content in the anterior pituitary of the prepubertal rat

The effects of thyroid and gonadal status on the content of substance P in the anterior pituitary (AP-SP) were examined in prepubertal rats. A sex difference in AP-SP is evident by age 50 days [males, 287 +/- 35 fmol/mg protein (mean +/- SE); females, 103 +/- 17; P less than 0.05], and this difference becomes greater by 75 days (males, 543 +/- 54; females, 146 +/- 11.5; P less than 0.01). Hypothyroidism was induced in male and female pups by giving lactating dams 0.1% methimazole (wt/vol) in their drinking water after parturition. There was a marked and significant increase in AP-SP in 21-day-old hypothyroid compared to euthyroid control pups. Male pups were made thyrotoxic by daily treatment with T4 (10 micrograms/rat, sc) from age 8 to 15 days. AP-SP was 4 times lower in the thyrotoxic than in the euthyroid pups (P less than 0.001). Rats ovariectomized at age 22 days and killed on day 35 revealed no change in AP-SP, in contrast to the rise in AP-SP in the ovariectomized adult rat. Female pups were treated with dihydrotestosterone (DHT; 50 micrograms/day) or testosterone (50 micrograms/day) from age 8-20 days. Neither androgen induced a change in AP-SP. Female pups which received estradiol (E2; 0.5 micrograms/day) or testosterone (75 micrograms/day) from age 8-20 days also had no change in AP-SP. As opposed to the lack of effect of E2 and DHT on AP-SP in female rats younger than 22 days, E2 (1 microgram/100 g BW daily) caused a decrease and DHT (100 micrograms/100 g BW daily) caused an increase in AP-SP in female rats treated from 22-35 days of age [E2, 91 +/- 6.9; DHT, 226 +/- 31 (P less than 0.05 vs. control for both); control, 154 +/- 13]. We conclude that the responsiveness of AP-SP to alterations in thyroid status is present at the youngest age studied. In contrast, the responsiveness of AP-SP to changes in the levels of gonadal steroids is absent in the infantile period and requires a maturational process that becomes evident during the juvenile state of sexual development.