Thyroid function and 3,3'-diiodothyronine sulfate cross-reactive substance (compound W) in maternal hyperthyroidism with antithyroid treatment.

OBJECTIVE: To test whether the serial measurement of maternal levels of compound W, a 3,3'-diiodothyronine sulfate cross-reactive substance, can serve as a potential indicator of fetal thyroid function in pregnant women receiving antithyroid medication. METHODS: Compound W was measured repeatedly in serum of pregnant women with hyperthyroidism treated with antithyroid medication. Free thyroxine levels of mothers and serum thyroid-stimulating hormone levels of 1-day-old neonates were analyzed by local clinical or state laboratories. RESULTS: Use of minimal antithyroid medication impaired the progressive increase of compound W seen in euthyroid mothers during pregnancy. At term, depressed compound W levels in maternal serum were found in 7 of 22 pregnancies; in 1 case, maternal compound W was suppressed and newborn thyroid-stimulating hormone was elevated. Seven mothers with treated hyperthyroidism failed to show an increase in serum levels of compound W after midterm. CONCLUSION: Normal progression of maternal serum compound W may be an index of normal fetal thyroid development in mothers with hyperthyroidism treated with necessary antithyroid medication.

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy.

Melanin pigment displays strong photo- and radioprotective properties, suggesting that inhibition melanogenesis could increase sensitivity of melanoma to ionizing radiation. We tested this concept in human melanoma cells cultured in either Ham's F10 medium to maintain amelanotic phenotype or DMEM to induce/stimulate melanin production, respectively; N-phenylthiourea (PTU) and D-penicillamine were used as an inhibitor of melanogenesis. Melanogenic activity was evaluated by visual inspection (color of cell pellets) or by measurement of tyrosinase (dopa oxidase) activity assay. Amelanotic cells or cells with various melanin content were exposed to gamma radiation and tested for viability and colony forming capability. Gamma radiation at doses of 2-15 Gy inhibited cell viability and colony forming efficiency in dose- and time-dependent manner, but pigmented melanoma cells were significantly more resistant to gamma radiation than nonpigmented cells (p < 0.05-0.001). Both PTU and D-penicillamine inhibited strongly tyrosinase activity and melanin production in melanoma cells (p < 0.05-0.001). Furthermore, inhibition of melanogenesis by PTU or D-penicillamine resulted in enhancement of melanoma cells sensitivity to killing by gamma rays. In conclusion, the results of these cell culture experiments give support to a clinical trial of pharmacologically induced decrease in melanin synthesis to enhance the efficacy of radiotherapy in advanced melanomas.

Lithium therapy: an unusual cause of elevated and diffuse radioactive iodine uptake.

Lithium carbonate, a widely used treatment for bipolar disorders, is associated with goiter, hypothyroidism and thyrotoxicosis. However, the effect of lithium to increase radioactive iodine uptake has received little attention, thus, making Lithium a confounding factor in the interpretation of thyroid radionuclide studies. We herein report a case of misinterpreted high radioactive iodine uptake in a euthyroid, lithium-treated goitrous patient. We conclude that lithium therapy should be considered in the etiologic diagnoses of patients with goiter and homogenously elevated radioiodine uptake. It is pertinent to recognize this phenomenon in order to prevent unwarranted treatment with radioactive iodine or thionamides.

The lysophosphatidic acid type 2 receptor is required for protection against radiation-induced intestinal injury.

BACKGROUND & AIMS: We recently identified lysophosphatidic acid (LPA) as a potent antiapoptotic agent for the intestinal epithelium. The objective of the present study was to evaluate the effect of octadecenyl thiophosphate (OTP), a novel rationally designed, metabolically stabilized LPA mimic, on radiation-induced apoptosis of intestinal epithelial cells in vitro and in vivo. METHODS: The receptors and signaling pathways activated by OTP were examined in IEC-6 and RH7777 cell lines and wild-type and LPA(1) and LPA(2) knockout mice exposed to different apoptotic stimuli. RESULTS: OTP was more efficacious than LPA in reducing gamma irradiation-, camptothecin-, or tumor necrosis factor alpha/cycloheximide-induced apoptosis and caspase-3-8, and caspase-9 activity in the IEC-6 cell line. In RH7777 cells lacking LPA receptors, OTP selectively protected LPA(2) but not LPA(1) and LPA(3) transfectants. In C57BL/6 and LPA(1) knockout mice exposed to 15 Gy gamma irradiation, orally applied OTP reduced the number of apoptotic bodies and activated caspase-3-positive cells but was ineffective in LPA(2) knockout mice. OTP, with higher efficacy than LPA, enhanced intestinal crypt survival in C57BL/6 mice but was without any effect in LPA(2) knockout mice. Intraperitoneally administered OTP reduced death caused by lethal dose (LD)(100/30) radiation by 50%. CONCLUSIONS: Our data indicate that OTP is a highly effective antiapoptotic agent that engages similar prosurvival pathways to LPA through the LPA(2) receptor subtype.

Initial clinical experience imaging scatterer size and strain in thyroid nodules.

OBJECTIVE: This article describes a new research ultrasound scanner that can be programmed to produce elastograms and backscatter parametric images in real time. Its performance was evaluated in a clinical setting. METHODS: Radio frequency data were acquired from 13 patients with thyroid nodules and from 4 normal thyroids, along with reference phantom data. Scatterer size was deduced by measuring the backscatter versus frequency and fitting data to a model. Strain was obtained by a cross-correlation method, comparing precompression and postcompression radio frequency signals. Scatterer size contrast was defined as the observed contrast between the "normal" and "abnormal" tissue in the same gland or, when considering diffuse conditions, by comparing with normal values. Strain contrast was estimated if abnormal and normal tissue was captured in the same palpation, that is, excluding diffuse disease, which was the case for 9 subjects. RESULTS: On scatterer size images, 4 nodules exhibited positive contrast versus the adjacent normal parenchyma, indicating larger scatterers. Five nodules were isoechoic, and 4 had negative contrast. Four nodules exhibited positive strain contrast, indicating that they were softer than the normal parenchyma. Two nodules had the same brightness, and 3 were darker than the background thyroid tissue on strain images. CONCLUSIONS: Contrast was observed between nodules and thyroid parenchymal tissue for both types of parametric images. Further work is needed to determine whether the diagnostic importance of these parameters in characterizing thyroid nodules might be worthwhile. Both modes must be of a sufficient frame rate to provide real-time feedback to operators, which will require further work.

Transfer of 131I into human breast milk and transfer coefficients for radiological dose assessments.

Data on transfer of radioiodine into human milk are rare in the literature. Data from sixteen publications were reviewed and analyzed to estimate the transfer coefficient (f(hm)*, having units of d L(-1)). The data on the radioiodine concentration in breast milk were analyzed by two methods: direct numerical integration and integration of a fitted exponential model. In general, the integrated fitted functions were greater. The fitted functions likely better describe the transfer into milk since few data sets sampled mothers' milk near the time of maximum excretion. The derived transfer coefficient values seem to represent two populations. The first group was those individuals who had very low excretions, including those where thyroid and mammary uptake was impaired by the administration of stable iodine or iodinated compounds. The second group included those with much higher excretions. The second group, termed the "normal-excretion" group, had transfers of iodine to milk that were more than ten-fold higher than in the "low-excretion" group. The derived milk transfer coefficient data for the low- and normal-excretion groups fitted to lognormal distributions gave geometric means, (geometric standard deviations), of 0.043 d L(-1) (2.1, n = 14) and 0.37 d L(-1) (1.5, n = 12), respectively. Estimates of the effective half-time (time from maximum concentration to half the value) were determined for the low- and normal-excretion groups separately. There was evidence that the effective half-time was longer for the normal- than for the low-excretion group; the geometric mean (and geometric standard deviation) were 12 (1.7) and 8.5 (2.6) h, respectively, though the difference was not statistically significant. The geometric mean times to maximum milk concentration in the low- and normal-excretion groups were nearly identical, 9.4 (3.1) and 9.0 (1.6) h, respectively. The data show that administration of large doses of stable iodine (commonly used to block uptake of iodine into the thyroid) is also an effective means to block radioiodine transfer into milk. Thus, protecting the mother's thyroid also protects the nursing infant. Despite inadequacies of available data describing the transfer of radioiodine to human milk within a healthy population of women, the values of f(hm)* provided here are believed to be the best available for use in radiological assessments. These values are particularly applicable to lactating women having normal diets and availability to stable iodine, as in the United States.