OBJECTIVETo 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.METHODSCompound 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.RESULTSUse 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.CONCLUSIONNormal progression of maternal serum compound W may be an index of normal fetal thyroid development in mothers with hyperthyroidism treated with necessary antithyroid medication.

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. © 2008 Wiley‐Liss, Inc.

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.

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.

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.

A 26 year old African American male with Graves' disease, on methimazole and propranolol in preparation for ablation with radioactive iodine, was instructed to stop methimazole. About one week later he presented to the emergency room reporting acute onset of weakness of lower extremities along with palpitations and racing of heart. Abrupt onset of weakness one day prior to admission did not let him leave the bed. Review of systems otherwise was unremarkable. Family history was positive for Graves' disease. On physical examination, blood pressure: 150/74, pulse: 145 (sinus tachycardia), afebrile. He exhibited severe exophthalmus and diffuse goiter. Muscle strength of lower extremities was 1/5 bilaterally and deep tendon reflexes were 1+. Neurological examination otherwise was nonfocal. His FT4 at the time of stopping methimazole was 4.4 ng/dL (normal range: 0.58-1.64 ng/dL) but at the time of paralysis had increased to more than 5.8 ng/dL. His total T3 was increased to more than 800 ng/dL (normal range: 87-178). TSI was 414 (normal < 130). His potassium at the time of stopping methimazole was 4.3 but at presentation was 2.1. His ALT and AST also at the time of presentation increased to 92 and 91 but after control of symptoms using a high dose of propranolol were normalized. Ionized calcium at presentation was 1.6 mM (normal range 1.12 to 1.32 mM) and later with control of thyrotoxicosis returned to normal. Following replacement of potassium and treatment with a high dose of propranolol to control hyperthyroid state, hypokalemia resolved and muscle strength came back to normal. Thyrotoxic hypokalemic periodic paralysis (THPP) is a common complication of hyperthyroidism among Asians but is an uncommon problem in the United States, where most cases have been described in Caucasians and rarely in African Americans. Graves' disease is the most common cause of THPP in affected patients, but it has been reported with other causes of thyrotoxicosis. Potassium replacement during an acute attack will shorten the duration of the episode. In our African American case, replacement of potassium and treatment with propranolol and, later, ablation with radioactive iodine led to resolution of hypokalemia and weakness.

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.

Reports from 1950 to 1960 suggest that goiter was frequent in the Chernobyl area and vigorous efforts were undertaken to distribute iodine supplements. There resulted enthusiastic reports stating that endemic goiter was no longer a problem. During the 1970s, the distribution of iodized salt became undependable and by 1980, goiter incidence was reported to have increased. Four to ten years after the Chernobyl nuclear accident, severe iodine deficiency was unusual but goiter by ultrasound measurement was found in more than 35% of the children. Unusual thyroid cancer appeared and its prevalence continues to increase.

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7-25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 1), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0-22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.3 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients although complications may require close follow-up in a multidisciplinary setting.

Casual urine samples were collected to determine iodine excretion of 1680 Belarus children during 1990-1994. The subjects, 8-16 years old, were from nine different regions of Belarus; 60% were from the Gomel oblast, which has been associated with relatively high levels of radioiodine fallout and increased incidence of thyroid cancer. Most of the median values indicate borderline/low iodine intake or mild iodine deficiency. Ranges were wide but 163 children excreted < 20 micrograms I/l urine and they should be considered severely deficient in iodine.

Journal Article Iodine deficiency in Ukraine Get access Elena V Bolshova, Elena V Bolshova Kiev Research Institute of Endocrinology and Metabolism Kiev, Ukraine Search for other works by this author on: Oxford Academic Google Scholar Nikolai D Tronko, Nikolai D Tronko Kiev Research Institute of Endocrinology and Metabolism Kiev, Ukraine Search for other works by this author on: Oxford Academic Google Scholar Lester Van Middlesworth, Lester Van Middlesworth Kiev Research Institute of Endocrinology and Metabolism Kiev, Ukraine Search for other works by this author on: Oxford Academic Google Scholar Lester Van Middleswort Lester Van Middleswort Dept. Physiology and Biophysics, University of Tennessee, Memphis, TN 38163, USA Corresponding author. Fax no.: (901) 528-7126 Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 129, Issue 6, Dec 1993, Page 594, https://doi.org/10.1530/acta.0.1290594 Published: 01 December 1993