Urinary iodine and thyroglobulin are useful markers in infants suspected of congenital hypothyroidism based on newborn screening.

OBJECTIVES: Iodine deficiency and excess both cause thyroid dysfunction. Few data describe the relationship between iodine status and outcomes of congenital hypothyroidism (CH) in iodine-sufficient areas. We investigated urinary iodine (UI) concentration and its relationship with the clinical course of CH. METHODS: We reviewed and retrospectively analyzed patients with positive newborn screening (NBS) for CH from January 2012 to June 2019 in Japan, obtaining UI and UI-urine creatinine ratio (UI/Cr), serum TSH, free T4, free T3 and thyroglobulin (Tg) at the first visit, TSH at NBS, levothyroxine (LT4) dose, and subsequent doses. A UI value of 100-299 µg/L was considered adequate. RESULTS: Forty-eight patients were included. Median UI and UI/Cr were 325 µg/L and 3,930 µg/gCr, respectively. UI was high (≥300 µg/L) in 26 (54%) and low (≤99 µg/L) in 11 (23%). LT4 was administered to 34 patients. Iodine status was not related to the need for treatment. We found a U-shaped relationship between Tg and UI/Cr. Patients with high Tg (≥400 ng/mL) and abnormal UI levels required significantly lower LT4 doses (≤20 µg/day) at three years of age. Even if they showed severe hypothyroidism initially, they did not need subsequent dose increments. CONCLUSIONS: Abnormal UI levels with Tg elevation were associated with lower LT4 dose requirements. The evaluation of iodine status and Tg concentrations were considered useful in patients suspected of CH.

Evolución del estado de nutrición de yodo en gestantes del area sanitaria de Pamplona / Change over time in the iodine nutritional status of pregnant women from the Pamplona healthcare region

INTRODUCCIÓN: La ingesta adecuada de yodo es esencial durante el embarazo. Sin embargo, una parte de la población gestante de nuestro país persiste en una situación de yododeficiencia. Un estudio previo realizado en embarazadas del área sanitaria de Pamplona mostró una yoduria insuficiente (125 mcg/l) y un bajo consumo de sal yodada. El objetivo del presente trabajo es conocer la ingesta de yodo y analizar la evolución del estado de yodación en gestantes de nuestro medio en los últimos años. MÉTODOS: Estudio observacional de 400 gestantes de primer trimestre sin antecedentes conocidos de enfermedad tiroidea. Se cumplimentó un cuestionario de consumo de yodo. Como marcadores del estado de yodación se analizaron la yoduria en una muestra simple de orina y la tiroglobulina sérica, y se calculó el volumen tiroideo mediante ecografía cervical. RESULTADOS: El 70,5% de las participantes consumía sal yodada (55,3% pregestacional) y el 98,5% suplementos farmacológicos con yodo (dosis 202,6±30,1 mcg/día). La mediana de la yoduria fue 242 mcg/l (138,5-415,5 mcg/l) y de la tiroglobulina 12,3 mcg/l (8,39 mcg/l). El consumo de sal yodada se asoció a mayor yoduria y a un menor volumen tiroideo. No se encontraron diferencias en los parámetros estudiados en función del consumo de lácteos, pescado o huevos. CONCLUSIONES: La ingesta de yodo en gestantes de Pamplona ha aumentado, tanto a expensas del empleo de sal yodada como de la dosis de la suplementación farmacológica. Esto ha permitido alcanzar un estado de yodación adecuado

INTRODUCTION: Adequate iodine intake is essential during pregnancy. A previous study of pregnant women from the Pamplona healthcare region showed mild iodine deficiency (mean urinary iodine level, 125 mcg/L). This study was intended to ascertain the iodine intake of pregnant women in our region and to analyze the change over time in their iodine nutritional status. METHODS: An observational study of 400 women in their first trimester of pregnancy. An iodine intake questionnaire was administered. To assess iodine status, urinary iodine concentration (UIC) was measured in a simple urine sample, and serum thyroglobulin levels were determined. In addition, thyroid volume was measured by cervical ultrasound examination. RESULTS: Iodized salt was used by 70.5% of all participants (55.3% since the pre-gestational period) and 98.5% of them received iodine-containing supplements (mean dose, 202.6±30.1 mcg/day). Mean urinary iodine concentration was 242 mcg/L (138.5-415.5 mcg/L) and the mean serum thyroglobulin level was 12.3 mcg/L (8.3-9 mcg/L). Iodized salt intake was associated with higher UICs and lower thyroid volume. No differences were found in any of the tested parameters regarding the intake of dairy products, fish, or eggs. CONCLUSIONS: Iodine intake by pregnant women in Pamplona has increased due to a greater use of iodized salt and to higher doses of iodine supplements. As a result of this, an adequate iodine status has been achieved in the last decade

Urinary Exosomal Thyroglobulin in Thyroid Cancer Patients With Post-ablative Therapy: A New Biomarker in Thyroid Cancer.

Background: Most patients with thyroid cancer typically receive thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Exosomes are nanovesicles secreted into extracellular environments, including plasma, saliva, urine, and other body fluids of patients with cancer. We try to find the early prognostic and exosomal biological markers of urine. Methods: We analyzed urinary exosomal proteins, including thyroglobulin and galectin-3, to identify early prognostic biological markers in urine for patients receiving operation and radioactive iodine ablative therapy. We enrolled sixteen newly diagnosed patients with papillary thyroid carcinoma and follicular thyroid carcinoma. We collect all patient's urine samples before operation, immediately after operation, post-operatively at three and six months (4 collections per patient). The levels of pre-operative and post-ablative of U-Ex Tg and galectin-3 in patients with thyroid cancer were measured. Results: Trends in urinary thyroglobulin concentrations in patients with post-ablative thyroid cancer were detected in the first sixteen patients. Importantly, serum thyroglobulin was not detected in five patients after operation and radioactive I-131 ablation, while U-Ex Tg still showed an increasing trend, which implicating the probable recurrence of thyroid cancer. This is the first study to evaluate whether U-Ex Tg is a future biological marker as a substitute for serum thyroglobulin. Conclusion: Our study have developed a brand-new evaluation for tracking thyroid cancer. The most useful scenario in using a test that is potentially more sensitive than existing serological testing is to eliminate the suspicion of recurrence and remove subjects from long term follow up. Trial Registration: ClinicalTrials.gov: NCT02862470; 5, August 2016. https://clinicaltrials.gov/ct2/show/NCT02862470?term=NCT02862470&rank=1. ClinicalTrials.gov: NCT03488134; 3, August 2018. https://clinicaltrials.gov/ct2/show/NCT03488134?term=NCT03488134&draw=2&rank=1.

Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt.

Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8-10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 µg/L (females 106 µg/L, males 131 µg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100-199 µg/L). The median Tg concentration was 8.7 µg/L, which was <10 µg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food-only model was 65 µg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 µg/day. The mean iodine intake from the food-plus-iodised salt model was 101 µg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate.

Iodine status in pre-school children prior to mandatory iodine fortification in Australia.

The iodine status of children between the ages of 5 and 15 years has been routinely assessed in many countries, but few studies have examined iodine status in pre-school children. We conducted a cross-sectional study of pre-school children living in Adelaide, South Australia, between 2005 and 2007. Children 1-5 years old were identified using a unique sampling strategy to ensure that the study population was representative. A 3-day weighed diet record, a blood sample and a urine sample were obtained from each child. The median urinary iodine concentration (UIC) of the children (n = 279) was 129 µg L(-1), indicating iodine sufficiency (normal range: 100-199 µg L(-1)), but 35% of the children had a UIC < 100 µg L(-1). The median thyroglobulin concentration of children (n = 217) was 24 µg L(-1) and thyroglobulin concentration declined with increasing age (P = 0.024). The mean daily iodine intake was 76 µg. The intake of iodine was lower than expected and highlights difficulties in accurately assessing iodine intakes. Further studies are needed to monitor dietary changes and iodine status in this age group since the implementation of mandatory fortification of bread with iodised salt in Australia in 2009.

Neonatal thyroid status in an area of iodine sufficiency.

BACKGROUND: Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency. METHODS: Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 µg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated. RESULTS: Fifty-two pregnant women (38%) had median UIE<150 µg/l and 86 had (62%) UIE ≥ 150 µg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 µg/l, 97 and 213 µg/l, 93 and 227 µg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles. CONCLUSION: This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

The prevalence of iodine deficiency, serum thyroglobulin, anti-thyroglobulin and thyroid peroxidase antibody levels in the urban areas of Kayseri, Central Anatolia.

BACKGROUND: The prevalence of goitre and urinary iodine excretion (UIE) indicate endemic iodine deficiency (ID) in a population. Previous studies have shown that Kayseri is one of the most iodine-deficient areas in Turkey. The aim of this study was to determine the prevalence of goitre, evaluate the degree of ID, its effects on thyroid functions and volume of subjects living in wide outer skirts of the old volcano Erciyes, at 1655 m and 1350 m altitudes. METHODS: UIE was determined in 209 school-age children (SAC) aged between 10 and 14 years and in 183 adults. Thyroid volume (TV) of subjects was performed used by both palpation and ultrasonography (USG). In addition, serum free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), thyroglobulin (Tg), anti-Tg and anti thyroid peroxidase (TPO) antibody levels were measured. RESULTS: The prevalence of goitre according to palpation and USG among SAC was found as 50.7 and 58.4% respectively, as 65.0 and 57.9% among adults. Although mean UIC of whole subjects was 30+/-34 microg/l indicated moderate iodine (I) deficiency, 55.4% of the subjects' UIE was <20 microg/l. While the serum fT3, TSH, anti-TPO, Tg levels, body mass index (BMI), TV of SAC and adults (except BMI) with goitre were higher than those of without goitre, serum fT4 and UIE were lower than those of without goitre. CONCLUSIONS: The population living in two areas was exposed to consequences of severe and moderate ID and also endemic goitre due to geographical characteristics of the area. A plan of action including sufficient I intake of people should be planned and be implemented effectively.

Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation.

The main steps in the management of differentiated thyroid cancer are thyroidectomy, treatment with iodine-131 ((131)I), and follow-up with whole-body scanning (WBS) and serum thyroglobulin (Tg) determination. Both (131)I treatment and follow-up require maximum stimulation of normal or pathological thyroid remnants by TSH. The use of recombinant human TSH (rhTSH) has been shown to be useful for follow-up, whereas previous reports are not univocal regarding the use of (131)I postsurgical ablation of thyroid remnants, at least when low doses (30 mCi) of (131)I are administered. A possible explanation for the diminished effectiveness of (131)I treatment after rhTSH may be the interference of iodine content of L-thyroxine (L-T4) therapy during the protocol of administration of rhTSH. We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. The study included two groups of patients: group 1 included 16 patients with differentiated thyroid cancer (15 papillary cancers and 1 follicular cancer, stages I and II), who were treated with 30 mCi (131)I with the aid of rhTSH, using the standard protocol but stopping L-T4 as stated previously; and group 2 included 24 patients with the same features (histology and stage) of disease treated with 30 mCi in the hypothyroid state after L-T4 withdrawal. In both groups, serum TSH reached a very good stimulation level [76-210 U/liter (mean, 112 +/- 11 SE) and 38-82 U/liter (mean, 51 +/- 3 SE), respectively]. At the first WBS (after (131)I treatment), all patients showed thyroid remnants. Furthermore, two patients of the first group and three patients of the second group showed lymph node metastases. After 1 yr, all patients were studied again and underwent WBS with a tracer dose of (131)I and serum Tg measurement using rhTSH with the same protocol in both groups. The percentage of ablation (undetectable Tg and a negative WBS) was higher, although not reaching statistical significance, in patients treated with rhTSH: 81.2% in patients treated by rhTSH withdrawal and 75.0% in patients treated by L-T4 withdrawal, respectively. No patient experienced symptoms of hypothyroidism during the 4 d of L-T4 interruption, and serum T4 remained in the normal range. Urinary iodine was analyzed in both groups and compared with a control group of patients who received, for diagnostic purposes, rhTSH without stopping L-T4. In the first group, urinary iodine was 47.2 +/- 4.0 microg/liter (mean +/- SE; P = 0.21 vs. the second group, P = 0.019 vs. control group). In the second group, urinary iodine was 38.6 +/- 4.0 microg/liter (mean +/- SE; P < 0.001 vs. control group); urinary iodine in the control group was 76.4 +/- 9.3 microg/liter (mean +/- SE). Our data show that rhTSH, as administered in the protocol stated previously, allows at least the same rate of ablation of thyroid remnants when low doses (30 mCi) of (131)I are used. The possible role of interference of iodine content in L-T4 is not surprising if we consider that the amount of iodine in 30 mCi is negligible (5 microg) compared with the amount of iodine content in a daily dose of T(4) ( approximately 50 microg). The cost of rhTSH seems modest compared with the high cost of complex therapeutic regimens in other areas of oncology and in consideration of the well-being of patients and of the high level of effectiveness of the treatment.

No influence of simvastatin treatment on platelet function in vivo in patients with hypercholesterolemia.

Hypercholesterolemia is associated with platelet activation. Reduction of plasma cholesterol levels by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin has been found to improve certain aspects of platelet function in vitro and in vivo, but controlled trials are largely lacking. The present randomized, double-blind, crossover study was performed to evaluate whether 10- to 12-week treatment with simvastatin or placebo affects platelet function in vivo in 23 hypercholesterolemic men. Measurements were performed at rest and during mental stress. Simvastatin treatment reduced plasma total cholesterol levels by 18 +/- 2% and low density lipoprotein cholesterol levels by 26 +/- 2% (P < .001 for both), whereas high density lipoprotein cholesterol levels increased slightly (6 +/- 2%, P < .05). Platelet aggregability as assessed by filtragometry ex vivo was unaffected by simvastatin treatment both at rest and during mental stress. Plasma beta-thromboglobulin levels, which reflect platelet secretion, were also unaltered by simvastatin treatment both at rest (antilog of the mean: 20.2 versus 20.0 ng/mL during placebo) and during mental stress. Moreover, nocturnal excretion of 11-dehydrothromboxane B2 in urine did not differ between placebo and active treatment: 218 versus 216 ng/mmol creatinine, respectively. The corresponding values for urinary excretion of high-molecular-weight beta-thromboglobulin were 1.78 versus 1.92 ng/mmol creatinine. Thus, simvastatin treatment had no clear-cut effect on platelet function, as assessed by four different in vivo related platelet function variables, in hypercholesterolemic men.

Prenatal diagnosis of a thyroglobulin synthesis defect in goats.

A strain of goats with congenital goitre due to a thyroglobulin (Tg) synthesis defect was studied. All goats excreted low molecular weight iodinated material (LOMWIOM) in their urine, but non-goitrous goats excreted in the LOMWIOM fraction less than 5 micrograms iodine per 24 h and the goitrous ones more than 15 micrograms iodine per 24 h. Prenatal diagnosis of the Tg synthesis defect in goats is possible since non-goitrous goats pregnant with goitrous kids excrete in the LOMWIOM fraction more than 10 micrograms iodine per 24 h while non-goitrous goats pregnant with non-goitrous kids excrete 10 micrograms or less iodine per 24 h as LOMWIOM. In 24 out of 25 cases a correct diagnosis could be made in the last 47 days of pregnancy. We argue that prenatal diagnosis of analogous defects in man may also be possible, using the excretion of LOMWIOM in maternal urine as yard-stick. By means of field desorption mass spectrometry (FOMS) and high performance liquid chromatography (HPLC) monoiodohistidine was identified as the major component of the LOMWIOM fraction in the urine of goitrous goats.