Iodine Metabolism and Thyroid Function During the Perinatal Period: Maternal-Neonatal Correlation and Effects of Topical Povidone-Iodine Skin Disinfectants.

An adequate maternal iodine intake during pregnancy and lactation is essential for growth and mental development in fetuses and newborns. There are limited data on perinatal iodine metabolism in mothers and infants, as well as the effect of povidone-iodine (PVP-I) antiseptics used in cesarean delivery. The urinary iodine concentration (UIC), serum iodine, thyrotropin (TSH), free thyroxine (FT4), and breast milk iodine concentration (BMIC) were measured consecutively in a total of 327 mothers and 249 term-infants in two prospective studies. The maternal median UIC was 164 µg/L in the third trimester, increased to 256 µg/L at 44 h after birth, and then decreased to 116 µg/L 1 month later. The BMIC on the 4th and 32th postpartum days was 17.6 and 13.5 µg/100 g, respectively. In neonatal infants born to the mothers unexposed to PVP-I, the median UIC was 131 µg/L in the first voiding urine and increased to 272 µg/L on day 4 and then slightly decreased to 265 µg/L on day 28 suggesting sufficient iodine reserve at birth. PVP-I antiseptics containing 1 g of iodine for skin preparation at cesarean delivery transiently increased maternal serum iodine concentration (1.9-fold), UIC (7.8-fold) at 41 h after surgery and BMIC, while it had little effect on maternal TSH, FT4, and neonatal UIC, TSH, or FT4. The iodine status of pregnant women and their infants was adequate in this population; however, the UIC in lactating mothers at one postpartum month was low enough to suggest iodine deficiency or near iodine deficiency. Further studies are necessary.

Variability and Seasonal Change of Urinary Selenium, Molybdenum, and Iodine Excretion in Healthy Young Japanese Adults.

Selenium (Se), molybdenum (Mo), and iodine (I) are essential trace elements or nutrients and their adequate intake is essential for human health. These elements in foods are easily absorbed from the digestive tract and excreted predominantly into the urine, and their nutritional status is reflected in urinary excretion; however, information on the variability of urinary excretion is limited. To characterize the urinary Se, Mo, and I concentrations and their intra- and inter-individual coefficients of variation (CV), correlation, and seasonal change, spot urine samples were collected from 24 healthy university students, 10 males and 14 females, with the mean age of 20.6 years, for 10 consecutive days in each of the four seasons according to a defined schedule of an interval of 3 months throughout 1 year. The median Se, Mo, and I concentrations for all urine samples (n = 947) were 52.8, 127.0, and 223 µg/L, respectively. The Se and Mo intakes were highest in summer and lowest in spring, while the I intake was highest in autumn and lowest in summer. In all three elements, the intra-individual CVs were smaller than their inter-individual CVs. The log-transformed intra- and inter-individual CVs were 10.5 and 14.7% for Se, 12.3 and 15.1% for Mo, and 15.5 and 18.1% for I. There was no gender difference in Se and I concentrations, while Mo and Mo/Cr values in males were higher than those in females. Our results suggest adequate nutritional status of Se, Mo, and I with a relatively smaller variability of dietary intake except for I in this population.

Gestational trimester-specific reference ranges for serum thyrotropin and free thyroxine in Japanese.

Thyroid diseases in pregnant and lactating women may result in adverse outcomes for both mothers and infants. A reference range for thyroid function is required in different areas; however, few studies on the gestational change or reference ranges of thyrotropin (TSH) and free thyroxine (FT4) concentrations for Japanese pregnant women have been reported. To establish the gestational trimester-specific reference ranges of serum TSH and FT4 concentrations, our previously published data on 481 pregnant women with the mean age of 30.8 years who provided serum samples as early as gestational week (GW) 6 was compiled by using their percentile values. The overall median urinary iodine concentration (UIC) during pregnancy was 201 µg/L suggesting adequate iodine intake. The prevalence of positive serum thyroid autoantibody (ThAb), i.e., antithyroid peroxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb), was 11.4%. The reference ranges (2.5-97.5th percentile) of serum TSH and FT4 concentration calculated for samples with negative TgAb and TPOAb were 0.04-6.06 mIU/L in the first trimester (T1), 0.31-3.11 mIU/L in the second trimester (T2) and 0.48-3.93 mIU/L in the third trimester (T3) for TSH, and 1.10-1.87 ng/dL (T1), 0.76-1.56 ng/dL (T2) and 0.76-1.14 ng/dL (T3) for FT4. Compared to published data around the world in the 2017 American Thyroid Association (ATA) guideline, both the upper and lower limits of our TSH and FT4 reference ranges in the first trimester were higher than those in other countries. Further research is necessary in larger samples.

Iodine intake in healthy Japanese aged from 6 to 70 years residing in the same district.

Iodine is an essential component of thyroid hormones and a dietary micronutrient for humans, and adequate iodine intake is necessary to maintain thyroid function. A population's iodine intake and nutritional status are assessed based on urinary iodine excretion. There are few studies on iodine nutritional status for all age groups residing in the same area in Japan. Between 2010 and 2017, a total of 769 healthy subjects aged 6.4-73 years in three sites in Yokohama City, were enrolled in the survey. The urinary iodine concentration (UIC), iodine to creatinine (Cr) ratio (UI/Cr) and estimated 24-h urinary iodine excretion (UIE) in single spot urine samples were measured, and habitual dietary iodine intake was assessed by food frequency questionnaires. The estimated 24-h UIE was calculated using individual predicted 24-h creatinine excretion by the validated equations developed for healthy Japanese children and adults which vary by age, gender and anthropometry. The median UIC for all participants was 219 µg/L, suggesting adequate iodine intake for this population. There was an increasing trend in median UI/Cr and estimated 24-h UIE by age. A significant correlation between UIC and UI/Cr (r = 0.6378), UIC and estimated 24-h UIE (r = 0.6804), and UI/Cr and estimated 24-h UIE (r = 0.5756) were observed. These estimates can be feasible, convenient and alternative methods to 24-h urine collection in order to assess iodine status in some populations such as ethnically or racially homogeneous and well-nourished people. Additional studies are required to validate these findings.

Studies on urinary excretion and variability of dietary iodine in healthy Japanese adults.

The daily consumption of iodine in Japan is higher than in most countries, and there are few reports on iodine metabolism and variance of habitual iodine ingestion in an iodine-sufficient area. To elucidate the patterns of short-term urinary iodine excretion (UIE) and long-term variability of habitual iodine intake, the urinary iodine excretion process after a high dietary iodine load of 3 mg was observed in eight Japanese adults under strict supervision with complete urine collections for three days. In addition, estimated UIE and dietary iodine intake (DII) were assessed in 24 university students using repeated spot urine samples of ten consecutive days and a food frequency questionnaire in each of the four seasons. Approximately 50, 75 and 90% of orally ingested iodine was excreted into the urine at 8, 13 and 22 hours after ingestion, respectively. Almost an equal amount of ingested iodine in meals was cleared within 33.5 h after eating with a maximum excretion rate at 3-4 h. There was a high fluctuation in the UIE and DII in the university students. The intra- and inter-individual crude coefficients of variation were 123 or 294.7% for UIE, and 58.3 or 88.7% for DII, respectively, indicating a higher variance of habitual iodine intake than in other countries. The frequency of occurrence for UIE above 3 mg was every 43 days. Rapid renal clearance of iodine and high variability as well as low frequency of dietary iodine intake might prevent people from being exposed to an excess iodine intake over the long term in Japan.

Current Iodine Status in Japan: A Cross-sectional Nationwide Survey of Schoolchildren, 2014-2019.

CONTEXT: Japan has been regarded as a long-standing iodine-sufficient country without iodine fortification; however, data on nationwide iodine status are lacking. OBJECTIVE: This study aimed to characterize the iodine status in Japan. METHODS: From 2014 through 2019, a nationwide school-based survey was conducted across all districts in Japan. Urinary iodine concentration (UIC), creatinine (Cr) concentration, and anthropometry were assessed in healthy school-aged children (SAC) aged 6 to 12 years. Their iodine status is regarded as generally representative of the nation's iodine status. RESULTS: A total of 32 025 children participated. The overall median UIC was 269 µg/L, which was within the World Health Organization's adequacy range. There was a regional difference in UIC values within 14 regions, and the lowest and highest median UICs were found in Tanegashima Island (209 µg/L) and Nakashibetsu, Hokkaido (1071 µg/L), respectively. The median UIC ≥ 300 µg/L was observed in 12 of 46 regions. By using estimated 24-hour urinary iodine excretion (UIE), the prevalence of SAC exceeding the upper tolerable limit of iodine for Japanese children was from 5.2% to 13.7%. The UIC values did not change with age, body surface area and body mass index percentile, whereas the Cr concentration simultaneously increased suggesting the effect of urinary creatinine on UI/Cr and estimated 24-hour UIE values. CONCLUSIONS: The iodine intake of Japanese people is adequate, but in some areas it is excessive. The incidence and prevalence of thyroid disorders associated with iodine intake should be obtained, especially in the areas where high amounts of iodine are consumed.

Gestational changes of thyroid function and urinary iodine in thyroid antibody-negative Japanese women.

Iodine is an essential nutrient for thyroid hormone synthesis, and iodine deficiency especially in pregnant and lactating women results in serious damage to their infants. To characterize iodine nutrition throughout gestation by using a food frequency questionnaire (FFQ) and urinary iodine concentration (UIC) measurement, and to establish appropriate gestational age-specific reference ranges for serum TSH and FT4 in thyroid autoantibody (ThAb) negative euthyroid Japanese women, a total number of 563 pregnant women including 422 subjects with negative ThAbs, 105 postpartum women and their 297 newborn infants were included in the study. Dietary iodine intake (DII) was evaluated by FFQ. Serum TSH, FT4 and UIC were sequentially determined in the three trimesters of pregnancy and at the 31st postpartum day. The overall median UICs throughout pregnancy and in the postpartum period were 224.0 and 135.0 µg/L, respectively, suggesting sufficient iodine nutrition. The median DII was 842.4 µg/day in pregnant women. The median UIC in the first trimester (215.9 µg/L) significantly decreased in the second trimester (136.0 µg/L). The prevalence of pregnant women with a UIC below 150 µg/L was 31.6% and that in lactating women with a UIC below 100 µg/L was 33.3%. The pattern of gestational change in serum TSH and FT4 was comparable to that in iodine-sufficient areas. A substantial percentage of women might be at risk for iodine deficiency if there is a restriction of iodine-rich foods. However, iodine supplementation for pregnant women must be carefully balanced against the risk of iodine excess particularly in Japan. Further research in larger samples is needed.

Iodine status of pregnant and postpartum Japanese women: effect of iodine intake on maternal and neonatal thyroid function in an iodine-sufficient area.

BACKGROUND: Iodine deficiency in pregnant and lactating women results in serious damage to their fetuses, newborns, and weaning infants. The effect of dietary iodine intake on maternal and infantile thyroid function has not been well studied in iodine-sufficient areas, and there are few data on appropriate gestational age-specific reference ranges for urinary iodine excretion during pregnancy and lactation. OBJECTIVES: The aim of the study was to characterize the gestational change of urinary iodine excretion in Japanese women and to assess the effects of iodine status on thyroid function in mother and infant. METHODS: A total of 934 Japanese women and their 722 newborn infants were enrolled in the study. Iodine and creatinine concentrations were determined in spot urine samples in the three trimesters of pregnancy and the postpartum period at 34.0 d after delivery. Serum thyroperoxidase antibody and thyroglobulin antibody, TSH, and free T(4) were measured in each trimester, and neonatal TSH was measured on postnatal d 4. RESULTS: The overall median urinary iodine concentration (UIC) during pregnancy was 219.0 µg/liter, higher than that in postpartum women (135.0 µg/liter). The prevalence of pregnant women with low UIC less than 100 µg/liter or high UIC greater than 500 µg/liter was 16.1 and 22.2%, respectively. Urinary iodine excretion decreased from 221.0 µg/liter in the first trimester to 208.0 µg/liter in the second trimester to 193.0 µg/liter in the third trimester, and then remained at 135.0 µg/liter postpartum. [corrected]. The maternal UIC correlated positively with serum TSH during pregnancy. There was no significant difference in UIC between subjects with positive thyroid autoantibodies and those with negative antibodies. CONCLUSIONS: Iodine intake assessed by UIC in Japanese pregnant women is regarded as sufficient and not excessive according to World Health Organization criteria. Although the data are local, our results provide additional information on the reference range for UIC throughout gestation in iodine-sufficient areas.

Thyroid ultrasound volume, structure and function after long-term high exposure of large population to polychlorinated biphenyls, pesticides and dioxin.

We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from polluted district in East Slovakia (POLL) and two neighboring upstream and upwind located districts of background pollution (BCGR). By ultrasound we estimated the thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high-resolution gas chromatography. In 320 subjects also selected hydroxylated and methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), -furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were estimated. Urinary iodine was measured by automatic microplate method. Reciprocal positive association was found between three major POPs (PCBs, DDE and HCB), the levels of these and also PCDDs plus PCDFs in polluted area being considerably higher than in background pollution area. ThV in groups of males and females from POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in age and sex matched groups from BCGR with low PCBs level. In 1,048 males and females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756 ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1)) it was not. These findings supported the view on the additional effect of PCBs on ThV other than that of age. Since the urinary iodine in both districts showed optimal range, any interfering effect of unsatisfactory iodine intake on ThV may be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased serum level of TPOab and TSH resulting in subclinical or overt thyroid hypofunction was positively associated with sex, age and organochlorine levels. The increase of such frequency in males with POPs levels was much more abrupt than that in females. No considerable differences in the frequency of thyroid nodules as related to PCBs level were found.

Smaller thyroid gland volume with high urinary iodine excretion in Japanese schoolchildren: normative reference values in an iodine-sufficient area and comparison with the WHO/ICCIDD reference.

Iodine deficiency disorders (IDDs) are serious global public health problems and approximately 2 billion people are at risk of IDD complications. Urine iodine and thyroid size by ultrasound in school-age children are important indicators for assessing IDD in a population. Interpretation of sonographically measured thyroid volume requires valid reference criteria from iodine-sufficient populations, and in 2003 WHO (World Health Organization)/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) proposed new international reference values for thyroid volume in children aged 6-12 years. To establish a normative reference of thyroid volume and characterize the current status of iodine nutrition in Japanese schoolchildren in Tokyo, where iodine deficiency has never existed, a total of 654 subjects aged 6-12 years (317 girls and 337 boys) in three primary schools were enrolled in the study in 2002. Thyroid volume was determined by using the standardized method recommended by WHO/ICCIDD and the iodine concentration in spot urine samples and the anthropometric measurements were evaluated. Thyroid volume was positively correlated with the children's age, height, weight, or BSA. Regardless of gender the computed median and 97th percentile thyroid volumes based on age or BSA in Japanese children were generally lower than the corresponding values recently reported in iodine-sufficient areas, although these values were slightly higher (5-13%) than those in the 2003 WHO/ICCIDD international reference. The computed median value of urinary iodine concentration was 281.6 microg/L (303.7 microg/gCre) and extremely high values exceeding 1,000 microg/L were found in 16% of the subjects. The present study clearly indicated a high iodine intake in Japanese schoolchildren and also established reference values for thyroid volume that might be applicable to countries in the Far East as a population-specific local reference.

Fish from industrially polluted freshwater as the main source of organochlorinated pollutants and increased frequency of thyroid disorders and dysglycemia.

In a certain area of Michalovce district in East Slovakia, heavy industrial pollution by polychlorinated biphenyls (PCBs) developed in 1955-1984 and very high PCB levels in environmental and human samples are still persisting. Recently, a total of 2045 adults from this and the surrounding background pollution area have been examined using questionnaire data, thyroid volume by ultrasound (ThV), urinary iodine and serum levels of 15 PCB congeners, hexachlorobenzene (HCB), 2,2'-2-bis(4-chlorobiphenyl)-1,1-dichloroethylene (DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), alpha-, beta- and gamma-hexachlorocyclohexane (HCH), thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase antibodies (TPOab) and fasting glucose. As based on our previous findings of strikingly high level of PCBs in fish from high pollution area (e.g. mean level of 375430 ng/g lipid) and considerably lower, but still relatively high level in background pollution area (e.g. mean PCB level of 5150 ng/g), the information on the frequency of fish meals and approximate annual consumption of fish from local waters was obtained by questionnaires. The association of contaminated fish consumption with very high blood levels of PCBs, DDE and HCB and increased ThV as well as with increased frequency of positive TPOab, high values of FT4 and impaired fasting glucose (IFG) was found. These associations were also confirmed in 16 marital pairs from high pollution area with very high PCB level in both members associated with high fish consumption. It was concluded that, due to persistent heavy pollution of waters, soil and food chain namely by PCBs, but also by pesticides (e.g. DDE and HCB) resulting from their previous extensive use in agriculture, the fish from local waters still remains the most important source of these toxic pollutants which results in considerable adverse health effects.

Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

New reference values for thyroid volume by ultrasound in iodine-sufficient schoolchildren: a World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group Report.

BACKGROUND: Goiter prevalence in school-age children is an indicator of the severity of iodine deficiency disorders (IDDs) in a population. In areas of mild-to-moderate IDDs, measurement of thyroid volume (Tvol) by ultrasound is preferable to palpation for grading goiter, but interpretation requires reference criteria from iodine-sufficient children. OBJECTIVE: The study aim was to establish international reference values for Tvol by ultrasound in 6-12-y-old children that could be used to define goiter in the context of IDD monitoring. DESIGN: Tvol was measured by ultrasound in 6-12-y-old children living in areas of long-term iodine sufficiency in North and South America, central Europe, the eastern Mediterranean, Africa, and the western Pacific. Measurements were made by 2 experienced examiners using validated techniques. Data were log transformed, used to calculate percentiles on the basis of the Gaussian distribution, and then transformed back to the linear scale. Age- and body surface area (BSA)-specific 97th percentiles for Tvol were calculated for boys and girls. RESULTS: The sample included 3529 children evenly divided between boys and girls at each year ( +/- SD age: 9.3 +/- 1.9 y). The range of median urinary iodine concentrations for the 6 study sites was 118-288 micro g/L. There were significant differences in age- and BSA-adjusted mean Tvols between sites, which suggests that population-specific references in countries with long-standing iodine sufficiency may be more accurate than is a single international reference. However, overall differences in age- and BSA-adjusted Tvols between sites were modest relative to the population and measurement variability, which supports the use of a single, site-independent set of references. CONCLUSION: These new international reference values for Tvol by ultrasound can be used for goiter screening in the context of IDD monitoring.

Immunohistochemical Heterogeneity Within Clinically Nonfunctioning Pituitary Adenomas.

To investigate whether adenohypophysial hormone expression is heterogeneous within individual clinically nonfunctioning pituitary adenomas, immunohistochemical examinations were performed on tissues obtained by multiple sampling of 11 adenomas. Stained sections were assessed by morphometric image analysis as well as semiquantitative estimation under microscopy. All tumors except one were immunopositive for one or more gonadotropins. Results were divided into five grades based on the proportion of immunoreactive cells per section. Semiquantitative estimation showed only a one-grade difference among samples from the same tumor in four cases for FSHB and in two cases for LHB. These qualitative similarities between multiple samples were confirmed by morphometric image analysis. From the practical standpoint of making a diagnosis of nonfunctioning pituitary adenoma, it is not necessary to take into account immunohistochemical heterogeneity within an individual tumor, and immunohistochemical findings in a given sample obtained at surgery can be regarded as representative of the entire adenoma.

Idiopathic giant-cell granuloma of the pituitary with unusual clinical and histological features.

A surgically treated idiopathic giant-cell granuloma of the pituitary in a 48-year-old man is described. Relative to previously reported cases, this case was unusual both clinically and histologically. Diabetes insipidus was the initial, and a prominent clinical, manifestation. Histological studies showed caseating granuloma or fibrosis in addition to a typical giant-cell granuloma. This is the first published documentation of the association of caseous necrosis in a patient diagnosed as having idiopathic giant-cell granuloma of the pituitary.Endocr Pathol 4:169-173, 1993.

Intrasellar gangliocytoma with multiple immunoreactivities.

The authors report a rare case of intrasellar gangliocytoma without endocrinopathy. The tumor, removed by transsphenoidal surgery, exhibited immunoreactivities for VIP and galanin in the cytoplasm of several nerve cells, a-subunit, somatostatin, and serotonin in the cytoplasm of few nerve cells. Our case indicates that gangliocytomas can produce unusual combinations of peptides which, despite their known biologic activity, do not invariably cause clinical abnormalities.