Regulation of iodide uptake in placental primary cultures.

BACKGROUND: Maintenance of adequate iodide supply to the developing fetus is dependent not only on maternal dietary iodine intake but also on placental iodide transport. The objective of this study was to examine the effects of different pregnancy-associated hormones on the uptake of radioiodide by the placenta and to determine if iodide transporter expression is affected by hormone incubation. METHODS: Primary cultures of placental trophoblast cells were established from placentas obtained at term from pre-labor caesarean sections. They were pre-incubated with 17ß-estradiol, prolactin, oxytocin, human chorionic gonadotropin (hCG) and progesterone either singly or in combination over 12 h with (125)I uptake being measured after 6 h. RNA was isolated from placental trophoblasts and real-time RT-PCR performed using sodium iodide symporter (NIS) and pendrin (PDS) probes. RESULTS: Significant dose response increments in (125)I uptake by trophoblast cells (p < 0.01) were observed following incubation with hCG (60% increase), oxytocin (45% increase) and prolactin (32% increase). Although progesterone (50-200 ng/ml) and 17ß-estradiol (1,000-15,000 pg/ml) alone produced no significant differences in uptake, they facilitated increased uptake when combined with prolactin or oxytocin, with a combination of all four hormones producing the greatest increase (82%). Increased (125)I uptake was accompanied by corresponding increments in NIS mRNA (ratio 1.52) compared to untreated control cells. No significantly increased expression levels of PDS were observed. CONCLUSIONS: Pregnancy-associated hormones, particularly oxytocin and hCG, have a role in promoting placental iodide uptake which may protect the fetus against iodine deficiency.

Is placental iodine content related to dietary iodine intake?

OBJECTIVE: Delivery of iodine to the foetus depends not only on maternal dietary iodine intake but also on the presence of a functioning placental transport system. A role for the placenta as an iodine storage organ has been suggested, and this study compares the iodine content of placentas from women giving birth at term in Ireland and Iran, areas with median urinary iodine of 79 and 206 µg/l respectively. DESIGN: Placental cotyledon iodine was measured using an alkaline ashing technique with Sandell-Kolthoff kinetic colorimetry. Samples were taken from six sites from the centre and periphery of each cotyledon. Placentas (Ireland n = 58; Iran n = 45) were obtained from consecutive euthyroid women delivering at term. RESULTS: The median placental iodine (µg/g wet weight) was significantly higher in Iranian than in Irish women (187·2 µg/g vs 34·3 µg/g; P < 0·001). The distribution of individual placental iodine values showed that values >50µg/g were found in 71·0% of Iranian and in only 21·0% of Irish samples. In Irish subjects, the relationship of placental iodine to pregnant population urinary iodine (UI) (ng/g:µg/l) was 1:2 (40:79), while in Iranians this ratio is closer to 1:1 (211:206). CONCLUSIONS: These findings, by demonstrating an apparent ability of the placenta to store iodine in a concentration-dependent manner, suggest a hitherto undetected role for the placenta. Whether placental iodine has a role in protecting the foetus from inadequacies in maternal dietary iodine intake is as yet unknown.

Does iodine gas released from seaweed contribute to dietary iodine intake?

Thyroid hormone levels sufficient for brain development and normal metabolism require a minimal supply of iodine, mainly dietary. Living near the sea may confer advantages for iodine intake. Iodine (I(2)) gas released from seaweeds may, through respiration, supply a significant fraction of daily iodine requirements. Gaseous iodine released over seaweed beds was measured by a new gas chromatography-mass spectrometry (GC-MS)-based method and iodine intake assessed by measuring urinary iodine (UI) excretion. Urine samples were obtained from female schoolchildren living in coastal seaweed rich and low seaweed abundance and inland areas of Ireland. Median I(2) ranged 154-905 pg/L (daytime downwind), with higher values (~1,287 pg/L) on still nights, 1,145-3,132 pg/L (over seaweed). A rough estimate of daily gaseous iodine intake in coastal areas, based upon an arbitrary respiration of 10,000L, ranged from 1 to 20 µg/day. Despite this relatively low potential I(2) intake, UI in populations living near a seaweed hotspot were much higher than in lower abundance seaweed coastal or inland areas (158, 71 and 58 µg/L, respectively). Higher values >150 µg/L were observed in 45.6% of (seaweed rich), 3.6% (lower seaweed), 2.3% (inland)) supporting the hypothesis that iodine intake in coastal regions may be dependent on seaweed abundance rather than proximity to the sea. The findings do not exclude the possibility of a significant role for iodine inhalation in influencing iodine status. Despite lacking iodized salt, coastal communities in seaweed-rich areas can maintain an adequate iodine supply. This observation brings new meaning to the expression "Sea air is good for you!"

Changing patterns of thyroid carcinoma.

BACKGROUND: To assess changing trends in histological types of thyroid cancer in an Irish hospital over the past 30 years. METHODS: Biographical data, tumour characteristics, treatment and outcome from 190 patients with thyroid carcinoma from 1970 to 2000 were reviewed retrospectively. RESULTS: Detailed records of 190 patients with thyroid cancer were identified with a mean age at presentation of 50 years. From 1970 to 1979 the distribution of histological types was: papillary carcinoma; 9 patients (4.7%), follicular; 17 patients (8.9%), anaplastic; 9 patients (4.7%), medullary; 1 patient (0.5%) and lymphoma; 1 patient (0.5%). From 1980 to 1989 papillary carcinoma accounted for 32 patients (16.8%), follicular; 14 patients (7.3%), anaplastic; 13 patients (6.8%), medullary; 7 patients (3.7%) and lymphoma; 5 patients (2.6%). From 1990 to 1999 papillary cancer accounted for 48 patients (25.2%), follicular; 14 patients (7.3%), anaplastic; 8 patients (4.2%), medullary; 7 patients (3.7%) and lymphoma; 5 patients (2.6%). Survival rates were significantly better for those aged less than 45 years (P < 0.0001), female sex (P < 0.01) and those with papillary carcinoma (P < 0.01). CONCLUSIONS: This study demonstrated a significant increase in the incidence of papillary carcinoma. This may be related to increasing dietary iodine intake and may be significant as papillary carcinoma is associated with a more favourable prognosis.

Short-term changes in maternal and neonatal urinary iodine excretion.

Investigation of maternal urinary iodine (UI) excretion in the immediate antenatal and early postpartum periods showed a precipitous fall in median values from 93 microg/L antenatally to 36 microg/L at delivery subsequently rising to 49 microg/L and 63 microg/L at days 3 and 10 postpartum respectively. The fate of ingested iodine not appearing in the maternal urine is unknown but measurement of UI in babies born to nursing mothers suggested transfer from the mother with median neonatal values of 117 and 159 microg/L being recorded at days 3 and 10. While maternal UI seemed to relatively unaffected by breast feeding, median UI from breast feeding babies (148 microg/L) was significantly greater than in those bottle feeding (50 microg/L). This was also reflected by the finding that no breast feeding baby had a UI values < 50 microg/L in comparison to 50% of bottle feeders. The depressed values in mothers and relatively high values in their infants could present a false picture and suggest the need to defer any investigations of iodine status at this time. The findings do however suggest a need for further investigations aimed at determining the fate of iodine ingested perinatally and its possible physiological significance in maintaining thyroid status in the mother and neonate.

Iodine intake in pregnancy in Ireland--a cause for concern?

BACKGROUND: Adequate dietary iodine intake is necessary to maintain maternal thyroid function at a level permitting normal neuropsychological development of the foetus. AIMS AND METHODS: To determine dietary iodine status by measuring urinary iodine excretion (UIE), proportional to dietary intake, in Irish mothers during the first trimester of pregnancy. RESULTS: Median UIE showed seasonal variations, being lower in summer than in winter. The median values in pregnant women were, summer 45microg/l, winter 68microg/l. Equivalent values for controls were 43 and 91microg/l respectively. UIE required to achieve WHO recommended daily iodine intakes would be 120-180microg/l. In the Irish subjects UIE values suggestive of iodine deficiency (<50microg/l) were observed in 55% of pregnant women tested in summer and 23% in winter. Dairy milk iodine, a major dietary iodine source, showed similar variation. CONCLUSIONS: While there is as yet no available evidence of widespread thyroid hypofunction in the Irish obstetric population, the findings are a cause of concern, which if confirmed by a more comprehensive investigation, may indicate the need for iodine prophylaxis.

Iodine uptake and loss-can frequent strenuous exercise induce iodine deficiency?

Most of the daily dietary iodine intake (approximately 90 %) will be excreted in the urine; measurement of urinary iodine excretion is thus routinely used as an index of dietary iodine intake. However, urinary excretion is not the only means of iodine loss. Subjects such as athletes or those participating in vigorous exercise can lose a considerable amount of iodine in sweat, depending on environmental factors such as temperature and humidity. In areas of lower to moderate dietary iodine intake, loss in sweat can equal that in urine. Although electrolyte loss in sweat is well-recognized and replacement strategies are adopted, there is less recognition of potential iodine loss. Crude calculations reveal that if sweat iodide losses are not replaced, dietary stores could be depleted in an athlete undergoing a regular training regime. The significance of these losses could be increased in areas where dietary iodine intake is lower in the summer months. Although there is little doubt that excessive sweating can induce a relative iodine deficiency state, there is no case as yet for iodine supplementation in those that take vigorous exercise. However, sustained iodine loss may have implications for thyroid status and possibly consequences for athletic performance.

Thyroglobulin autoantibodies in iodized subjects: relationship between epitope specificities and longitudinal antibody activity.

INTRODUCTION: We previously reported a high thyroglobulin autoantibodies (TgAb) prevalence in healthy Sri Lankans after iodine supplementation. In the present study 58 TgAb-positive schoolgirls were followed up after 5 years of continued iodination. The objectives were: (1) to observe the longitudinal profile of TgAb epitope specificities and (2) to examine the relationship between these specificities and the course of thyroid autoimmunity in this population. METHODS: Paired subjects' sera (at onset and at 5-year follow-up) were tested for TgAb, thyroid peroxidase antibody (TPOAb), and TgAb epitope-specificity. Epitope reactivity was determined by employing a panel of 10 murine monoclonal antibodies (Tg-mAbs) directed against 6 Tg antigenic clusters (I-VI) in competitive enzyme-linked immunosorbent assay (ELISA) reactions with test sera. RESULTS: The overall pattern of epitope recognition in individual subject's sera remained preserved over the time period. Nine subjects showed restricted specificities while majority of the subjects were broadly heterogeneous. At follow-up, median TgAb concentration in the restricted group was higher than in the unrestricted (1650 versus 110 kIU/L; p < 0.005). Epitope specificity was a stronger determinant of TgAb persistence than the height of the initial TgAb response or the TPOAb status of subjects. CONCLUSION: Tg epitope reactivity pattern in iodised populations may identify subjects at greater risk of developing autoimmune thyroid disease (AITD).

Sequential studies on thyroid antibodies during pregnancy.

Thyroid antibodies were measured sequentially in 25 pregnant women from a Sri Lankan population. A high prevalence of antithyroid antibodies, particularly antithyroglobulin antibodies (TgAb) had previously been demonstrated in female schoolchildren drawn from this population. In the present study TgAb were detected in 36.8% of nonpregnant controls while thyroid peroxidase antibody (TPOAb) positivity was present in 26.3%. The prevalence of both antibodies in the pregnancy study group showed a progressive decline compared to nonpregnant controls throughout gestation becoming undetectable in the third trimester. The results are consistent with an immunosuppressive effect of pregnancy in a population in whom high thyroid autoantibody titers may have resulted from a recent salt iodization program.

Thyroglobulin epitope recognition in a post iodine-supplemented Sri Lankan population.

OBJECTIVE: We previously reported a high prevalence of raised thyroglobulin autoantibodies (TgAb) in apparently healthy Sri Lankan schoolgirls following salt iodination. To characterize these antibodies further we determined the epitopes on thyroglobulin (Tg) with which they react and compared these with serum obtained from both healthy subjects and established autoimmune thyroid disease (AITD) patients from the UK. To extend our study to a wider population within Sri Lanka, we in addition determined the epitopes recognized by a group of AITD patients selected from a thyroid clinic in Sri Lanka, as well as apparently healthy female Sri Lankan tea workers of distinct ethnicity from the schoolgirls and AITD patients. DESIGN: Sri Lankan schoolgirls (n = 282) and adult female tea estate workers (n = 208) were examined for thyroid autoimmune markers. Sera with high TgAb (> 98 kIU/l) were selected from these two groups (n = 36 and 45, respectively) to study epitope-binding patterns. We also examined the sera from 16 AITD patients attending a thyroid clinic in Colombo, 16 patients with AITD from the thyroid clinic at the University Hospital of Wales and 16 sera from healthy control UK women with no evidence of thyroid disease. To determine the epitopes on Tg recognized by the subjects' TgAb, we employed a panel of Tg mouse monoclonal antibodies labelled with alkaline phosphatase in a competitive enzyme-linked immunosorbent assay reaction with the subjects' serum. RESULTS AND CONCLUSIONS: A majority of the Sri Lankan schoolgirls did not react with the immunodominant epitopes and did not differ significantly from healthy subjects from the UK in their Tg epitope recognition pattern. On the other hand, tea estate workers and Sri Lankan AITD patients recognized typical autoimmune thyroid disease epitopes and, in addition, recognized a separate cluster not previously associated with either the autoimmune state or the healthy state. The significance of this cluster requires further clarification.

Evolution of thyroid autoimmunity during iodine prophylaxis--the Sri Lankan experience.

OBJECTIVE: To study the evolution of thyroid autoimmunity, in relation to the change in goitre prevalence, during 3 Years of iodine prophylaxis in Sri Lanka. METHODS: Two groups of Sri Lankan schoolgirls between the ages of 10.8 and 17.5 Years were studied in 1998 (401 girls) and 2001 (282 girls). A prospective study was performed in 42 schoolgirls who were thyroid autoantibody (Ab)-positive (+ve) in 1998. Anthropometric measures, urinary iodine excretion (UIE), thyroid Volume, free thyroxine, free tri-iodothyronine, TSH, and thyroglobulin (Tg) and thyroid peroxidase (TPO) Ab were evaluated in all 683 girls. RESULTS: Goitre prevalence was significantly lower in 2001 compared with 1998 related to age (2.9% compared with 20.2%) and body surface area (11.6% compared with 40.8%), although UIE was unchanged. Prevalence of thyroid Ab in 2001 was also lower (23.4% compared with 49.9%); among those with the Ab, 34.8% had TgAb alone and 46.9% had a combination of TgAb+TPOAb, compared with 82.0% TgAb alone in 1998. In 2001, subclinical hypothyroidism was more frequent in Ab+ve (6.3%) than Ab-negative girls (1.0%). A cohort of 42 Ab+ve schoolgirls in 1998 (34 with TgAb alone, eight with TgAb+TPOAb) were evaluated again in 2001. Only 10 of them (23.8%) remained Ab+ve (mostly TPOAb+/-TgAb) in 2001. CONCLUSIONS: This study demonstrates that: (1) in 2001, goitre prevalence and thyroid autoimmunity rates were significantly lower than in 1998; (2) the pattern of thyroid Ab was different in the two surveys; (3) in 2001 alone, the occurrence of hypothyroidism was correlated with the presence of thyroid autoimmunity. These results indicate an evolution of thyroid autoimmune markers during the course of iodine prophylaxis, which has not been described before.

Hypothyroidism and aging: the Rosses' survey.

An earlier impression of a high prevalence of hypothyroidism in a general practice (4,190 patients including 1,544 adult females aged 18 years or more with 544 aged 50 years or more) in the Rosses, a coastal area in the northwest of Ireland was confirmed by this study. The accumulated prevalence of overt spontaneous primary hypothyroidism was 8.6% in 544 females aged 50 years or more but only 0.9% in the 1,000 females between 18 and 50 years of age. This prevalence was approximately twice that of an Irish National general practice population sample of 4,314 females aged 50 years or more (8.6% vs. 4.6%) p < 0.001. The reasons for this difference are unclear but may reflect the high level of opportunistic screening carried out in West Donegal. Thyroid peroxidase antibodies measured by radioimmunoassay were found in 75.6% of hypothyroid patients compared to 18.6% of practice controls (p < 0.01). Neither HLA-DRB1, DQA1, and DQB1 phenotype frequencies nor dietary iodine intake (median urinary iodine excretion 104 microg/L) appeared to be contributory factors. The finding of an 8.6% accumulated prevalence of hypothyroidism in females greater than 50 years of age when a population is aggressively investigated demonstrates the relative importance of its contribution to total morbidity and suggests that the disorder may be underdiagnosed, thus supporting the concept of targeted screening in this age group.

Increased prevalence of thyroglobulin antibodies in Sri Lankan schoolgirls--is iodine the cause?

OBJECTIVE: Iodine deficiency was the likely cause of a high prevalence of goitre previously in Sri Lankan schoolchildren. Salt iodination was made compulsory in 1993 but there has been no recent study, using modern techniques, of its benefits or harmful effects. METHODS: Three hundred and sixty-seven schoolgirls between the ages of 11 and 16 years had ultrasound thyroid volume, free thyroxine (T4), free tri-iodothyronine (T3), thyrotrophin (TSH), anti-thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) antibodies, and urine iodine concentrations measured. RESULTS: Median ultrasound thyroid volume ranged from 4.8 ml (11-year-old girls) to 8.6 ml (16-year-old girls) with an age-related increase. Median urine iodine concentrations ranged from 105 to 152 microg/l. Free T4 and free T3 were normal in all, but TSH was elevated in four subjects (5. 53-41.29 mU/l). However, the prevalence of TgAb was markedly raised, ranging between 14.3% (11-year-old girls) and 69.7% (16-year-old girls) (P<0.03). In contrast, the prevalence of TPOAb was 10% or less in all age groups. CONCLUSIONS: Normal median thyroid volumes, iodine concentrations and thyroid function would indicate that iodine deficiency is not a major problem in this group. The high prevalence of TgAb, hitherto unreported, most likely reflects excessive iodination of Tg resulting in increased immunogenicity. There is an urgent need to continuously monitor the adequacy and risks of iodination in this population.

Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.

In the thyroid, active transport of iodide is under control of the TSH-dependent Na+/I- symporter (NIS), whereas in the breast such control is less well understood. In this study, NIS expression was demonstrated by RT-PCR in 2 of 2 fibroadenomata and 6 of 7 breast carcinoma messenger ribonucleic acid isolates. In addition, mean total tissue iodine levels of 80.9 +/- 9.5 ng I/mg protein in 23 benign tumors (fibroadenomata) were significantly higher than those in 19 breast cancers taken from either the tumor (18.2 +/- 4.6 ng I/mg) or morphologically normal tissue taken from within the tumor-bearing breast (31.8 +/- 4.9 ng I/mg; P < 0.05 in each case). Inhibition of 125I uptake into NIS-transfected CHO cells was observed in serum from 20 of 105 (19.0%) breast carcinoma, 8 of 49 (16.3%) benign breast disease, and 27 of 86 (31.4%) Graves' patients, but in only 1 of 33 (3.0%) age-matched female controls. IgG purified from serum of patients showing positive 125I uptake inhibition also inhibited iodide uptake, suggesting that such inhibition was antibody mediated. 125I uptake inhibition was significantly associated with thyroid peroxidase antibody positivity (P < 0.05) in sera from breast cancer patients, but not in those with benign breast disease, once again suggesting an association between thyroid autoimmunity and breast carcinoma.

Assessment of goiter in an area of endemic iodine deficiency.

Urinary iodone (UI) excretion and sonographically measured thyroid volume were investigated in 195 subjects living in 6 separate villages in the Casamance region of southeastern Senegal, West Africa. A comparison of goiter prevalence using thyroid palpation and volume measurement and of iodine excretion expressed as micrograms per gram (microg/g) creatinine or micrograms per deciliter (microg/dl) urine was undertaken, and possible pathogenetic factors were investigated. Ultrasound measured thyroid volumes were above the recommended upper limit of the reference range for an area replete in iodine in 83.1% or females, 52.3% of males, and 80.0% of children aged 13 years or younger. Overall sensitivity and specificity for palpation compared to sonographically demonstrated thyroid enlargement was 51.7% and 91.5%, respectively. Thyroid enlargement was not associated with ethnic origin, thiocyanate ingestion, HLA DR/DQ phenotype frequency, or thyroid growth-stimulating immunoglobulin (TGI) positivity. Median UI was 32 microg/g creatinine with 65.0% having values consistent with iodine deficiency (< 50 microg/g). When results were expressed as micrograms per deciliter, the percentage having values consistent with iodine deficiency (< 5.0 microg/dl) increased to 95.7%. The findings suggest a primary role for iodine deficiency in goitrogenesis in the study population. They demonstrate that classification of the severity of the endemia in this or other study populations in areas of iodine deficiency is dependent on the methods used to determine goiter prevalence (palpation or ultrasound measured thyroid enlargement), or dietary iodine status (iodine excretion expressed as micrograms per gram creatinine or micrograms per deciliter urine).

Variation in iodine handling during normal pregnancy.

Reports in the literature are divided on changes in thyroid volume and urinary iodine excretion (UI) during normal pregnancy. Reports from Ireland, an area of modest dietary iodine intake (median UI 70 microg/L) showed an increase in UI that rose to a median value of 135 microg/L in the first trimester (T1) and continued at 124 microg/L in the second (T2) and 122 microg/L in the third trimester (T3). In parallel with the increase in UI, mean ultrasound measured thyroid volume increased by a maximum of 47% over nonpregnant values in the third trimester (T3). Although these findings were consistent with studies in Cardiff, UK (median UI 73 microg/L), which also showed a pregnancy-associated rise in UI excretion (maximum 176 microg/L) accompanied by a 30% increase in median thyroid volume, they differed from findings in Sri Lanka (median UI 146 microg/L), a country in which a successful program of salt iodination has recently been implemented, which showed no significant changes in UI excretion (T3 maximum 154 microg/L) but did show a modest (20%) maximum increase in median thyroid volume at T3. Prospective studies on Irish subjects showed that median UI fell precipitously to nonpregnant control values (76 microg/L) at delivery. In addition, UI in neonates sampled at 3-days postdelivery showed that excretion was greater in breast-fed than in bottle fed infants. Differences in reported UI excretion patterns during pregnancy may may reflect the existence of a threshold above which increased renal clearance results in increased iodine loss but that is masked at higher iodine intakes. Assuming constant dietary iodine intake during pregnancy, any increased urine loss will inevitably lead to negative iodine balance and thyroid depletion. In these circumstances, increased thyroid volume may in part be a compensatory mechanism to allow for greater iodine storage.

Vertebral shape: automatic measurement with active shape models.

The shape and appearance of the spine on lateral dual x-ray absorptiometry scans were statistically modeled. To measure vertebral shape accurately, rapidly, and automatically with a computer, this trained model was matched to findings on previously unseen scans. The technique obtained entire shape information, was faster than manual analysis, and was as accurate as human observers in the measurement of vertebral shape.

Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma.

The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.

Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake.

Differences in pregnancy-associated alterations in thyroid volume and urinary iodine (UI) excretion have been attributed to geographical variations in dietary iodine intake. In this study, ultrasound-measured thyroid volume and UI excretion were assessed during the 3 trimesters of pregnancy, at delivery, and at 6 weeks postpartum. Urine specimens also were obtained from mothers and both breast- and formula-feeding infants at 3 days after delivery. Thyroid volume showed a significant increase (maximum 47.0%), compared with nonpregnant control values over the 3 trimesters of pregnancy, which occurred as early as the first trimester and was paralleled by increased UI excretion, followed in turn by a precipitous fall at delivery. UI excretion in breast-feeding neonates (100 +/- 6.8 micrograms/L) was significantly higher than in their mothers (76 +/- 5.6 micrograms/L; p < 0.01) but was significantly lower (43 +/- 3.5 micrograms/L) in formula-fed infants. The results suggest that in an area of moderate dietary iodine intake, UI loss during pregnancy may result in maternal thyroid enlargement. The ability of the breast to transport iodine compensates for this loss in breast-fed infants, but this protection may be lost in formula feeding.