Iodine nutrition in breast-fed infants is impaired by maternal smoking

Lack of iodine for thyroid hormone formation during the fetal stage and/or the first years of life may lead to developmental brain damage. During the period of breastfeeding, thyroid function of the infant depends on iodine in maternal milk. We studied healthy, pregnant women admitted for delivery and their newborn infants. Cotinine in urine and serum was used to classify mothers as smokers (n = 50) or nonsmokers (n = 90). Smoking and nonsmoking mothers had identical urinary iodine on d 5 after delivery, but smoking was associated with reduced iodine content in breast milk (smokers 26.0 micro g/liter vs. nonsmokers 53.8 micro g/liter; geometric mean, P < 0.001) and in the infants' urine (smokers 33.3 micro g/liter, vs. nonsmokers 50.4 micro g/liter, P = 0.005). Results were consistent in multivariate linear models and by logistic regression analysis. The odds ratio for smoking vs. nonsmoking mothers to have lower breast milk than urinary iodine content was 8.4 (95% confidence interval, 3.5-20.1). In smokers, iodine transfer into breast milk correlated negatively to urinary cotinine concentration. Smoking mothers had significantly higher serum levels of thiocyanate, which may competitively inhibit the sodium-iodide symporter responsible for iodide transport in the lactating mammary gland. Smoking during the period of breastfeeding increases the risk of iodine deficiency-induced brain damage in the child. Women who breastfeed should not smoke, but if they do, an extra iodine supplement should be considered.     

Thyroid function in breast-fed infants whose mothers take high doses of methimazole

Recently, a few studies have shown the safety of methimazole (MMI) therapy of thyrotoxic lactating mothers on thyroid function of their infants. However, it is not known whether the effect of moderately high doses of MMI therapy on lactating mothers can be dangerous for breast-fed infants. Eighty-eight thyrotoxic lactating mothers and their infants were studied. 46 received 20 mg MMI and 42 were given 30 mg MMI during the first month, 10 mg for the second and 5-10 mg for additional 10 months of therapy. Serum T4, T3 and TSH concentrations and in hyperthyroid MMI treated mothers and their RT3U were measured in hyperthyroid MMI treated mothers and their infants, before and at 1, 2, 6, and 12 months after initiation of therapy. Serum MMI was measured in the infants of thyrotoxic mothers taking 20-30 mg MMI. Mean+/-SD of free T4 index (FT4I) in thyrotoxic mothers treated with 20 and 30 mg MMI for one month decreased from 20.1+/-4.2 to 9.7+/-1.5 (p<0.001) and from 20.6+/-4.8 to 8.6+/-3.0 (p<0.001), respectively. Values for free T3 index (FT3I) decreased from 587+/-53 to 180+/-39 (p<0.001) and from 610+/-49 to 151+/-31 (p<0.001) in those treated with 20 and 30 mg MMI, respectively. By the end of one month 5 had elevated FT4I or FT3I or both and 12 had elevated TSH. The dose of MMI was adjusted and thyroid function remained normal up to 12 months of MMI therapy in thyrotoxic lactating mothers. Serum T4, T3 and TSH concentrations of breast-fed infants were normal before and up to 12 months of MMI therapy of their breast-feeding mothers. The lowest T4 and T3 and the highest TSH values were 101 nmol/l, 1.8 nmol/l and 4.1 mU/l, respectively. Serum MMI levels were <0.03 in 7 and 0.03, 0.034 and 0.035 microg/ml in the other 3 infants. We conclude that the treatment of hyperthyroid lactating mothers with doses of 20-30 mg MMI day does not cause deleterious effects on thyroid function of their breast-fed infants.     

Thyroid function in a cassava-eating population affected by epidemic spastic paraparesis

Thyroid function was studied in a rural population in Mozambique that had been affected by an epidemic of spastic paraparesis attributed to dietary cyanide exposure from cassava. Laboratory investigation on a sample of this population demonstrated very high levels of serum and urinary thiocyanate, indicating a heavy exposure to cyanide. The urinary excretion of iodine was within normal limits, indicating an adequate intake of iodine. The serum levels of FT4I were somewhat decreased and serum FT3I, T3/T4 ratio and TSH were somewhat raised. This hormone pattern suggests an adaptation to the antithyroid effect of thiocyanate, but not overt hypothyroidism. A follow-up study on school children was performed, and it also demonstrated high thiocyanate exposure, adequate intake of iodine, and absence of endemic goitre. The results show that if iodine supply is adequate, the thyroid gland is capable of adaptation to a heavy body burden of thiocyanate without development of overt hypothyroidism or goitre.     

Plasma cholesteryl ester transfer protein activity is high in infants and is not affected by thyroid hormones

We investigated the effects of thyroid dysfunction on cholesteryl ester transfer protein (CETP) by studying plasma CETP activity in hypothyroid infants before and after they were rendered euthyroid by L-thyroxine (LT4) replacement therapy. To exclude environmental factors possibly affecting plasma CETP activity, we selected hypothyroid infants to study plasma CETP activity. Plasma CETP activity was measured as the rate of radiolabeled cholesteryl ester transfer from high-density lipoprotein (HDL) to serum apolipoprotein B (apo B)-containing lipoproteins in plasma from 14 hypothyroid infants before and 2 months after LT4 replacement, 23 normal infants, and 61 normal adults. Relationships between CETP and thyroid hormones were examined separately in the 14 hypothyroid infants and 32 euthyroid infants, including the 14 above-described hypothyroid infants and an additional 18 treated hypothyroid infants. Serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were also determined on an autoanalyzer system in our hospital. In contrast to previous reports, we found no differences in plasma CETP activity between hypothyroid infants and age-matched normal infants. LT4 substitution did not cause any changes in plasma CETP activity after therapy. Plasma CETP activity showed no correlation with serum TSH, FT4, and FT3 levels. Both hypothyroid and normal infants were found to have significantly higher plasma CETP activity than normal adults. From these results, we conclude that in infants thyroid hormones do not affect plasma CETP activity, and normal infants have high plasma CETP activity, compared with normal adults.     

Thyroid function and morphology in patients affected by Williams syndrome

OBJECTIVE: To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of patients with Williams syndrome (WS). METHODS: Serum concentrations of free-T3, free-T4, TSH, thyroperoxidase antibodies (TPOA) and thyroglobulin antibodies (TgA), as well as ultrasonographic data, of 20 patients with WS (12 females and eight males), aged 1.7-34.9 years, were evaluated. RESULTS: Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%). Thyroid antibodies were negative in all patients. Fourteen patients (70%) showed thyroid hypoplasia involving the entire gland. In these patients, the left thyroid lobe appeared usually, but not significantly, reduced compared with the right thyroid lobe. One patient (5%) showed thyroid hemiagenesis. Only five patients (25%) showed a thyroid with normal volume, and of these five, one patient showed marked thyroid hypoplasia of the left lobe. In all WS patients with diagnosis of subclinical or overt hypothyroidism, thyroid hypoplasia was detected. No cases of subclinical or overt hypothyroidism were found in WS with normal thyroid volume. CONCLUSIONS: This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients. Patients with WS should be monitored for thyroid function and a thyroid ultrasound screening should be considered, especially in those patients with changes in thyroid function.     

Male reproductive function is not affected in prolactin receptor-deficient mice

Mice with a targeted disruption of the prolactin (PRL) receptor gene were used to study the physiological role of PRL in the control of the male reproductive function. Fertility parameters as well as body and reproductive organ weights (epididymis and testes) were unaffected in PRL receptor knockout mice. Testicular histology and sperm reserves were also normal. Compared with wild-type animals, knockout mice had no significant difference in basal plasma LH, FSH, and testosterone levels, and the weight of seminal vesicles and prostate was unaffected. Moreover, no alteration was detected in human chorionic gonadotropin-induced testosterone levels. It is concluded that the absence of PRL signaling is not detrimental to male testicular function and to fertility in the mouse.     

Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained

It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.     

Iodine sufficiency and measurements of thyroid function in maternal hypothyroidism

OBJECTIVES: To test the hypothesis that thyroglobulin (Tg) and free T4 (FT4) concentrations more than 2SD from the control mean are not increased in pregnancy in an iodine replete area in the absence of elevated TSH concentrations. The second hypothesis to be tested was that if such abnormalities in FT4 and Tg in the absence of elevated TSH concentrations were to exist they would not be associated with lowered IQs in the progeny. DESIGN: Cross-sectional study in New England comparing TSH, Tg, antibodies to Tg and FT4 in volunteer nonpregnant women 20-40 years old with those in hypothyroid mothers and matched euthyroid control mothers. The results are contrasted with those from similar studies reported from iodine deficient areas. SUBJECTS: Sera obtained at 17 weeks gestation and stored at -20 degrees C for 8 years were retrieved and analysed from 62 mothers with subclinical hypothyroidism and 124 matched euthyroid mothers. The diagnosis of hypothyroidism was made by finding a TSH concentration > 97.7 percentiile for 25 000 consecutive pregnant women. Sera were also analysed from 53 healthy nonpregnant volunteer women aged 20-40 years. MEASUREMENTS: TSH, Tg and Tg antibodies were measured in the sera of the nonpregnant volunteers, and Tg and Tg antibodies in the sera of the pregnant women who had previously been analysed for TSH and FT4. The incidence of FT4 concentrations below the 2.3 percentile of nonpregnant laboratory controls was compared for the euthyroid and hypothyroid mothers and the laboratory normal controls. RESULTS: Thirty-one per cent of the 62 hypothyroid mothers had FT4 concentrations below the 2.3 percentile compared with only one (0.8%) of the euthyroid mothers. Mean Tg concentrations did not differ between the nonpregnant controls and the euthyroid pregnant women, 14 +/- 10 vs. 16 +/- 10 micro g/l. Tg concentration in the hypothyroid mothers was 44 +/- 61, significantly greater than for either of the euthyroid control groups, P < 0.005. Positive antibodies to Tg were found in 9% and 10% of the control groups and 57% of the hypothyroid mothers, P < 0.0005. When TSH is included as an independent variable in multiple linear and logistic regressions, FT4 and Tg no longer correlate significantly with IQs. CONCLUSIONS: The incidences of FT4 concentrations more than 2SD below the control mean and of Tg > 2SD above the control mean are significantly increased in hypothyroid mothers in iodlne-sufficient New England. However, in the absence of elevated TSH concentrations, the incidences of such abnormalities in FT4 and TG are negligible. Indeed, concentrations for FT4, Tg and Tg antibodies for nonpregnant and pregnant controls in our iodine-replete area do not differ significantly from each other or from previously reported normative concentrations with the methods used. Thus, pregnancy in New England neither increases Tg nor lowers FT4 concentrations.     

Cardiac function in borderline hypothyroidism: a study by pulsed wave tissue Doppler imaging

OBJECTIVE: In subclinical hypothyroidism (SH), impaired diastolic function has been documented at rest and on effort, while systolic dysfunction has only been assessed on effort. DESIGN: The aim of the present study was: (a) to further assess systolic function at rest in SH; and (b) to ascertain whether cardiac dysfunction could precede TSH increase in euthyroid patients with a high risk of developing SH. METHODS: We studied 32 patients with classical Hashimoto's thyroiditis (22 with increased serum TSH (> 3 mU/ml - group A), and 10 with normal serum TSH (< 3 mU/ml - group B)); a third group (C), which included 13 healthy controls. All subjects underwent pulsed wave tissue Doppler imaging (PWTDI) to accurately quantify the global and regional left ventricular function. RESULTS: When compared with group C, PWTDI indices showed that in both groups A and B there was a significant impairment of systolic ejection (P < 0.001 and P < 0.05, respectively), a delay in diastolic relaxation (P < 0.001 and P < 0.05, respectively) and a decrease in the compliance to the ventricular filling (P < 0.05). Several significant correlations were found between PWTDI parameters and serum-free T(3) and T(4) and TSH concentrations. CONCLUSION: PWTDI is a sensitive technique that allows detection of both diastolic and systolic abnormalities, not only in patients with SH, but also in euthyroid subjects with a high risk of developing thyroid failure. Futhermore, the significant correlations of several PWTDI indices with serum FT(3) and TSH concentrations strongly support the concept of a continuum spectrum of a slight thyroid failure in autoimmune thyroiditis extending to subjects with serum TSH still within the normal range.     

Thyroid hormones and 5'-deiodinase in the rat fetus late in gestation: effects of maternal hypothyroidism

Having previously observed that T4 and T3 levels in fetal rat brain and brown adipose tissue are clearly higher than expected from their low circulating levels, we have now studied thyroid hormone concentrations and 5'-deiodinase activities (5'D) in several other rat fetal tissues during the last 6 days of gestation (dg), namely 17-22 dg. This period comprises the onset of fetal thyroid activity. Total thyroidal T4 and T3 contents increased 100- and 400-fold, respectively; T4 concentrations increased 8- to 10-fold in plasma, carcass, lung, and liver, and T3 increased 4.5- to 9-fold, except in plasma and liver, where T3 levels increased less than 2-fold in plasma and 3-fold in liver. During this developmental period 5'D activity increased 5- and 10-fold in fetal liver and lung, respectively. In fetuses from hypothyroid [thyroidectomized (T)] dams, body weight was lower than in fetuses from normal dams. Total thyroidal T4 and T3 contents were initially the same, but decreased markedly in fetuses from T dams by the end of gestation. At the earliest fetal ages studied (17-18 dg) T4 and T3 concentrations were lower in carcass, liver, lung, and brain, although near term there were no consistent differences between the fetal tissues from T and control dams, probably because of compensatory stimulation of thyroidal secretion. Liver 5'D was decreased by 50% throughout gestation, and lung 5'D activities were lower by the end of gestation. Thyroid hormones in placentas from T dams were very low, but increased by the end of gestation because of the contribution by the fetal thyroid. Present results describe the ontogenic profiles for thyroid hormone concentrations and 5'D activities during late fetal development; active regulatory mechanisms are already present at this age. It has been frequently stated that rat fetuses near term are deficient in thyroid hormones, and that their thyroid hormone economy is independent of maternal thyroid status, but present results show that near term, T4 and T3 concentrations in several tissues reach levels that are 50% or more of those described for adult animals, and that fetal thyroid function is influenced by maternal hypothyroidism.     

Impaired endothelial function in patients with cryptogenic stroke and patent foramen ovale is not affected by closure

Introduction

Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS) and migraine with aura (MA). Endothelial dysfunction (ED) is a risk factor for development of cardiovascular disease, but might also be involved in migraine pathophysiology. Short‐term worsening of migraine has been described after closure of PFO. We evaluated endothelial function in patients with CS and PFO, before and after closure of PFO, and in patients with migraine, whether changes in endothelial function was related to a change in migraine frequency.

Material and Methods

Patients with CS and PFO were included; 20 with planned closure of PFO and seven controls on medical treatment only. Endothelial function was assessed by peripheral arterial tonometry (EndoPat^R) and biomarkers of endothelial activation. Patients were followed longitudinally at baseline, day 1, 1 month, and 6 months. A headache diary was used to assess migraine frequency.

Result

Mean age of the cohort was 45.4 years, and migraine prevalence was 50% whereof 84.6% had MA. Median EndoPat^R index (RHI) at baseline was 1.60 (IQR 1.41‐2.00). There was no change in RHI over time, either in closure patients (P = 0.66), nor in controls (P = 0.31), and there was no change in biomarkers of endothelial activation. Three migraine patients experienced worsening of migraine frequency directly after closure.

Discussion

Endothelial function did not change after closure of PFO. Although patients were lacking cardiovascular risk factors, a high proportion had impaired endothelial function. Whether ED can have predictive value, identifying PFO at higher risk for recurrent stroke warrants further investigations.

     

Left ventricular function in acute hypothyroidism: a Doppler echocardiography study.

BACKGROUND: Acute changes in cardiac parameters may occur after L-thyroxine withdrawal in patients totally thyroidectomized for thyroid cancer. The literature data regarding cardiac function in acute hypothyroidism are limited and discordant. METHODS: In order to evaluate the effects of acute hypothyroidism on cardiac function, 20 athyreotic patients (3 males, 17 females, mean age 46.4 +/- 8.6 years, range 18-58 years) underwent Doppler echocardiography during L-thyroxine therapy (euthyroid phase) and 5 weeks after hormone therapy withdrawal (hypothyroid phase). RESULTS: Significant changes in the left ventricular mass (83 +/- 12 vs 93 +/- 17 g/m2, p = 0.004) and end-diastolic volume (56 +/- 9 vs 50 +/- 9 ml/m2, p = 0.01) were found. Among systolic function parameters, the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio (0.33 +/- 0.07 vs 0.40 +/- 0.08, p = 0.0002), aortic peak flow velocity corrected for heart rate (3.9 +/- 0.7 vs 3.5 +/- 0.5 cm/s, p = 0.02) and mean aortic acceleration corrected for heart rate (45 +/- 15 vs 38 +/- 9 cm/s2, p = 0.007) showed significant variations, whereas the left ventricular fractional shortening (39 +/- 5 vs 40 +/- 6%, p = NS) and ejection fraction (69 +/- 6 vs 68 +/- 7%, p = NS) did not change. Among diastolic function parameters, only the E-wave velocity decreased (73 +/- 17 vs 65 +/- 12 cm/s, p = 0.01); no significant modification was found in the A-wave velocity (62 +/- 19 vs 58 +/- 14 cm/s, p = NS), E/A ratio (1.2 +/- 0.5 vs 1.1 +/- 0.3, p = NS), isovolumic relaxation time (93 +/- 16 vs 95 +/- 37 ms, p = NS) and E-wave deceleration time (233 +/- 48 vs 235 +/- 45 ms, p = NS). The pattern of left ventricular filling remained unchanged, except in 2 patients. The Suga-Sagawa's index, a known parameter of myocardial contractility, was unchanged (5.6 +/- 2 vs 6.1 +/- 2 mmHg/ml, p = NS). The systemic vascular resistance increased (1511 +/- 599 vs 2216 +/- 408 dynes-s-cm(-5), p = 0.002), while the stroke index (39 +/- 8 vs 33 +/- 7 ml/m2, p = 0.001) and cardiac index (2.74 +/- 0.6 vs 2.07 +/- 0.5 l/min/m2, p = 0.0001) significantly decreased. CONCLUSIONS: Acute hypothyroidism was associated with left ventricular systolic dysfunction, probably due to pre- and afterload alterations rather than to an impaired myocardial contractility. The diastolic function was not significantly modified. An increase in cardiac mass was also found, possibly a consequence of early interstitial myxedema. Unlike the PEP/LVET ratio, both the fractional shortening and ejection fraction may be unreliable indicators of left ventricular systolic dysfunction in patients with acute hypothyroidism.     

Thyroid abnormalities in patients treated with lenalidomide for hematological malignancies: results of a retrospective case review

Lenalidomide is an antiangiogenic drug associated with hypothyroidism. We describe a case-series of lenalidomide use in hematological cancers and the prevalence of thyroid abnormalities. We reviewed medical records of patients treated with lenalidomide at a single center form 2005 to 2010 and extracted demographic, clinical, and laboratory data. Of 170 patients with confirmed lenalidomide use (age 64.9 ± 15 years), 148 were treated for multiple myeloma and 6% had thyroid abnormalities attributable only to lenalidomide. In patients with a previous diagnosis of thyroid dysfunction, the addition of lenalidomide therapy was associated with a higher incidence of subsequent TFTF abnormality (17%) as compared to patients with no previous diagnosis of thyroid dysfunction (6%) (P=0.0001). Many patients (44%) with pre-existing disease and a change in thyroid function before or while on lenalidomide had no further follow-up of their thyroid abnormalities, Of 20 patients who did not undergo any thyroid function testing either before starting or while on lenalidomide for a median of 9.4 months (± 6.5), 35% developed new symptoms compatible with hypothyroidism, including worsened fating, constipation or cold intolerance. Symptoms of thyroid dysfunction overlap with side effects of lenalidomide. Thyroid hormone levels are not regularly evaluated in patients on lenalidomide. While on this treatment, thyroid abnormalities can occur in patients with no previous diagnoses and in patients with pre-existing abnormalities. Because symptoms of thyroid dysfunction could be alleviated by appropriate treatment, thyroid function should be evaluated during the course of lenalidomide to improve patients quality of life.