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Biomedical subjects

P P Smyth

Publications and source records attributed to P P Smyth.

At least 19 recordsLinked to original sources

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.

Animals↗

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.

Aging↗

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.

Animals↗

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.

Adolescent↗

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.

Diet↗

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).

Adolescent↗

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.

Absorptiometry, Photon↗

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.

Adult↗

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.

Adolescent↗

Application of computer texture analysis to the Singh Index.

The Singh Index, which describes trabecular patterns in the proximal femur, has been used as a predictor for hip fractures and as an indicator of osteopenia. Evidence suggests that its contribution to the assessment of hip fracture risk is in its description of the structural properties of the femur. However, subjectivity in its determination may limit its practical value. In this study, we have used computer texture analysis to characterize the textural changes in trabecular bone which occur in osteoporosis. Texture analysis of the proximal femur was used to rank radiographs of 25 cadaver femora by Singh grading. These rankings were compared with those performed by two experienced radiologists. The computer method performed better than the least consistent individual radiologist, but not as well as the two radiologists in combination. The method required no radiologist's time after the system had been 'trained' from a set of example radiographs. The method has potential for use in large studies in which speed and consistency of measurement are important.

Bone Density↗

The thyroid and breast cancer: a significant association?

The coincidence of thyroid disorders and breast cancer has long been a subject of debate. Associations with hyperthyroidism, hypothyroidism, thyroiditis and nontoxic goitre have been reported. Although no convincing evidence exists of a causal role for overt thyroid disease in breast cancer, the preponderance of published work favours an association with hypothyroidism. Geographical variations in the incidence of breast cancer have been attributed to differences in dietary iodine intake and an effect of iodide on the breast has been postulated. Recent reports have shown a direct association between thyroid enlargement, as assessed by ultrasound, and breast cancer. Although the exact mechanism for the demonstrated association between diseases of the thyroid and breast cancer remains to be elucidated, there is at least the possibility that the presence of thyroid abnormalities may influence breast cancer progression and this alone should stimulate awareness into the coincidence of the two disorders.

Breast Neoplasms↗

A direct relationship between thyroid enlargement and breast cancer.

Despite extensive study, evidence to support a direct relationship between diseases of the thyroid and breast has not been established. In this study thyroid volume was assessed by ultrasound in 200 patients with breast cancer and 354 with benign breast disease. Results were compared to appropriate female control groups. Both mean thyroid volume (21.1 +/- 1.4 mL) and the percentage of individual patients with enlarged (> 18.0 mL) thyroid glands (41.5%) were significantly greater in the breast cancer group than equivalent values (13.2 +/- 0.5 mL and 10.5%, respectively) in age-matched controls (P < 0.01 in both cases). The mean thyroid volume of 14.5 +/- 0.34 mL in patients with benign breast disease was also significantly greater than that of 12.5 +/- 0.38 mL in younger controls (P < 0.01). The results support a direct association between breast cancer and increased thyroid volume as mean thyroid volumes and the percentage of individual patients with enlarged thyroid glands were similar in those studied both before (20.8 +/- 1.3 mL and 43.0%) and after (21.4 +/- 1.6 mL and 40.0%) therapies for breast cancer. Although there is no evidence that thyroid enlargement represents a risk factor for breast cancer, the results emphasize the importance of raising the consciousness of the coincidence of both disorders.

Adult↗

Thyroid disorders and breast cancer.

We have investigated the controversial association between diseases of the thyroid gland and breast carcinoma using methodology which allows positive exclusion of cases of breast disease from control groups and the detection of subclinical alterations in thyroid volume using high resolution ultrasonography, thus addressing the deficiencies of earlier studies. Whereas the prevalence of hyperthyroidism and hypothyroidism in patients with breast carcinoma and in healthy controls without clinical evidence of breast disease was similar, non-toxic goitre was more than twice as common in the breast carcinoma patients. Thyroid volumes were also significantly higher in breast carcinoma patients than in controls; using World Health Organisation criteria, 45.5% of breast carcinoma patients had thyroid enlargement compared with only 10.5% of controls. Finally, antithyroid peroxidase autoantibodies were twice as common in breast cancer patients than in controls. These findings provide clear evidence of a relationship between thyroid disease and breast carcinoma, although the mechanisms underlying this relationship require further study, future studies of breast cancer risk factors should therefore include assessment of thyroid function, antibody status and volume.

Breast Neoplasms↗

Thyroid disease and breast cancer.

A review of the literature on the relationship between thyroid disorders and breast cancer does not provide conclusive evidence for the establishment of a causal relationship as breast cancer has been associated with hypothyroidism, hyperthyroidism and nontoxic goiter. Most reports on the association of thyroid enlargement and breast cancer have emanated from areas of endemic iodine deficiency and these reports have relied on neck palpation. The contribution of the present study is in the application of the highly sensitive technique of diagnostic ultrasound to the investigation of subtle changes in thyroid volume and anatomy in patients with breast cancer. The mean thyroid volume of 20.4 +/- 1.0 ml in 184 breast cancer patients was significantly greater than that of 12.9 +/- 1.2 ml in age-matched controls (p < 0.01). Also the number of individual patients with breast cancer having enlarged thyroid glands (73/184; 39.7%) was significantly greater than the corresponding number (13/150; 8.6%) in the control group (p < 0.001). There was a direct correlation between thyroid enlargement and breast tumour staging. Both mean thyroid volume and % of enlarged thyroids were identical in groups of patients scanned after (Retrospective Group) and before (Prospective Group) various therapies for breast cancer, thus excluding therapeutic intervention as a cause for thyroid enlargement. The results indicate a direct relationship between the two disorders perhaps involving a common growth stimulus and emphasise the importance of raising the consciousness of the coincidence of both disorders.

Adult↗

Quantitative cytochemistry of glucose-6-phosphate dehydrogenase in benign and malignant breast tumours.

Glucose-6-phosphate dehydrogenase (G6PD) activity was quantified cytochemically in mammary epithelial cells within frozen tissue sections from 38 patients with breast cancer and 44 with benign breast disease. G6PD activities were measured under atmospheres of both N2 and O2. The mean (S.E.) G6PD value 2.5 (0.23) IE U/min measured in N2 in mammary epithelial cells from the group of malignancies was significantly greater than that of 1.6 (0.37) IE U/min in the benign group (P less than 0.001), but there was considerable overlap between individual values. G6PD measured in O2 was detectable in 84% of malignancies compared to only 14% of benign biopsies and the group mean of 1.3 (0.18) IE U/min in the former was significantly greater than that of 0.35 (0.20) IE U/min in the latter (P less than 0.001). Significant correlations between G6PD activities measured in N2 and O2 were observed in both groups. The techniques present a sensitive method of identifying increases in G6PD activity in mammary epithelial cells and provide an assay that in a majority of cases permits the separation of malignant from benign tissues.

Adenofibroma↗

Premorphological metabolic changes in human breast carcinogenesis.

Malignant breast tissue is characterized by morphological and metabolic changes when compared with normal breast tissue. In this study, the cytochemical measurement of glucose-6-phosphate dehydrogenase (G6PD) activity was used to detect abnormal metabolism in breast tissue and to determine whether abnormal metabolic activity precedes morphological change during human breast carcinogenesis. Normal and benign breast tissue, morphologically normal tissue from cancer-containing breasts, and malignant breast tissue were studied. In malignant tissue, mean(s.e.m.) G6PD activity was significantly increased when compared with normal and benign tissue (9.69(2.3) versus 27.02(1.7) mean integrated extinction (MIE) x 100, P less than 0.01). G6PD activity was increased in morphologically normal tissue from cancer-containing breasts when compared with normal and benign breast tissue from breasts with no known cancer (27.02(1.7) versus 18.42(2.6) MIE x 100, P less than 0.05). These findings suggest that metabolic abnormalities precede morphological changes in breast carcinogenesis. Abnormal metabolism can be detected widely within a cancer-containing breast. The detection of such abnormality may prove helpful in identifying patients at high risk of developing breast cancer.

Adult↗