Thyroid dysfunction in pregnancy. Fetal loss and follow-up evaluation of surviving infants.
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In the last decade, numerous scientific evidence suggested possible adverse health effects from exposure to electromagnetic fields (EMF'S) and the use of mobile phones. According to some studies EMF induced changes of trans-membrane Ca++ flux may lead to altered metabolism and/or secretion of neurohormones including TSH, ACTH, GH, prolactin and melatonin. The aim of this research was to analyse the effects of mobile phone use on thyroid function and to evaluate the possible role of occupational stress. 2598 employees (1355 men and 1243 women) with different duties (vendors, operators and network technicians) were included in the study. Exposure to EMF'S, generated by mobile phones, was assessed both by submitting a questionnaire directly to the employees and acquiring data regarding conversation times. The workers were divided into three groups on the basis of their personal mobile phone use. Moreover, a group of 160 workers with TSH values below 0.4 UI/l was characterized. No statistically significant difference regarding TSH values below 0.4 UI/l was observed among workers with different duties but there was a greater prevalence of subjects with low SH values among 192 employees with more than 33 hrs./month conversation time; this difference was statistically significant (p<0.05). On the basis of our data, it is not possible to establish whether this result is determined by exposure to EMF'S from mobile phones of by the stress of using these instruments.
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Thyrotoxicosis is often perceived as a reversible disorder without long-term consequences, perhaps because of the availability of effective treatments, but recent evidence suggests that there may, in fact, be adverse outcomes. Long-term follow-up studies have revealed increased mortality from cardiovascular and cerebrovascular disease in those with a past history of overt hyperthyroidism treated with radioiodine as well as in those with subclinical hyperthyroidism indicated by a low serum TSH concentration. Thyroid hormones exert direct effects on the myocardium as well as the systemic vasculature predisposing to dysrhythmias, especially supraventricular. Effects of thyroid hormones on the autonomic nervous system may also contribute to arrhythmogenesis. Atrial fibrillation is a recognized complication of hyperthyroidism that predisposes to embolic events. Development of atrial fibrillation, together with other supraventricular dysrhythmias (both clinically obvious and those detected only by Holter monitoring) in those with hyperthyroidism may account for increased vascular mortality. Improved detection of supraventricular dysrhythmias and therapeutic intervention (e.g. anticoagulants, antiarrhythmics) may improve the long-term vascular prognosis, but their role remains to be established in large therapeutic trials.
The identification and sequencing of the ob gene and its product, leptin, in 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. Since its discovery, leptin has been the subject of an enormous amount of work especially within the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state. It is not clear whether leptin and the melanocortin pathways interact with the thyroid axis under physiological conditions other than during starvation or in response to severe illness, both states in which the hypothalamo-pituitary-thyroid axis may be severely suppressed. In addition to the suggested central relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid hormone involvement in thermogenesis and regulation of uncoupling proteins. In this review, we have focused on leptin in relation to thyroid pathophysiology.
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Administration of cadmium chloride (2.5 mg/kg body weight/day) to chickens daily for 15 days decreased serum triiodothyronine (T3) concentration (by 68.75%) without altering the levels of serum thyroxine (T4). Hepatic 5'-monodeiodinase (5'D-I) and superoxide dismutase (SOD) activities were also decreased (by 90.47% and 20.81% respectively) with a concomitant increase in lipid peroxidation (LPO, by 206.25%). Administration of the antioxidant vitamin E (alpha-tocopherol, 5 mg/kg body weight on alternate days) to cadmium intoxicated chickens restored thyroid function by maintaining normal hepatic 5'D-I activity and serum thyroid hormone concentrations. It also prevented cadmium-induced increase in LPO. We conclude that the metal-induced inhibition in hepatic 5'D-I activity is mediated through LPO.
Considerable evidence for a genetically induced antigen-specific defect in suppressor T lymphocytes as the basis for AITD has been derived from several laboratories and via different types of experimental techniques. This defect may result from abnormal antigen presentation to T lymphocytes via an aberrant antigen-specific HLA-related gene. In addition, there is now evidence for additive effects on reducing generalized suppressor T lymphocyte numbers and function by environmental factors as well as hyperthyroidism itself. These effects would be superimposed on the organ-specific defect. Such effects on generalized suppressor T lymphocyte numbers may act as precipitating and self-perpetuating factors. Presentation of the antigen by the thyroid cell via HLA-DR expression on its cell membrane does occur as a result of IFN-gamma production by T lymphocytes. This appears to be secondary to the initial specific immune assault and is not a primary inductive step. Although it may be important as an amplifying intermediate factor, antigen presentation cannot perpetuate the process in the absence of the underlying immune disorder. There is, indeed, no evidence for an underlying antigenic abnormality or stimulus in human autoimmune thyroid disease, and the initiating event would appear to be due to perturbation of the generalized immune system superimposed on the organ-specific immunoregulatory abnormality. Variations in the serologic and clinical expression of AITD would appear to depend on the severity of the original organ-specific disturbance in suppressor T lymphocyte function, plus the added factor of environmental influences playing on generalized suppressor T lymphocyte function and numbers. Remissions in Graves' disease brought about by antithyroid drugs may well be via their effect on modulating thyroid cell activity; this then reduces thyrocyte-immunocyte signaling, allowing remission to occur in those patients with a partial organ-specific defect in suppressor T lymphocytes.
The tap to half relaxation time of tendon achilles reflex was measured in thirty control subjects, forty-five thyrotoxic and sixty hypothyroid patients. The half relaxation time in the control males and females was 279.33 +/- 76.39 msec and 320.00 +/- 52.37 msec. respectively. In thyrotoxic males and females the half relaxation time was 256.67 +/- 31.62 msec (P less than 0.01) and 252.50 +/- 47.68 msec (P less than 0.01) respectively. Amongst the hypothyroid male and female patients the half relaxation time was 405.0 +/- 35.56 msec (P less than 0.01) and 422.5 +/- 115.36 (P less than 0.01) respectively. As all these values were statistically significant, we consider the photomotographic measurement of ankle reflex as an important aid to the diagnosis of thyroid hormone imbalances.
Dose-response curves to noradrenaline in the presence and absence of beta-receptor antagonists were established with isolated atria from euthyroid, hypothyroid and hyperthyroid rats. Baseline atrial rate and Emax were significantly lower than normal in the hypothyroid group and significantly higher than normal in the hyperthyroid group. Differences between the groups were minimal for pD2 and range of response to noradrenaline. The response to beta-receptor antagonists was the same in all 3 groups with the exception of the hypothyroid group which showed an attenuated increase in baseline atrial rate with compounds possessing partial agonist activity. This was particularly marked for practolol. These results do not provide evidence for an altered responsiveness to catecholamines due to altered thyroid status but suggest that thyroid hormones have a direct action on cardiac tissue.
Prenatal plus neonatal administration of methimazole (MMI), a procedure provoking marked hypothyroidism in rats, increased by about 100% the thymic content of oxytocin and severely (by approximately 80%) decreased the thymus weight, compared to euthyroid counterparts. Adult-onset, propylthiouracyl (PTU)-induced hypothyroidism, while provoking thymic involution, or thyroxine (T4) hyperthyroidism, did not affect oxytocin concentrations. Thymic involution and increases in thymus oxytoxin could also be obtained with repeated administration of the potent glucocorticoid dexamethasone. However, since corticosterone, unless subchronically injected at largely supraphysiological doses, was previously shown to have no influence on thymic parameters of young adult rats, a major involvement of the neonatal adrenal axis in oxytocin alterations could be excluded. It is suggested that the ontogenesis of thymic oxytocin production is under thyroid control.
Isometric contraction of the adductor pollicis by stimulating the ulnar nerve was determined in 20 normal adult subjects. We measured mechanical latency, electro-mechanical latency, contraction time, time to half relaxation and isometric twitch force. Besides that we registered the compound muscle action potential and the nerve conduction velocity. The median nerve was used to elicit the nerve action potential and to determine conduction velocity and relative refractory period. In 6 pat. with hypothyroidism and in 7 pat. with hyperthyroidism the above mentioned parameters were measured. There was a significant change concerning contractile properties, i.e. muscular contraction became slower in hypothyroidism and faster in hyperthyroidism as compared to values obtained in the control group. The isometric twitch force was reduced in both conditions. To assure the close relationship between thyroid hormone (L-thyroxin) and muscle contraction a group of patients who have undergone thyroidectomy was investigated in the same way. Muscle and nerve parameters were determined during a levothyroxin-therapy and in a period without any treatment. The same phenomenon was observed, i.e. reduction of twitch velocity in the hypothyroid state. The twitch force was not reduced in this group. The close relationship between thyroid hormone and contractile properties allows a discrimination between hypo-and hyperthyroid state and a control of thyroxin substitution.
Lipid metabolism was examined in patients with hyper- or hypothyroidism. Compared with corresponding age and sex matched controls, serum total cholesterol (T-chol), low density lipoprotein cholesterol (LDL-chol), phospholipid (PL) and LDL levels were significantly low and free fatty acid (FFA) levels were high with apparently normal triglyceride (TG), very low density lipoprotein (VLDL) and high density lipoprotein cholesterol (HDL-chol) levels in 61 hyperthyroid patients, while T-chol, LDL-chol, TG, PL, VLDL and LDL levels were high with normal FFA and HDL-chol levels in 31 hypothyroid patients. Serum lipid levels were then repeatedly measured in 7 men and 7 women with hyperthyroid Graves' disease before treatment (stage I), just after the patients became euthyroid with anti-thyroid drug (stage II) and more than 2 months after the patients remained euthyroid (stage III). Serum T-chol, LDL-chol, PL and LDL levels were low at stage I, significantly elevated at stage II and then normalized at stage III. Transient but significant elevation of serum TG, VLDL and HDL-chol levels at stage II were also observed in men. Accelerated catabolism and anabolism of lipid has been reported in hyperthyroidism. Transient elevation of serum lipid levels suggests a more rapid improvement in catabolism than in anabolism of lipid in an early stage of the medical treatment for hyperthyroidism.
Fasting serum gastrin levels measured by radioimmunoassay were found to be elevated in patients with hyperthyroidism and low in patients with hypothyroidism. The oral administration of beef extracts resulted in more increase of serum gastrin in hyperthyroid patients than in normal subjects. After restoration of the euthyroid state by treatment, no more increase in serum gastrin levels was observed. Slight correlation between gastrin levels and serum T3 levels was observed in pretreated hyperthyroid patients (r = 0.40), but significant correlation between them was found after restoration of the euthyroid state by treatment (r = 0.50). However, it seemed to be able to divide into two groups in the pretreated patients. One was a patient group whose gastrin levels correlated closely to serum T3 levels (r = 0.83, p less than 0.01). The other was a group whose serum gastrin levels remained in low even in high T3 levels (r = 0.81, p less than 0.01). Different sensitivity to thyroid hormone in the G-cells of gastrointestinal tract may exist in these two groups, because patients age and duration of their illness were not different between them.
One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.
There is currently much interest in measurements of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9 +/- 1.9 nmol/l, mean +/- SD, n = 15) and non-hirsute (1.9 +/- 0.6 nmol/l, n = 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 +/- 0.8 nmol/l, n = 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P less than 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 +/- 0.4 nmol/l, n = 5) and women receiving oral contraceptive therapy (0.6 +/- 0.4 nmol/l, n = 28) but increased in hyperthyroid women (4.0 +/- 0.6 nmol/l, n = 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.