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PubMed1992

Characteristics of type III iodothyronine deiodinase.

Type III iodothyronine deiodinase (ID-III) catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2, representing an important pathway for the inactivation of thyroid hormone. High activities of this "oncofetal" enzyme are found in rat brain, skin and fetal intestine, rat and human placenta, chick embryo liver, monkey hepatocarcinoma cells, human colon carcinoma cells, and tadpole liver. ID-III shows substrate preference for T3 over T4; Km values are approximately 10-fold lower for T3 than for T4 but Vmax values are similar. In contrast to the marked ontogenic pattern of ID-III in different tissues, the enzyme shows little change under pathophysiological conditions, such as fasting and thyroid dysfunction. Brain ID-III activity is decreased in hypo- and increased in hyperthyroidism, but the changes are small. Reaction of brain and placenta microsomes with BrAc 125I-T3 results in extensive labeling of a 32 kDa protein (p32). However, the relationship of p32 with ID-III is not clear, since labeling of p32 is also observed in tissues without ID-III activity and is not inhibited with a large excess of substrate.

Animals↗
PubMed1996

Short-term prognosis of depression in adults with Down's syndrome: association with thyroid status and effects on adaptive behaviour.

Findings for Down's syndrome adults with depression were compared to those for non-depressed Down's syndrome controls. Mean age of onset of depression was 30.1 years, the majority of subjects were female and biological more so than psychotic symptoms were presenting features. No statistically significant association between depression and thyroid dysfunction was found. For the depressed group, scores for level of adaptive functioning were significantly lower and those for maladaptive behaviour significantly higher. At one-year follow-up, although some improvement was found, the majority of depressed subjects were still symptomatic. The short-term prognosis for depression in adults with Down's syndrome appears to be poor but possibly better the earlier the age of onset.

Adolescent↗
PubMed1972

A genetic study of infantile and juvenile myasthenia gravis.

From the present study, and from reports in the literature, two forms of childhood myasthenia emerge. There is an early-onset form (with onset of symptoms under 2 years of age) where the illness is milder but more persistent, and where there is frequent occurrence of myasthenia in sibs. Such cases are likely to be inherited as an autosomal recessive, although it is possible that they represent the extreme edge of a multifactorial distribution of combined genetic and environmental aetiology. The second group (with onset of symptoms between the age of 2 and 20 years) clinically resembles adult myasthenia, which is associated with autoimmunity and an increased incidence of thyroid dysfunction. Some genetic contribution occurs in this form but it is less marked than with the early-onset cases and there is no recognizable pattern of inheritance. As secondary cases are even less common among the families of adult myasthenics, it is likely that individuals with most genetic predisposition to myasthenia tend to develop symptoms early, and that non-genetic factors are relatively more important for the development of myasthenia in adults.

Adolescent↗
PubMed1991

Prevalence of autoantibodies to thyroperoxidase in patients with various thyroid and autoimmune diseases.

An original radioimmunoassay for quantitation of circulating autoantibodies (aAb) to thyroperoxidase (TPO) proved to be well suited for large scale routine testing. The present study was aimed to assess the prevalence of aAb to TPO in patients with various thyroid and autoimmune disease and, for comparison, in women referred for reproductive disorders and indication of in vitro fertilization. Anti-TPO aAb were measured in sera from 32 healthy subjects and 262 patients thoroughly investigated for thyroid dysfunction. As determined in healthy subjects, the normal level of aAb to TPO in serum ranged from 0.30 to 3.07 mg/l (of affinity-purified) anti-TPO aAb. Anti-TPO and anti-MIC aAb levels were both normal in 115 patients and correlated well (r = 0.835, P less than 0.001) in the remaining 147 patients. Coexistence of normal level of anti-TPO aAb and abnormal level of anti-MIC aAb was found in 4 patients and ascribed to a lack of specificity or sensitivity of the test for anti-MIC aAb. Coexistence of abnormal level of anti-TPO aAb and normal level of anti-MIC aAb was found in 67 patients of whom 62 presented only slightly elevated (3.1 to 10.0 mg/l) anti-TPO aAb concentration; the 5 remaining patients, all with overt thyroid autoimmune disease, showed anti-TPO levels between 10.7 to 100.7 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Effects of various pathological conditions on the nuclear T3 receptors of rat cerebral cortex: comparison with liver.

The binding capacity and relative affinities of the nuclear triiodothyronine receptors were measured in the cerebral cortex and liver tissues of the rat under several conditions involving energy deprivation. Protracted hypothyroidism caused significant increases in binding capacity in both brain and liver representing a probable direct tissue response to this specific thyroidal dysfunction. Three conditions affecting glucose homeostasis: fasting, glucagon administration and insulin-induced acute hypoglycemia, caused a significant decrease in nuclear binding capacity measured by in vitro binding assay in liver but did not affect brain receptors indicating a tissue specific response to these altered energy states. Lowering of available oxygen (hypoxia) also appeared to cause a slight decrease in binding capacity in the cerebral cortex measured in vitro. On the other hand, total depletion of oxygen (anoxia) showed a progressive increase in binding of a lower affinity nature in the cerebral cortex and liver. A similar change in binding and affinity was seen in the progression of the post-mortem condition in the cerebral cortex and liver resulting from a probable general alteration of the chromosomal material. These results illustrate the degree and nature of alterations of a specific nuclear regulatory component, the thyroid hormone receptor, under several pathological conditions.

Animals↗
PubMed1987

Technical and clinical performance of six sensitive immunoradiometric assays of thyrotropin in serum.

We evaluated the analytical and clinical performance of six commercial immunoradiometric assay kits for thyrotropin (TSH) in serum in 218 subjects, with and without thyroid dysfunction. Detection limits of the six kits were lower (from 0.07 to 0.25 milli-int. unit/L) than that of conventional TSH RIA (0.7 milli-int. unit/L). Precision was adequate over a wide range of concentrations, although interassay CVs at very low concentrations were good for only two kits (7.3% and 13.1%). Results by all the kits correlated to about the same degree with the TSH RIA (r = 0.92 to 0.98). All showed a positive correlation between both the basal and post-thyroliberin (TRH)-stimulation values for TSH (r = 0.78 to 0.88), and all showed similar euthyroid reference ranges for basal concentrations of TSH. With four of the six kits we could clearly distinguish most of the hyperthyroid patients from healthy euthyroids; however, basal and post-TRH TSH values were not sufficient to discriminate among groups of patients with different grades of thyroid hyperfunction.

Adolescent↗
PubMed2005

Erythrocyte glutathione levels in lithium-induced hypothyroidism.

BACKGROUND AND OBJECTIVE: Lithium, widely used in the prophylaxis of psychiatric patients with bipolar affective disorders, is well known to induce thyroid alterations. However, a possible metabolic linkage between blood thyroxine levels and its regulatory function on erythrocyte glutathione concentration has not yet been evaluated in lithium-treated patients. The aim of this study was to assess the antioxidative capacity of erythrocytes in lithium-induced hypothyroidism before and after thyroxine replacement. PATIENTS AND METHODS: Thyroid ultrasound with clinical and laboratory evaluation of thyroid function and thyroid-stimulating hormone assay were performed prior to and at 6-month intervals during lithium prophylaxis in 76 patients with bipolar affective disorders. The daily lithium dosage was adjusted to 600-1200 mg and the mean duration of treatment was 2.2 +/- 0.4 years. Final assessment revealed that 12 patients had evidence of primary hypothyroidism, and these were assigned as the test group. Lithium prophylaxis was supplemented with thyroxine at a dosage of 100 mg/day within 6 months after thyroid dysfunction was diagnosed. Red blood cell superoxide dismutase activities and the glutathione contents were measured before and after thyroxine replacement. In order to assess the effect of long-term lithium administration on red blood cell glutathione and superoxide dismutase levels, 12 patients who had not developed hypothyroidism during the follow-up period were selected for the lithium-treated euthyroid group. Mann Whitney U-test and Wilcoxon rank sum W-test were used for comparison of data. RESULTS: A comparison of the lithium-treated test group with healthy volunteers and their own values after thyroxine replacement revealed a significant decrease in red blood cell glutathione concentrations (p = 0.000) in the hypothyroid state. However, no clinically significant changes were observed in red blood cell superoxide dismutase activities of the test group. A statistical survey also demonstrated that there was no significant difference in the thyroid-stimulating hormone values as well as the red blood cell glutathione contents or superoxide dismutase activities between healthy controls and lithium-treated euthyroid subjects. CONCLUSIONS: It is most likely that lithium primarily inhibited hormone production in the thyroid and that this led to a compensatory increase in thyroid-stimulating hormone secretion with a significant decrease in the red blood cell glutathione content. While the red blood cell glutathione content of hypothyroid patients was reduced to 40% of the post-thyroxine level, unchanged superoxide dismutase activity might render the erythrocytes vulnerable to oxidative stress and ultimately haemolysis. Thyroxine replacement during lithium prophylaxis of psychiatric patients is advisable in order to prevent subclinical hypothyroidism and related defects of erythrocyte antioxidant capacity.

Antioxidants↗
PubMedDate not supplied

Effects of thyroid status on pituitary gonadotropin and testicular reserve in men.

This investigation was conducted to evaluate the effect of thyroid dysfunction on the pituitary-gonadal axis. Ten men with Graves' disease and 5 hypothyroid patients were studied; 10 normal males were studied as a control group. In untreated conditions hyperthyroidism was associated with a normal serum-free testosterone concentration, an increased serum of 17OHP levels, a reduced testosterone response to hCG stimulation, and a hyperresponse of LH to GnRH. These abnormalities reverted after normalization of high FT4 serum levels. Untreated hypothyroid men showed a normal hormone sex response to hCG, but the LH responst to GnRH was reduced, with a tendency to improve after T4 supplementation. There was a strong and significant negative correlation between FT4 and testosterone response, expressed as an area under the curve, and a positive correlation with LH response to GnRH. Despite normal basal free testosterone concentrations, 70% of hyperthyroid and 60% of hypothyroid patients had complaints of decreased libido. The results suggest that thyroid hormones play an important dual pituitary-gonadal effect that is reflected by an impairment of testicular testosterone synthesis associated to hyperresponse to LH in hyperthyroidism and a defective LH response to GnRH in hypothyroidism.

17-alpha-Hydroxyprogesterone↗
PubMed1979

[The thyroid gland of the newborn infant and postnatal iodine overload].

Severe iodine-induced hypothyroidism was recently diagnosed in several neonates raising the responsibility of the iodine antiseptic agents routinely used in these patients. Postnatal iodine overload due to cutaneous application of these agents (povidone iodine and fluorescinated alcoholic-iodine solution) was studied in 5 patients. Thyroid function studies were performed in iodine-overload neonates and in control neonates with comparable gestional age. Results indicated strong evidence of cutaneous absorption of iodine from the antiseptic agents used, leading to hypothyroidism in 12 of them. The frequency and the severity of thyroid dysfunction was closely related to the degree of prematurity. Full recovery was observed in all cases after withdrawal of the iodine-containing agents. It is therefore recommended to avoid any postnatal use of iodine preparations in neonates, mainly in preterm infants, and to use iodine antiseptic agents with great caution, when necessary during the neonatal period.

Anti-Infective Agents, Local↗
PubMed1977

A 280-day tolerance-efficacy study with mibolerone for suppression of estrus in the cat.

Mibolerone, a synthetic anabolic steroid, prevented estrus in domesticated cats when orally given a daily dose of 50 microng over a 180-day period. Doses of 20 microng daily and 50 microng given once a week failed to prevent estrus. Treatment with the 50-microng dose each day for 6 months had no apparent effects on subsequent estrus, mating, queening, or litter size. Kittens born to queens which had been treated did not have obvious developmental defects. Systemic metabolic changes produced by treatment were detected only in thyroid function, as revealed in dose- and time-related changes in serum cholesterol concentrations, thyroid gland weights, and thyroid histology. Clinical evidence of thyroid dysfunction was not apparent during the 6 months of treatment. Clinical and microscopic evidence of slight masculinization was apparent in cats after 3 months of treatment with 20 or 50 microng per day. Masculinizing changes consisted of thickening of the cervical dermis and clitoral hypertrophy. Behavioral changes were not observed. The apparent mechanism of action of mibolerone in the cat is the suppression of the release of pituitary luteinizing hormone.

Anabolic Agents↗
PubMed1995

Plasma neurotensin levels in humans: relation to hormone levels in diseases involving the hypothalamo-pituitary-thyroid axis.

This study was aimed to investigate, in humans, the possible relationship between plasma neurotensin (NT) levels and the activity of the hypothalamo-pituitary-thyroid axis. Neurotensin was measured by radioimmunoassay in 14 healthy adult volunteers and in 41 patients among whom 10 were considered as controls and 31 had thyroid dysfunction according to free thyroxine and thyrotropin plasma values. Basal NT levels were not significantly different in healthy adults and in control patients: 9.7 +/- 1.1 fmol/ml (mean +/- SEM) vs 13.3 +/- 2.9 fmol/ml, respectively. In patients with central hypothyroidism the NT level was significantly lower (5.7 +/- 1.2 vs healthy volunteers and controls; p < 0.05) and in patients with peripheral hypothyroidism and hyperthyroidism the NT level was significantly higher (35.9 +/- 12.8 and 29.9 +/- 9.5 fmol/ml, respectively, vs healthy adults (p < 0.01) and vs controls (p < 0.05)). After thyrotropin-releasing hormone (TRH) injection (250 micrograms iv) in nine subjects (two control patients, five patients with hypothyroidism and two patients with hyperthyroidism), NT levels decreased independently of the endocrine status from mean values of 13.4 +/- 8.4 at basal level to 7.3 +/- 0.8 fmol/ml 30 min after injection (p < 0.01 on paired percentage decrease values). These data suggest that plasma NT levels in humans depend upon the pituitary-thyroid status and indicate that TRH could exert a negative regulation on circulating NT levels.

Adult↗
PubMed2001

Serum calcium in thyroid disease.

Thyroid hormones are believed to influence calcium metabolism. In the present prospective study we investigated the influence of various thryroid diseases on serum calcium levels. In addition to screening for thyroid diseases we measured serum calcium concentrations (S-Ca) in individuals who came to our outpatient service for thyroid diseases from 1992 to 1998. 13,387 persons, among them 9017 patients with thyroid diseases and 4370 persons without thyroid dysfunction, were studied. S-Ca was found to be higher in patients with hyperthyroidism (2.36 +/- 0.11 mmol/L n = 1201, p < 0.05) than in those with subclinical hyperthyroidism (2.33 +/- 0.11 mmol/L, n = 494), with euthyroid goiter (2.32 +/- 0.10 mmol/l, n = 5599), with hypothyroidism (2.31 +/- 0.11 mmol/L, 344), with subclinical hypothyroidism (2.32 +/- 0.10 mmol/L, n = 1290) and in healthy persons (2.31 +/- 0.11 mmol/L, n = 4370). 173/13,387 persons had serum calcium levels < 2.1 mmol/L, among them 31 patients with hypoparathyroidism after strumectomy (31/592) and 2 patients with primary hypoparathyroidism. 106/13,387 persons showed a S-Ca of > 2.6 mmol/L, which in 30 cases was due to primary hyperparathyroidism. Of 55 persons with S-Ca of > 2.6 mmol/L and without any other reason for hypercalcaemia, 31 were found to be in a hyperthyroid state. In conclusion, a clinically not relevant influence on S-Ca was demonstrated in patients with hyperthyroidism as compared with other thyroid diseases and individuals with no thyroid diseases. Measurement of S-Ca in every patient being referred to a thyroid outpatient department is recommended because of the frequent occurrence of postoperative hypoparathyroidism and primary hyperparathyroidism in this setting.

Adolescent↗
PubMed1989

Reversible alteration of red cell lithium-sodium countertransport in patients with thyroid disease.

Thyroid hormones may alter red blood cell (RBC) sodium content and transport. The functional importance of lithium-sodium (Li-Na) countertransport in regulating sodium (Na) transport in vascular smooth muscle and kidney by Na-H countertransport and the potential effect of thyroid hormone on these processes led us to study Li-Na countertransport and other sodium transporters in RBCs of patients with thyroid dysfunction. Patients with untreated hypothyroidism (10) and hyperthyroidism (10) were studied, along with normal subjects (10). The mean value for Li-Na countertransport was significantly higher in the hypothyroid group [0.46 +/- 0.08 (+/- SE) mmol/L cell.h; P less than 0.05] and lower in the hyperthyroid group (0.15 +/- 0.04 mmol/L cell.h; P less than 0.05) compared to that in the normal subjects (0.25 +/- 0.03 mmol/L cell.h). When all groups were combined, significant negative correlations were found between Li-Na countertransport and serum T4 (r = -0.48; P less than 0.01), free T4 index (r = -0.42; P less than 0.05), and serum T3 (r = -0.38; P less than 0.05). Li-Na countertransport was positively correlated with serum triglyceride (r = 0.57; P less than 0.01), but not with serum cholesterol levels (r = 0.28; P = NS). The values became normal in subsets of the hypothyroid (n = 5) and hyperthyroid groups (n = 5) during treatment. We found a bidirectional effect of thyroid status on RBC Li-Na countertransport, which was reversible when serum thyroid hormone levels became normal. Changes in Li-Na countertransport, a pathway of Na-H exchange, may influence renal sodium handling and vascular tone in patients with thyroid disease and contribute to abnormalities such as hypertension that occur in patients with hypothyroidism.

Biological Transport↗
PubMed1976

Plasma catecholamine concentrations in hyperthyroidism and hypothyroidism.

Using a modification of the fluorometric method of Anton and Sayre, we have measured the plasma epinephrine (E) and norepinephrine (NE) concentrations in patients with thyroid dysfunction. There was no significant difference in plasma E in hyperthyroid or hypothyroid subjects, the values being similar to those observed in normal subjects. There was a striking relationship between age and plasma NE in the euthyroid individuals (r = 0.685, p less than 0.001, n = 41). Observed plasma NE concentrations were similar in control subjects (21.05 +/- 1.6 ng/100 ml; mean +/- SEM) and hyperthyroid patients (22.33+/- 2.0 ng/100 ml). However, plasma NE was significantly increased in hypothyroidism (35.46 +/- 3.9 ng/100 ml; p less than 0.01) and remained statistically different when the age factor was excluded (31.31 +/- 2.67 ng/100 ml; p less than 0.025). There was no correlation between plasma NE and serum thyroxine (T4), free thyroxine (FT4), or triiodothyronine (T3), in any of the three groups studied. These data indicate that hyperthyroidism is accompanied by normal plasma NE concentrations and that hypothyroidism is associated with significantly increased plasma NE concentrations, possible in an attempt to compensate for the lack of thyroid hormones.

Age Factors↗
PubMed1985

Betablockers compared with antithyroid drugs as preoperative treatment in hyperthyroidism: drug tolerance, complications, and postoperative thyroid function.

Subtotal thyroid resection or hemithyroidectomy was performed for hyperthyroidism on two groups of patients: 84 treated before surgery with antithyroid drugs and thyroxin and 111 given only beta-blocking agents before surgery. These two patient groups were compared with reference to preoperative medication, operation, immediate postoperative course, and late results, with follow-up for 3 to 7 years. The advantages of beta-blockers compared with conventional antithyroid medication were lack of adverse reactions, rapid effect of treatment, considerably shortened preoperative treatment time, and fewer outpatient visits, with consequent financial benefit. No disadvantages of beta-blockers were found except that 18% of the patients required additional propranolol in the immediate postoperative period. There were no surgical complications in either group other than a mild persistent hypocalcemia in two patients from the beta-blocked group. The serum thyrotropin levels during the first 6 postoperative months were significantly higher in the patients treated with antithyroid drugs. The frequency of postoperative thyroid dysfunction showed no intergroup difference during the observation period. Signs of hypofunction, necessitating thyroxin supplementation, were observed in 28.6% of patients in the antithyroid drug/thyroxin group and in 25.7% in the beta-blocker group. Toxic recurrence occurred in 1.8% of the group that received beta-blockers and in 1.2% of the other patients. The study demonstrated that beta-adrenoceptor blockade is a safe method for preoperative treatment in hyperthyroidism, with advantages for patients and regarding costs.

Adrenergic beta-Antagonists↗
PubMed2004

Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects.

Hypothyroidism during pregnancy is associated with adverse outcomes that can be ameliorated or prevented by adequate therapy with thyroxine. Currently, there are no guidelines for universal screening for thyroid dysfunction in pregnant women or in women of reproductive age. Therefore, it is important to recognize those groups of women who may be at higher risk for development of hypothyroidism so that serum TSH testing may be performed with appropriate initiation of thyroxine therapy. In addition, the thyroxine therapy of women with established hypothyroidism should be optimized prior to conception and during pregnancy when the thyroxine dosage requirement generally increases early in gestation. The diverse etiologies of maternal hypothyroidism may require different increments in thyroxine dose during pregnancy, and generally the postpartum dosage requirement returns to pre-pregnancy levels.

Female↗
PubMed1995

Pregnancy outcome after gestational exposure to amiodarone in Canada.

OBJECTIVE: Our purpose was to quantitate the risk of perinatal thyroid dysfunction and other amiodarone-induced adverse effects among infants exposed in utero to amiodarone. STUDY DESIGN: A historic cohort study of gestational exposure to amiodarone was conducted by contacting Canadian cardiac electrophysiologists. RESULTS: Twelve cases were identified. Of six with first-trimester exposure, one child had congenital nystagmus with synchronous head titubation. There was one case each of transient neonatal hypothyroidism (9%) and hyperthyroidism (9%). A fourth child, exposed to amiodarone from 20 weeks' gestation, had developmental delay, hypotonia, hypertelorism, and micrognathia. Four small-for-gestational-age infants were also exposed to beta-blockers, which in addition to maternal cardiac disease, have been recognized to cause growth restriction. beta-Blockers may also have contributed to bradycardia in one of the three fetuses in whom this was observed. CONCLUSIONS: Gestational exposure to amiodarone may be complicated by perinatal hypothyroidism or hyperthyroidism and possibly neurologic abnormalities, intrauterine growth retardation or fetal bradycardia. Concomitant beta-blocker therapy should probably be avoided. Full neonatal thyroid function tests and developmental follow-up are recommended.

Adrenergic beta-Antagonists↗
PubMed1986

Reduced serum carnosinase activity in hypothyroidism.

Carnosinase hydrolyses carnosine in muscle, and its deficiency is associated with extensive neuromuscular abnormalities. We measured serum carnosinase activity in patients with thyroid dysfunction which often involves neuromuscular systems. In hyperthyroidism, the carnosinase activity was not significantly different from that in normal subjects. In hypothyroidism, however, it was significantly lower than that in normal subjects. The activity examined in five patients with hypothyroidism returned to normal after replacement therapy. In hypothyroidism, the carnosinase activity showed significant correlation with concentration of serum thyroxine and negative correlation with serum creatine kinase activity. This finding may be of practical importance in the differential diagnosis of disorders causing carnosinase deficiency.

Clinical Enzyme Tests↗