HUMAN LYMPHOCYTE BINDING AND DEIODINATION OF THYROID HORMONES IN RELATION TO THYROID FUNCTION

1975 ◽  
Vol 80 (4) ◽  
pp. 642-656 ◽  
Author(s):  
Ann-Charlotte Holm ◽  
Thérèse Lemarchand-Béraud ◽  
Bianca-Rosa Scazziga ◽  
Serge Cuttelod

ABSTRACT The human lymphocyte has been investigated regarding its function as a thyroid hormone target cell. Binding and deiodination of the thyroid hormones were determined after simultaneous incubation of 131I-labelled L-thyroxine (131I-T4) and 125I-labelled L-triiodothyronine (125I-T3) with lymphocytes from healthy subjects, from hyperthyroid and primary hypothyroid patients before and after treatment. The mean percentages of binding, 8.0 ± 0.5 (mean ± sem) for 131I-T4, and 9.7 ± 0.4 for 125I-T3 in the control group, were increased in the hyperthyroids to 10.1 ± 0.4 and 12.7 ± 0.6 respectively, and in the hypothyroids to 10.9 ± 0.7 and 12.8 ± 0.6. All elevated values returned to normal with successful treatment. The mean percentage of deiodination, 12.0 ± 1.7 for 131I-T4, and 6.5 ± 0.9 for 125I-T3 in the control group, showed a threefold increase in the hyperthyroid patients, to 35.9 ± 3.2 and 20.2 ± 1.9 respectively and remained unaltered in the hypothyroid patients. The values of successfully treated hyperthyroid patients were normal and those of the treated hypothyroid patients below normal. Human TSH added to the incubation medium stimulated the binding of both hormones, without influencing deiodination. Thus TSH might be active at the peripheral cellular level. This could contribute to the explanation of the increased binding by lymphocytes from primary hypothyroid patients with high serum concentrations of TSH. A preliminary analysis of the binding characteristics revealed an equilibrium affinity constant of 1.03·1010 m−1 for T3, and of 3.97· 109 m−1 for T4, with corresponding total numbers of binding sites of 1500 and 2000 per cell. It is concluded that, since lymphocyte activities closely reflect the thyroid function, these cells are well suited for studies on the peripheral fate of thyroid hormones and their cellular receptors.

1977 ◽  
Vol 85 (4) ◽  
pp. 760-768 ◽  
Author(s):  
S. Nistrup Madsen

ABSTRACT The glucagon stimulated increase in plasma cyclic AMP has been studied in 17 healthy subjects, in 13 hyperthyroid and in 14 hypothyroid patients. Six hyperthyroid and 2 hypothyroid patients were re-investigated after at least 15 months of treatment. The results show: 1) The glucagon stimulated cyclic AMP response is significantly increased in hyperthyroid patients considered as a group, and is reduced in patients with hypothyroidism. 2) Three hyperthyroid and 4 hypothyroid patients showed a normal response to iv glucagon, indicating that the plasma cyclic AMP response to iv glucagon is not a sensitive test for the evaluation of peripheral thyroid states. This suggests that the effects of thyroid hormones in the liver does not necessarily follow the effects in other tissues. 3) Re-investigation of treated patients showed that the cyclic AMP response can be normalized by treatment, both in hyperthyroidism and in hypothyroidism. However, in patients treated for hyperthyroidism a hyper-response to glucagon can continue after blood levels of thyroid hormones are reduced to normal. This suggests an inertia in the loss of the hyper-response to glucagon, once a hyperfunction has been induced. A similar inertia in the loss of glucagon sensitivity in hypothyroidism could explain the large number of normal tests in hypothyroid patients.


1977 ◽  
Vol 85 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Th. Lemarchand-Béraud ◽  
A.-Ch. Holm ◽  
B. R. Scazziga

ABSTRACT In an investigation of thyroxine (T4) and triiodothyronine (T3) receptors in humans, the lymphocyte was chosen as the target cell. This study was performed to elucidate whether T3 and T4 bind to different receptors, if T4 is bound only after conversion into T3, and whether there is any modification of the receptors in hyper- and hypothyroidism. Lymphocytes were found to possess a high-affinity, limited-capacity binding sites for both T4 and T3. The mean equilibrium affinity constant (Ka) was 2.28 · 1010 ± 0.21 m−1 for T3, and 0.98 · 1010 ± 0.16 m−1 for T4. The mean number of saturable binding sites was 115 for T3, and 102 for T4. The binding capacities and affinities also determined in the lymphocyte nuclei isolated after incubation of the intact cell, were similar to those observed in the intact cells. In competition experiments, labelled T4 was as readily displaced by T3 as by T4 itself, whereas labelled T3 was displaced only by a 40 times higher concentration of T4 than T3. These observations suggest identical receptors for the two hormones and a binding of T4 as such, provided it is not in competition with T3. In lymphocytes from hyperthyroid patients, receptor affinities and numbers remained unchanged. In lymphocytes from hypothyroid patients, the affinity was normal, but the mean number of T3 binding sites was increased to 310 (P < 0.001), to return to normal after a few months of treatment.


1980 ◽  
Vol 93 (4) ◽  
pp. 424-429 ◽  
Author(s):  
J. L. Alvarez-Sala ◽  
M. A. Urbán ◽  
J. J. Sicilia ◽  
A. J. Diaz Fdez ◽  
F. Fdez Mendieta ◽  
...  

Abstract. In 21 hyperthyroid female patients studied on 29 occasions, high levels of red-cell 2,3-diphosphoglycerate (2,3-DPG) have been found (5.75 ± 0.7 mm) which, compared to a euthyroid control group (4.88 ± 0.4 mm), could not be accounted for by differences in haematocrit, haemoglobin or phosphataemia. A significant correlation was found (P < 0.05) between serum thyroid hormones and the 2,3-DPG concentration in the hyperthyroid patients. Eight of these patients were reexamined after treatment and normalization of thyroid function, showed a regression to normal 2,3-DPG values (4.81 ± 0.6 mm) which could not be attributed to variations in haematocrit, haemoglobin or phosphataemia either. We therefore deduce that the shift to the right in the haemoglobin oxygen dissociation curve observed in patients of this type may be due to an increase in the red-cell 2,3-DPG content.


1987 ◽  
Vol 33 (11) ◽  
pp. 2096-2100 ◽  
Author(s):  
M P Bounaud ◽  
J Y Bounaud ◽  
M H Bouin-Pineau ◽  
L Orget ◽  
F Begon

Abstract A new chemiluminometric immunoassay of thyrotropin (TSH) involves antibody labeled with acridinium ester ("Magic Lite System," Ciba Corning Diagnostic Corp.). The assay is rapid, with two incubations totaling 2.5 h, requires two standards per run, and takes 10 s per sample for the quantification step. Analytical performance, within- and between-run reproducibilities, and linearity were excellent. The detection limit is 0.04 milli-int. unit/L. Results correlated well with those obtained by immunoradiometric assay (RIA-gnost hTSH, Hoechst-Behring) and immunofluorometric assay (hTSH Delfia, LKB): r = 0.975. TSH measurements in 32 euthyroid subjects ranged from 0.4 to 4.8 milli-int. units/L (mean 1.35 milli-int. units/L). TSH values for 51 hypothyroid and subclinically hypothyroid patients ranged from 2 to 65 milli-int. units/L. TSH values for 33 hyperthyroid patients (less than 0.14 milli-int. unit/L, less than 0.04 milli-int. unit/L in 16 of the 33) were clearly lower than for most untreated euthyroid subjects. For 169 other individuals whose thyroid function was being routinely assessed. TSH ranged from 0.4 to 4.8 milli-int. units/L, three had TSH less than 0.14 milli-int. unit/L, and four had TSH between 0.14 and 0.4 milli-int. unit/L. This system is as efficient and reliable for screening for thyroid function as the two comparison systems.


1968 ◽  
Vol 59 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Knut Kirkeby ◽  
Inger Bjerkedal

ABSTRACT Plasma post heparin lipoprotein lipase activity (LLA) has been studied in patients with hyper- and hypothyroidism and in rabbits made thyrotoxic with thyroxine. The hypothyroid patients had high triglyceride and low LLA values as compared with a control group of healthy subjects. Statistically highly significant negative correlation was found between the triglycerides in fasting patients and the post heparin LLA, indicating a causal relationship, possibly with disturbance of chylomicron degradation due to low LLA in the arterial wall. However, relatively low LLA values were also demonstrated in hyperthyroid patients as well as in rabbits following treatment with thyroxine for 3 weeks. A stimulating effect of the thyroid hormones on the synthesis and degradation of lipoprotein lipase may be a possible explanation for these apparently contradictory findings.


2003 ◽  
Vol 88 (12) ◽  
pp. 5605-5608 ◽  
Author(s):  
Martin Haluzik ◽  
Jara Nedvidkova ◽  
Vladimir Bartak ◽  
Ivana Dostalova ◽  
Petr Vlcek ◽  
...  

Abstract Thyroid hormones play a major role in lipid metabolism. However, whether they directly affect lipolysis locally in the adipose tissue remains unknown. Therefore, we measured abdominal sc adipose tissue norepinephrine (NE), basal, and isoprenaline-stimulated lipolysis in 12 hypothyroid patients (HYPO), six hyperthyroid patients (HYPER), and 12 healthy controls by in vivo microdialysis. Adipose tissue NE was decreased in HYPO and increased in HYPER compared with controls (90.4 ± 2.9 and 458.0 ± 69.1 vs. 294.9 ± 19.5 pmol/liter, P &lt; 0.01). Similarly, basal lipolysis, assessed by glycerol assay, was lower in HYPO and higher in HYPER than in controls (88.2 ± 9.9 and 566.0 ± 42.0 vs. 214.3 ± 5.1 μmol/liter P &lt; 0.01). The relative magnitude of isoprenaline-induced glycerol increase was smaller in HYPO (39 ± 19.4%, P &lt; 0.05 vs. basal) and higher in HYPER (277 ± 30.4%, P &lt; 0.01) than in controls (117 ± 5.6%, P &lt; 0.01). The corresponding changes in NE after isoprenaline stimulation were as follows: 120 ± 9.2% (P &lt; 0.05), 503 ± 113% (P &lt; 0.01), and 267 ± 17.2 (P &lt; 0.01). In summary, by affecting local NE levels and adrenergic postreceptor signaling, thyroid hormones may influence the lipolysis rate in the abdominal sc adipose tissue.


1987 ◽  
Vol 114 (4) ◽  
pp. 503-508 ◽  
Author(s):  
I. Orden ◽  
J. Pie ◽  
M. G. Juste ◽  
J. A. Marsella ◽  
C. Blasco

Abstract. The aim of this work was to estimate the daily urinary excretion of free and conjugated thyroxine using a direct radioimmunoassay and enzyme hydrolysis. The renal clearance of free T4 was also determined. The mean urinary values of free and total T4 (mean ± 1 sd) in 112 euthyroid controls were 1353 ± 496 and 1855 ± 651 pmol/24 h, respectively. Urinary excretion of free hormone in 13 hyperthyroid patients was 5552 ± 4320 pmol/24 h and total T4 was 8122 ± 7219 pmol/24 h. Urinary free T4 excretion was 223 ± 223 pmol/24 h in hypothyroid patients and total T4 was 542 ± 490 pmol/24 h. These results indicate that daily urinary T4 excretion is a good indicator of thyroid function. The mean renal clearance of free T4 was 52 ± 19 ml/min (mean ± 1 sd) in euthyroid patients, 53.7 ± 12.3 ml/min in hyperthyroid patients, and 67.6 ± 13.1 ml/min in hypothyroid patients. We estimated the endogenous creatinine renal clearance as a control of the renal filtration rate. The data suggest that there is T4 filtration of unbound T4 and partial tubular reabsorption. Further experimental studies will be necessary to clarify the renal handling of thyroxine as well as the fate of reabsorbed T4.


Author(s):  
S M Gow ◽  
K Nicol ◽  
J Seth ◽  
G Caldwell ◽  
A D Toft ◽  
...  

A new, coated well immunoradiometric assay (IRMA) for thyrotrophin (TSH) in serum has been evaluated with a view to its use as a first-line test of thyroid function. The Amerwell TSH IRMA is simple, rapid to perform (2·5 h) and the assay sensitivity was 0·07 mU/L with a working range (intra-assay CV <10%) of 0·3–100 mU/L. The mean inter-assay CV was 6·6% for TSH concentrations of 0·30–30·7 mU/L. The method compared favourably with an in-house TSH radioimmunoassay and an alternative commercial IRMA. In consecutive referrals to a thyroid clinic all patients with overt hyperthyroidism ( n = 103) had undetectable TSH concentrations and in those with subclinical hyperthyroidism ( n = 14), TSH was undetectable in 10 and below the reference range in four. The 95% confidence interval for 63 euthyroid serum samples was 0·36–4·3 mU/L. All hypothyroid patients ( n = 20) had increased TSH concentrations. TSH concentrations in pregnancy did not differ significantly from euthyroid TSH values. From 1916 routine tests, 13 undetectable TSH values were found in which thyroid hormone levels were normal and the patients had no known thyroid disorder. The assay appears suitable as a first-line test of thyroid function, but further assessment in a routine laboratory setting is required.


2010 ◽  
Vol 33 (5) ◽  
pp. 271 ◽  
Author(s):  
Abdollah Jafarzadeh ◽  
Masoud Poorgholami ◽  
Nazanin Izadi ◽  
Maryam Nemati ◽  
Mohammad Rezayati

Aims: Thyroid hormones have been shown to influence the immune system and haematopoiesis. The aim of this study was to evaluate some immunological and hematological parameters in peripheral blood of hypo- or hyperthyroid women. Materials and Methods: Blood samples were collected from 50 women with hypothyroid disease, 50 women with hyperthyroid disease and a control group consisting of 50 sex - and age - matched euthyroid subjects. Thyroid function assesed according to measurent of T3, T4 and TSH levels. The complete blood count (CBC), total and differential counts of white blood cells (WBC), serum levels of immunoglobulins (IgG, IgA, IgM and IgE) and C3 and C4 complement components determined in three groups by using standard immunological and hematological methods. Results: In hyperthyroid women the mean serum concentrations of IgG (2312.4±584 mg/dl), IgA (296± 87 mg/dl) and IgE ( 301± 264 IU/ml) were significantly higher than those found in the control group (1539± 974 mg/dl, P < 0.0003; 234± 116 mg/dl, P < 0.01; 109.8±115 IU/ml, P < 0.0001, respectively) and the mean MCV was significantly lower in comparison with the euthyroid group (P < 0.05). Hypothyroid patients had higher serum IgE concentrations in comparison with the euthyroid group (179.8± 218 IU/ml vs. 109.8± 115 IU/ml; P < 0.047). The mean serum C3 concentration in hypothyroid patients was also significantly higher in comparison with the euthyroid group (138.7± 36.6 mg/ml vs. 117.8± 32.1 mg/dl; P < 0.01). In the hypothyroid group the mean eosinophil count was markedly higher in comparison with the hyperthyroid group (P < 0.06) and the mean count of RBC and the levels of some RBC-related indices, such as hematocrit and hemoglobin, were significantly lower in comparison with the euthyroid group (P < 0.05). Conclusion: These results indicate hypergammablobulinemia and lower MVC in hyperythyroid patients, and higher IgE levels, C3 levels and eosinophil count as well as anemia in hypothyroid patients.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A824-A825
Author(s):  
Freddy Jean Karlo Toloza Bonilla ◽  
Yuanjie Mao ◽  
Lakshmi P Menon ◽  
Gemy Maria George ◽  
Madhura Borikar ◽  
...  

Abstract Background: Thyroid disorders are very prevalent and could affect virtually the entire human body, including cognitive and psychiatric domains. However, the relationship between thyroid dysfunction and suicide is still controversial. Material and Methods: A systematic review and meta-analysis was conducted to describe the association of thyroid function with suicide ideation/attempt in adults. A comprehensive search from databases’ inception (MEDLINE, EMBASE, Cochrane, PsycINFO, PsycArticles, PSYNDEX and Scopus) to July 20, 2018 was conducted with no language restrictions. We included studies that reported mean values and standard deviation (SD) of thyroid hormone levels [Thyroid-stimulant hormone (TSH), free T4 (FT4), free T3 (FT3), total T4 (TT4), and total T3 (TT3)] in patients with suicide ideation/attempt compared with controls. Four reviewers worked independently and in duplicate for assessment of inclusion criteria, data extraction, and assessment of risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each subgroup. Random-effects models for meta-analyses were applied. Results: Overall, 2278 articles were identified, and 13 observational studies met the inclusion criteria. These studies involved 2651 participants, including 817 participants diagnosed with suicidal ideation/attempt. Group sizes of patients with suicide ideation/attempt ranged from 7 to 122 participants with mean age ranging from 23 to 49 years. Control group sizes ranged from 8 to 464 participants with mean age ranging from 24 to 50 years. Two studies included only women, two studies included only men, and 9 studies included both (% female range: 29 to 78%). Patients with suicide ideation/attempt had lower levels of FT3 (-0.19 pg/mL; P=0.04) and TT4 (-0.23 µg/dL; P=0.05) compared to controls. There were no differences in TSH, TT3 or FT4 levels between groups. In a subgroup analysis comparing current suicidal ideation vs current suicidal attempt vs history of suicidal ideation/attempt with the control group, there were no differences in any of the thyroid function tests. None of the included studies compared rates of overt/subclinical thyroid disease among groups. The overall risk of bias of the included studies was low-to-moderate. Conclusions: There is scarce evidence regarding the association of thyroid disorders and suicide. We found statistically significant lower thyroid hormone levels in patients with suicidal ideation/attempt. The clinical implications of this finding remain unknown and further research is needed to evaluate the association of thyroid disorders with suicide.


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