THYROID FUNCTION AND PLASMA CYCLIC AMP RESPONSE TO INTRAVENOUS GLUCAGON

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.

1987 ◽  
Vol 114 (4) ◽  
pp. 559-564 ◽  
Author(s):  
C. Ferrari ◽  
A. Paracchi ◽  
E. Parisio ◽  
F. Codecasa ◽  
M. Mucci ◽  
...  

Abstract. Serum total and free T4 and T3, thyroxinebinding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 μg, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism. Nevertheless, the finding that both FT4 and FT3 are in the normal range in some patients with mild and in most with subclinical hypothyroidism indicates that increased TSH secretion remains the most sensitive index of thyroid failure.


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.


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.


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 < 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 < 0.01). The relative magnitude of isoprenaline-induced glycerol increase was smaller in HYPO (39 ± 19.4%, P < 0.05 vs. basal) and higher in HYPER (277 ± 30.4%, P < 0.01) than in controls (117 ± 5.6%, P < 0.01). The corresponding changes in NE after isoprenaline stimulation were as follows: 120 ± 9.2% (P < 0.05), 503 ± 113% (P < 0.01), and 267 ± 17.2 (P < 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.


1984 ◽  
Vol 105 (4) ◽  
pp. 482-486 ◽  
Author(s):  
Anna-Stina Suhonen ◽  
Juhani Leppäluoto ◽  
Jorma Salmi

Abstract. Urine samples from 8 healthy subjects, from 16 patients with primary hypothyroidism and 8 patients with Graves' hyperthyroidism were pre-purified in SP-Sephadex-C-25 cation-exchange-chromatography, subjected to reverse phase high-pressure liquid chromatography (HPLC) with 0.01 M ammonium acetate pH 4 as a polar and propanol as a non-polar solvent with a 1%/min gradient and assayed in our TRH radioimmunoassay. Urine TRH-immunoreactivity levels were measured before and after 3 months of treatment with thyroxine or methimazole. The urine TRH-levels in healthy subjects were 5.5 ± 1.4 ng/l (mean ± sem, n = 8). In the hypothyroid patients, the urine TRH levels were 50.6 ±40 ng/l before and 71.7 ± 45.3 ng/l after 3 months of treatment with thyroxine. These values did not significantly differ from those in healthy subjects. The large variations were due to highly elevated values in 3 patients. In 2 hypothyroid patients with initially high urine TRH values, 67 and 657 ng/l, urine TRH was measured 5 and 18 months later and was found to have decreased to 5 and 11 ng/l. In the hyperthyroid patients, urine TRH levels were 10.3 ± 3.9 ng/l before and 8.9 ± 3.3 ng/l after the treatment with methimazole and did not differ significantly from the levels in healthy subjects. After 3 months of treatment, the hyper- and the hypothyroid patients were euthyroid. Our results show, that, except in 2 hypothyroid patients, there does not appear to be any relationship between urine TRH levels and serum TSH or thyroid hormone levels in hypothyroid and hyperthyroid patients.


1997 ◽  
Vol 82 (3) ◽  
pp. 771-776 ◽  
Author(s):  
Henryk Zulewski ◽  
Beat Müller ◽  
Pascale Exer ◽  
André R. Miserez ◽  
Jean-Jacques Staub

Abstract The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 ± 2.7 vs. 4.4 ± 2.2 vs. 3.4 ± 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 ± 1.6 vs. 2.1 ± 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = −0.52 (P < 0.0004), and that with T3 was r = −0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r =− 0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.


2005 ◽  
Vol 153 (5) ◽  
pp. 643-649 ◽  
Author(s):  
Anne Lene Dalkjær Riis ◽  
Troels Krarup Hansen ◽  
Steffen Thiel ◽  
Claus Højbjerg Gravholt ◽  
Signe Gjedde ◽  
...  

Background: Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields. Methods: To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves’ hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic auto-immune thyroiditis before and after L-thyroxine substitution. Results: In all hyperthyroid patients, MBL levels were increased – median (range), 1886 ng/ml (1478–7344) – before treatment and decreased to 954 ng/ml (312–3222) after treatment (P = 0.01, paired comparison: Wilcoxon’s signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312–1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356–2488) (P = 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20–457) compared with 979 ng/ml (214–1533) after L-thyroxine substitution (P = 0.03, paired comparison: Wilcoxon’s signed ranks test). Conclusion: Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.


1985 ◽  
Vol 108 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Stig Valdemarsson ◽  
Birger Fagher ◽  
Pavo Hedner ◽  
Mario Monti ◽  
Peter Nilsson-Ehle

Abstract. Direct microcalorimetry was used for measurements of heat production in cell suspensions of platelets and adipocytes, obtained from hypothyroid patients before and after 3 months on full l-thyroxine substitution. Platelet heat production was significantly lower than normal before treatment and increased in all 10 patients studied; the mean value increased from 51.3 ± 1.6 fW/cell before to 57.1 ± 1.8 fW/cell after therapy (P< 0.001). Similarily, adipocyte heat production was initially significantly lower than normal and increased during treatment in all 6 patients investigated. The mean value for heat production per adipocyte was 18.8 ± 1.7 pW/cell before and 32.4 ± 2.5 pW/cell after therapy (P < 0.025), which is still below the level recorded in lean healthy subjects. The adipocyte size did not change significantly. The increase in adipocyte heat production was correlated to the increase in S-triiodothyronine levels (r = 0.84, P <0.05). In hypothyroidism, the total metabolic activity seems to be comparatively more reduced in adipocytes than in platelets. A difference may exist between these cells with regard to recovery of normal metabolic acitivity during treatment for hypothyroidism. Direct microcalorimetry appears to be an adequate method for monitoring net metabolic effects of thyroid hormones in these cells.


1995 ◽  
Vol 132 (5) ◽  
pp. 594-598 ◽  
Author(s):  
Sonia C Dumoulin ◽  
Bertrand P Perret ◽  
Antoine P Bennet ◽  
Philippe J Caron

Dumoulin SC, Perret BP, Bennet AP, Caron PJ. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans. Eur J Endocrinol 1995;132:594–8. ISSN 0804–4643 Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) levels were evaluated in euthyroid (N = 111), hyper- (N = 58) and hypothyroid (N = 38) men, in pre- and postmenopausal women (study 1) and in hyper- (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or levothyroxine therapy (study 2). The SHBG levels are increased in hyper- and decreased in hypothyroid patients, whereas CBG levels are increased in hypo- and decreased in hyperthyroid patients. The SHBG levels are higher in women than in men with similar thyroid status. Plasma SHBG levels are correlated positively whereas CBG levels are correlated negatively with free thyroid hormone concentrations in men as well as women. In hypothyroid patients, SHBG concentrations increased (p < 0.01) and CBG concentrations decreased (p < 0.01) during levothyroxine treatment. In hyperthyroid patients, SHBG concentrations decreased (p < 0.01) and CBG concentrations increased (p < 0.01) during antithyroid treatment. The SHBG and CBG concentrations in treated hypo- and hyperthyroid patients were not significantly different from those of euthyroid controls. Our data indicate that SHBG and CBG levels depend on thyroid status. Corticosteroid-binding globulin is an index of thyroid hormone action at the liver level whose changes are opposite to those of SHBG in hyper- and hypothyroidism. Philippe Caron, Service d'Endocrinologie et Maladies Métaboliques, CHU Rangueil, 1 Avenue J Poulhès, 31054 Toulouse Cedex, France


1974 ◽  
Vol 77 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Klaus Kølendorf ◽  
Kaj Siersbæk-Nielsen ◽  
Jens Mølholm Hansen ◽  
Thorkild Friis

ABSTRACT A new in vitro thyroid function test, "Effective Thyroxine Ratio" (ETR®) has been tested in 170 patients, and the ETR values in patients with normal and abnormal thyroid function have been compared to the concentration of absolute free thyroxine and free thyroxine index in serum. Among 42 hyperthyroid patients tested with ETR, 13 had values within normal range (30.9 per cent). Three of 18 hypothyroid patients had normal values (16.8 per cent). Eighty-nine per cent of 27 pregnant women and all of 17 patients treated with genuine oestrogens had ETR values within normal range. A high positive correlation was found between values of ETR, absolute free thyroxine in serum (r = 0.62) and free thyroxine index (r = 0.83).


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