scholarly journals Thyroglobulin Gene Mutations Producing Defective Intracellular Transport of Thyroglobulin Are Associated with Increased Thyroidal Type 2 Iodothyronine Deiodinase Activity

2007 ◽  
Vol 92 (4) ◽  
pp. 1451-1457 ◽  
Author(s):  
Yasuhiko Kanou ◽  
Akira Hishinuma ◽  
Katsuhiko Tsunekawa ◽  
Koji Seki ◽  
Yutaka Mizuno ◽  
...  

Abstract Context: Most patients with defective synthesis and/or secretion of thyroglobulin (Tg) present relatively high serum free T3 (FT3) concentrations with disproportionately low free T4 (FT4) resulting in a high FT3/FT4 ratio. The mechanism of this change in FT3/FT4 ratio remains unknown. Objective: We hypothesize that increased type 2 iodothyronine deiodinase (D2) activity in the thyroid gland may explain the higher FT3/FT4 ratio that is frequently observed in patients with abnormal Tg synthesis. Design: We recently identified a compound heterozygous patient (patient A) with a Tg G2356R mutation and one previously described (C1245R) that is known to cause a defect in intracellular transport of Tg. In the current study, after determining the abnormality caused by G2356R, we measured D2 activity as well as its mRNA level in the thyroid gland. We also measured the thyroidal D2 activity in three patients with Tg transport defect and in normal thyroid tissue. Results: Morphological and biochemical analysis of the thyroid gland from patient A, complemented by a pulse-chase experiment, revealed that G2356R produces a defect in intracellular Tg transport. D2 activity but not type 1 deiodinase in thyroid glands of patients with abnormal Tg transport was significantly higher than in normal thyroid glands, whereas D2 mRNA level in patient A was comparable with that in normal thyroid glands. Furthermore, there was a positive correlation between D2 activity and FT3/FT4 ratios. Conclusion: Increased thyroidal D2 activity in the thyroid gland is responsible for the higher FT3/FT4 ratios in patients with defective intracellular Tg transport.

2021 ◽  
pp. 1-8
Author(s):  
Niamh McGrath ◽  
Colin Patrick Hawkes ◽  
Stephanie Ryan ◽  
Philip Mayne ◽  
Nuala Murphy

Scintigraphy using technetium-99m (<sup>99m</sup>Tc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of <sup>99m</sup>Tc uptake. <b><i>Aims:</i></b> We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using <sup>99m</sup>Tc and to describe the clinical characteristics and natural history in these infants. <b><i>Methods:</i></b> The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. <b><i>Results:</i></b> Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. <b><i>Conclusion:</i></b> Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.


2011 ◽  
Vol 164 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Mitsuru Ito ◽  
Nagaoki Toyoda ◽  
Emiko Nomura ◽  
Yuuki Takamura ◽  
Nobuyuki Amino ◽  
...  

Objective3,5,3′-triiodothyronine-predominant Graves' disease (T3-P-GD) is characterized by a persistently high serum T3 level and normal or even lower serum thyroxine (T4) level during antithyroid drug therapy. The source of this high serum T3 level has not been clarified. Our objective was to evaluate the contribution of type 1 and type 2 iodothyronine deiodinase (D1 (or DIO1) and D2 (or DIO2) respectively) in the thyroid gland to the high serum T3 level in T3-P-GD.MethodsWe measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T3-P-GD (n=13) and common-type GD (CT-GD) (n=18) who had been treated with methimazole up until thyroidectomy.ResultsThyroidal D1 activity in patients with T3-P-GD (492.7±201.3 pmol/mg prot per h) was significantly higher (P<0.05) than that in patients with CT-GD (320.7±151.9 pmol/mg prot per h). On the other hand, thyroidal D2 activity in patients with T3-P-GD (823.9±596.4 fmol/mg prot per h) was markedly higher (P<0.005) than that in patients with CT-GD (194.8±131.6 fmol/mg prot per h). There was a significant correlation between the thyroidal D1 activity in patients with T3-P-GD and CT-GD and the serum FT3-to-FT4 ratio (r=0.370, P<0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT3-to-FT4 ratio (r=0.676, P<0.001).ConclusionsOur results suggest that the increment of thyroidal deiodinase activity, namely D1 and especially D2 activities, may be responsible for the higher serum FT3-to-FT4 ratio in T3-P-GD.


2020 ◽  
Vol 19 (1) ◽  
pp. 53-60
Author(s):  
N. P. Tkachuk ◽  
I. S. Davydenko

In spite of a considerable efficacy of conservative treatment of goiter, surgery remains the main method of treatment of such patients. Though, on the one hand, total thyroidectomy inevitably results in the development of postsurgical hypothyroidism, on the other hand – in case organ-saving surgery is performed the risk of postsurgical relapse arises. Modern morphological methods are directed to detection of oncological risk of nodular formations, and recommendations concerning an adequate volume of surgery taking into account probability of relapse are practically lacking. Therefore, the objective of the study was finding criteria of a relapsing risk by means of investigation of morphological peculiarities of the parenchymal-stromal correlations in the thyroid gland with recurrent nodular and primary nodular (multinodular) goiter without signs of functional disorders. In the course of the research according to the examined correlation parameters of the parenchyma and stroma various forms of nodular goiter were found to differ from the thyroid tissue without pathological changes by a number of parameters. In particular, specific weight of the parenchyma on an average increases reliably in the tissue of nodular goiter with its various variants in comparison with the thyroid gland without pathological changes. Together with the increase of the parenchymal specific weight in nodular goiter the amount of colloid on an average decreases, and a specific dependence on the kind of goiter is observed – colloid volume decreases from goiter with slow growth to goiter with quick growth, and it is the smallest with goiter relapse. Quantitative analysis of the goiter tissue stromal component demonstrates a considerable increase of its specific volume in comparison with normal thyroid tissue. Evaluation of changes of the morphometric parameters in the thyroid follicles found that in case of nodular goiter with slow growth the percentage of follicles with colloid is close to 100%. On an average it does not differ from that of the normal thyroid tissue. At the same time, in case of nodular goiter with quick growth the percentage of follicles with colloid decreases sharply, and in case of relapse it appears to be still less than that in nodular goiter with quick growth. Besides, with nodular goiter the diameter of follicles on an average increases in comparison with the normal thyroid tissue. In a number of cases it can be estimated as macrofollicular goiter. At the same time, the diameter of follicles is smaller in nodular goiter with quick growth. It is still less in case of goiter relapse. The size of follicles becomes sharply diverse in case of nodular goiter with slow growth, but it decreases in case of nodular goiter with quick growth and relapse. Consequently, recurrent nodular goiter is mostly similar to that of primary nodular goiter with a quick growth, though certain differences between them exist. The peculiarities found enable to suggest that nodular goiter with a quick growth possesses more chances for relapse.


1966 ◽  
Vol 51 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Franz K. Bauer ◽  
Boris Catz

ABSTRACT Eighteen euthyroid patients with progressive malignant exophthalmos, of whom 16 had been treated by other forms of therapy, were treated with large therapeutic doses of radioactive iodine in an effort to ablate their thyroid glands. In four of the patients no functioning thyroid tissue could be demonstrated; in the others thyroid tissue can still be demonstrated with 5 mc doses of 131I preceded by thyrotrophin. In all patients, marked improvement of the infiltrative changes of ophthalmopathy resulted. Proptosis improved but in none of them did it regress completely to normal. The doses of radioactive iodine required to destroy thyroid remnants were much larger than the doses employed in the treatment of hyperthyroidism. It is suggested that the thyroid gland plays an important part in the complex problem of progressive exophthalmos and the presence of LATS, although its precise role remains to be determined.


2007 ◽  
Vol 39 (7) ◽  
pp. 538-541 ◽  
Author(s):  
P. Lisboa ◽  
A. Cabanelas ◽  
F. Curty ◽  
K. Oliveira ◽  
T. Ortiga-Carvalho ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A957-A957
Author(s):  
Banu Erturk ◽  
Selcuk Dagdelen

Abstract Objective: Incretins are expressed in thyroid tissue but without clearly-known clinical significance in human. The long-term effect of GLP-1 receptor activation on the thyroid is unknown. In the literature, liragludite-related thyroiditis has not been reported yet and here we wanted to draw attention to this association. Case Summary: A 52-year-old woman with type 2 diabetes mellitus presented with thyroid tenderness, tremor and fever. Her lab results were as follows: undetectable TSH, free T4 (FT4) = 2,4 ng/dl (0.93-1.7), free T3 (FT3) = 4.4 pg/mL (2-4.4). Erythrocyte sedimentation rate (ESR) was 60 mm/hour, C-reactive protein (CRP) was 80 mg/L. Thyroid autoantibodies were negative. USG revealed that thyroid gland was in normal localization and the right lobe was 24x22x46 mm and the left lobe was 20x21x45 mm, isthmus thickness was 5 mm. The parenchyma was heterogeneous, coarsely granular, with bilateral patchy hypoechoic areas. All these findings suggested that the patient had subacute thyroiditis. When we examine the etiological factors of subacute thyroiditis in the patient, there was no history of trauma, no previous viral or bacterial illness, contrast agent exposure. But, she had only been using liraglutide for a week. Firstly liraglutide therapy was ceased and than 20 mg prednisolone and 40 mg beta-blocker therapy was initiated. At the 8 weeks’ of cessation, patient had no symptoms. Also thyroid function tests and other laboratory values were all in normal limits. Conclusions: It has been proven by previous studies that liraglutide has several effects on the thyroid gland. Liraglutide therapy might be related to subacute thyroiditis, as well.


Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1735-1743 ◽  
Author(s):  
Marcelo A. Christoffolete ◽  
Rogério Ribeiro ◽  
Praful Singru ◽  
Csaba Fekete ◽  
Wagner S. da Silva ◽  
...  

T4, the main product of thyroid secretion, is a critical signal in plasma that mediates the TSH-negative feedback mechanism. As a prohormone, T4 must be converted to T3 to acquire biological activity; thus, type 2 iodothyronine deiodinase (D2) is expected to play a critical role in this feedback mechanism. However, the mechanistic details of this pathway are still missing because, counterintuitively, D2 activity is rapidly lost in the presence of T4 by a ubiquitin-proteasomal mechanism. In the present study, we demonstrate that D2 and TSH are coexpressed in rat pituitary thyrotrophs and that hypothyroidism increases D2 expression in these cells. Studies using two murine-derived thyrotroph cells, TtT-97 and TαT1, demonstrate high expression of D2 in thyrotrophs and confirm its sensitivity to negative regulation by T4-induced proteasomal degradation of this enzyme. Despite this, expression of the Dio2 gene in TαT1 cells is higher than their T4-induced D2 ubiquitinating capacity. As a result, D2 activity and net T3 production in these cells are sustained, even at free T4 concentrations that are severalfold above the physiological range. In this system, free T4 concentrations and net D2-mediated T3 production correlated negatively with TSHβ gene expression. These results resolve the apparent paradox between the homeostatic regulation of D2 and its role in mediating the critical mechanism by which T4 triggers the TSH-negative feedback.


1969 ◽  
Vol 60 (4) ◽  
pp. 689-695 ◽  
Author(s):  
O. Helmer Sorensen ◽  
S. Pors Nielsen

ABSTRACT Acid extracts of chicken ultimobranchial and thyroid glands were assayed in the rat for their effects on serum calcium and phosphate. The concentration of a hypocalcaemic factor in the ultimobranchial tissue was more than 100 times greater than that found in pig thyroid tissue. No hypocalcaemic activity was found in the chicken thyroid gland. An extract of the ultimobranchial glands was found to have a significant hypophosphataemic effect in the rat. This fact combined with the parallelism of the log dose-response curves found for the ultimobranchial gland extract and a calcitonin standard, suggests that hypocalcaemic factor is similar to mammalian calcitonin.


1970 ◽  
Vol 63 (2) ◽  
pp. 351-358
Author(s):  
G. Riccabona ◽  
L. Obendorf ◽  
P. Huber

ABSTRACT In a series of in vitro studies an attempt was made to quantitate thyroidal iodide transport in goitres and normal thyroid glands. All the specimens were obtained from patients living in an endemic goitre area. The iodide transport capacity was shown to be higher in normal thyroid tissue than in goitres. These findings in diseased glands represent an obvious impairment of the adaptation mechanism to iodine deficiency, and can explain the growth of goitres when iodide supply is only slightly diminished. As thyroidal iodide transport is known to be related to the energy metabolism of the thyroid gland, it is suggested, that disturbances of thyroidal energy and phospolipid metabolism might be responsible for the observed insufficiency of the thyroidal iodide pump in endemic goitres.


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