scholarly journals The Amino Acid Transporter Mct10/Tat1 Is Important to Maintain the TSH Receptor at Its Canonical Basolateral Localization and Assures Regular Turnover of Thyroid Follicle Cells in Male Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5776
Author(s):  
Vaishnavi Venugopalan ◽  
Alaa Al-Hashimi ◽  
Jonas Weber ◽  
Maren Rehders ◽  
Maria Qatato ◽  
...  

Cathepsin K-mediated thyroglobulin proteolysis contributes to thyroid hormone (TH) liberation, while TH transporters like Mct8 and Mct10 ensure TH release from thyroid follicles into the blood circulation. Thus, thyroid stimulating hormone (TSH) released upon TH demand binds to TSH receptors of thyrocytes, where it triggers Gαq-mediated short-term effects like cathepsin-mediated thyroglobulin utilization, and Gαs-mediated long-term signaling responses like thyroglobulin biosynthesis and thyrocyte proliferation. As reported recently, mice lacking Mct8 and Mct10 on a cathepsin K-deficient background exhibit excessive thyroglobulin proteolysis hinting towards altered TSH receptor signaling. Indeed, a combination of canonical basolateral and non-canonical vesicular TSH receptor localization was observed in Ctsk−/−/Mct8−/y/Mct10−/− mice, which implies prolonged Gαs-mediated signaling since endo-lysosomal down-regulation of the TSH receptor was not detected. Inspection of single knockout genotypes revealed that the TSH receptor localizes basolaterally in Ctsk−/− and Mct8−/y mice, whereas its localization is restricted to vesicles in Mct10−/− thyrocytes. The additional lack of cathepsin K reverses this effect, because Ctsk−/−/Mct10−/− mice display TSH receptors basolaterally, thereby indicating that cathepsin K and Mct10 contribute to TSH receptor homeostasis by maintaining its canonical localization in thyrocytes. Moreover, Mct10−/− mice displayed reduced numbers of dead thyrocytes, while their thyroid gland morphology was comparable to wild-type controls. In contrast, Mct8−/y, Mct8−/y/Mct10−/−, and Ctsk−/−/Mct8−/y/Mct10−/− mice showed enlarged thyroid follicles and increased cell death, indicating that Mct8 deficiency results in altered thyroid morphology. We conclude that vesicular TSH receptor localization does not result in different thyroid tissue architecture; however, Mct10 deficiency possibly modulates TSH receptor signaling for regulating thyrocyte survival.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shimpei Iwata ◽  
Kenji Tsumura ◽  
Kenji Ashida ◽  
Ichiro Tokubuchi ◽  
Mutsuyuki Demiya ◽  
...  

Abstract Background Thyroid stimulating hormone (TSH) receptor and local infiltrate lymphocytes have been considered as major pathological factors for developing thyroid-related ophthalmopathy. Overexpression of insulin-like growth factor-I (IGF-I) receptor has emerged as a promising therapeutic target for refractory patients. However, the relationship between activation of growth hormone (GH)/IGF-I receptor signaling and development or exacerbation of thyroid ophthalmopathy has not been elucidated. Herein we describe a case that provides further clarification into the association between thyroid-related ophthalmopathy and GH/IGF-I receptor signaling. Case presentation A 62-year-old Japanese female diagnosed with thyroid-related ophthalmopathy was admitted to Kurume University Hospital. She had received daily administration of GH subcutaneously for severe GH deficiency; however, serum IGF-I levels were greater than + 2 standard deviation based on her age and sex. She exhibited mild thyrotoxicosis and elevation in levels of TSH-stimulating antibody. Discontinuation of GH administration attenuated the clinical activity scores of her thyroid-related ophthalmopathy. Additionally, concomitant use of glucocorticoid and radiation therapies resulted in further improvement of thyroid-related ophthalmopathy. The glucocorticoid administration was reduced sequentially, followed by successful termination. Thereafter, the patient did not undergo recurrence of thyroid-related ophthalmopathy and maintained serum IGF-I levels within normal physiological levels. Conclusions We describe here a case in which development of thyroid-related ophthalmopathy occurred upon initiation of GH administration. GH/IGF-I signaling was highlighted as a risk factor of developing thyroid-related ophthalmopathy. Additionally, aberrant TSH receptor expression was suggested to be a primary pathophysiological mechanism within the development of thyroid-related ophthalmopathy. Physicians should be aware of the risks incurred via GH administration, especially for patients of advanced age, for induction of thyroid-related ophthalmopathy.


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.


2019 ◽  
Vol 10 (4) ◽  
pp. 3178-3181
Author(s):  
Punitha S ◽  
Vedha pal jeyamani ◽  
Sindhu S ◽  
Bhuvaneshwari P ◽  
Arshath A

Thyroid carcinoma is the majority widespread endocraine malignancy in that papillary thyroid cancer is a well-differentiated type. Since hyperthyroidism protects from thyroid cancer due to lack of reproduction of thyroid tissue by the thyroid-stimulating hormone. The papillary carcinoma is the fast-growing and metastases to local region rapidly. A 60 years old post menopausal women with a known case of hypertension of past 6 years on treatment and with hyperthyroidism of past 2 months was presented in the outpatient department in the hospital with chief complaints of mass in the neck with dyphagia, cough, breathlessness, sense of fullness and odynophagia of past 2 weeks. On physical and general examination patient found with diffuse thyroid swelling with enlarged right sided lymph node. The patient was diagnosed with papillary thyroid caricinoma with various investigation reports includes CT Scan, Immouno history chemistry reports, Histopathology and Two fine-needle aspiration biopsies. The patient has undergone 6 cycles of chemotherapy with the corticosteroids, anti-cancer drugs which includes Vincristine, Cyclophosphamide, Doxorubicin, anti- emetic drugs and also with H2 receptor blockers. The papillary thyroid cancer is common and occurs predominantly in females than in males and with good prognosis and decreased death rates. The higher level of thyroid function is very rare in case of PTC.


2020 ◽  
Vol 7 (8) ◽  
pp. 584-588
Author(s):  
Hasan İkbal Atılgan ◽  
Hülya Yalçın

Objective: Radioactive iodine (RAI) is used to ablate residual thyroid tissue after total thyroidectomy. The aim of this study was to evaluate the response according to the12th-month results of thyroid cancer patients and to investigate the changes in response level during follow-up. Materials and Methods: The study included 97 patients, comprising 88 (90.7%) females and 9 (9.3%) males, with a mean age of 41.68±13.25 years. None of the patients had lymph node or distant metastasis and all received RAI therapy. Thyroid-stimulating hormone (TSH), thyroglobulin (TG), and anti-TG levels and neck USG were examined in the 12th-month. Response to therapy was evaluated as an excellent response, biochemical incomplete response, structural incomplete response, or indeterminate response. Results: In the 12th month, 80 patients (82.47%) had excellent response, 13 patients (13.40%) had an indeterminate response, 3 patients (3.09%) had structural incomplete response and 1 patient (1.03 %) had biochemical incomplete response. Of the 80 patients with excellent response, 15 had no follow-up after the 12th month. The remaining 65 patients were followed up for 31.11±9.58 months. The response changed to indeterminate in the 18th month in 1 (1.54%) patient and to structural incomplete response in the 35th month in 1 (1.54%) patient. The 13 patients with indeterminate responses were followed up for 20.61±6.28 months. Conclusion: The TG level at 12th months provides accurate data about the course of the disease especially in patients with excellent responses. Patients with excellent response in the 12th month may be followed up less often and those with the indeterminate or incomplete responses should be followed up more often.


2016 ◽  
Vol 45 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Marufa Mustari ◽  
MA Hasanat ◽  
Qamrul Hasan ◽  
Sadiqa Tuqan ◽  
Md Shah Emran ◽  
...  

Polycystic ovarian syndrome (PCOS) is a common disorder for female with fertile age. Along with other clinical and biochemical manifestations, thyroid function and prolactin level may be altered in patients with PCOS. This study aimed to evaluate the clinical and biochemical status, as well as alteration of thyroid stimulating hormone (TSH), prolactin (PRL) level in patients with PCOS. Present study comprised of 100 diagnosed PCOS patients according to revised Rotterdem Consensus criteria. All patients were studied for serum testosterone, LH (lutenizing hormone), FSH (follicle stimulating hormone), blood glucose, lipid profile as well as TSH, FT4 (free thyroxin) and prolactin level. Out of 100 PCOS patients 97 had hirsutism, 64 had acanthosis nigricans, where menstrual irregularities were in 94 patients. Diastolic blood pressure (74±1.1 vs. 77±0.9, mmHg; p=0.017), total cholesterol (163±5.3 vs. 193±6.2 mg/dl; p<0.001), low density lipoprotein (LDL, 104±3.7 vs. 124±4.9 mg/dl; p=0.002) and frequency of acanthosis (25% vs. 75%; p<0.001) were significantly higher among the patients having BMI>25 Kg/m2 than those of have ? 25 Kg/m2. Among the fertile women (n=53), 47% had primary and 41.5% had secondary infertility; whereas of the total patients, 21% had altered thyroid function and 6.1% had raised prolactin (PRL, ng/ml) level. Differences of TSH (4.1±3.6 vs. 3.5±6.8, mIU/L; p=0.725) was not significant; whereas level of PRL (13.87±6.9vs. 9.4±5.2 ng/ml; p=0.018) was significantly higher in the group of primary infertility. Hirsutism, menstrual disturbance and acanthosis were very common in PCOS. Both primary and secondary sterility were also commonly observed and PRL was higher in primary infertility. About one fifth of PCOS had altered thyroid function.Bangladesh Med J. 2016 Jan; 45 (1): 1-5


2004 ◽  
Vol 60 (1) ◽  
pp. 49-53 ◽  
Author(s):  
Makoto Iitaka ◽  
Nils G. Morgenthaler ◽  
Naoko Momotani ◽  
Atsuo Nagata ◽  
Naofumi Ishikawa ◽  
...  

PEDIATRICS ◽  
1985 ◽  
Vol 76 (5) ◽  
pp. 734-740
Author(s):  
Stephen H. LaFranchi ◽  
Cheryl E. Hanna ◽  
Patricia L. Krainz ◽  
Michael R. Skeels ◽  
Richard S. Miyahira ◽  
...  

To determine the benefit of collecting two routine specimens to test for congenital hypothyroidism, we examined the results of our newborn screening program during the last 9.5 years. The Northwest Regional Screening Program (NWRSP) performs a primary thyroxine test with thyroid-stimulating hormone determinations on the lowest 10% of dried blood filter paper specimens. An initial specimen is obtained in the newborn period, and a routine second specimen is collected at approximately 4 to 6 weeks of age in all infants born in Oregon and 25% of infants born in Idaho, Montana, Alaska, and Nevada. Between May 1975 and October 1984, 182 infants with primary hypothyroidism were detected from 811,917 infants screened, a prevalence rate of 1:4,461. The routine second specimen led to the diagnosis of 19 infants of 484,604 infants screened, a detection rate of 1:25,505. When infants detected by the second screen were compared with those detected by the first screen, they had higher thyroxine and lower thyroidstimulating hormone concentrations on filter paper and serum specimens. When thyroid scanning was used, all but one infant detected by the second screen had some residual thyroid tissue, whereas 35% of infants detected by the first screen had thyroid aplasia. Skeletal maturation was more likely to be normal in infants detected by the second screen. These infants appear to have milder hypothyroidism due to a later age of onset or slower evolution of thyroid failure. At a cost of $31,881 per infant detected by the second screen, the NWRSP found it cost-effective to obtain a routine second specimen.


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