T3 TOXICOSIS IN ADOLESCENCE: PRESENTATION AS RECURRENT HYPERTHYROIDISM

PEDIATRICS ◽  
1973 ◽  
Vol 52 (5) ◽  
pp. 649-652
Author(s):  
T. W. AvRuskin ◽  
S. Tang ◽  
L. Shenkman ◽  
C. S. Hollander
Keyword(s):  
Female Patient ◽  
Intravenous Infusion ◽  
Pediatric Population ◽  
Normal Serum ◽  
Thyrotropin Releasing Hormone ◽  
Graves Disease ◽  
Adolescent Patient ◽  
Serum T3 ◽  
Recurrent Hyperthyroidism ◽  
Serum Tsh

The second adolescent patient with recurrent hyperthyroidism caused by isolated hypersecretion of T3 (T3 toxicosis) has been discovered. In 1969, this 17-year-old female patient initially presented with conventional Graves' disease was treated with propylthiouracil, but discontinued her medication after three months. Two and one-half half years later, she developed clinical and laboratory tory features of recurrent Graves' disease, save for a normal total and free thyroxine (T4). Serum T3 by radioimmunoassay was elevated (210 ng/100 ml) and thyroid binding globulin capacity for T4 was normal. Serum TSH was not detectable and failed to rise after intravenous infusion of 400 mg thyrotropin-releasing hormone. Other parameters of T3 toxicosis, as noted in adults with this syndrome, were confirmed. T3 toxicosis presenting as recurrent hyperthyroidism may be more common than previously recognized in the pediatric population.

A study of thyroid function after subtotal thyroidectomy for Graves' disease: particularly on TRH tests, T3 suppression tests and antithyroid antibodies in euthyroid patients

1983 ◽  
Vol 103 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Osamu Fukino ◽  
Hajime Tamai ◽  
Shinichi Fujii ◽  
Noriyuki Ohsako ◽  
Sunao Matsubayashi ◽  
...  
Keyword(s):  
Elevated Serum ◽  
Subtotal Thyroidectomy ◽  
Graves Disease ◽  
Trh Test ◽  
Antithyroid Antibodies ◽  
Abnormal Response ◽  
Suppression Test ◽  
Recurrent Hyperthyroidism ◽  
Serum Tsh

Abstract. Of 305 patients who underwent subtotal thyroidectomy for Graves' disease between 1969 and 1975, recurrent hyperthyroidism was found in 31 (10.2%) and hypothyroidism in 18 (5.9%). The remaining 256 patients were clinically euthyroid, but an elevated serum TSH level was found in 104 (34.1%) and an elevated serum T3 level in 19 (6.28%). In 57 of 133 clinically and biochemically euthyroid patients, a TRH test, T3 suppression test and measurement of antithyroid antibodies were performed. Twenty-nine of the 57 patients (50.9%) showed an abnormal response to TRH. Eight of these (14.0%) showed an impaired or absent response. The T3 suppression test showed that 15 of the 57 patients (26.3%) were non-suppressible. Positive antithyroid antibodies, especially antimicrosomal antibodies, were more frequent in non-suppressible and TRH-non-responsive patients than in suppressible and TRH-responsive patients. It is suggested that after operation for Graves' disease: 1) only half of the clinically euthyroid patients were biochemically euthyroid, 2) of the clinically and biochemically euthyroid patients, there were many with abnormalities in TRH responsiveness and T3 suppressibility, and 3) thyroid functional status is unstable and long careful follow-up is important after operation for Graves' disease.

scholarly journals T4 + T3 combination therapy: any progress?

Endocrine ◽  
2019 ◽  
Vol 66 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Wilmar M. Wiersinga
Keyword(s):  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Normal Serum ◽  
Thyroid Function Tests ◽  
Pressure Groups ◽  
Persistent Symptoms ◽  
House Of Lords ◽  
Serum T3 ◽  
With Memory ◽  
Serum Tsh

Abstract Guidelines on T4 + T3 combination therapy were published in 2012. This review investigates whether the issue is better understood 7 years later. Dissatisfaction with the outcome of T4 monotherapy remains high. Persistent symptoms consist mostly of fatigue, weight gain, problems with memory and thinking and mood disturbances. T4 monotherapy is associated with low serum T3 levels, which often require TSH-suppressive doses of L-T4 for normalization. Peripheral tissue thyroid function tests during T4 treatment indicate mild hyperthyroidism at TSH < 0.03 mU/L and mild hypothyroidism at TSH 0.3–5.0 mU/L; tissues are closest to euthyroidism at TSH 0.03–0.3 mU/L. This is explained by the finding that whereas T4 is usually ubiquinated and targeted for proteasomal degradation, hypothalamic T4 is rather stable and less sensitive to ubiquination. A normal serum TSH consequently does not necessarily indicate a euthyroid state. Persistent symptoms in L-T4 treated patients despite a normal serum TSH remain incompletely understood. One hypothesis is that a SNP (Thr92Ala) in DIO2 (required for local production of T3 out of T4) interferes with its kinetics and/or action, resulting in a local hypothyroid state in the brain. Effective treatment of persistent symptoms has not yet realized. One may try T4 + T3 combination treatment in selected patients as an experimental n = 1 study. The 2012 ETA guidelines are still valid for this purpose. More well-designed randomized clinical trials in selected patients are key in order to make progress. In the meantime the whole issue has become rather complicated by commercial and political overtones, as evident from skyrocketing prices of T3 tablets, aggressive pressure groups and motions in the House of Lords.

A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells

1987 ◽  
Vol 115 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Kanji Kasagi ◽  
Junji Konishi ◽  
Yasuhiro Iida ◽  
Yasutaka Tokuda ◽  
Keisuke Arai ◽  
...  
Keyword(s):  
Fold Increase ◽  
Graves Disease ◽  
Thyroid Cells ◽  
Thyroid Stimulating Antibodies ◽  
Silent Thyroiditis ◽  
Poorly Differentiated ◽  
Pre Treatment ◽  
Rat Thyroid ◽  
Serum Tsh ◽  
Bovine Tsh

Abstract. A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37°C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies.

scholarly journals Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats

2005 ◽  
Vol 153 (3) ◽  
pp. 429-434 ◽  
Author(s):  
P Cettour-Rose ◽  
T J Visser ◽  
A G Burger ◽  
F Rohner-Jeanrenaud
Keyword(s):  
Specific Inhibitor ◽  
Adult Rats ◽  
Reverse T3 ◽  
Brown Adipose ◽  
Tsh Secretion ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Tsh ◽  
Tsh Levels

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3). Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4. Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal. Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.

scholarly journals Determinants of Extraocular Muscle Volume in Patients with Graves' Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Samer El-Kaissi ◽  
Jack R. Wall
Keyword(s):  
Extraocular Muscle ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Thyroid Scintigraphy ◽  
Free T4 ◽  
Receptor Antibody ◽  
Tsh Receptor Antibody ◽  
Antibody Positivity ◽  
Serum Tsh

Background. To examine factors contributing to extraocular muscle (EOM) volume enlargement in patients with Graves’ hyperthyroidism.Methods. EOM volumes were measured with orbital magnetic resonance imaging (MRI) in 39 patients with recently diagnosed Graves’ disease, and compared to EOM volumes of 13 normal volunteers. Thyroid function tests, uptake on thyroid scintigraphy, anti-TSH-receptor antibody positivity and other parameters were then evaluated in patients with EOM enlargement.Results. 31/39 patients had one or more enlarged EOM, of whom only 2 patients had clinical EOM dysfunction. Compared to Graves’ disease patients with normal EOM volumes, those with EOM enlargement had significantly higher mean serum TSH (0.020±0.005versus0.007±0.002mIU/L;Pvalue 0.012), free-T4 (52.9±3.3versus41.2±1.7 pmol/L;Pvalue 0.003) and technetium uptake on thyroid scintigraphy (13.51±1.7%versus8.55±1.6%;Pvalue 0.045). There were no differences between the 2 groups in anti-TSH-receptor antibody positivity, the proportion of males, tobacco smokers, or those with active ophthalmopathy.Conclusions. Patients with recently diagnosed Graves’ disease and EOM volume enlargement have higher serum TSH and more severe hyperthyroidism than patients with normal EOM volumes, with no difference in anti-TSH-receptor antibody positivity between the two groups.

scholarly journals Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1180-1191 ◽  
Author(s):  
Xiao-Hui Liao ◽  
Caterina Di Cosmo ◽  
Alexandra M. Dumitrescu ◽  
Arturo Hernandez ◽  
Jacqueline Van Sande ◽  
...  
Keyword(s):  
Growth Response ◽  
Pituitary Thyroid Axis ◽  
Severe Impairment ◽  
Serum T3 ◽  
Serum T4 ◽  
Thyroid Axis ◽  
Mct8 Deficiency ◽  
The Brain ◽  
Insight Into ◽  
Serum Tsh

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.

scholarly journals Bevacizumab as a treatment for hereditary hemorrhagic telangiectasia in children: a case report

2017 ◽  
pp. 88-93 ◽  
Author(s):  
Fabio E Ospina ◽  
Alex Echeverri ◽  
Iván Posso Osorio ◽  
Lina Jaimes ◽  
Jaiber Gutierrez ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Female Patient ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Pediatric Population ◽  
Adult Population ◽  
Autosomal Dominant Disorder ◽  
Arteriovenous Shunts ◽  
Clinical Benefits ◽  
Oxygen Requirements ◽  
Endothelial Growth Factor

Case description: Five-year-old female patient with hereditary hemorrhagic telangiectasia.Clinical Findings: Deterioration of cardiopulmonary function with higher oxygen requirements secondary to pulmonary arteriovenous shunts, epistaxis.Treatment and Outcome: The patient was treated with the monoclonal antibody bevacizumab, which inhibits the vascular endothelial growth factor, with good clinical outcome.Clinical Relevance: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations in different organs, making its clinical presentations varied. Systemic therapeutic options for a generalized disease are limited. The monoclonal antibody bevacizumab, seems to be a good option in this disorder. Although reported as successful in adult population, its use in pediatric population has not yet been reported. Here we report the use of bevacizumab in a 5-year-old female patient with hereditary hemorrhagic telangiectasia, showing clinical benefits and good outcome.

Clinical and Morphologic Findings of Familial Goiter in Bongo Antelope (Tragelaphus eurycerus)

1995 ◽  
Vol 32 (3) ◽  
pp. 242-249 ◽  
Author(s):  
C. A. Schiller ◽  
R. J. Montali ◽  
S. Doi ◽  
E. F. Grollman
Keyword(s):  
Thyroid Stimulating Hormone ◽  
Normal Serum ◽  
Follicular Epithelium ◽  
Adult Onset ◽  
Human Beings ◽  
Cyclic Activity ◽  
Congenital Goiter ◽  
Thyroid Glands ◽  
Serum T3 ◽  
Familial Goiter

Inherited defects of thyroglobulin synthesis resulting in congenital goiter are well described in certain breeds of domestic ungulates and in human beings. Goiter associated with synthesis of an abnormal thyroglobulin and the presence of thyroidal albumin was identified in five closely related bongo antelopes ( Tragelaphus eurycerus). The goiter had an adult onset, and the affected bongos appeared to remain euthyroid with normal serum T3 and T4 values, normal serum cholesterol concentrations, and nonelevated concentrations of circulating thyroid stimulating hormone (TSH). Goitrous bongos had significant reproductive difficulties, including reduced cyclic activity and prolonged gestations, but were otherwise normal. Over the course of the disease, the thyroid glands greatly enlarged (up to 10 × 20 cm) and became polycystic. Microscopically, there was an admixture of giant colloid-filled follicles and follicles of normal size lined with variable follicular epithelium ranging from squamoid to mildly to moderately hyperplastic. The pathogenesis of goiter in the bongo may reflect a mixture of genetic predisposition coupled with environmental factors, including a period of exposure to a goitrogen.

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