Disappearance of Thyrotropin-Blocking Antibodies and Spontaneous Recovery from Hypothyroidism in Autoimmune Thyroiditis

Takasu, Nobuyuki; Yamada, Takashi; Takasu, Mika; Komiya, Ichiro; Nagasawa, Yoshitaka; Asawa, Takayuki; Shinoda, Takeshi; Aizawa, Toru; Koizumi, Youichi

doi:10.1056/nejm199202203260803

Cited by 155 publications

(109 citation statements)

References 38 publications

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“…Alloxan at cytotoxic doses induces cell death presumably through the production of reactive oxygen species. 24,25) Prolonged hyperglycemia caused by diabetes is known to induce oxidative stress in various tissues. 26,27) Taken together, the available data suggest that neurons in the ARN are susceptible to oxidative stress induced by hyperglycemia in the diabetic state; and thus the death of the neurons takes place resulting in the decline in GK and HK activities as well as GK mRNA level in the ARN.…”

Section: Discussionmentioning

confidence: 99%

Decline in Glucokinase Activity in the Arcuate Nucleus of Streptozotocin-Induced Diabetic Rats

Nishio

Toyoda

Hiramatsu

et al. 2006

Biological & Pharmaceutical Bulletin

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Glucokinase (GK) is known to be the critical glucose sensor of pancreatic B-cells. However, the localization and functional role of GK in the brain remains to be elucidated. In this study, we measured both the activity and mRNA level of GK in the hypothalamic nuclei and the cortex of rats injected intraperitoneally with streptozotocin or vehicle. GK activity was measured by a fluorometric assay; and the GK mRNA level, by use of the realtime reverse transcription polymerase chain reaction. GK activity in vehicle-treated rats was high in the arcuate nucleus, moderate or low in the ventromedial nucleus, lateral hypothalamic area, and paraventricular nucleus, and very low in the cortex. The order of GK mRNA level was almost the same as that of GK activity. GK activity and GK mRNA level only in the arcuate nucleus of streptozotocin-treated rats at 7 d, but not at 2 d, after treatment were lower than those of vehicle-treated rats. The results suggest that prolonged hyperglycemia induced by diabetes decreased the activity of GK in the arcuate nucleus.Key words glucokinase activity; glucokinase mRNA; hyperglycemia; hypothalamus; arcuate nucleus © 2006 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: q0391504@ccmailg.meijo-u.ac.jp the reaction was started by the addition of glucose. The rate of increase in fluorescence of NADH at excitation and emission wavelengths of 340 and 450 nm, respectively, was recorded for about 5 min. HK activity was measured at a glucose concentration of 0.5 mM, and GK activity was estimated as the difference between activities at 0.5 and 50 mM glucose.Fluorescence Real-Time RT-PCR for GK mRNA Brain samples (about 1 mg) were transferred to 100 ml of TRIzol (Invitrogen, Carlsbad, CA, U.S.A.) immediately after their collection and homogenized with a Teflon pestle. Total RNA was extracted according to the protocol of the manufacturer. Single-stranded cDNA was synthesized from 1 mg of total RNA with a 1st strand cDNA synthesis kit for RT-PCR (Roche Diagnostics, Mannheim, Germany). GK mRNA was quantified with the ABI PRISM 7700 Sequence Detection System (Applied Biosystems, Foster, CA, U.S.A.). For detection of GK mRNA (GenBank accession no. M25807), PCR primer sets for GK (forward: 5Ј-CAAGCTGCACCC-GAGCTT-3Ј, reverse: 5Ј-TGATTCGATGAAGGTGATTTC-G-3Ј) and carboxyfluorescein (FAM)-labeled and carboxytetramethylrhodamine (TAMRA)-labeled TaqMan probes for GK (5Ј-TCAGCCTGCGCACACTGGCG-3Ј) were purchased from Nihon Gene Research Laboratories (Sendai, Japan). In each well of the plate, 12.5 ml of TaqMan Universal PCR Master mix (4304437; Applied Biosystems, Foster, CA, U.S.A.), 10 pmol of primers, 1.5 ml of cDNA samples, and 5.0 pmol of GK probe were applied to give a total volume of 25 ml. PCR settings were as follows: 40 cycles for 15 s at 95°C and for 1 min at 60°C. The amount of each mRNA was standardized by the graded dilution of highly concentrated cDNA samples from the hypothalamus. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA level, an endogenous reference...

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Section: Discussionmentioning

confidence: 99%

Decline in Glucokinase Activity in the Arcuate Nucleus of Streptozotocin-Induced Diabetic Rats

Nishio

Toyoda

Hiramatsu

et al. 2006

Biological & Pharmaceutical Bulletin

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“…2,[6][7][8] A evolução de tirotoxicose/hipertiroidismo subclínico para hipotiroidismo clínico pode enquadrar-se simplesmente na história natural da TL, cujo processo destrutivo autoimune condiciona libertação das hormonas tiroideias (tirotoxicose transitória), e posterior hipotiroidismo inerente à destruição glandular e consequente diminuição da reserva funcional da tiróide. A este processo, no entanto, pode-se ter associado a ação bloqueadora dos TRAbs.…”

Section: Discussionunclassified

Hipotiroidismo Associado a Anticorpos Anti-Receptor da Hormona TSH com Ação Bloqueadora Determinada In Vitro

Marques¹,

Chikh

Charrié

et al. 2015

Acta Med Port

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RESUMOOs anticorpos anti-receptor da hormona estimulante da tiróide causam habitualmente hipertiroidismo. No entanto, a sua atividade pode ser bloqueadora, condicionando o hipotiroidismo. Apresenta-se o caso de uma doente do sexo feminino, 11 anos, com diabetes mellitus tipo 1, doença celíaca e tiroidite linfocítica em eutiroidismo ao diagnóstico. Cerca de dois anos após a avaliação inicial, a hormona estimulante da tiróide apresentava-se suprimida com T4 livre normal. Nove meses depois, a evolução foi para hipotiroidismo notandose concomitantemente elevação dos anticorpos anti-receptor da hormona estimulante da tiróide, mantendo-se a doente sempre assintomática. Células chinese hamster ovary foram transfetadas com o receptor de hormona estimulante da tiróide, e após incubação com o soro da doente, verificou-se uma atividade bloqueadora 'moderada' dos anticorpos anti-receptor da hormona estimulante da tiróide, excluindo-se ação estimuladora concomitante. Neste caso, o reconhecimento da ação bloqueadora dos anticorpos anti-receptor da hormona estimulante da tiróide detetados no soro suporta a hipótese de uma etiologia multifatorial para o hipotiroidismo que, na ausência dos testes in vitro, tenderíamos a interpretar unicamente como sequela do processo destrutivo associado à tiroidite linfocítica. Palavras-chave: Doença de Graves; Hipotiroidismo; Receptores da Tireotropina; Tireoidite Autoimune. ABSTRACTThyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient´s serum; it was estimated a 'moderate' blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis. Keywords: Graves Disease; Hypothyroidism; Receptors, Thyrotropin; Thyroiditis, Autoimmune. INTRODUÇÃOOs anticorpos anti-receptor da hormona estimulante da tiróide (TRAbs) ao ligarem-se a este receptor têm, habitualmente, uma ação similar à da hormona estimulante da tirói-de (TSH) conduzindo à produção de hormonas tiroideias. Os TRAbs são causa direta da doença de Graves (DG), a principal forma de hipertiroidismo.1...

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“…Treatment is generally recommended in patients with any symptoms potentially attributable to hypothyroidism especially if the TSH level is >10 mU per liter, and the patient is at high risk for progressing to overt hypothyroidism because of strongly positive TPO antibodies, age > 45 years, and male sex. Up to a quarter of patients with hypothyroidism due to AITD treated with thyroxine for >1 year experience a spontaneous recovery with disappearance of autoantibodies [57] suggesting that hypothyroidism due to thyrotropin-blocking antibodies can be the cause of transient as well as permanent hypothyroidism. Concomitant with a gradual increase in serum free T4 and T3 levels, and a fall in TSH levels, there was a gradual decrease in thyroid volume of 32% in 13 women with Hashimoto thyroiditis, all with initially high TPO antibody titers [58].…”

Section: Treatmentmentioning

confidence: 99%

Hashimoto’s Thyroiditis and Encephalopathy

Younger¹

2017

WJNS

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Although very rare, the literature describes cases of Hashimoto encephalopathy attesting to its occurrence. Affected patients present with seizures, stroke-like episodes, transient focal and global neurological deficits, and a variety of neuropsychiatric disturbance from dementia to hallucinations and psychosis. The encephalopathy evolves with concomitantly elevated anti-thyroid peroxidase antibodies, independent from hormonal thyroid function setting it apart from thyrotoxicosis and myxedema. A new patient reported with Hashimoto's encephalopathy, in whom neurocognitive impairment and stroke-like onset of hemiparesis and hemiparkinsonism correlated with brain magnetic resonance imaging fused with positron emission tomography.

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Disappearance of Thyrotropin-Blocking Antibodies and Spontaneous Recovery from Hypothyroidism in Autoimmune Thyroiditis

Cited by 155 publications

References 38 publications

Decline in Glucokinase Activity in the Arcuate Nucleus of Streptozotocin-Induced Diabetic Rats

Decline in Glucokinase Activity in the Arcuate Nucleus of Streptozotocin-Induced Diabetic Rats

Hipotiroidismo Associado a Anticorpos Anti-Receptor da Hormona TSH com Ação Bloqueadora Determinada In Vitro

Hashimoto’s Thyroiditis and Encephalopathy

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