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  • 1
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    Online Resource
    The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study
    Japan Endocrine Society ; 2020
    In:  Endocrine Journal Vol. 67, No. 8 ( 2020), p. 859-868
    Details
    In: Endocrine Journal, Japan Endocrine Society, Vol. 67, No. 8 ( 2020), p. 859-868
    Type of Medium: Online Resource
    ISSN: 0918-8959 , 1348-4540
    URL: Article
    DOI: 10.1507/endocrj.EJ19-0604
    Language: English
    Publisher: Japan Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2133773-1
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  • 2
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    Nicotinic acetylcholine receptor signaling regulates inositol‐requiring enzyme 1α activation to protect β‐cells against terminal unfolded protein response under irremediable endoplasmic reticulum stress
    Wiley ; 2020
    In:  Journal of Diabetes Investigation Vol. 11, No. 4 ( 2020-07), p. 801-813
    Details
    In: Journal of Diabetes Investigation, Wiley, Vol. 11, No. 4 ( 2020-07), p. 801-813
    Abstract: Under irremediable endoplasmic reticulum (ER) stress, hyperactivated inositol‐requiring enzyme 1α (IRE1α) triggers the terminal unfolded protein response (T‐UPR), causing crucial cell dysfunction and apoptosis. We hypothesized that nicotinic acetylcholine receptor (nAChR) signaling regulates IRE1α activation to protect β‐cells from the T‐UPR under ER stress. Materials and Methods The effects of nicotine on IRE1α activation and key T‐UPR markers, thioredoxin‐interacting protein and insulin/proinsulin, were analyzed by real‐time polymerase chain reaction and western blotting in rat INS‐1 and human EndoC‐βH1 β‐cell lines. Doxycycline‐inducible IRE1α overexpression or ER stress agents were used to induce IRE1α activation. An α7 subunit‐specific nAChR agonist (PNU‐282987) and small interfering ribonucleic acid for α7 subunit‐specific nAChR were used to modulate nAChR signaling. Results Nicotine inhibits the increase in thioredoxin‐interacting protein and the decrease in insulin 1/proinsulin expression levels induced by either forced IRE1α hyperactivation or ER stress agents. Nicotine attenuated X‐box‐binding protein‐1 messenger ribonucleic acid site‐specific splicing and IRE1α autophosphorylation induced by ER stress. Furthermore, PNU‐282987 attenuated T‐UPR induction by either forced IRE1α activation or ER stress agents. The effects of nicotine on attenuating thioredoxin‐interacting protein and preserving insulin 1 expression levels were attenuated by pharmacological and genetic inhibition of α7 nAChR. Finally, nicotine suppressed apoptosis induced by either forced IRE1α activation or ER stress agents. Conclusions Our findings suggest that nAChR signaling regulates IRE1α activation to protect β‐cells from the T‐UPR and apoptosis under ER stress partly through α7 nAChR. Targeting nAChR signaling to inhibit the T‐UPR cascade may therefore hold therapeutic promise by thwarting β‐cell death in diabetes.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    URL: Article
    DOI: 10.1111/jdi.v11.4
    DOI: 10.1111/jdi.13211
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2542077-X
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  • 3
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    Comparative analysis of human leucocyte antigen between idiopathic and anti‐PD‐1 antibody induced isolated adrenocorticotropic hormone deficiency: A pilot study
    Wiley ; 2019
    In:  Clinical Endocrinology Vol. 91, No. 6 ( 2019-12), p. 786-792
    Details
    In: Clinical Endocrinology, Wiley, Vol. 91, No. 6 ( 2019-12), p. 786-792
    Abstract: Adult‐onset idiopathic isolated adrenocorticotropic hormone deficiency (id‐IAD) is a rare disease with unknown aetiology. Recently, numerous cases of anti‐PD‐1 antibody‐induced IAD (PD1‐IAD) have been reported, but the clinical course, predictive factors and relationship to id‐IAD have not been clarified. Moreover, associations of id‐IAD and PD1‐IAD with human leucocyte antigen (HLA) require elucidation. Methods Clinical characteristics of 13 Japanese patients with id‐IAD and eight Japanese patients with PD1‐IAD were analysed, and HLA‐typing test was performed for each patient. Allele and haplotype frequencies of the patients were compared to those of healthy Japanese controls. Results In the HLA allele and haplotype analyses of id‐IAD, the frequencies of HLA‐C*14:02, HLA‐DPB1*05:01, HLA‐DRB1*04:05‐DQB1*04:01‐DPB1*05:01 and HLA‐DRB1*09:01‐DQB1*03:03‐DPB1*05:01 were significantly increased. On the other hand, HLA alleles account for PD1‐IAD susceptibility as follows: HLA‐DQB1*06:01, HLA‐DPB1*09:01 and HLA‐DRB5*01:02. Moreover, protective effect for HLA‐C*03:03 was suggested in combined id‐IAD and PD1‐IAD patients. Comparison of the effects of HLA on id‐IAD and PD1‐IAD revealed some differences. Alleles or haplotypes frequencies increased in id‐IAD group were as follows: HLA‐DPB1*05:01, HLA‐DRB1*09:01, HLA‐DRB4*01:03:02, HLA‐DQB1*03:03 and HLA‐DRB1*09:01‐DQB1*03:03. In clinical settings, hyponatremia, disturbance of consciousness and hypoglycaemia were less frequently seen in patients with PD1‐IAD than in patients with id‐IAD. Conclusions Distinct clinical characteristics and predisposing HLA allele contributions were proposed between id‐IAD and PD1‐IAD. Further investigations with greater number of cases are warranted to clarify the detailed mechanisms of id‐IAD and PD1‐IAD.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.v91.6
    DOI: 10.1111/cen.14082
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2004597-9
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  • 4
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    Hypopituitarism and cranial nerve involvement mimicking Tolosa-Hunt syndrome as the initially presenting feature of diffuse large B-cell lymphoma: a case report
    Springer Science and Business Media LLC ; 2022
    In:  BMC Endocrine Disorders Vol. 22, No. 1 ( 2022-12)
    Details
    In: BMC Endocrine Disorders, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: Early diagnosis of lymphoma involving the central nervous system is sometimes difficult but emergent to avoid the delay of therapeutic initiation. Pituitary insufficiencies are usually associated with lymphoma in the pituitary gland. There have been no cases of lymphoma originating from extra pituitary gland with hypopituitarism that simultaneously presenting unilateral upper cranial nerve palsies and ophthalmalgia. These symptoms are mostly caused by neoplastic involvement of the skull base or benign diseases such as Tolosa-Hunt syndrome (THS). We report a case of lymphoma with unique clinical courses initially presenting hypopituitarism and symptoms mimicking THS with a mass in sphenoidal and cavernous sinuses accompanying sphenoidal bone erosion. Case presentation. A 71-year-old woman visited our hospital with left ophthalmalgia, ptosis, and diplopia. Neurological findings revealed left oculomotor, trochlear and abducent nerve palsies. Endocrine tests indicated partial hypopituitarism. Initial CT and MRI revealed that a mass in sphenoidal and cavernous sinuses had invaded the sella with osteolysis of the sphenoid bone. At around four weeks, almost all the symptoms of cranial nerve palsies were relieved. Seven weeks later, she had a high fever and cervical lymph node (CLN) swellings. CLN biopsy revealed CD20-positive B-cells. She was diagnosed with diffuse large B-cell lymphoma (DLBCL). 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) revealed elevated uptake at the erosion lesion of the sphenoidal bone, but not the pituitary gland. After chemotherapy, all the symptoms related to systemic lymphoma were relieved, but partial hypopituitarism remained. The mass in sphenoidal and cavernous sinuses and elevated uptake by PET/CT were dissolved. Conclusion This case of DLBCL had a unique clinical course; initial presentation of hypopituitarism and symptoms mimicking THS. There was also rare demonstration of mass lesions related to DLBCL in the sphenoidal and cavernous sinuses compressing the pituitary gland through an eroded area of the sphenoidal bone. It should be clinically cautioned that DLBCL can be associated with erosion of the sphenoidal bone and cause both hypopituitarism and THS-mimicking symptoms.
    Type of Medium: Online Resource
    ISSN: 1472-6823
    URL: Article
    DOI: 10.1186/s12902-022-00973-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2091323-0
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  • 5
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    IL-1β directly suppress ghrelin mRNA expression in ghrelin-producing cells
    Elsevier BV ; 2017
    In:  Molecular and Cellular Endocrinology Vol. 447 ( 2017-05), p. 45-51
    Details
    In: Molecular and Cellular Endocrinology, Elsevier BV, Vol. 447 ( 2017-05), p. 45-51
    Type of Medium: Online Resource
    ISSN: 0303-7207
    URL: Article
    DOI: 10.1016/j.mce.2017.02.032
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1500651-7
    SSG: 12
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  • 6
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    Thyroid function, glycemic control, and diabetic nephropathy in patients with type 2 diabetes over 24 months: prospective observational study
    Springer Science and Business Media LLC ; 2023
    In:  BMC Endocrine Disorders Vol. 23, No. 1 ( 2023-07-10)
    Details
    In: BMC Endocrine Disorders, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-07-10)
    Abstract: The higher prevalence of thyroid dysfunction in type 1 diabetes patients has been well established, whereas it is a matter of debate whether that is also observed in type 2 diabetes patients. This study was conducted to reveal whether higher prevalence of thyroid dysfunction is observed in patients with type 2 diabetes. Methods We examined thyroid functions and thyroid autoantibodies in 200 patients with type 2 diabetes and 225 controls, with 24 months follow up for those with type 2 diabetes. Results Serum free triiodothyronine (fT3) levels and fT3/free thyroxine (fT4) ratio were significantly lower, while fT4 levels were significantly higher in patients with type 2 diabetes. The number of patients with thyroid dysfunction or patients positive for thyroid autoantibodies were not different between the two groups. The fT3/fT4 ratio was positively and negatively correlated with serum c-peptide and HbA1c levels, respectively, suggesting that the difference can be attributable to insulin resistance and diabetic control. In the follow-up observation, we found no significant correlation between basal thyrotropin (TSH), fT3, fT4 or fT3/fT4 ratio with the amounts of changes of HbA1c levels at 12 or 24 months after the basal measurements. There was a negative relationship between TSH levels and eGFR at baseline measurements, but TSH levels did not seem to predict future decline of eGFR levels. No relationship was observed between urine albumin/ g‧cre levels and thyroid function. Conclusion Thyroid dysfunction and thyroid autoantibodies were not different in prevalence between patients with type 2 diabetes and controls, although in patients with type 2 diabetes, the fT3/fT4 ratio was decreased. Basal thyroid function did not predict future diabetes control or renal function within 24 months of follow-up.
    Type of Medium: Online Resource
    ISSN: 1472-6823
    URL: Article
    DOI: 10.1186/s12902-023-01393-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 7
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    SAT-433 The Influence of Thyroid Autoimmunity on Pregnancy Outcome in Infertile Women
    The Endocrine Society ; 2020
    In:  Journal of the Endocrine Society Vol. 4, No. Supplement_1 ( 2020-05-08)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background: Women with subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) reportedly have high risks of miscarriage and preterm birth. Infertile women undergoing assisted reproductive technology (ART) are recommended for levothyroxine (L-T4) supplementation to maintain TSH levels below 2.5 mIU/mL according to ATA guideline; however, insufficient evidence exists to determine whether L-T4 treatment for infertile women with TSH levels between 2.5 and 5.0 mIU/mL. Objective: To clarify the influence of TAI on pregnancy in infertile women under L-T4 treatment to maintain TSH levels below 2.5 mIU/mL, and to compare its influence depending on fertility treatments. Methods: A total of 595 infertile women who visited a fertility clinic between January 2013 and December 2015 were prospectively recruited to this study. Five patients with Graves’ disease were excluded and remained 590 women were included in the analysis. Infertile women with TSH levels above 2.5 mIU/mL were treated with L-T4 followed by evaluation of fertility status and pregnancy outcomes. Factors affecting pregnancy were analyzed statistically depending on fertility treatments. Written informed consent was obtained from all patients, and the study protocol was approved by the Ethics Committee. Results: The proportion of SCH and thyroid peroxidase antibodies (TPOAb).positivity was 19.6% and 10.4%, respectively. Women who did not become pregnant were older than those who became pregnant (p=0.003), but no influence of thyroid-associated factors on pregnancy was confirmed. Pregnancy outcome contrarily showed that women who had a miscarriage were older (p & lt;0.001) and higher TPOAb titers (p=0.038) than those who had a live birth. In addition, higher age (OR 26.4, p & lt;0.001) and high TPOAb titer (OR 11.8, p=0.043) were decided as risk factors for miscarriage through multiple logistic regression analysis. Among women who treated with intrauterine insemination, TPOAb titers were higher in women who had a miscarriage than in those who had a live birth (p=0.040). We further focused on the difference between ART methods including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Women undergoing IVF had higher TPOAb titers in women who had miscarriage than those who had a live birth (p=0.023), but in women undergoing ICSI there was no association between TPOAb titers and pregnancy outcome. Conclusion: Infertile women with high TPOAb titers are susceptible to miscarriage despite appropriate L-T4 treatment. The influence of TPOAb titers as well as TPOAb positivity on pregnancy should be considered, when undergoing fertility treatments.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvaa046.1624
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
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  • 8
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    Expression of unfolded protein response markers in the pheochromocytoma with Waardenburg syndrome: a case report
    Springer Science and Business Media LLC ; 2020
    In:  BMC Endocrine Disorders Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Endocrine Disorders, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: It is clinically emergent to further understand the pathological mechanism to advance therapeutic strategy for endocrine tumors. A high amount of secretory protein with tumorigenic triggers are thought to induce unfolded protein response in endoplasmic reticulum in endocrine tumors, but its evidence is limited. Case presentation A 40-year-old woman had an approximately 10-year history of intermittent headaches. After the incidental detection of a mass in her right adrenal gland by CT scan, she was admitted to our hospital. She had been diagnosed as type 1 Waardenburg syndrome with the symptoms of dystopia canthorum, blue iris, and left sensorineural hearing loss. Urinary catecholamine levels were markedly elevated. 123 I-MIBG scintigraphy showed uptake in the mass in her adrenal gland. After the adrenalectomy, her headaches disappeared and urinary catecholamine levels decreased to normal range within 2 weeks. Genome sequencing revealed germline mutation of c.A175T (p.Ile59Phe) in transcription factor PAX3 gene and somatic novel mutation of c.1893_1898del (p. Asp631_Leu633delinsGlu) in proto-oncogene RET in her pheochromocytoma. RNA expression levels of RET were increased 139 times in her pheochromocytoma compared with her normal adrenal gland. Those of unfolded protein response markers, Bip/GRP78, CHOP, ATF4, and ATF6, were also increased in the pheochromocytoma. Conclusion We report a rare case of pheochromocytoma with type 1 Waardenburg syndrome. This is the first case to show the activation of unfolded protein response in the pheochromocytoma with the novel somatic mutation in RET gene. Our findings may support that unfolded protein response is activated in endocrine tumors, which potentially could be a candidate of therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1472-6823
    URL: Article
    DOI: 10.1186/s12902-020-00574-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2091323-0
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  • 9
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    Early detection of euglycemic ketoacidosis during thoracic surgery associated with empagliflozin in a patient with type 2 diabetes: A case report
    Wiley ; 2021
    In:  Journal of Diabetes Investigation Vol. 12, No. 4 ( 2021-04), p. 664-667
    Details
    In: Journal of Diabetes Investigation, Wiley, Vol. 12, No. 4 ( 2021-04), p. 664-667
    Abstract: We report the first case of intraoperatively detected euglycemic diabetic ketoacidosis (DKA) associated with sodium–glucose cotransporter 2 inhibitors during thoracic surgery. A 59‐year‐old man had a 12‐year history of type 2 diabetes mellitus treated with insulin and empagliflozin. The patient developed bacterial empyema and was initiated with antibiotics at a local hospital. Owing to the persistence of his symptoms, he was transferred to our hospital after the medication of empagliflozin the day before surgery. After overnight fasting, the patient underwent thoracoscopic debridement and intrathoracic lavage surgery. During this surgery, he was noted to have euglycemic ketosis and acidosis, and diagnosed as euglycemic DKA. Immediately after the consultation in our department, the patient underwent treatment for DKA. He awoke from anesthesia normally and showed no symptoms of DKA. DKA gradually resolved over the next 24 h. Early identification and management are critical for rapid recovery from perioperative euglycemic DKA associated with sodium–glucose cotransporter 2 inhibitors, especially during thoracic surgery.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    URL: Article
    DOI: 10.1111/jdi.v12.4
    DOI: 10.1111/jdi.13365
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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