Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 69, Issue 11
Displaying 1-14 of 14 articles from this issue
OBITUARY
TOWARD JES 100TH ANNIVERSARY
POSITION STATEMENT
  • The Working Group for Renaming Diabetes Insipidus, Hiroshi Arima, Timo ...
    Article type: Position Statement
    2022 Volume 69 Issue 11 Pages 1281-1284
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: October 14, 2022
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    What’s in a name? That which we call a rose/By any other name would smell as sweet.” (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare’s implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and pediatric endocrine societies now proposes changing the name of “diabetes insipidus” to “Arginine Vasopressin Deficiency (AVP-D)” for central etiologies, and “Arginine Vasopressin Resistance (AVP-R)” for nephrogenic etiologies. This editorial provides both the historical context and the rational for this proposed name change.

REVIEW
  • Yuji Nagayama, Eijun Nishihara
    Article type: Review
    2022 Volume 69 Issue 11 Pages 1285-1293
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: September 27, 2022
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    The thyrotropin receptor (TSHR) plays critical roles in thyroid growth and function and in the pathogenesis of several thyroid diseases including Graves’ hyperthyroidism and ophthalmopathy, non-autoimmune hyperthyroidism and thyroid cancer. Several low-molecular weight compounds (LMWCs) and anti-TSHR monoclonal antibodies (mAbs) with receptor antagonistic and inverse agonistic activities have been reported. The former binds to the pocket formed by the receptor transmembrane bundle, and the latter to the extracellular TSH binding site. Both are effective inhibitors of TSH/thyroid stimulating antibody-stimulated cAMP and/or hyaluronic acid production in TSHR-expressing cells. Anti-insulin-like growth factor 1 inhibitors are also found to inhibit TSHR signaling. Each agent has advantages and disadvantages; for example, mAbs have a higher affinity and longer half-life but are more costly than LMWCs. At present, mAbs appear most promising, yet the development of more efficacious LMWCs is desirable. These agents are anticipated to be efficacious not only for the above-mentioned diseases but also for resistance to thyroid hormone and have utility for thyroid cancer radionuclide scintigraphy/therapy as a new theranostic.

    Editor's pick

    Molecular research on agonists / antagonists / inverse agonists in a variety of G-protein coupled receptors (GPCRs) has long attracted robust attention of endocrinologists. In this issue, Dr. Nagayama and Dr. Nishihara contributes an encyclopedic, well-organized article on the update of antagonists / inverse agonists research around the thyrotropin receptor (TSHR), providing us with promising therapeutic potential for Graves’ hyperthyroidism, non-autoimmune hyperthyroidism, thyroid cancer and resistance to thyroid hormone.

ORIGINAL
  • Youn Huh, Ga Eun Nam, Jisun Lim, Hye Soon Park
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1295-1302
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: June 28, 2022
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    High blood glucose level and non-alcoholic fatty liver disease (NAFLD) in adolescents are long-term risk factors for cardiovascular diseases and poor prognosis. We investigated recent trends of high blood glucose levels and NAFLD among Korean adolescents aged 12–18 years. We conducted a cross-sectional analysis using data of 5,685 adolescents aged 12–18 years from the Korea National Health and Nutrition Examination Surveys (KNHANES), from 2007–2009 to 2016–2018. Linear trends in the prevalence of high blood glucose level, NAFLD, and associated factors were assessed using multivariable logistic regression analyses. During the study period, the odds ratios for high blood glucose level and NAFLD increased significantly in both sexes and in girls, respectively (p for trend <0.05). Over-consumption of total calories in boys and fat intake in boys and girls increased significantly (p for trend <0.05). In Korean adolescents, the prevalence of high blood glucose level and NAFLD has increased recently. Efforts to modify the associated factors and further research to determine the public health measures are warranted to prevent these metabolic abnormalities in adolescents.

  • Yuko Akehi, Makito Tanabe, Hiromi Yano, Yuichi Takashi, Daiji Kawanami ...
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1303-1312
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: July 14, 2022
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    Supplementary material

    The Aging Males’ Symptoms (AMS) score, developed to screen for late-onset hypogonadism (LOH), contains 17 questions regarding mental, physical, and sexual parameters. In the Japanese guidelines, a free testosterone (FT) <8.5 pg/mL is recommended for testosterone treatment. However, previous studies have shown no correlation between total AMS scores and testosterone concentration. We aimed to develop a better questionnaire for the detection of testosterone deficiency in men, for the diagnosis of LOH. In 234 Japanese men, aged 40–64 years, we analyzed the relationships of AMS with serum total testosterone (TT), FT, calculated FT (cFT), and calculated bioavailable testosterone (cBT), and identified useful questions for the detection of testosterone deficiency. Four scores, a decrease in muscular strength, a decrease in ability to perform sexually or the frequency, a decrease in the number of morning erections, and a decrease in sexual desire/libido, were negatively associated with two or more of the above four testosterone parameters, and the sum of these four scores (named the selective score) correlated with TT and cFT, independent of age. Statistical analysis revealed an association between insulin resistance and testosterone deficiency, and a higher selective score in smokers than non-smokers. Cubic function model analysis and logistic regression analysis revealed that selective scores ≥10 corresponded with the testosterone concentrations recommended for the diagnosis of LOH, including FT <8.5 pg/mL, independent of age, insulin resistance, and smoking. Thus, the selective score represents a simple and useful means for screening of testosterone deficiency in Japanese men, as an indicator of LOH.

  • Mamoru Morikawa, Takashi Sugiyama, Yuji Hiramatsu, Norimasa Sagawa
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1313-1322
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: July 01, 2022
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    This study aimed to investigate the relationship between gestational diabetes mellitus (GDM) screening methods and GDM incidences. In 2018, a national questionnaire was administered at 231 institutions (56.6%) of all 408 perinatal medical centers in Japan. Of 100,485 women, 2,982 (3.0%) were diagnosed with GDM during their first pregnancy period (FPP) and 7,289 (7.3%) were diagnosed with GDM during their middle pregnancy period (MPP). The proportion of women diagnosed with GDM during FPP and MPP using 95 mg/dL as the cutoff value (CV) for random plasma glucose (PG) at FPP (4.3% and 9.2%) was significantly higher than that of women diagnosed with GDM using 100 mg/dL as the CV for random PG (2.7% and 6.9%, p < 0.0001, respectively). Compared with women screened for GDM using “random PG and random PG,” women who were screened for GDM using “random PG and 50-g glucose challenge test (GCT)” had a significantly higher incidence of GDM (6.6% versus 8.9%, p < 0.0001). Using random PG and 50-g GCT, the incidence of GDM among women diagnosed at MPP using a CV of 95 mg/dL at FPP was significantly higher than that of women diagnosed using a CV of 100 mg/dL (16.5% versus 7.8%: p < 0.0001). While, using “random PG and random PG,” the incidences of GDM among women were similar between institutions using a CV of 100 mg/dL and those using a CV of 95 mg/dL at FPP (6.7% versus 6.9%: p = 0.3581). This study showed random PG as a first-step screening method in MPP may overlook women with GDM.

  • Ilan Shimon, Zaina Adnan, Dania Hirsch, Hadar Duskin-Bitan, Amit Akiro ...
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1323-1328
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: June 22, 2022
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    Patients with acromegaly usually present with the classical signs of acromegaly, whereas patients without the specific signs or symptoms are rarely diagnosed. This unique entity can be named “subclinical acromegaly”. This was a retrospective study. Our study group consisted of 6 patients (4 females) with incidentally diagnosed acromegaly, most following head MRI for unrelated reasons and without the specific signs of acromegaly. Mean age at diagnosis was 48.8 ± 19.2 years. Baseline IGF-1 ranged between 1.3–2.0 × upper limit of normal (ULN). MRI depicted a pituitary microadenoma in 5 patients, and one patient presented with a 12 mm intra-sellar macroadenoma. Mean calculated SAGIT clinical score was 4.8. Three patients underwent trans-sphenoidal resection; two achieved hormonal remission and one improved but did not normalize IGF-1 following surgery. Four patients (including one following surgery) were given somatostatin analogs, and three normalized IGF-1. Several patients improved clinically following treatment, reporting improvement in snoring, hypertension, or weight loss, and pituitary adenoma decreased in size in 2 patients that responded to medical treatment. We report a series of 6 patients with very mild and subclinical acromegaly. It is uncertain whether all such patients will gain clinical benefit from treatment, but most experienced clinical improvement due to treatment.

  • Masatoshi Yamamoto, Naoyoshi Onoda, Akira Miyauchi, Makoto Fujishima, ...
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1329-1333
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: June 25, 2022
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    Hypoparathyroidism is a major complication of thyroid surgery. To avoid this complication, visual identification of the parathyroid glands is essential. However, its effectiveness depends heavily on the surgeon’s expertise. Here, we describe a novel method, the gauze blotting technique, to immunochemically identify the parathyroid glands during thyroid surgery. Twenty-three patients who underwent thyroid lobectomy were enrolled in this study; 16 and 7 had benign and malignant thyroid diseases, respectively. After visually identifying candidate nodules for the parathyroid gland, a piece of dry gauze (5 mm × 10 mm) was applied to each tissue until it was moistened by exudates from the tissue. Pieces of gauze were also applied to the thyroid gland and adipose tissue located away from the candidate nodules. The gauze was immersed in saline, and the intact PTH (i-PTH) level of the supernatant was measured. The median PTH level for the parathyroid glands was 1,060 pg/mL, which was significantly higher than that for the thyroid gland (34 pg/mL) and adipose tissue (28 pg/mL) (p < 0.001). The cut-off value to distinguish the parathyroid gland from other tissues was 68 pg/mL with a positive predictive value, negative predictive value, sensitivity, and specificity of 84.6%, 88.8%, 86.8%, and 86.7%, respectively. A value ≥250 pg/mL yielded a 100% positive predictive value. Our novel gauze blotting technique can identify the parathyroid glands without damaging tissues during thyroid surgery.

  • Kai Yoshimura, Masaaki Yamamoto, Tomoya Inoue, Hidenori Fukuoka, Keiji ...
    Article type: Original
    2022 Volume 69 Issue 11 Pages 1335-1342
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: July 14, 2022
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    Coronavirus disease 2019 (COVID-19) is associated with endocrine disorders, but their long-term clinical course remains unclear. We here report the 15-month clinical course for an individual with multiple endocrine disorders of the pituitary gland and testis likely triggered by COVID-19. A 65-year-old man with no history of endocrinopathy was admitted for acute COVID-19 pneumonia. Although his respiratory condition improved after administration of antiviral drugs, his blood pressure dropped suddenly to a preshock level and was refractory to vasopressors. The circulating adrenocorticotropic hormone (ACTH) and cortisol concentrations were low, and secondary adrenal insufficiency was suspected. Administration of hydrocortisone rapidly ameliorated the hypotension, and the patient was discharged taking 15 mg of hydrocortisone daily. An insulin tolerance test performed 3 months later revealed impaired ACTH, cortisol, and growth hormone (GH) responses, indicative of combined hypopituitarism. The patient also manifested symptoms of hypogonadism, and a hormonal workup suggested primary hypogonadism. At 12 months after discharge, GH and ACTH responses had recovered completely and partially, respectively. After another 3 months, basal ACTH and cortisol levels had been restored to the normal range and the patient discontinued hydrocortisone replacement without exacerbation of symptoms, although his hypogonadism persisted. The patient thus developed transient GH and ACTH deficiency that lasted for more than a year as well as persistent primary hypogonadism during intensive care for COVID-19. Certain prolonged symptoms of COVID-19 might be accounted for by such hormonal disturbance.

NOTE
  • Tomoyasu Fukui, Nobuaki Takehana, Yusaku Mori, Munenori Hiromura, Mich ...
    Article type: Note
    2022 Volume 69 Issue 11 Pages 1343-1349
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: June 24, 2022
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    To evaluate the clinical efficacy of a new enzyme-linked immunosorbent assay (ELISA) system for simultaneously detecting three islet cell autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) (3 Screen ICA ELISA) in Japanese patients with acute-onset type 1 diabetes (T1D). In addition, clinical factors affecting the 3 Screen ICA ELISA index were investigated. We compared the positivity values of 3 Screen ICA ELISA with that of each autoantibody alone in 97 patients with acute-onset T1D (mean age 48.7 years, 49% male) and 100 non-diabetic subjects (mean age 47.0 years, 50% male). Serum thyroid stimulating hormone receptor antibody, thyroid peroxidase antibody (TPOAb) and thyroglobulin autoantibody levels were also evaluated. The cut-off value of the 3 Screen ICA ELISA was determined based on the 97th percentile of 100 non-diabetic controls (threshold for positivity, ≥14 index). The mean age of disease onset and duration of diabetes were 34.2 years and 14.5 years, respectively. Among all T1D patients, the positivity of 3 Screen ICA ELISA was 71.1%, while that of GADA, IA-2A, and ZnT8A were 59.8%, 25.8%, and 25.8%, respectively. The median 3 Screen ICA index was 121.9 (8.7–468.2) and was associated with titers of each autoantibody, most so with GADA, and was significantly higher in TPOAb-positive patients than in TPOAb-negative patients. Our findings suggests that the 3 Screen ICA ELISA may be a time-saving diagnostic tool for evaluating islet autoantibodies in acute-onset T1D patients.

  • Yasuhiro Ito, Akira Miyauchi, Mitsuyoshi Hirokawa, Minoru Kihara, Naoy ...
    Article type: Note
    2022 Volume 69 Issue 11 Pages 1351-1356
    Published: 2022
    Released on J-STAGE: November 28, 2022
    Advance online publication: June 29, 2022
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    Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or adjacent to, the thyroid. We analyzed the backgrounds, clinicopathological features, and prognosis of 20 patients with ITTC, treated at our hospital. Thirteen of the 15 patients (86%) who underwent ultrasonography were diagnosed as malignant, based on imaging findings. 16 of the 17 patients (93%) who underwent cytology, were diagnosed or suspected to be malignant. Locally curative surgery (thyroidectomy and lymph node dissection) was performed for 19 patients. Large tumor size (>4 cm) was positively related to pathological node metastasis (p = 0.0389). Fourteen patients, including nine Ex-positive patients, underwent adjuvant external beam radiotherapy (EBRT) of the neck after surgery. Two patients showed recurrence of thyroid bed after and neither of them underwent adjuvant EBRT after surgery. Two patients who underwent EBRT showed recurrences of the lateral nodes (level V and level II), but they were easily dissected by re-operation. Ten- and 20-year local recurrence-free survival rates were 84.9% and 60.6%, respectively. To date, four patients showed distant recurrence, and 10- and 20-year distant recurrence-free survival rates were 75.0% and 75.0%, respectively. Our findings indicate that 1) the prognosis of ITTC is generally favorable, and 2) large tumor size is significantly related to lymph node metastasis. Two patients showing recurrence of the central region did not undergo EBRT; thus, further comparative studies are desirable to elucidate whether EBRT can prevent significant local recurrence.

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