Publications by authors named "Michiyo Mizota"

10 Publications

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Subacute thyroiditis presenting with creeping in a 6-year-old boy.

Clin Pediatr Endocrinol 2021 5;30(1):75-78. Epub 2021 Jan 5.

Department of Pediatrics, Tanegashima Medical Center, Nishinoomote-city, Japan.

Among the types of acute thyroiditis, subacute thyroiditis (SAT) is rare in children, and there is limited knowledge regarding its characteristics in pediatric cases. We present a case of SAT in a 6-yr-old boy who was brought to our hospital with high fever and pain in the front portion of the neck. Acute suppurative thyroiditis (AST), which is common in children, was suspected initially. Tenderness observed in the thyroid corresponded to a hypoechoic region on ultrasonography. The tenderness subsequently shifted to the isthmus, which was evident as a hypoechoic region on ultrasonography. Movement of hypoechoicity is typical of creeping thyroiditis, wherein the pain and tenderness can be unilateral or may start on one side and subsequently shift to the contralateral side after days or even weeks. Based on this characteristic and changes in laboratory parameters, the patient was diagnosed as a case of creeping thyroiditis. Improvement was observed in the patient without the use of anti-inflammatory drugs. At the 2-yr follow-up, the patient did not have thyrotoxicosis or relapse. Although AST is more prevalent than SAT in children, ultrasonography findings of creeping thyroiditis may be an important indicator for the diagnosis of SAT in pediatric patients.
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http://dx.doi.org/10.1297/cpe.30.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783128PMC
January 2021

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

J Clin Endocrinol Metab 2020 05;105(5)

Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.

Context: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed.

Objective: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures.

Methods: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients.

Results: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient.

Conclusions: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
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http://dx.doi.org/10.1210/clinem/dgaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108682PMC
May 2020

Risk Factors and the Prevention of Weight Gain During Induction Chemotherapy in Children With Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2018 08;40(6):e334-e337

Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Weight gain is often observed in children with acute lymphoblastic leukemia (ALL) who undergo chemotherapy including steroids. An increase in body mass index (BMI)-standard deviation score (SDS) during induction therapy is reported as a risk factor for obesity after treatment. However, risk factors of an increase in BMI-SDS during induction therapy are not known. Ninety-six patients with ALL who were treated at our hospital between 1996 January and September 2013 were analyzed retrospectively. Daily body weight measurement was initiated in July 2005 in an attempt to control weight. Fifty-four patients were boys and 42 were girls. The median age at onset was 5.1 years (0.5-16.6 y), and 7.3% of patients were overweight/obese at onset. BMI-SDS increased +0.1% (-3.3% to +3.2%) during induction therapy. BMI-SDS increased by 1 and 2 or more SDs in 20% and 3% of patients, respectively. In multivariate analysis, non-high-risk treatment and earlier treatment start date (before daily body weight measurement) were independent risk factors. Ten percent of patients were overweight/obese at 3 years after completion therapy, and high BMI-SDS after induction therapy was a risk factor. Daily body weight measurement might prevent excess weight gain during induction therapy, resulting in patients maintaining a healthy weight after ALL treatment.
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http://dx.doi.org/10.1097/MPH.0000000000001098DOI Listing
August 2018

Proximal promoter of the cytochrome P450 oxidoreductase gene: identification of microdeletions involving the untranslated exon 1 and critical function of the SP1 binding sites.

J Clin Endocrinol Metab 2011 Nov 7;96(11):E1881-7. Epub 2011 Sep 7.

National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo 157-8535, Japan.

Context: POR (cytochrome P450 oxidoreductase) is a ubiquitously expressed gene encoding an electron donor to all microsomal P450 enzymes and several non-P450 enzymes. POR mutations cause an autosomal recessive disorder characterized by skeletal dysplasia, adrenal dysfunction, and disorders of sex development. Although recent studies have indicated the presence of a CpG-rich region characteristic of housekeeping genes around the untranslated exon 1 (exon 1U) and a tropic effect of thyroid hormone on POR expression via thyroid hormone receptor-β, detailed regulatory mechanisms for the POR expression remain to be clarified.

Objective: Our objective was to report a pivotal element of the proximal promoter of POR.

Results: We first studied three patients (cases 1-3) with POR deficiency due to compound heterozygosity with an p.R457H mutation and transcription failure of an apparently normal allele, by oligoarray comparative genomic hybridization and serial direct sequencing of the deletion fusion points. Consequently, a 2,487-bp microdeletion involving exon 1U was identified in case 1 and an identical 49,604-bp deletion involving exon 1U and exon 1 was found in cases 2 and 3. We next analyzed the 2,487-bp region commonly deleted in cases 1-3 by in silico analysis, DNA binding analysis, luciferase assays, and methylation analysis. The results showed a critical function of the evolutionally conserved SP1 binding sites just upstream of exon 1U, especially the binding site at the position -26/-17, in the transcription of POR.

Conclusions: The results suggest that the SP1 binding sites constitute an essential element of the POR proximal promoter.
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http://dx.doi.org/10.1210/jc.2011-1337DOI Listing
November 2011

Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion.

J Clin Endocrinol Metab 2010 Aug 9;95(8):4043-7. Epub 2010 Jun 9.

Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, Japan.

Context: Mutations of multiple transcription factor genes involved in pituitary development have been identified in a minor portion of patients with combined pituitary hormone deficiency (CPHD). However, copy number aberrations involving such genes have been poorly investigated in patients with CPHD.

Objective: We aimed to report the results of mutation and gene copy number analyses in patients with CPHD.

Subjects And Methods: Seventy-one Japanese patients with CPHD were examined for mutations and gene copy number aberrations affecting POU1F1, PROP1, HESX1, LHX3, LHX4, and SOX3 by PCR-direct sequencing and multiplex ligation-dependent probe amplification. When a deletion was indicated, it was further studied by fluorescence in situ hybridization, oligoarray comparative genomic hybridization, and serial sequencing for long PCR products encompassing the deletion junction.

Results: We identified a de novo heterozygous 522,009-bp deletion involving LHX4 in a patient with CPHD (GH, TSH, PRL, LH, and FSH deficiencies), anterior pituitary hypoplasia, ectopic posterior pituitary, and underdeveloped sella turcica. We also identified five novel heterozygous missense substitutions (p.V201I and p.H387P in LHX4, p.T63M and p.A322T in LHX3, and p.V53L in SOX3) that were assessed as rare variants by sequencing analyses for control subjects and available parents and by functional studies and in silico analyses.

Conclusions: The results imply the rarity of abnormalities affecting the six genes in patients with CPHD and the significance of the gene copy number analysis in such patients.
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http://dx.doi.org/10.1210/jc.2010-0150DOI Listing
August 2010

Kawasaki syndrome and 21-hydroxylase deficiency.

Pediatr Int 2008 Feb;50(1):119-20

Division of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

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http://dx.doi.org/10.1111/j.1442-200X.2007.02520.xDOI Listing
February 2008

A case with hyperthyroidism who had been treated with thyroid hormone because of congenital hypothyroidism.

Clin Pediatr Endocrinol 2005 12;14(2):59-64. Epub 2005 Aug 12.

Department of Pediatrics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.

We encountered a case with hyperthyroidism at the age of 14 who had been diagnosed with congenital hypothyroidism (CH) and had received thyroid hormone replacement therapy. At the age of 16 d, the patient was referred to our hospital because of positive results at neonatal screening for CH. Serum level of TSH was 91.0 μU/ml and serum level of T4 was 6.9 μg/dl. The patient was diagnosed as having hypothyroidism, and hormone replacement therapy was started. Thereafter the dosage of thyroid hormone was adjusted and increased gradually as he grew to a maximum dose of 110 μg/day at the age of 11. Until the age of 13, the patient's serum levels of TSH were within the normal range; then, at the age of 13 yr and 4 mo, his serum level of TSH dropped to a level below the detectable range. The dosage of administered thyroid hormone was tapered off and eventually eliminated at the age of 14. A thyroid scan and a radioactive iodine uptake test demonstrated a diffuse goiter with homogeneous uptake of radioactive iodine; the uptake rate was 60% at 24 h, and the serum level of TSH receptor antibody (TRAb) was 62.5% at that time. Administration of an antithyroid drug was started after confirmation that our patient had developed hyperthyroidism. There have been no case reports similar to our case.
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http://dx.doi.org/10.1297/cpe.14.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004835PMC
May 2014

Retrospective analysis of infants designated as positive on mass-screening for congenital hypothyroidism at kagoshima university.

Clin Pediatr Endocrinol 2005 12;14(2):49-57. Epub 2005 Aug 12.

Department of Pediatrics, Kagoshima University, Kagoshima, Japan.

Mass-screening for congenital hypothyroidism has identified cases of mild hypothyroidism, transient hypothyroidism, and transient hyperthyrotropinemia as well as typical hypothyroidism. In this paper, we examine the clinical data of the cases found positive in the screening test at our hospital. From 1989 to 1999 there were 72 patients with positive screening tests who started levothyroxine sodium (l-T4; Thyradin-S) as supplement therapy. At the age of 3 to 4 yr the patients were re-evaluated to determine whether treatment should be continued. Thyroid scintigraphies were done at the same time. We divided these cases into 4 groups. Those in group 1A started l-T4 in early infancy without a TRH test because of obvious clinical evidence of hypothyroidism, and treatment was continued after re-evaluation (n=37). Those in group 1B also started treatment in early infancy without a TRH test, but treatment was discontinued after re-evaluation (n=20). Patients in group 2A started l-T4 after evaluation by a TRH test and treatment was continued after re-evaluation (n=14), while those in group 2B started treatment after a TRH test, but after re-evaluation, treatment was discontinued (n=1). In group 2A, only a low dose of l-T4 was needed, and a slightly elevated TSH and slightly decreased free T4 (FT4) were observed after the drug washout period. However, these patients had an exaggerated response to the TRH test at re-evaluation. These findings indicate that this group, forming not a small part of whole screening-positive subjects, had mild hypothyroidism. Such patients require careful follow-up and repeated evaluation to determine whether treatment should be continued.
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http://dx.doi.org/10.1297/cpe.14.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004834PMC
May 2014

Bilateral asynchronous adrenocortical adenoma in a girl with beckwith-wiedemann syndrome.

Clin Pediatr Endocrinol 2005 14;14(1):23-6. Epub 2005 Feb 14.

Departments of Pathology, Tohoku University School of Medicine, Sendai, Japan.

We report a case of asynchronous occurrence of bilateral adrenocortical adenoma in a 13-yr-old girl with Beckwith-Wiedemann syndrome. A right virilizing adrenal adenoma was surgically removed at age 6, following clinical manifestation of virilization such as acne, voice change, clitoris hypertrophy and overgrowth. Histopathological examination of the resected specimen revealed an adrenocortical adenoma predominantly composed of eosinophilic tumor cells expressing all the steroidogenic enzymes. High serum levels of DHEA-S (6,380 ng/ml) and testosterone (547 ng/dl) were noted prior to the operation. Postoperative course was unremarkable. Menstruation started at age 11, with a regular interval. At the age of 13 yr old, a high serum level of DHEA-S (8,250 ng/ml) was detected. In contrast to the episode of virilization at age 6, however, the serum testosterone level was not so high (122 ng/dl), and no clinical symptoms of virilization were apparent. Abdominal ultrasonography demonstrated the presence of a left adrenocortical adenoma. Pathological examination of the resected specimen revealed a circumscribed and well encapsulated tumor with essentially the same histological features as the tumor previously removed, except that the tumor cells showed a more prominent morphological similarity to the fetal adrenal cortex and did not express 3β HSD. The absence of virilization at the second episode was due to the relatively low serum level of testosterone compared with that of DHEA-S.
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http://dx.doi.org/10.1297/cpe.14.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004928PMC
May 2014