SUN-594 Skeletal Dysplasia and Growth Failure in Congenital Hypothyroidism Due to a Novel Form of Generalized Thyroid Hormone Resistance

Background: Thyroid hormone exerts systemic actions mediated by its specific receptors. These actions encompass a wide array of functions, including energy homeostasis, skeletal growth, neural development, cardiac function, and gastrointestinal function. There are two thyroid hormone receptors, thyr...

Full description

Saved in:
Bibliographic Details
Published inJournal of the Endocrine Society Vol. 3; no. Supplement_1
Main Authors Mitts, Matthew, Gongidi, Preetam, Hamilton, Luke, Steelman, Joel
Format Journal Article
LanguageEnglish
Published Washington, DC Endocrine Society 30.04.2019
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Background: Thyroid hormone exerts systemic actions mediated by its specific receptors. These actions encompass a wide array of functions, including energy homeostasis, skeletal growth, neural development, cardiac function, and gastrointestinal function. There are two thyroid hormone receptors, thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) which are encoded by genes on two different chromosomes and with differing tissue distributions. Only mutations in THRB were known until recently with a reported incidence of 1 in ~40,000. Mutations in thyroid receptor THRA have recently been discovered and are exceedingly rare, with 14 cases documented in the past five years. We report a case of a patient with generalized thyroid hormone resistance due to THRA mutation. Clinical Case: Patient was born to non-consanguineous parents at term and was appropriate for gestational age. Prenatal ultrasound was suspect for shortened long bones. Congenital heart disease (ASD and VSD) were detected at birth. Genetics consultation confirmed ultrasound concern with finding of mild rhizomelia. Patient had coarse facial features, macroglossia, and dysmorphic appearance. Initial genetics work-up showed normal chromosomes, normal newborn screening, and normal metabolic studies. Genetics was concerned for possible mucopolysaccharidosis, but further testing ordered did not confirm this diagnosis. Patient exhibited post-natal growth failure after birth with length well below 3 rd percentile by 18 months old. Delayed developmental milestones (verbal > motor) were noted. Thyroid function tests between birth and 11 months old were normal. Thyroid function testing at 11 months old were suspect for central hypothyroidism with free T4 0.6 ng/dl (0.6-1.3) and TSH 1.07 uIU/ml (0.71-5.81). Cranial MRI scan showed no abnormalities in hypothalamic-pituitary area. Levothyroxine 37.5 mcg was started, and thyroid function tests normalized. However, little change was seen clinically in patient’s growth pattern or development. Whole exome screening performed in 2013 demonstrated a heterozygous mutation in the THRA gene consistent with generalized thyroid hormone resistance from this mutation. Liothyronine treatment was added in 2014. Growth has continued to be extremely slow with current height standard deviation score of -4.2. Patient is developmentally delayed and non-verbal. Conclusions: A constellation of findings including post-natal growth failure, skeletal findings, and prominent verbal developmental delays are seen in generalized thyroid hormone resistance due to THRA mutation. The subtle presentation of this condition is different from congenital hypothyroidism or generalized thyroid hormone resistance due to THRB mutation. Presentation of this case will hopefully help pediatric specialist to recognize and test for this condition more promptly.
AbstractList Background: Thyroid hormone exerts systemic actions mediated by its specific receptors. These actions encompass a wide array of functions, including energy homeostasis, skeletal growth, neural development, cardiac function, and gastrointestinal function. There are two thyroid hormone receptors, thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) which are encoded by genes on two different chromosomes and with differing tissue distributions. Only mutations in THRB were known until recently with a reported incidence of 1 in ~40,000. Mutations in thyroid receptor THRA have recently been discovered and are exceedingly rare, with 14 cases documented in the past five years. We report a case of a patient with generalized thyroid hormone resistance due to THRA mutation. Clinical Case: Patient was born to non-consanguineous parents at term and was appropriate for gestational age. Prenatal ultrasound was suspect for shortened long bones. Congenital heart disease (ASD and VSD) were detected at birth. Genetics consultation confirmed ultrasound concern with finding of mild rhizomelia. Patient had coarse facial features, macroglossia, and dysmorphic appearance. Initial genetics work-up showed normal chromosomes, normal newborn screening, and normal metabolic studies. Genetics was concerned for possible mucopolysaccharidosis, but further testing ordered did not confirm this diagnosis. Patient exhibited post-natal growth failure after birth with length well below 3 rd percentile by 18 months old. Delayed developmental milestones (verbal > motor) were noted. Thyroid function tests between birth and 11 months old were normal. Thyroid function testing at 11 months old were suspect for central hypothyroidism with free T4 0.6 ng/dl (0.6-1.3) and TSH 1.07 uIU/ml (0.71-5.81). Cranial MRI scan showed no abnormalities in hypothalamic-pituitary area. Levothyroxine 37.5 mcg was started, and thyroid function tests normalized. However, little change was seen clinically in patient’s growth pattern or development. Whole exome screening performed in 2013 demonstrated a heterozygous mutation in the THRA gene consistent with generalized thyroid hormone resistance from this mutation. Liothyronine treatment was added in 2014. Growth has continued to be extremely slow with current height standard deviation score of -4.2. Patient is developmentally delayed and non-verbal. Conclusions: A constellation of findings including post-natal growth failure, skeletal findings, and prominent verbal developmental delays are seen in generalized thyroid hormone resistance due to THRA mutation. The subtle presentation of this condition is different from congenital hypothyroidism or generalized thyroid hormone resistance due to THRB mutation. Presentation of this case will hopefully help pediatric specialist to recognize and test for this condition more promptly.
Author Hamilton, Luke
Mitts, Matthew
Gongidi, Preetam
Steelman, Joel
AuthorAffiliation Cook Childrens Medical Center, Fort Worth, TX, United States
University of North Texas Health Science Center, Fort Worth, TX, United States
AuthorAffiliation_xml – name: Cook Childrens Medical Center, Fort Worth, TX, United States
– name: University of North Texas Health Science Center, Fort Worth, TX, United States
Author_xml – sequence: 1
  givenname: Matthew
  surname: Mitts
  fullname: Mitts, Matthew
  organization: University of North Texas Health Science Center, Fort Worth, TX, United States
– sequence: 2
  givenname: Preetam
  surname: Gongidi
  fullname: Gongidi, Preetam
  organization: Cook Childrens Medical Center, Fort Worth, TX, United States
– sequence: 3
  givenname: Luke
  surname: Hamilton
  fullname: Hamilton, Luke
  organization: Cook Childrens Medical Center, Fort Worth, TX, United States
– sequence: 4
  givenname: Joel
  surname: Steelman
  fullname: Steelman, Joel
  organization: Cook Childrens Medical Center, Fort Worth, TX, United States
BookMark eNpVUU1LAzEQDaKg1p69zh9Yu0l2N81FkGpboShYPYdsdmpTd5OSbCv1F_iz3dIiepqB98HMe5fk1HmHhFzT9IYymg5W8YalVCbzt6ckl9kJuWCZYAmVgp3-2c9JP8ZVmnZUnsksuyDfRwXMP7DGVtdwv4vrWkerQbsKJsF_tksYa1tvAoJ1MPLuHZ3dU6e7tW-Xu-BtZWMD9xuE1oOGJ7_FGsY-NOAXMEGHQdf2Cyt4PbBh2mHdB_CC0cZWO4NX5Gyh64j94-yRt_HD62iazJ4nj6O7WWIoL7Kk0AWWw4zSvBIp8oJKyYUZamNKXhpTCGZyIaShUpdFyapS0ByHVBrDSpZngvfI7cF3vSkbrAy6tjtOrYNtdNgpr636jzi7VO9-q4o851wWncHgYGCCjzHg4ldLU7UvQ62i2pehumhVFy3_AaM2giw
ContentType Journal Article
Copyright Copyright © 2019 Endocrine Society 2019
Copyright_xml – notice: Copyright © 2019 Endocrine Society 2019
DBID AAYXX
CITATION
5PM
DOI 10.1210/js.2019-SUN-594
DatabaseName CrossRef
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
DatabaseTitleList
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 2472-1972
ExternalDocumentID 10_1210_js_2019_SUN_594
GroupedDBID 0R~
53G
AAFWJ
AAPPN
AAPXW
AAVAP
AAYXX
ABEJV
ABPTD
ABXVV
ACGFS
ADBBV
AENZO
AFULF
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAYMD
BCNDV
BTTYL
CITATION
EBS
EJD
EMOBN
GROUPED_DOAJ
H13
HYE
IAO
KQ8
KSI
ML0
M~E
O9-
OK1
ROX
RPM
TJX
TOX
5PM
AFPKN
ID FETCH-LOGICAL-c1364-6a6eb84115d70e3619937c8accb3bcc672c5779c19ab6b2db715e819cc2b25473
IEDL.DBID RPM
ISSN 2472-1972
IngestDate Tue Sep 17 21:00:51 EDT 2024
Fri Dec 06 06:22:26 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue Supplement_1
Language English
License https://creativecommons.org/licenses/by-nc-nd/4.0
This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c1364-6a6eb84115d70e3619937c8accb3bcc672c5779c19ab6b2db715e819cc2b25473
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553396/
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_6553396
crossref_primary_10_1210_js_2019_SUN_594
PublicationCentury 2000
PublicationDate 20190430
PublicationDateYYYYMMDD 2019-04-30
PublicationDate_xml – month: 4
  year: 2019
  text: 20190430
  day: 30
PublicationDecade 2010
PublicationPlace Washington, DC
PublicationPlace_xml – name: Washington, DC
PublicationTitle Journal of the Endocrine Society
PublicationYear 2019
Publisher Endocrine Society
Publisher_xml – name: Endocrine Society
SSID ssj0001934944
Score 2.1174688
Snippet Background: Thyroid hormone exerts systemic actions mediated by its specific receptors. These actions encompass a wide array of functions, including energy...
SourceID pubmedcentral
crossref
SourceType Open Access Repository
Aggregation Database
SubjectTerms Thyroid
Title SUN-594 Skeletal Dysplasia and Growth Failure in Congenital Hypothyroidism Due to a Novel Form of Generalized Thyroid Hormone Resistance
URI https://pubmed.ncbi.nlm.nih.gov/PMC6553396
Volume 3
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV09T8MwELUoA2JBfIpv3cDAkpa0iR2PqKVUSC0IWqlbZDuuCLRJRAtS-QX8bO7cFLUrixc7seQ75d6L794xdiVVY6SpoYnRQnlEIDw5inwv0lQHGTlZM8q26PHOIHgYhsMNFi5rYVzSvtFpNRtPqln66nIri4mpLfPEak_dJg8RpEheq7AKht8Viu5-rEhSXAlKGR-qUHkjWW5fei-DnhfKYC0CrWdCroSW9i7bKTEh3C723mMbNttnW93y1vuA_ZSvhJd3DBKIlqE1nxau_hFUlsA9UunZK7RVSjnmkGbQzKlkivqBQGdekDE-8jRJpxNofVqY5aCgl3_ZMbQRskI-glJ9Ov22CfQXq6GDc3lm4dlOCWSidxyyQfuu3-x4ZQcFz_gNHnhccaujAFFfIm5sg1O2njCRMkY3tDFc1E0ohDS-VJrreqKFH1rECMbUdZ26Eh-xzQx3OmZgE8SGyNXwi6CR0o2kEtLyQJKNFY4n7Hp5qnGxEMqIiWCgAeK3aUwGiPG0YjytEybWTv1vPUldr8-gBzjJ69Lip_9-8oxtOx9w90DnbHP28WkvEE7M9KWj4ZfOiXDsPw5_Abxy0UM
link.rule.ids 230,314,727,780,784,864,885,27924,27925,53791,53793
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3JTsMwELVYJOCCWMXOHDhwCSVNYsdHVChhaYWglbhFtuOKAE0qWpDgC_hsZtwU0SuXXGzH0swofhO_ecPYkVRBT1NDE6OF8iiB8GQv9r1YUx1k7GTNiG3R5kk3vH6MHmdYNKmFcaR9o_OT4rV_UuRPjls56JvahCdWu2s1eIQgRfLaLJuPAiH9P0m6-7UiSXMlrIR8qEblmYS5fek9dNteJMOpM2iaC_nncGmusOUKFcLZePdVNmOLNbbQqu6919l39Up4eMFjAvEynH8OB64CElSRwSUm06MnaKqcWOaQF9AoqWiKOoJA8jkgd7yVeZYP-3D-bmFUgoJ2-WFfoYmgFcoeVPrT-ZfNoDOeDQmOlYWFezskmInxscG6zYtOI_GqHgqe8QMeelxxq-MQcV8mTm3Aia8nTKyM0YE2hou6iYSQxpdKc13PtPAjiyjBmLquU1_iTTZX4E5bDGyG6BCzNfwmaEzqelIJaXkoycsKn9vseGLVdDCWykgpxUAHpM_DlByQorVStNY2E1NW_51PYtfTIxgDTvS68vnOv1cessWk07pNb6_aN7tsycWDuxXaY3Ojt3e7j-BipA9cKP0AB7_Shw
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT-MwELZ4SBWX1T4F7IM5cOCSdtMkdnxE7WbL7hJVC5V6i2zHEQGaRKQgwS_gZ--MG1btlUsutpNoZhR_E3_zDWPHUgWFpoYmRgvlUQLhySL2vVhTHWTsZM2IbZHyySz8NY_ma62-HGnf6LJf3S76VXnluJXNwgxeeGKD6fmIRwhSJB80eTHYZrtRgEG2lqi73yuSdFfCTsyH6lSuSZzbl97FLPUiGW7sQ5t8yLUNJnnL3nTIEE5Xb_CObdnqPeudd2ffH9hzd0u4uMGtAjEzjB_bxlVBgqpy-IkJ9fIKElUS0xzKCkY1FU5RVxCYPDbkkru6zMt2AeN7C8saFKT1g72FBIEr1AV0GtTlk83hcjUbJjhWVxb-2pagJsbIRzZLflyOJl7XR8EzfsBDjytudRwi9svFdxtw4uwJEytjdKCN4WJoIiGk8aXSXA9zLfzIIlIwZqiH1Jv4E9up8En7DGyOCBEzNvwuaEzsCqmEtDyU5GmF1wN28mLVrFnJZWSUZqADsus2IwdkaK0MrXXAxIbV_88nwevNEYwDJ3zd-f3w1SuPWG86TrI_Z-nvz2zPhYM7GPrCdpZ39_Yr4oul_uYi6R8IhdOa
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SUN-594+Skeletal+Dysplasia+and+Growth+Failure+in+Congenital+Hypothyroidism+Due+to+a+Novel+Form+of+Generalized+Thyroid+Hormone+Resistance&rft.jtitle=Journal+of+the+Endocrine+Society&rft.au=Mitts%2C+Matthew&rft.au=Gongidi%2C+Preetam&rft.au=Hamilton%2C+Luke&rft.au=Steelman%2C+Joel&rft.date=2019-04-30&rft.pub=Endocrine+Society&rft.eissn=2472-1972&rft.volume=3&rft.issue=Suppl+1&rft_id=info:doi/10.1210%2Fjs.2019-SUN-594&rft.externalDBID=PMC6553396
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2472-1972&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2472-1972&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2472-1972&client=summon