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Thyroid hormone metabolism, abnormal, 3(THMA3)

MedGen UID:
1824065
•Concept ID:
C5774292
•
Disease or Syndrome
Synonym: THMA3
 
Gene (location): TRU-TCA1-1 (19q13.32)
 
Monarch Initiative: MONDO:0859354
OMIM®: 620198

Definition

Abnormal thyroid hormone metabolism-3 (THMA3) is characterized by euthyroid hyperthyroxinemia, with elevated free T4 and reverse T3 levels, and normal TSH (see 188540) and free T3 levels. Patients also show low plasma selenium levels and reduced levels of stress-related selenoproteins (Schoenmakers et al., 2016; Geslot et al., 2021). For a discussion of genetic heterogeneity of abnormal thyroid hormone metabolism, see THMA1 (609698). [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
•Concept ID:
C0000737
•
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
See: Feature record | Search on this feature
Easy fatigability
MedGen UID:
373253
•Concept ID:
C1837098
•
Finding
Increased susceptibility to fatigue.
See: Feature record | Search on this feature
Muscle weakness
MedGen UID:
57735
•Concept ID:
C0151786
•
Finding
Reduced strength of muscles.
See: Feature record | Search on this feature
Decreased circulating selenium concentration
MedGen UID:
1756605
•Concept ID:
C5421674
•
Finding
An abnormally reduced concentration of selenium in the blood circulation.
See: Feature record | Search on this feature
Euthyroid hyperthyroxinemia
MedGen UID:
867191
•Concept ID:
C4021549
•
Disease or Syndrome
Increased levels of thyroxine without evidence of clinical thyroid disease.
See: Feature record | Search on this feature
Increased circulating free T3
MedGen UID:
867466
•Concept ID:
C4021843
•
Finding
An elevated concentration of free 3,3',5-triiodo-L-thyronine in the blood circulation.
See: Feature record | Search on this feature
Abnormal thyroid-stimulating hormone level
MedGen UID:
1384219
•Concept ID:
C4476968
•
Finding
Any deviation from the normal amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.
See: Feature record | Search on this feature
Abnormal circulating free T3 concentration
MedGen UID:
1689152
•Concept ID:
C5139194
•
Finding
A deviation from the normal concentration of free triiodothyronine (T3) in the blood circulation. A proportion of T3 is bound to plasma proteins in the blood, including mainly thyroxine binding globulin, transthyretin, and albumin. T3 that is not bound to a protein is referred to as free T3.
See: Feature record | Search on this feature
Abnormal circulating free T4 concentration
MedGen UID:
1732628
•Concept ID:
C5421590
•
Finding
A deviation from the normal concentration of free thyroxine (T4) in the blood circulation. Circulating T4 is almost entirely bound to specific transport proteins such as thyroxine-binding globulin (TBG) but it is the unbound (free) fraction that is able to enter tissues and exert effects.
See: Feature record | Search on this feature
Increased circulating free T4 concentration
MedGen UID:
1771990
•Concept ID:
C5421591
•
Finding
An elevated concentration of free thyroxine (fT4) in the blood circulation.
See: Feature record | Search on this feature
Elevated circulating reverse T3 concentration
MedGen UID:
1815050
•Concept ID:
C5706144
•
Finding
Abnormally increased concentration of reverse T3 (3,3',5'-triiodothyronine or rT3) in the blood circulation.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.
Soh SB, Aw TC
Ann Lab Med 2019 Jan;39(1):3-14. doi: 10.3343/alm.2019.39.1.3. PMID: 30215224Free PMC Article
Update of newborn screening and therapy for congenital hypothyroidism.
American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK
Pediatrics 2006 Jun;117(6):2290-303. doi: 10.1542/peds.2006-0915. PMID: 16740880
Congenital hypothyroidism and transient thyrotropin excess: differential diagnosis of abnormal newborn thyroid screening.
Wilson BE, Netzloff ML
Ann Clin Lab Sci 1982 May-Jun;12(3):223-33. PMID: 6178352

Recent clinical studies

Etiology

Endocrinological Treatment Targets for Depressive Disorder.
Yoon S, Kim YK
Adv Exp Med Biol 2024;1456:3-25. doi: 10.1007/978-981-97-4402-2_1. PMID: 39261421
Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.
Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth, Korevaar TIM, Derakhshan A, Taylor PN, Meima M, Chen L, Bliddal S, Carty DM, Meems M, Vaidya B, Shields B, Ghafoor F, Popova PV, Mosso L, Oken E, Suvanto E, Hisada A, Yoshinaga J, Brown SJ, Bassols J, Auvinen J, Bramer WM, López-Bermejo A, Dayan C, Boucai L, Vafeiadi M, Grineva EN, Tkachuck AS, Pop VJM, Vrijkotte TG, Guxens M, Chatzi L, Sunyer J, Jiménez-Zabala A, Riaño I, Murcia M, Lu X, Mukhtar S, Delles C, Feldt-Rasmussen U, Nelson SM, Alexander EK, Chaker L, Männistö T, Walsh JP, Pearce EN, Steegers EAP, Peeters RP
JAMA 2019 Aug 20;322(7):632-641. doi: 10.1001/jama.2019.10931. PMID: 31429897Free PMC Article
Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis.
Zerenturk EJ, Sharpe LJ, Ikonen E, Brown AJ
Prog Lipid Res 2013 Oct;52(4):666-80. Epub 2013 Oct 2 doi: 10.1016/j.plipres.2013.09.002. PMID: 24095826
The clinical significance of subclinical thyroid dysfunction.
Biondi B, Cooper DS
Endocr Rev 2008 Feb;29(1):76-131. Epub 2007 Nov 8 doi: 10.1210/er.2006-0043. PMID: 17991805
Coregulator-related diseases.
Yanase T, Adachi M, Goto K, Takayanagi R, Nawata H
Intern Med 2004 May;43(5):368-73. doi: 10.2169/internalmedicine.43.368. PMID: 15206547

Diagnosis

Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.
Soh SB, Aw TC
Ann Lab Med 2019 Jan;39(1):3-14. doi: 10.3343/alm.2019.39.1.3. PMID: 30215224Free PMC Article
Thyroid storm: an updated review.
Chiha M, Samarasinghe S, Kabaker AS
J Intensive Care Med 2015 Mar;30(3):131-40. Epub 2013 Aug 5 doi: 10.1177/0885066613498053. PMID: 23920160
Molecular aspects of thyroid hormone actions.
Cheng SY, Leonard JL, Davis PJ
Endocr Rev 2010 Apr;31(2):139-70. Epub 2010 Jan 5 doi: 10.1210/er.2009-0007. PMID: 20051527Free PMC Article
The clinical significance of subclinical thyroid dysfunction.
Biondi B, Cooper DS
Endocr Rev 2008 Feb;29(1):76-131. Epub 2007 Nov 8 doi: 10.1210/er.2006-0043. PMID: 17991805
Coregulator-related diseases.
Yanase T, Adachi M, Goto K, Takayanagi R, Nawata H
Intern Med 2004 May;43(5):368-73. doi: 10.2169/internalmedicine.43.368. PMID: 15206547

Therapy

Endocrinological Treatment Targets for Depressive Disorder.
Yoon S, Kim YK
Adv Exp Med Biol 2024;1456:3-25. doi: 10.1007/978-981-97-4402-2_1. PMID: 39261421
Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.
Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I
N Engl J Med 2022 Mar 10;386(10):923-932. doi: 10.1056/NEJMoa2111953. PMID: 35263518
Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults.
Caron P, Grunenwald S, Persani L, Borson-Chazot F, Leroy R, Duntas L
Rev Endocr Metab Disord 2022 Jun;23(3):463-483. Epub 2021 Oct 20 doi: 10.1007/s11154-021-09691-9. PMID: 34671932Free PMC Article
Role of iodine, selenium and other micronutrients in thyroid function and disorders.
Triggiani V, Tafaro E, Giagulli VA, Sabbà C, Resta F, Licchelli B, Guastamacchia E
Endocr Metab Immune Disord Drug Targets 2009 Sep;9(3):277-94. Epub 2009 Sep 1 doi: 10.2174/187153009789044392. PMID: 19594417
Euthyroid hyperthyroxinemia.
Borst GC, Eil C, Burman KD
Ann Intern Med 1983 Mar;98(3):366-78. doi: 10.7326/0003-4819-98-3-366. PMID: 6187257

Prognosis

Cardiac Amyloidosis Due to Transthyretin Protein: A Review.
Ruberg FL, Maurer MS
JAMA 2024 Mar 5;331(9):778-791. doi: 10.1001/jama.2024.0442. PMID: 38441582Free PMC Article
Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.
Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I
N Engl J Med 2022 Mar 10;386(10):923-932. doi: 10.1056/NEJMoa2111953. PMID: 35263518
Fetal and Neonatal Thyroid Dysfunction.
Léger J, Delcour C, Carel JC
J Clin Endocrinol Metab 2022 Feb 17;107(3):836-846. doi: 10.1210/clinem/dgab747. PMID: 34636892
Congenital hypothyroidism.
Rastogi MV, LaFranchi SH
Orphanet J Rare Dis 2010 Jun 10;5:17. doi: 10.1186/1750-1172-5-17. PMID: 20537182Free PMC Article
The clinical significance of subclinical thyroid dysfunction.
Biondi B, Cooper DS
Endocr Rev 2008 Feb;29(1):76-131. Epub 2007 Nov 8 doi: 10.1210/er.2006-0043. PMID: 17991805

Clinical prediction guides

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.
Toloza FJK, Derakhshan A, Männistö T, Bliddal S, Popova PV, Carty DM, Chen L, Taylor P, Mosso L, Oken E, Suvanto E, Itoh S, Kishi R, Bassols J, Auvinen J, López-Bermejo A, Brown SJ, Boucai L, Hisada A, Yoshinaga J, Shilova E, Grineva EN, Vrijkotte TGM, Sunyer J, Jiménez-Zabala A, Riaño-Galan I, Lopez-Espinosa MJ, Prokop LJ, Singh Ospina N, Brito JP, Rodriguez-Gutierrez R, Alexander EK, Chaker L, Pearce EN, Peeters RP, Feldt-Rasmussen U, Guxens M, Chatzi L, Delles C, Roeters van Lennep JE, Pop VJM, Lu X, Walsh JP, Nelson SM, Korevaar TIM, Maraka S
Lancet Diabetes Endocrinol 2022 Apr;10(4):243-252. Epub 2022 Mar 4 doi: 10.1016/S2213-8587(22)00007-9. PMID: 35255260Free PMC Article
Thyroid storm: an updated review.
Chiha M, Samarasinghe S, Kabaker AS
J Intensive Care Med 2015 Mar;30(3):131-40. Epub 2013 Aug 5 doi: 10.1177/0885066613498053. PMID: 23920160
Coregulator-related diseases.
Yanase T, Adachi M, Goto K, Takayanagi R, Nawata H
Intern Med 2004 May;43(5):368-73. doi: 10.2169/internalmedicine.43.368. PMID: 15206547
Glycolytic overload and the genesis of breast cancer.
Robson JR
Med Hypotheses 1984 Mar;13(3):233-52. doi: 10.1016/0306-9877(84)90160-9. PMID: 6371457
X-chromosome linked inheritance of decreased thyroxine-binding globulin.
Malvaux P, De Nayer P
Arch Dis Child 1972 Aug;47(254):635-8. doi: 10.1136/adc.47.254.635. PMID: 4625785Free PMC Article

Recent systematic reviews

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.
Toloza FJK, Derakhshan A, Männistö T, Bliddal S, Popova PV, Carty DM, Chen L, Taylor P, Mosso L, Oken E, Suvanto E, Itoh S, Kishi R, Bassols J, Auvinen J, López-Bermejo A, Brown SJ, Boucai L, Hisada A, Yoshinaga J, Shilova E, Grineva EN, Vrijkotte TGM, Sunyer J, Jiménez-Zabala A, Riaño-Galan I, Lopez-Espinosa MJ, Prokop LJ, Singh Ospina N, Brito JP, Rodriguez-Gutierrez R, Alexander EK, Chaker L, Pearce EN, Peeters RP, Feldt-Rasmussen U, Guxens M, Chatzi L, Delles C, Roeters van Lennep JE, Pop VJM, Lu X, Walsh JP, Nelson SM, Korevaar TIM, Maraka S
Lancet Diabetes Endocrinol 2022 Apr;10(4):243-252. Epub 2022 Mar 4 doi: 10.1016/S2213-8587(22)00007-9. PMID: 35255260Free PMC Article
Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.
Srinivasan V, Lee JH, Menon K, Zimmerman JJ, Bembea MM, Agus MSD; Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Collaborative
Pediatrics 2022 Jan 1;149(1 Suppl 1):S84-S90. doi: 10.1542/peds.2021-052888M. PMID: 34970672
Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis.
Derakhshan A, Peeters RP, Taylor PN, Bliddal S, Carty DM, Meems M, Vaidya B, Chen L, Knight BA, Ghafoor F, Popova PV, Mosso L, Oken E, Suvanto E, Hisada A, Yoshinaga J, Brown SJ, Bassols J, Auvinen J, Bramer WM, López-Bermejo A, Dayan CM, French R, Boucai L, Vafeiadi M, Grineva EN, Pop VJM, Vrijkotte TG, Chatzi L, Sunyer J, Jiménez-Zabala A, Riaño I, Rebagliato M, Lu X, Pirzada A, Männistö T, Delles C, Feldt-Rasmussen U, Alexander EK, Nelson SM, Chaker L, Pearce EN, Guxens M, Steegers EAP, Walsh JP, Korevaar TIM
Lancet Diabetes Endocrinol 2020 Jun;8(6):501-510. doi: 10.1016/S2213-8587(20)30061-9. PMID: 32445737Free PMC Article
Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.
Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth, Korevaar TIM, Derakhshan A, Taylor PN, Meima M, Chen L, Bliddal S, Carty DM, Meems M, Vaidya B, Shields B, Ghafoor F, Popova PV, Mosso L, Oken E, Suvanto E, Hisada A, Yoshinaga J, Brown SJ, Bassols J, Auvinen J, Bramer WM, López-Bermejo A, Dayan C, Boucai L, Vafeiadi M, Grineva EN, Tkachuck AS, Pop VJM, Vrijkotte TG, Guxens M, Chatzi L, Sunyer J, Jiménez-Zabala A, Riaño I, Murcia M, Lu X, Mukhtar S, Delles C, Feldt-Rasmussen U, Nelson SM, Alexander EK, Chaker L, Männistö T, Walsh JP, Pearce EN, Steegers EAP, Peeters RP
JAMA 2019 Aug 20;322(7):632-641. doi: 10.1001/jama.2019.10931. PMID: 31429897Free PMC Article
Thyroid function during ovarian stimulation: a systematic review.
Mintziori G, Goulis DG, Toulis KA, Venetis CA, Kolibianakis EM, Tarlatzis BC
Fertil Steril 2011 Sep;96(3):780-5. Epub 2011 Jul 13 doi: 10.1016/j.fertnstert.2011.06.020. PMID: 21742326

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