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Congenital central hypothyroidism

MedGen UID:
927869
•Concept ID:
C4302200
•
Disease or Syndrome
Synonyms: Central congenital hypothyroidism; central congenital hypothyroidism; central hypothyroidism; hypothalamic-pituitary hypothyroidism; Secondary hypothyroidism; secondary hypothyroidism; thyroid stimulating hormone deficiency; thyrotropin deficiency; TSH deficiency
SNOMED CT: Congenital central hypothyroidism (722938007)
 
Monarch Initiative: MONDO:0016410
Orphanet: ORPHA226298

Definition

Central or secondary congenital hypothyroidism is a type of permanent congenital hypothyroidism (see this term) characterized by permanent thyroid hormone deficiency that is present from birth and secondary to a disorder in the thyroid-stimulating hormone (TSH) - thyrotropin-releasing hormone (TRH) system. [from ORDO]

Professional guidelines

PubMed

Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?
Boelen A, Zwaveling-Soonawala N, Heijboer AC, van Trotsenburg ASP
Eur Thyroid J 2023 Jul 27;12(4) doi: 10.1530/ETJ-23-0041. PMID: 37326450Free PMC Article
Diagnosis and Management of Central Congenital Hypothyroidism.
Lauffer P, Zwaveling-Soonawala N, Naafs JC, Boelen A, van Trotsenburg ASP
Front Endocrinol (Lausanne) 2021;12:686317. Epub 2021 Sep 9 doi: 10.3389/fendo.2021.686317. PMID: 34566885Free PMC Article
Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection.
Braslavsky D, Méndez MV, Prieto L, Keselman A, Enacan R, Gruñeiro-Papendieck L, Jullien N, Savenau A, Reynaud R, Brue T, Bergadá I, Chiesa A
Horm Res Paediatr 2017;88(3-4):274-280. Epub 2017 Sep 12 doi: 10.1159/000480293. PMID: 28898885

Recent clinical studies

Etiology

Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data.
Naafs JC, Vendrig LM, Limpens J, van der Lee HJ, Duijnhoven RG, Marchal JP, van Trotsenburg AS, Zwaveling-Soonawala N
Eur J Endocrinol 2020 Mar;182(3):351-361. doi: 10.1530/EJE-19-0874. PMID: 31961799
Mortality in Children With Early-Detected Congenital Central Hypothyroidism.
Zwaveling-Soonawala N, Naafs JC, Verkerk PH, van Trotsenburg ASP
J Clin Endocrinol Metab 2018 Aug 1;103(8):3078-3082. doi: 10.1210/jc.2018-00629. PMID: 29889220
TSH and FT4 Concentrations in Congenital Central Hypothyroidism and Mild Congenital Thyroidal Hypothyroidism.
Zwaveling-Soonawala N, van Trotsenburg ASP, Verkerk PH
J Clin Endocrinol Metab 2018 Apr 1;103(4):1342-1348. doi: 10.1210/jc.2017-01577. PMID: 29325028
The syndrome of central hypothyroidism and macroorchidism: IGSF1 controls TRHR and FSHB expression by differential modulation of pituitary TGFβ and Activin pathways.
García M, Barrio R, García-Lavandeira M, Garcia-Rendueles AR, Escudero A, Díaz-Rodríguez E, Gorbenko Del Blanco D, Fernández A, de Rijke YB, Vallespín E, Nevado J, Lapunzina P, Matre V, Hinkle PM, Hokken-Koelega AC, de Miguel MP, Cameselle-Teijeiro JM, Nistal M, Alvarez CV, Moreno JC
Sci Rep 2017 Mar 6;7:42937. doi: 10.1038/srep42937. PMID: 28262687Free PMC Article
Mutations in TBL1X Are Associated With Central Hypothyroidism.
Heinen CA, Losekoot M, Sun Y, Watson PJ, Fairall L, Joustra SD, Zwaveling-Soonawala N, Oostdijk W, van den Akker EL, Alders M, Santen GW, van Rijn RR, Dreschler WA, Surovtseva OV, Biermasz NR, Hennekam RC, Wit JM, Schwabe JW, Boelen A, Fliers E, van Trotsenburg AS
J Clin Endocrinol Metab 2016 Dec;101(12):4564-4573. Epub 2016 Sep 7 doi: 10.1210/jc.2016-2531. PMID: 27603907Free PMC Article

Diagnosis

Congenital Central Hypothyroidism Caused by a Novel IGSF1 Variant Identified in a French Family.
Fourneaux R, Castets S, Godefroy A, Grelet M, Abeillon-du Payrat J, Saveanu A, Castinetti F, Reynaud R
Horm Res Paediatr 2022;95(3):296-303. Epub 2022 Mar 29 doi: 10.1159/000524233. PMID: 35350016
Congenital isolated central hypothyroidism: Novel mutations and their functional implications.
Boelen A, van Trotsenburg ASP, Fliers E
Handb Clin Neurol 2021;180:161-169. doi: 10.1016/B978-0-12-820107-7.00010-0. PMID: 34225927
Mortality in Children With Early-Detected Congenital Central Hypothyroidism.
Zwaveling-Soonawala N, Naafs JC, Verkerk PH, van Trotsenburg ASP
J Clin Endocrinol Metab 2018 Aug 1;103(8):3078-3082. doi: 10.1210/jc.2018-00629. PMID: 29889220
TSH and FT4 Concentrations in Congenital Central Hypothyroidism and Mild Congenital Thyroidal Hypothyroidism.
Zwaveling-Soonawala N, van Trotsenburg ASP, Verkerk PH
J Clin Endocrinol Metab 2018 Apr 1;103(4):1342-1348. doi: 10.1210/jc.2017-01577. PMID: 29325028
Detecting Congenital Central Hypothyroidism by Newborn Screening: Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency.
Connelly KJ, Pierce MJ, Hanna C, LaFranchi SH
Horm Res Paediatr 2017;88(5):331-338. Epub 2017 Sep 14 doi: 10.1159/000479367. PMID: 28910808

Therapy

Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome.
Nikolaou M, Vasilakis IA, Marinakis NM, Tilemis FN, Zellos A, Lykopoulou E, Traeger-Synodinos J, Kanaka-Gantenbein C
Hormones (Athens) 2023 Sep;22(3):515-520. Epub 2023 Jul 26 doi: 10.1007/s42000-023-00468-0. PMID: 37493943
Mild Isolated Congenital Central Hypothyroidism Due to a Novel Homozygous Variant in TSHB: A Case Report.
Lauffer P, Bikker H, Boelen A, Jöbsis JJ, van Trotsenburg ASP, Zwaveling-Soonawala N
Thyroid 2022 Apr;32(4):472-474. doi: 10.1089/thy.2021.0651. PMID: 35102753
Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data.
Naafs JC, Vendrig LM, Limpens J, van der Lee HJ, Duijnhoven RG, Marchal JP, van Trotsenburg AS, Zwaveling-Soonawala N
Eur J Endocrinol 2020 Mar;182(3):351-361. doi: 10.1530/EJE-19-0874. PMID: 31961799
A Japanese Family with Central Hypothyroidism Caused by a Novel IGSF1 Mutation.
Nishigaki S, Hamazaki T, Fujita K, Morikawa S, Tajima T, Shintaku H
Thyroid 2016 Dec;26(12):1701-1705. Epub 2016 Nov 21 doi: 10.1089/thy.2016.0005. PMID: 27762734
Compound heterozygous and homozygous mutations of the TSHbeta gene as a cause of congenital central hypothyroidism in Europe.
Karges B, LeHeup B, Schoenle E, Castro-Correia C, Fontoura M, Pfäffle R, Andler W, Debatin KM, Karges W
Horm Res 2004;62(3):149-55. Epub 2004 Aug 4 doi: 10.1159/000080071. PMID: 15297803

Prognosis

Mortality in Children With Early-Detected Congenital Central Hypothyroidism.
Zwaveling-Soonawala N, Naafs JC, Verkerk PH, van Trotsenburg ASP
J Clin Endocrinol Metab 2018 Aug 1;103(8):3078-3082. doi: 10.1210/jc.2018-00629. PMID: 29889220
A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation.
Yamaguchi T, Hothubo T, Morikawa S, Nakamura A, Mori T, Tajima T
J Pediatr Endocrinol Metab 2018 Mar 28;31(3):355-359. doi: 10.1515/jpem-2017-0144. PMID: 29425110
The syndrome of central hypothyroidism and macroorchidism: IGSF1 controls TRHR and FSHB expression by differential modulation of pituitary TGFβ and Activin pathways.
García M, Barrio R, García-Lavandeira M, Garcia-Rendueles AR, Escudero A, Díaz-Rodríguez E, Gorbenko Del Blanco D, Fernández A, de Rijke YB, Vallespín E, Nevado J, Lapunzina P, Matre V, Hinkle PM, Hokken-Koelega AC, de Miguel MP, Cameselle-Teijeiro JM, Nistal M, Alvarez CV, Moreno JC
Sci Rep 2017 Mar 6;7:42937. doi: 10.1038/srep42937. PMID: 28262687Free PMC Article
A TSHβ Variant with Impaired Immunoreactivity but Intact Biological Activity and Its Clinical Implications.
Pappa T, Johannesen J, Scherberg N, Torrent M, Dumitrescu A, Refetoff S
Thyroid 2015 Aug;25(8):869-76. Epub 2015 Jun 15 doi: 10.1089/thy.2015.0096. PMID: 25950606Free PMC Article
Two novel mutations of the TSH-beta subunit gene underlying congenital central hypothyroidism undetectable in neonatal TSH screening.
Baquedano MS, Ciaccio M, Dujovne N, Herzovich V, Longueira Y, Warman DM, Rivarola MA, Belgorosky A
J Clin Endocrinol Metab 2010 Sep;95(9):E98-103. Epub 2010 Jun 9 doi: 10.1210/jc.2010-0223. PMID: 20534762

Clinical prediction guides

Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data.
Naafs JC, Vendrig LM, Limpens J, van der Lee HJ, Duijnhoven RG, Marchal JP, van Trotsenburg AS, Zwaveling-Soonawala N
Eur J Endocrinol 2020 Mar;182(3):351-361. doi: 10.1530/EJE-19-0874. PMID: 31961799
Mortality in Children With Early-Detected Congenital Central Hypothyroidism.
Zwaveling-Soonawala N, Naafs JC, Verkerk PH, van Trotsenburg ASP
J Clin Endocrinol Metab 2018 Aug 1;103(8):3078-3082. doi: 10.1210/jc.2018-00629. PMID: 29889220
Mutations in TBL1X Are Associated With Central Hypothyroidism.
Heinen CA, Losekoot M, Sun Y, Watson PJ, Fairall L, Joustra SD, Zwaveling-Soonawala N, Oostdijk W, van den Akker EL, Alders M, Santen GW, van Rijn RR, Dreschler WA, Surovtseva OV, Biermasz NR, Hennekam RC, Wit JM, Schwabe JW, Boelen A, Fliers E, van Trotsenburg AS
J Clin Endocrinol Metab 2016 Dec;101(12):4564-4573. Epub 2016 Sep 7 doi: 10.1210/jc.2016-2531. PMID: 27603907Free PMC Article
Three novel IGSF1 mutations in four Japanese patients with X-linked congenital central hypothyroidism.
Nakamura A, Bak B, Silander TL, Lam J, Hotsubo T, Yorifuji T, Ishizu K, Bernard DJ, Tajima T
J Clin Endocrinol Metab 2013 Oct;98(10):E1682-91. Epub 2013 Aug 21 doi: 10.1210/jc.2013-1224. PMID: 23966245
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement.
Sun Y, Bak B, Schoenmakers N, van Trotsenburg AS, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SN, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TM, Hokken-Koelega AC, Del Blanco DG, Rangasami JJ, Ruivenkamp CA, Laros JF, Kriek M, Kant SG, Bosch CA, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GC, Pereira AM, den Dunnen JT, Wade MG, Breuning MH, Hennekam RC, Chatterjee K, Dattani MT, Wit JM, Bernard DJ
Nat Genet 2012 Dec;44(12):1375-81. Epub 2012 Nov 11 doi: 10.1038/ng.2453. PMID: 23143598Free PMC Article

Recent systematic reviews

Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data.
Naafs JC, Vendrig LM, Limpens J, van der Lee HJ, Duijnhoven RG, Marchal JP, van Trotsenburg AS, Zwaveling-Soonawala N
Eur J Endocrinol 2020 Mar;182(3):351-361. doi: 10.1530/EJE-19-0874. PMID: 31961799

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