MCID: CNT101
MIFTS: 36

Central Congenital Hypothyroidism

Categories: Endocrine diseases, Immune diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Central Congenital Hypothyroidism

MalaCards integrated aliases for Central Congenital Hypothyroidism:

Name: Central Congenital Hypothyroidism 20 58
Secondary Hypothyroidism 20 58 29 6 71

Classifications:

Orphanet: 58  
Rare endocrine diseases


Summaries for Central Congenital Hypothyroidism

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 226298DefinitionCentral 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.EpidemiologyPrevalence is unknown.Clinical descriptionThe clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment central hypothyroidism results in intellectual deficit and short stature.EtiologyCentral hypothyroidism usually results from defects of TSH production and is often part of a disorder causing congenital hypopituitarism (see this term), in which case the clinical signs may also include septo-optic dysplasia or cleft lip and/or palate as well as other signs of hypopituitarism, or part of a larger genetic syndrome such as pituitary stalk interruption syndrome (see this term). Mutations in genes regulating pituitary gland development including HESX1, LHX3, LHX4, POU1F1 and PROP1 (3p21.2-p21.1, 9q34.3, 1q25, 3p11 and 5q) may also cause central hypothyroidism. Central hypothyroidism may also result from isolated TSH deficiency (see this term), which is transmitted in an autosomal recessive manner and is caused by mutations in the TSHB subunit gene (1p13), or from TRH resistance (see this term) caused by mutations in the TRH receptor gene (TRHR; 8q23).Visit the Orphanet disease page for more resources.

MalaCards based summary : Central Congenital Hypothyroidism, also known as secondary hypothyroidism, is related to hypothyroidism, central, with testicular enlargement and congenital hypothyroidism. An important gene associated with Central Congenital Hypothyroidism is TSHB (Thyroid Stimulating Hormone Subunit Beta). Affiliated tissues include thyroid, pituitary and hypothalamus, and related phenotypes are sleep disturbance and constipation

Related Diseases for Central Congenital Hypothyroidism

Diseases in the Hypothyroidism family:

Congenital Hypothyroidism Central Congenital Hypothyroidism
Hypothyroidism Due to Iodide Transport Defect Rare Adult Hypothyroidism
Transient Congenital Hypothyroidism Rare Hypothyroidism
Primary Congenital Hypothyroidism Hypothyroidism Due to Deficient Transcription Factors Involved in Pituitary Development or Function
Congenital Hypothyroidism Due to Maternal Intake of Antithyroid Drugs Transient Congenital Hypothyroidism Due to Maternal Factor
Transient Congenital Hypothyroidism Due to Neonatal Factor Congenital Hypothyroidism Due to Transplacental Passage of Tsh-Binding Inhibitory Antibodies
Congenital Hypothyroidism Due to Developmental Anomaly

Diseases related to Central Congenital Hypothyroidism via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 52)
# Related Disease Score Top Affiliating Genes
1 hypothyroidism, central, with testicular enlargement 31.4 TSHB TRHR
2 congenital hypothyroidism 30.2 TSHB TRHR
3 hypothyroidism 30.1 TSHB TRHR
4 graves' disease 10.2
5 hypothyroidism, congenital, nongoitrous, 4 10.0
6 hypoglycemia 10.0
7 primary congenital hypothyroidism 10.0
8 hemochromatosis, type 1 9.9
9 goiter 9.9
10 hypogonadism 9.9
11 type 1 diabetes mellitus 9.9
12 graves disease 1 9.9
13 alacrima, achalasia, and mental retardation syndrome 9.9
14 helix syndrome 9.9
15 hypothyroidism, congenital, nongoitrous, 7 9.9
16 neonatal jaundice 9.9
17 pituitary gland disease 9.9
18 hyperthyroidism 9.9
19 hypopituitarism 9.9
20 congenital hypopituitarism 9.9
21 pituitary stalk interruption syndrome 9.9
22 systemic lupus erythematosus 9.7
23 myxedema 9.7
24 ocular motor apraxia 9.7
25 pituitary hormone deficiency, combined, 2 9.7
26 pituitary adenoma, prolactin-secreting 9.7
27 hemochromatosis, type 2a 9.7
28 astigmatism 9.7
29 nasopharyngeal carcinoma 9.7
30 diabetes mellitus, ketosis-prone 9.7
31 adrenal cortical adenoma 9.7
32 umbilical hernia 9.7
33 familial glucocorticoid deficiency 9.7
34 hypogonadotropic hypogonadism 9.7
35 hemochromatosis type 2 9.7
36 keratoconus 9.7
37 hemosiderosis 9.7
38 amenorrhea 9.7
39 constipation 9.7
40 empty sella syndrome 9.7
41 arthropathy 9.7
42 pituitary adenoma 9.7
43 myopathy 9.7
44 fibromyalgia 9.7
45 adenoma 9.7
46 lupus erythematosus 9.7
47 diabetes mellitus 9.7
48 diabetes insipidus 9.7
49 dwarfism 9.7
50 growth hormone deficiency 9.7

Graphical network of the top 20 diseases related to Central Congenital Hypothyroidism:



Diseases related to Central Congenital Hypothyroidism

Symptoms & Phenotypes for Central Congenital Hypothyroidism

Human phenotypes related to Central Congenital Hypothyroidism:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sleep disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0002360
2 constipation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002019
3 macroglossia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000158
4 coarse facial features 58 31 hallmark (90%) Very frequent (99-80%) HP:0000280
5 umbilical hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001537
6 fatigue 58 31 hallmark (90%) Very frequent (99-80%) HP:0012378
7 dry skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000958
8 abnormal fingernail morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0001231
9 jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0000952
10 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%) HP:0000239
11 feeding difficulties 58 31 hallmark (90%) Very frequent (99-80%) HP:0011968
12 hoarse cry 58 31 hallmark (90%) Very frequent (99-80%) HP:0001615
13 abdominal distention 58 31 hallmark (90%) Very frequent (99-80%) HP:0003270
14 hypotonia 31 hallmark (90%) HP:0001252
15 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
16 delayed speech and language development 58 31 frequent (33%) Frequent (79-30%) HP:0000750
17 cleft palate 58 31 frequent (33%) Frequent (79-30%) HP:0000175
18 abnormality of the hypothalamus-pituitary axis 58 31 frequent (33%) Frequent (79-30%) HP:0000864
19 septo-optic dysplasia 58 31 frequent (33%) Frequent (79-30%) HP:0100842
20 central hypothyroidism 58 31 frequent (33%) Frequent (79-30%) HP:0011787
21 abnormal eyebrow morphology 31 frequent (33%) HP:0000534
22 hypothyroidism 58 Very frequent (99-80%)
23 muscular hypotonia 58 Very frequent (99-80%)
24 abnormality of the face 58 Very frequent (99-80%)
25 abnormality of the endocrine system 58 Frequent (79-30%)
26 abnormality of the eyebrow 58 Frequent (79-30%)
27 oral cleft 58 Frequent (79-30%)

Drugs & Therapeutics for Central Congenital Hypothyroidism

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomised, Controlled, Crossover Study: Treatment With Thyroxin Compared to Thyroxin + Triiodothyronin in Patients With Secondary Hypothyroidism Completed NCT00360074 Phase 4 Thyroxin, Triiodothyronine

Search NIH Clinical Center for Central Congenital Hypothyroidism

Genetic Tests for Central Congenital Hypothyroidism

Genetic tests related to Central Congenital Hypothyroidism:

# Genetic test Affiliating Genes
1 Secondary Hypothyroidism 29 TSHB

Anatomical Context for Central Congenital Hypothyroidism

MalaCards organs/tissues related to Central Congenital Hypothyroidism:

40
Thyroid, Pituitary, Hypothalamus, Endothelial, Fetal Thyroid

Publications for Central Congenital Hypothyroidism

Articles related to Central Congenital Hypothyroidism:

(show top 50) (show all 340)
# Title Authors PMID Year
1
Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect. 61 6
15292359 2004
2
Congenital secondary hypothyroidism caused by exon skipping due to a homozygous donor splice site mutation in the TSHbeta-subunit gene. 6 61
11788671 2002
3
Congenital central hypothyroidism due to homozygous thyrotropin beta 313 Delta T mutation is caused by a Founder effect. 6
12364478 2002
4
New autosomal recessive mutation of the TSH-beta subunit gene causing central isolated hypothyroidism. 6
11549695 2001
5
Hyperplastic pituitary gland, high serum glycoprotein hormone alpha-subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSH beta gene. 6
11297590 2001
6
Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin beta-subunit gene follows an autosomal recessive inheritance. 6
9589689 1998
7
A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene. 6
8636437 1996
8
Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene. 6
1971148 1990
9
Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit. 6
2792087 1989
10
Low free thyroxine and normal thyroid-stimulating hormone in infants and children: possible causes and diagnostic work-up. 61
33585976 2021
11
Does early identification of central congenital hypothyroidism result in improved outcomes? 61
33517453 2021
12
Outcomes of pituitary apoplexy: a comparison of microadenomas and macroadenomas. 61
33462744 2021
13
USE OF THE FREE THYROXINE INDEX TO REFINE THE LOWER LIMIT OF A FREE THYROXINE IMMUNOASSAY FOR DETECTION OF SECONDARY HYPOTHYROIDISM. 61
33475506 2021
14
Retinal vein occlusion as the presenting feature of Cushing's syndrome. 61
33495181 2021
15
Hypothyroidism Due to Iodine Overload in Children Receiving Peritoneal Dialysis: A Report of 4 Cases. 61
32471796 2020
16
Congenital hypothyroidism: a 2020 consensus guidelines update An ENDO-EUROPEAN REFERENCE NETWORK (ERN) initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. 61
33272083 2020
17
Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening. 61
33107432 2020
18
Cognitive and motor outcome in patients with early-detected central congenital hypothyroidism compared with siblings. 61
33274354 2020
19
Pituitary Macroadenoma Presenting as Acromegaly and Subacute Pituitary Apoplexy: Case Report and Literature Review. 61
32923214 2020
20
Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency. 61
32462814 2020
21
Incidence of thyroid disease in patients with forefoot deformity. 61
31186135 2020
22
Quetiapine-Induced Central Hypothyroidism. 61
32036034 2020
23
Thyroid gland changes in patients with acromegaly. 61
32555993 2020
24
Novel Mutation in the Hemojuvelin Gene (HJV) in a Patient with Juvenile Hemochromatosis Presenting with Insulin-dependent Diabetes Mellitus, Secondary Hypothyroidism and Hypogonadism. 61
32327622 2020
25
Update on congenital hypothyroidism. 61
31789720 2020
26
[Thyroid dysfunctions secondary to cancer immunotherapy]. 61
31879018 2020
27
Pericardial Effusion as an Initial Presentation of Panhypopituitarism. 61
32309255 2020
28
A Remarkable Response of Granulomatous Hypophysitis to Infliximab in a Patient With a Background of Crohn's Disease-A Case Report. 61
32547497 2020
29
Symptomatic Pituitary Metastasis as Initial Manifestation of Renal Cell Carcinoma: Case Report and Review of Literature. 61
32908722 2020
30
A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy. 61
32793120 2020
31
Myoedema in secondary hypothyroidism: an often unelicited clinical sign of hypothyroid myopathy. 61
31843773 2019
32
The Pathogenic TSH β-subunit Variant C105Vfs114X Causes a Modified Signaling Profile at TSHR. 61
31703413 2019
33
Thyroid function in Klinefelter syndrome: a multicentre study from KING group. 61
30912057 2019
34
The Cutoff of Ferritin for Evaluation of Hypothyroidism in Patients With Thalassemia. 61
31008807 2019
35
Effectiveness of endoscopic transsphenoidal surgery for gonadotroph adenoma mimicking dementia: A case report. 61
31523603 2019
36
A case of Woodhouse-Sakati syndrome with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17. 61
31152917 2019
37
Severe hypoglycemia and hyponatremia caused by hypopituitarism in a female patient with type 1 diabetes: A case report. 61
31305453 2019
38
In primary care, is measuring free-thyroxine plus thyroid-stimulating hormone to detect hypopituitarism cost-effective? A cost utility analysis using Markov chain models. 61
31362968 2019
39
Hypopituitarism other than sellar and parasellar tumors or traumatic brain injury assessed in a tertiary hospital. 61
31372159 2019
40
[Manifestation of Graves' disease, resulting from radiosurgical treatment of acromegaly, in a patient with panhypopituitarism]. 61
31271712 2019
41
Cardiogenic Shock Requiring Extracorporeal Membrane Oxygenation Support in a Patient with Panhypopituitarism: A Case Report. 61
31497426 2019
42
Delayed hypopituitarism following Russell's viper envenomation: a case series and literature review. 61
30317419 2019
43
Extreme Short Stature and Severe Neurological Impairment in a 17-Year-Old Male With Untreated Combined Pituitary Hormone Deficiency Due to POU1F1 Mutation. 61
31316460 2019
44
Thyroid Disorders in Homozygous β-Thalassemia: Current Knowledge, Emerging Issues and Open Problems. 61
31205633 2019
45
A RECURRENT MUTATION IN TSHB GENE UNDERLYING CENTRAL CONGENITAL HYPOTHYROIDISM UNDETECTABLE IN NEONATAL SCREENING. 61
31166470 2019
46
Osteogenesis Imperfecta Due to Combined Heterozygous Mutations in Both COL1A1 and COL1A2, Coexisting With Pituitary Stalk Interruption Syndrome. 61
30984112 2019
47
Central Congenital Hypothyroidism Caused by a Novel Mutation, C47W, in the Cysteine Knot Region of TSHβ. 61
31914441 2019
48
Endocrine Disorders Are Prominent Clinical Features in Patients With Primary Antibody Deficiencies. 61
31543881 2019
49
A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome. 61
30086211 2018
50
DIAGNOSIS OF ENDOCRINE DISEASE: Congenital hypothyroidism: update and perspectives 61
30324792 2018

Variations for Central Congenital Hypothyroidism

ClinVar genetic disease variations for Central Congenital Hypothyroidism:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSHB NM_000549.5(TSHB):c.145G>A (p.Gly49Arg) SNV Pathogenic 12684 rs121918668 1:115576128-115576128 1:115033507-115033507
2 TSHB NM_000549.5(TSHB):c.94G>T (p.Glu32Ter) SNV Pathogenic 12685 rs121918669 1:115576077-115576077 1:115033456-115033456
3 TSHB TSHB, 1-BP DEL, 313T Deletion Pathogenic 12686
4 TSHB NM_000549.5(TSHB):c.162+5G>A SNV Pathogenic 12688 rs868637545 1:115576150-115576150 1:115033529-115033529
5 TSHB NM_000549.5(TSHB):c.373del (p.Cys125fs) Deletion Pathogenic 437070 rs755485552 1:115576804-115576804 1:115034183-115034183
6 TSHB NM_000549.5(TSHB):c.205C>T (p.Gln69Ter) SNV Likely pathogenic 12687 rs121918670 1:115576636-115576636 1:115034015-115034015
7 TSHB NM_000549.5(TSHB):c.256G>A (p.Gly86Arg) SNV Uncertain significance 291985 rs190110651 1:115576687-115576687 1:115034066-115034066
8 TSHB NM_000549.5(TSHB):c.*64T>C SNV Uncertain significance 875322 1:115576912-115576912 1:115034291-115034291
9 TSHB NM_000549.5(TSHB):c.374G>A (p.Cys125Tyr) SNV Uncertain significance 976259 1:115576805-115576805 1:115034184-115034184
10 TSHB NM_000549.5(TSHB):c.223A>G (p.Arg75Gly) SNV Likely benign 764732 rs201857310 1:115576654-115576654 1:115034033-115034033
11 TSHB NM_000549.5(TSHB):c.-13A>G SNV Likely benign 291984 rs77331078 1:115572470-115572470 1:115029849-115029849
12 TSHB NM_000549.5(TSHB):c.40A>G (p.Thr14Ala) SNV Benign 256640 rs10776792 1:115576023-115576023 1:115033402-115033402

Expression for Central Congenital Hypothyroidism

Search GEO for disease gene expression data for Central Congenital Hypothyroidism.

Pathways for Central Congenital Hypothyroidism

GO Terms for Central Congenital Hypothyroidism

Biological processes related to Central Congenital Hypothyroidism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor signaling pathway GO:0007186 8.62 TSHB TRHR

Sources for Central Congenital Hypothyroidism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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