MCID: CNT101
MIFTS: 34

Central Congenital Hypothyroidism

Categories: Rare diseases, Endocrine diseases, Immune diseases

Aliases & Classifications for Central Congenital Hypothyroidism

MalaCards integrated aliases for Central Congenital Hypothyroidism:

Name: Central Congenital Hypothyroidism 53
Secondary Hypothyroidism 53 29 6 73

Classifications:



Summaries for Central Congenital Hypothyroidism

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 226298Disease definitionCentral 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, and testicular enlargement and hypothyroidism, congenital, nongoitrous, 4. An important gene associated with Central Congenital Hypothyroidism is TSHB (Thyroid Stimulating Hormone Beta). The drugs Lenograstim and Etoposide have been mentioned in the context of this disorder. Affiliated tissues include thyroid, pituitary and hypothalamus, and related phenotypes are macroglossia and cleft palate

Related Diseases for Central Congenital Hypothyroidism

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:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 macroglossia 32 hallmark (90%) HP:0000158
2 cleft palate 32 frequent (33%) HP:0000175
3 large fontanelles 32 hallmark (90%) HP:0000239
4 coarse facial features 32 hallmark (90%) HP:0000280
5 abnormal eyebrow morphology 32 frequent (33%) HP:0000534
6 depressivity 32 frequent (33%) HP:0000716
7 delayed speech and language development 32 frequent (33%) HP:0000750
8 abnormality of the hypothalamus-pituitary axis 32 frequent (33%) HP:0000864
9 jaundice 32 hallmark (90%) HP:0000952
10 dry skin 32 hallmark (90%) HP:0000958
11 abnormality of the fingernails 32 hallmark (90%) HP:0001231
12 muscular hypotonia 32 hallmark (90%) HP:0001252
13 umbilical hernia 32 hallmark (90%) HP:0001537
14 hoarse cry 32 hallmark (90%) HP:0001615
15 constipation 32 hallmark (90%) HP:0002019
16 sleep disturbance 32 hallmark (90%) HP:0002360
17 abdominal distention 32 hallmark (90%) HP:0003270
18 central hypothyroidism 32 frequent (33%) HP:0011787
19 feeding difficulties 32 hallmark (90%) HP:0011968
20 fatigue 32 hallmark (90%) HP:0012378
21 septo-optic dysplasia 32 frequent (33%) HP:0100842

Drugs & Therapeutics for Central Congenital Hypothyroidism

Drugs for Central Congenital Hypothyroidism (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 62)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lenograstim Approved, Investigational Phase 3 135968-09-1
2
Etoposide Approved Phase 3 33419-42-0 36462
3
Cisplatin Approved Phase 3 15663-27-1 84093 441203 2767
4
Carboplatin Approved Phase 3 41575-94-4 10339178 498142 38904
5
Vincristine Approved, Investigational Phase 3 2068-78-2, 57-22-7 5978
6
Methotrexate Approved Phase 3 1959-05-2, 59-05-2 126941
7
Thiotepa Approved, Investigational Phase 3 52-24-4 5453
8
Cyclophosphamide Approved, Investigational Phase 3 50-18-0, 6055-19-2 2907
9
Levoleucovorin Approved, Investigational Phase 3 68538-85-2
10
leucovorin Approved, Nutraceutical Phase 3 58-05-9 143 6006
11
Folic Acid Approved, Nutraceutical, Vet_approved Phase 3 59-30-3 6037
12 Alkylating Agents Phase 3
13 Adjuvants, Immunologic Phase 3
14 Micronutrients Phase 3
15 Folic Acid Antagonists Phase 3
16 Topoisomerase Inhibitors Phase 3
17 Dermatologic Agents Phase 3
18 Trace Elements Phase 3
19 Nucleic Acid Synthesis Inhibitors Phase 3
20 Vitamin B Complex Phase 3
21 Vitamins Phase 3
22 Etoposide phosphate Phase 3
23 Immunosuppressive Agents Phase 3
24 Antidotes Phase 3
25 Protective Agents Phase 3
26 Antirheumatic Agents Phase 3
27 Antimetabolites Phase 3
28 Antimetabolites, Antineoplastic Phase 3
29 Antimitotic Agents Phase 3
30 Calcium, Dietary Phase 3
31 Antineoplastic Agents, Alkylating Phase 3
32 Antineoplastic Agents, Phytogenic Phase 3
33 Folate Nutraceutical Phase 3
34 Vitamin B9 Nutraceutical Phase 3
35
Salmon Calcitonin Approved, Investigational Phase 2 47931-85-1 16129616
36
Iron Approved Phase 2 7439-89-6 23925
37
Deferasirox Approved, Investigational Phase 2 201530-41-8 5493381
38
Calcitonin gene-related peptide Investigational Phase 2 83652-28-2
39 Hormones Phase 2,Not Applicable
40 calcitonin Phase 2
41 Thyrotropin-Releasing Hormone Phase 2
42 Hormone Antagonists Phase 2
43 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
44 Bone Density Conservation Agents Phase 2
45 Chelating Agents Phase 2
46 Iron Chelating Agents Phase 2
47 Estradiol valerate Approved, Investigational, Vet_approved Not Applicable 979-32-8
48
Estradiol Approved, Investigational, Vet_approved Not Applicable 50-28-2 5757
49
Testosterone Approved, Investigational Not Applicable 58-22-0 6013
50
Polyestradiol phosphate Approved Not Applicable 28014-46-2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation Completed NCT00360074 Phase 4 Thyroxin, Triiodothyronine
2 Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma Completed NCT00336024 Phase 3 etoposide;cyclophosphamide;cisplatin;carboplatin;thiotepa;methotrexate;leucovorin calcium;vincristine sulfate
3 Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities Completed NCT00054756 Phase 2 TRH (Thyrotropin Releasing Hormone)
4 Myelodysplastic Syndromes (MDS) Event Free Survival With Iron Chelation Therapy Study Active, not recruiting NCT00940602 Phase 2 Deferasirox;Deferasirox placebo
5 Central Hypothyroidism, a Novel Laboratory Measurement Unknown status NCT01280292 Not Applicable Eltroxin
6 Central Hypothyroidism and Cardiovascular Risk Completed NCT01574859
7 Drug Use Investigation of Somatropin for GHD-ADULTS. Completed NCT00601419 Somatropin
8 The PIT-TBI Pilot Study Active, not recruiting NCT02480985 Not Applicable

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:

41
Thyroid, Pituitary, Hypothalamus, Skin, Bone, Fetal Thyroid

Publications for Central Congenital Hypothyroidism

Articles related to Central Congenital Hypothyroidism:

(show all 20)
# Title Authors Year
1
Central congenital hypothyroidism caused by maternal thyrotoxicosis. ( 29572363 )
2018
2
Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection. ( 28898885 )
2017
3
A Novel Thyrotropin-Releasing Hormone Receptor Missense Mutation (P81R) in Central Congenital Hypothyroidism. ( 26735259 )
2016
4
Recent advances in central congenital hypothyroidism. ( 26416826 )
2015
5
[Secondary hypothyroidism after cervical irradiation: systematic evaluation of thyroid function in follow-up]. ( 25203955 )
2014
6
A novel deletion in the thyrotropin Beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey. ( 25012771 )
2014
7
Growth hormone deficiency, secondary hypothyroidism, and empty sella following treatment of childhood macroprolactinoma. ( 24251133 )
2013
8
Replacement therapy of secondary hypothyroidism in children born with low body weight improves mental development. ( 23020058 )
2012
9
Congenital adenohypophyseal hypoplasia associated with secondary hypothyroidism in a 2-week-old Portuguese water dog. ( 23204587 )
2012
10
Secondary hypothyroidism in hereditary hemochromatosis: recovery after iron depletion. ( 18205549 )
2008
11
Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000-2004): It's Prevalence and Clinical Characteristics. ( 24790365 )
2008
12
Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism. ( 15827096 )
2005
13
Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect. ( 15292359 )
2004
14
Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed. ( 14671180 )
2003
15
[Misinterpretation of elevated serum creatine kinase level in secondary hypothyroidism]. ( 11957791 )
2002
16
Congenital secondary hypothyroidism caused by exon skipping due to a homozygous donor splice site mutation in the TSHbeta-subunit gene. ( 11788671 )
2002
17
Transient secondary hypothyroidism in children after cardiac surgery. ( 9078538 )
1997
18
[A case of pseudo-TSH.PRL-producing pituitary adenoma with secondary hypothyroidism]. ( 1873088 )
1991
19
[Secondary hypothyroidism with thyrotropic hormone deficiency. Presentation of a case and review of the literature]. ( 4088528 )
1985
20
Transient secondary hypothyroidism and thyroxine binding globulin deficiency in leukemic children during polychemotherapy: an effect of L-asparaginase. ( 6167443 )
1981

Variations for Central Congenital Hypothyroidism

ClinVar genetic disease variations for Central Congenital Hypothyroidism:

6
(show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSHB NM_000549.4(TSHB): c.145G> A (p.Gly49Arg) single nucleotide variant Pathogenic rs121918668 GRCh37 Chromosome 1, 115576128: 115576128
2 TSHB NM_000549.4(TSHB): c.145G> A (p.Gly49Arg) single nucleotide variant Pathogenic rs121918668 GRCh38 Chromosome 1, 115033507: 115033507
3 TSHB NM_000549.4(TSHB): c.94G> T (p.Glu32Ter) single nucleotide variant Pathogenic rs121918669 GRCh37 Chromosome 1, 115576077: 115576077
4 TSHB NM_000549.4(TSHB): c.94G> T (p.Glu32Ter) single nucleotide variant Pathogenic rs121918669 GRCh38 Chromosome 1, 115033456: 115033456
5 TSHB TSHB, 1-BP DEL, 313T deletion Pathogenic
6 TSHB NM_000549.4(TSHB): c.205C> T (p.Gln69Ter) single nucleotide variant Pathogenic rs121918670 GRCh37 Chromosome 1, 115576636: 115576636
7 TSHB NM_000549.4(TSHB): c.205C> T (p.Gln69Ter) single nucleotide variant Pathogenic rs121918670 GRCh38 Chromosome 1, 115034015: 115034015
8 TSHB TSHB, IVS2, G-A, +5 single nucleotide variant Pathogenic
9 TSHB NM_000549.4(TSHB): c.40A> G (p.Thr14Ala) single nucleotide variant Benign rs10776792 GRCh38 Chromosome 1, 115033402: 115033402
10 TSHB NM_000549.4(TSHB): c.40A> G (p.Thr14Ala) single nucleotide variant Benign rs10776792 GRCh37 Chromosome 1, 115576023: 115576023
11 TSHB NM_000549.4(TSHB): c.373delT (p.Cys125Valfs) deletion Pathogenic/Likely pathogenic rs755485552 GRCh38 Chromosome 1, 115034183: 115034183
12 TSHB NM_000549.4(TSHB): c.373delT (p.Cys125Valfs) deletion Pathogenic/Likely pathogenic rs755485552 GRCh37 Chromosome 1, 115576804: 115576804

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

Sources for Central Congenital Hypothyroidism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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