MCID: CNT101
MIFTS: 30

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 49
Secondary Hypothyroidism 49 28 69

Classifications:



Summaries for Central Congenital Hypothyroidism

NIH Rare Diseases : 49 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. Last updated: 8/10/2010

MalaCards based summary : Central Congenital Hypothyroidism, also known as secondary hypothyroidism, is related to hypothyroidism, central, and testicular enlargement and hypothyroidism, congenital, nongoitrous, 4, and has symptoms including macroglossia, cleft palate and large fontanelles. An important gene associated with Central Congenital Hypothyroidism is TSHB (Thyroid Stimulating Hormone Beta). The drugs Vincristine and Etoposide have been mentioned in the context of this disorder. Affiliated tissues include thyroid, pituitary and hypothalamus.

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:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 macroglossia 31 hallmark (90%) HP:0000158
2 cleft palate 31 frequent (33%) HP:0000175
3 large fontanelles 31 hallmark (90%) HP:0000239
4 coarse facial features 31 hallmark (90%) HP:0000280
5 abnormal eyebrow morphology 31 frequent (33%) HP:0000534
6 depressivity 31 frequent (33%) HP:0000716
7 delayed speech and language development 31 frequent (33%) HP:0000750
8 abnormality of the hypothalamus-pituitary axis 31 frequent (33%) HP:0000864
9 jaundice 31 hallmark (90%) HP:0000952
10 dry skin 31 hallmark (90%) HP:0000958
11 abnormality of the fingernails 31 hallmark (90%) HP:0001231
12 muscular hypotonia 31 hallmark (90%) HP:0001252
13 umbilical hernia 31 hallmark (90%) HP:0001537
14 hoarse cry 31 hallmark (90%) HP:0001615
15 constipation 31 hallmark (90%) HP:0002019
16 sleep disturbance 31 hallmark (90%) HP:0002360
17 abdominal distention 31 hallmark (90%) HP:0003270
18 central hypothyroidism 31 frequent (33%) HP:0011787
19 feeding difficulties 31 hallmark (90%) HP:0011968
20 fatigue 31 hallmark (90%) HP:0012378
21 septo-optic dysplasia 31 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 57)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Vincristine Approved, Investigational Phase 3 2068-78-2, 57-22-7 5978
2
Etoposide Approved Phase 3 33419-42-0 36462
3
Cisplatin Approved Phase 3 15663-27-1 2767 441203 84093
4
Methotrexate Approved Phase 3 1959-05-2, 59-05-2 126941
5
Carboplatin Approved Phase 3 41575-94-4 10339178 38904 498142
6
Cyclophosphamide Approved, Investigational Phase 3 50-18-0, 6055-19-2 2907
7 Thiotepa Approved, Investigational Phase 3 52-24-4 5453
8
Lenograstim Approved, Investigational Phase 3 135968-09-1
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 Trace Elements Phase 3
18 Nucleic Acid Synthesis Inhibitors Phase 3
19 Dermatologic Agents Phase 3
20 Vitamin B Complex Phase 3
21 Vitamins Phase 3
22 Antidotes Phase 3
23 Etoposide phosphate Phase 3
24 Immunosuppressive Agents Phase 3
25 Antimetabolites Phase 3
26 Antimetabolites, Antineoplastic Phase 3
27 Protective Agents Phase 3
28 Antimitotic Agents Phase 3
29 Antineoplastic Agents, Phytogenic Phase 3
30 Antirheumatic Agents Phase 3
31 Calcium, Dietary Phase 3
32 Folate Nutraceutical Phase 3
33 Vitamin B9 Nutraceutical Phase 3
34
Salmon Calcitonin Approved, Investigational Phase 2 47931-85-1 16129616
35 Hormones Phase 2,Not Applicable
36 Calcitonin Gene-Related Peptide Phase 2
37 calcitonin Phase 2
38 Thyrotropin-Releasing Hormone Phase 2
39 Hormone Antagonists Phase 2
40 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
41 Bone Density Conservation Agents Phase 2
42
Testosterone Approved, Investigational 58-22-0 6013
43
Estradiol Approved, Investigational, Vet_approved 50-28-2 5757
44 insulin
45 Mitogens
46 Complement Factor I
47 Insulin, Globin Zinc
48 glucagon
49 Estradiol valerate 979-32-8
50 beta-endorphin

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 Central Hypothyroidism, a Novel Laboratory Measurement Unknown status NCT01280292 Not Applicable Eltroxin
5 Central Hypothyroidism and Cardiovascular Risk Completed NCT01574859
6 Drug Use Investigation of Somatropin for GHD-ADULTS. Completed NCT00601419 Somatropin
7 The PIT-TBI Pilot Study Active, not recruiting NCT02480985

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 28 TSHB

Anatomical Context for Central Congenital Hypothyroidism

MalaCards organs/tissues related to Central Congenital Hypothyroidism:

38
Thyroid, Pituitary, Hypothalamus, Skin, Fetal Thyroid

Publications for Central Congenital Hypothyroidism

Articles related to Central Congenital Hypothyroidism:

# Title Authors Year
1
Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection. ( 28898885 )
2017
2
A Novel Thyrotropin-Releasing Hormone Receptor Missense Mutation (P81R) in Central Congenital Hypothyroidism. ( 26735259 )
2016
3
Recent advances in central congenital hypothyroidism. ( 26416826 )
2015
4
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
5
Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000-2004): It's Prevalence and Clinical Characteristics. ( 24790365 )
2008
6
Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism. ( 15827096 )
2005
7
Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed. ( 14671180 )
2003

Variations for Central Congenital Hypothyroidism

ClinVar genetic disease variations for Central Congenital Hypothyroidism:

6
# 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.94G> T (p.Glu32Ter) single nucleotide variant Pathogenic rs121918669 GRCh37 Chromosome 1, 115576077: 115576077
3 TSHB TSHB, 1-BP DEL, 313T deletion Pathogenic
4 TSHB NM_000549.4(TSHB): c.205C> T (p.Gln69Ter) single nucleotide variant Pathogenic rs121918670 GRCh37 Chromosome 1, 115576636: 115576636
5 TSHB TSHB, IVS2, G-A, +5 single nucleotide variant Pathogenic
6 TSHB NM_000549.4(TSHB): c.373delT (p.Cys125Valfs) deletion 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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