Details of Disease

General Information of Disease (ID: DISLCGI6)

• Disease Name: Goiter
• Synonyms: goitre (disease); Thyromegaly; goiter (disease); goiter
• Definition: Enlargement of the thyroid gland usually caused by lack of iodine in the diet, hyperthyroidism, or thyroid nodules. Symptoms include difficulty in breathing and swallowing.
• Disease Hierarchy:
  DIS5T3X5: Thyroid disease
  DISLCGI6: Goiter
• Disease Identifiers:
  MONDO ID: MONDO_0005397
  MESH ID: D006042
  UMLS CUI: C0018021
  MedGen ID: 42270
  HPO ID: HP:0000853
  SNOMED CT ID: 3716002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Levothyroxine	DMHN027	Approved	Small molecular drug	[1]
Liothyronine	DM6IR3P	Approved	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ACVR1B	TTPKHTZ	Limited	Altered Expression	[3]
ACVR2A	TTX2DRI	Limited	Altered Expression	[3]
RGS12	TTP9AV7	Limited	Genetic Variation	[4]
F9	TTFEZ5Q	Strong	Biomarker	[5]
SLC5A5	TTW7HI9	Strong	Biomarker	[6]
SLCO1C1	TT340CE	Strong	Biomarker	[7]
TEK	TT9VGXW	Strong	Altered Expression	[8]
TPO	TT52XDZ	Strong	Biomarker	[9]
TRH	TT2Z39D	Strong	Biomarker	[10]
TSHR	TT6NYJA	Strong	Biomarker	[11]
THRB	TTGER3L	Definitive	Genetic Variation	[12]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PTGDS	DER3H9C	Limited	Genetic Variation	[13]

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DIO2	OTGPNSLH	Limited	Genetic Variation	[14]
GLIS3	OTBC960E	Limited	Biomarker	[15]
GRPEL1	OT8O00YJ	Limited	Genetic Variation	[4]
MPZL2	OTKFNDUI	Limited	Biomarker	[16]
PAX8	OTRPD9MI	Limited	Genetic Variation	[17]
TBXT	OTHCO2F0	Limited	Biomarker	[18]
CLCN5	OT9YXZSO	moderate	Biomarker	[19]
FOXD3	OTXYV6GO	moderate	Altered Expression	[20]
CCDC6	OTXRQDYG	Strong	Biomarker	[5]
CEP78	OTTAI5S2	Strong	Altered Expression	[21]
DUOX2	OTU14HCN	Strong	Genetic Variation	[9]
FAM83F	OTGGJRO7	Strong	Biomarker	[22]
IYD	OT8BQWTE	Strong	Genetic Variation	[23]
PTMA	OT2W4T1M	Strong	Altered Expression	[24]
PTMS	OT9PS4Q0	Strong	Altered Expression	[24]
RASSF2	OT2JHDO4	Strong	Posttranslational Modification	[25]
SNX5	OT6ZOWMU	Strong	Biomarker	[26]
TAS2R38	OTX5MM36	Strong	Biomarker	[5]
DUOXA2	OT7AZBZJ	Definitive	Genetic Variation	[27]
NKX2-1	OTCMEJTA	Definitive	Genetic Variation	[28]

References

• [1] Levothyroxine FDA Label
• [2] Liothyronine FDA Label
• [3] Activin A and activin receptors in the human thyroid: a link to the female predominance of goiter?.Horm Metab Res. 2000 Oct;32(10):390-400. doi: 10.1055/s-2007-978660.
• [4] Combined linkage analysis and exome sequencing identifies novel genes for familial goiter.J Hum Genet. 2013 Jun;58(6):366-77. doi: 10.1038/jhg.2013.20. Epub 2013 Mar 28.
• [5] Circulating ctDNA methylation quantification of two DNA methyl transferases in papillary thyroid carcinoma.J Cell Biochem. 2019 Oct;120(10):17422-17437. doi: 10.1002/jcb.29007. Epub 2019 May 24.
• [6] Regulation of thyroid sodium-iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species.Clin Exp Pharmacol Physiol. 2018 Apr;45(4):326-334. doi: 10.1111/1440-1681.12887. Epub 2017 Dec 19.
• [7] Neural Alterations and Hyperactivity of the Hypothalamic-Pituitary-Thyroid Axis in Oatp1c1 Deficiency.Thyroid. 2020 Jan;30(1):161-174. doi: 10.1089/thy.2019.0320.
• [8] Tie-2 is expressed on thyroid follicular cells, is increased in goiter, and is regulated by thyrotropin through cyclic adenosine 3',5'-monophosphate.J Clin Endocrinol Metab. 2001 Jun;86(6):2709-16. doi: 10.1210/jcem.86.6.7552.
• [9] Congenital Hypothyroidism due to Oligogenic Mutations in Two Sudanese Families.Thyroid. 2019 Feb;29(2):302-304. doi: 10.1089/thy.2018.0295. Epub 2018 Dec 18.
• [10] Familial partial peripheral and pituitary resistance to thyroid hormone: a frequently missed diagnosis?.Pediatrics. 1986 Dec;78(6):1114-22.
• [11] Association of FoxP3 promoter polymorphisms with the risk of Graves' disease in ethnic Kashmiri population.Gene. 2018 Sep 25;672:88-92. doi: 10.1016/j.gene.2018.06.023. Epub 2018 Jun 9.
• [12] Thyroid hormone receptors and resistance to thyroid hormone disorders.Nat Rev Endocrinol. 2014 Oct;10(10):582-91. doi: 10.1038/nrendo.2014.143. Epub 2014 Aug 19.
• [13] Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes.J Clin Endocrinol Metab. 2006 Jul;91(7):2678-81. doi: 10.1210/jc.2006-0142. Epub 2006 May 9.
• [14] Pendred syndrome in two Galician families: insights into clinical phenotypes through cellular, genetic, and molecular studies.J Clin Endocrinol Metab. 2008 Jan;93(1):267-77. doi: 10.1210/jc.2007-0539. Epub 2007 Oct 16.
• [15] GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation.J Clin Invest. 2017 Dec 1;127(12):4326-4337. doi: 10.1172/JCI94417. Epub 2017 Oct 30.
• [16] Analysis of the thyroid phenotype in 42 patients with Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct.Thyroid. 2014 Apr;24(4):639-48. doi: 10.1089/thy.2013.0164. Epub 2014 Jan 20.
• [17] Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism.Eur J Endocrinol. 2007 May;156(5):521-9. doi: 10.1530/EJE-06-0709.
• [18] Monitoring and Evaluation of Thyroid Function Tests, Serum Electrolytes and Creatinine Levels Before and After 131I Therapy.Endocr Metab Immune Disord Drug Targets. 2020;20(3):419-424. doi: 10.2174/1871530319666190829163413.
• [19] The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland.Endocrinology. 2006 Mar;147(3):1287-96. doi: 10.1210/en.2005-1149. Epub 2005 Nov 23.
• [20] A novel FoxD3 Variant Is Associated With Vitiligo and Elevated Thyroid Auto-Antibodies.J Clin Endocrinol Metab. 2015 Oct;100(10):E1335-42. doi: 10.1210/jc.2015-2126. Epub 2015 Aug 12.
• [21] Significance of CEP78 and WDR62 gene expressions in differentiated thyroid carcinoma: Possible predictors of lateral lymph node metastasis.Asia Pac J Clin Oncol. 2019 Oct;15(5):e154-e161. doi: 10.1111/ajco.13143. Epub 2019 Mar 18.
• [22] The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells.Front Endocrinol (Lausanne). 2019 Mar 1;10:134. doi: 10.3389/fendo.2019.00134. eCollection 2019.
• [23] Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations.Mol Cell Endocrinol. 2010 Jun 30;322(1-2):91-8. doi: 10.1016/j.mce.2010.03.010. Epub 2010 Mar 16.
• [24] Fine-needle aspiration biopsy-RT-PCR expression analysis of prothymosin alpha and parathymosin in thyroid: novel proliferation markers?.Neoplasma. 2007;54(1):57-62.
• [25] Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences.Mol Cancer. 2010 Sep 29;9:264. doi: 10.1186/1476-4598-9-264.
• [26] Loss of sorting nexin 5 stabilizes internalized growth factor receptors to promote thyroid cancer progression.J Pathol. 2017 Nov;243(3):342-353. doi: 10.1002/path.4951.
• [27] A novel missense mutation (I26M) in DUOXA2 causing congenital goiter hypothyroidism impairs NADPH oxidase activity but not protein expression.J Clin Endocrinol Metab. 2015 Apr;100(4):1225-9. doi: 10.1210/jc.2014-3964. Epub 2015 Feb 12.
• [28] Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis.Thyroid. 1997 Jun;7(3):383-7. doi: 10.1089/thy.1997.7.383.