Details of Disease

Disease Name

Hypopituitarism

pituitary hypofunction; pituitary hormone deficiency; pituitary insufficiency

Definition

A condition of diminution or cessation of secretion of one or more hormones from the anterior pituitary gland. This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions.

Disease Hierarchy

DIS7XB48: Pituitary gland disorder

DIS1QT3G: Hypopituitarism

Disease Identifiers

MONDO ID

MONDO_0005152

MESH ID

D007018

UMLS CUI

C0020635

MedGen ID

9386

HPO ID

HP:0040075

SNOMED CT ID

74728003

General Information of Disease (ID: DIS1QT3G)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Testosterone	DM7HUNW	Approved	Small molecular drug	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CYP17A1	TTRA5BZ	moderate	Biomarker	[2]
CYP19A1	TTSZLWK	moderate	Biomarker	[2]
ECE2	TT5U914	Strong	Biomarker	[3]
GHRHR	TTG4R8V	Strong	Genetic Variation	[4]
GLI2	TT045OH	Strong	Genetic Variation	[4]
GNRH1	TT0ID4A	Strong	Biomarker	[5]
GNRHR	TT8R70G	Strong	Biomarker	[6]
KISS1	TTU2O6T	Strong	Biomarker	[7]
KISS1R	TT3KBZY	Strong	Biomarker	[8]
PRL	TTJ2TSA	Strong	Altered Expression	[9]
PROKR2	TTM67AX	Strong	Genetic Variation	[10]
TACR3	TTBPGLU	Strong	Biomarker	[11]
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⏷ Show the Full List of 12 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Altered Expression	[12]
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This Disease Is Related to 21 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EIF2S3	OTARRES9	Limited	Biomarker	[13]
OTX2	OTTV05B1	Limited	Genetic Variation	[4]
POU1F1	OTXT8A5C	Limited	Genetic Variation	[14]
PROK2	OT70IFEZ	Limited	Genetic Variation	[15]
PROP1	OT8GF6N8	moderate	Biomarker	[16]
ACSM3	OT0AE1IV	Strong	Biomarker	[17]
ANOS1	OTZJT4KN	Strong	Genetic Variation	[18]
ARNT2	OTAQD3YV	Strong	Biomarker	[19]
CDON	OT81X593	Strong	Genetic Variation	[20]
CSHL1	OTQKU2F5	Strong	Biomarker	[21]
FOXA2	OTJOCVOY	Strong	Genetic Variation	[22]
GHRH	OT94U6MO	Strong	Biomarker	[23]
IGSF1	OT3XD6U2	Strong	Genetic Variation	[24]
LAMB2	OT71OI2Y	Strong	Genetic Variation	[25]
LHX4	OTVX3J6S	Strong	Genetic Variation	[26]
NONO	OTN36Q6U	Strong	Altered Expression	[27]
SHOC2	OTUNQ2CT	Strong	Genetic Variation	[28]
SIM1	OTYKFPKZ	Strong	Biomarker	[29]
SIX3	OTP5E3VU	Strong	Biomarker	[30]
SMPD3	OTHQBETH	Strong	Biomarker	[31]
SOX3	OT1CRCOB	Strong	Biomarker	[32]
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⏷ Show the Full List of 21 DOT(s)

References

1	Testosterone FDA Label
2	Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen.J Clin Endocrinol Metab. 2003 Sep;88(9):4144-8. doi: 10.1210/jc.2003-030495.
3	Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1.Autoimmunity. 2017 Jun;50(4):223-231. doi: 10.1080/08916934.2017.1332183. Epub 2017 May 30.
4	Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR.Endocr Connect. 2019 May 1;8(5):590-595. doi: 10.1530/EC-19-0085.
5	Sertoli cell androgen receptor DNA binding domain is essential for the completion of spermatogenesis.Endocrinology. 2009 Oct;150(10):4755-65. doi: 10.1210/en.2009-0416. Epub 2009 Jul 2.
6	A novel mouse model of hypogonadotrophic hypogonadism: N-ethyl-N-nitrosourea-induced gonadotropin-releasing hormone receptor gene mutation.Mol Endocrinol. 2005 Apr;19(4):972-81. doi: 10.1210/me.2004-0192. Epub 2004 Dec 29.
7	Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9. doi: 10.1073/pnas.0704114104. Epub 2007 Jun 11.
8	Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice.Endocrinology. 2012 Jan;153(1):316-28. doi: 10.1210/en.2011-1260. Epub 2011 Nov 8.
9	Severe congenital hypopituitarism with low prolactin levels and age-dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation.J Pediatr. 1998 Jun;132(6):1036-8. doi: 10.1016/s0022-3476(98)70405-6.
10	A heterozygous microdeletion of 20p12.2-3 encompassing PROKR2 and BMP2 in a patient with congenital hypopituitarism and growth hormone deficiency.Am J Med Genet A. 2017 Aug;173(8):2261-2267. doi: 10.1002/ajmg.a.38306. Epub 2017 Jun 6.
11	Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mice and men.Endocrinology. 2012 Mar;153(3):1498-508. doi: 10.1210/en.2011-1949. Epub 2012 Jan 17.
12	Cell proliferation and vascularization in mouse models of pituitary hormone deficiency.Mol Endocrinol. 2006 Jun;20(6):1378-90. doi: 10.1210/me.2005-0409. Epub 2006 Mar 23.
13	Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation.EBioMedicine. 2019 Apr;42:470-480. doi: 10.1016/j.ebiom.2019.03.013. Epub 2019 Mar 14.
14	Congenital hypopituitarism due to POU1F1 gene mutation.J Formos Med Assoc. 2011 Jan;110(1):58-61. doi: 10.1016/S0929-6646(11)60009-0.
15	Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia.J Clin Endocrinol Metab. 2013 Mar;98(3):E547-57. doi: 10.1210/jc.2012-3067. Epub 2013 Feb 5.
16	Therapy-Induced Growth and Sexual Maturation in a Developmentally Infantile Adult Patient with a PROP1 Mutation.Front Endocrinol (Lausanne). 2017 Nov 13;8:309. doi: 10.3389/fendo.2017.00309. eCollection 2017.
17	MANAGEMENT OF ENDOCRINE DISEASE: Neuroendocrine surveillance and management of neurosurgical patients.Eur J Endocrinol. 2017 May;176(5):R217-R233. doi: 10.1530/EJE-16-0962. Epub 2017 Feb 13.
18	Novel application of luciferase assay for the invitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD).Mol Cell Endocrinol. 2015 Dec 5;417:63-72. doi: 10.1016/j.mce.2015.09.010. Epub 2015 Sep 14.
19	ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies. Brain. 2013 Oct;136(Pt 10):3096-105. doi: 10.1093/brain/awt218. Epub 2013 Sep 10.
20	Classical and non-classical causes of GH deficiency in the paediatric age.Best Pract Res Clin Endocrinol Metab. 2016 Dec;30(6):705-736. doi: 10.1016/j.beem.2016.11.008. Epub 2016 Nov 24.
21	A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.Endocrinology. 2004 May;145(5):2531-41. doi: 10.1210/en.2003-1125. Epub 2004 Jan 15.
22	Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in FOXA2.J Clin Endocrinol Metab. 2018 Mar 1;103(3):1042-1047. doi: 10.1210/jc.2017-02157.
23	GH, but not GHRH, plays a role in the development of experimental autoimmune encephalomyelitis.Endocrinology. 2011 Oct;152(10):3803-10. doi: 10.1210/en.2011-1317. Epub 2011 Aug 16.
24	Identification of an IGSF1-specific deletion in a five-generation pedigree with X-linked Central Hypothyroidism without macroorchidism.Clin Endocrinol (Oxf). 2016 Oct;85(4):609-15. doi: 10.1111/cen.13094. Epub 2016 Jun 9.
25	Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism.J Clin Endocrinol Metab. 2020 Mar 1;105(3):595-9. doi: 10.1210/clinem/dgz216.
26	Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients.J Clin Endocrinol Metab. 2017 Jan 1;102(1):290-301. doi: 10.1210/jc.2016-3158.
27	Expanding the genetic and clinical spectrum of the NONO-associated X-linked intellectual disability syndrome.Am J Med Genet A. 2019 May;179(5):792-796. doi: 10.1002/ajmg.a.61091. Epub 2019 Feb 17.
28	Cleft palate and hypopituitarism in a patient with Noonan-like syndrome with loose anagen hair-1.Am J Med Genet A. 2018 Sep;176(9):2024-2027. doi: 10.1002/ajmg.a.40432. Epub 2018 Sep 21.
29	Endocrine phenotype of 6q16.1-q21 deletion involving SIM1 and Prader-Willi syndrome-like features.Am J Med Genet A. 2013 Dec;161A(12):3137-43. doi: 10.1002/ajmg.a.36149. Epub 2013 Aug 16.
30	Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.Dev Biol. 2008 Dec 15;324(2):322-33. doi: 10.1016/j.ydbio.2008.08.008. Epub 2008 Aug 18.
31	Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development.Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4554-9. doi: 10.1073/pnas.0406380102. Epub 2005 Mar 11.
32	Xq27.1 Duplication Encompassing SOX3: Variable Phenotype and Smallest Duplication Associated with Hypopituitarism to Date - A Large Case Series of Unrelated Patients and a Literature Review.Horm Res Paediatr. 2019;92(6):382-389. doi: 10.1159/000503784. Epub 2019 Nov 1.