Details of Disease

General Information of Disease (ID: DISAKJ4T)

• Disease Name: Panhypopituitarism
• Synonyms: complete hypopituitarism; Simmonds' disease; Simmond's disease
• Definition: Insufficient production of all the anterior pituitary hormones.
• Disease Hierarchy:
  DISW6YL6: Combined pituitary hormone deficiencies, genetic form
  DISAKJ4T: Panhypopituitarism
• Disease Identifiers:
  MONDO ID: MONDO_0019591
  MESH ID: C580003
  UMLS CUI: C0242343
  MedGen ID: 69171
  HPO ID: HP:0000871
  Orphanet ID: 90695
  SNOMED CT ID: 32390006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GHRHR	TTG4R8V	Disputed	Genetic Variation	[1]
FGF8	TTIUF3J	moderate	Genetic Variation	[2]
GH1	TTT3YKH	moderate	Biomarker	[3]
GLI2	TT045OH	moderate	Genetic Variation	[4]
PRL	TTJ2TSA	moderate	Genetic Variation	[5]
BRD2	TTDP48B	Strong	Biomarker	[6]
GNRH1	TT0ID4A	Strong	Biomarker	[7]
GNRHR	TT8R70G	Strong	Biomarker	[8]
KISS1	TTU2O6T	Strong	Biomarker	[9]
KISS1R	TT3KBZY	Strong	Biomarker	[10]
PROKR2	TTM67AX	Strong	Biomarker	[2]
SLC15A4	TTG2XRE	Strong	Genetic Variation	[11]
TACR3	TTBPGLU	Strong	Biomarker	[12]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	moderate	Genetic Variation	[11]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FOXA2	OTJOCVOY	Limited	Biomarker	[13]
PROP1	OT8GF6N8	Supportive	Autosomal recessive	[14]
SOX3	OT1CRCOB	Supportive	Autosomal recessive	[15]
POU1F1	OTXT8A5C	moderate	Genetic Variation	[16]
ANOS1	OTZJT4KN	Strong	Genetic Variation	[2]
CSHL1	OTQKU2F5	Strong	Biomarker	[17]
GHRH	OT94U6MO	Strong	Biomarker	[18]
LHX4	OTVX3J6S	Strong	Genetic Variation	[19]
PROK2	OT70IFEZ	Strong	Genetic Variation	[2]
RBM28	OT9A48WV	Strong	Genetic Variation	[20]
SIX3	OTP5E3VU	Strong	Biomarker	[21]
SMPD3	OTHQBETH	Strong	Biomarker	[22]

References

• [1] Genetic causes of isolated and combined pituitary hormone deficiency.Best Pract Res Clin Endocrinol Metab. 2016 Dec;30(6):679-691. doi: 10.1016/j.beem.2016.09.005. Epub 2016 Oct 15.
• [2] Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012 Apr;97(4):E694-9. doi: 10.1210/jc.2011-2938. Epub 2012 Feb 8.
• [3] Bilateral osteonecrosis of the hip in panhypopituitarism.BMJ Case Rep. 2019 Feb 13;12(2):e227471. doi: 10.1136/bcr-2018-227471.
• [4] Novel GLI2 mutations identified in patients with Combined Pituitary Hormone Deficiency (CPHD): Evidence for a pathogenic effect by functional characterization.Clin Endocrinol (Oxf). 2019 Mar;90(3):449-456. doi: 10.1111/cen.13914. Epub 2019 Jan 7.
• [5] Characterization of a Novel POU1F1 Mutation Identified on Screening 160 Growth Hormone Deficiency Patients.Horm Metab Res. 2019 Apr;51(4):248-255. doi: 10.1055/a-0867-1026. Epub 2019 Apr 25.
• [6] Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion.J Clin Endocrinol Metab. 2010 Aug;95(8):4043-7. doi: 10.1210/jc.2010-0150. Epub 2010 Jun 9.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency.Genet Med. 2018 Jul;20(7):728-736. doi: 10.1038/gim.2017.165. Epub 2017 Oct 26.
• [12] 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.
• [13] Expanding phenotype with severe midline brain anomalies and missense variant supports a causal role for FOXA2 in 20p11.2 deletion syndrome.Am J Med Genet A. 2019 Sep;179(9):1783-1790. doi: 10.1002/ajmg.a.61281. Epub 2019 Jul 11.
• [14] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [15] Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism. Am J Hum Genet. 2005 May;76(5):833-49. doi: 10.1086/430134. Epub 2005 Mar 30.
• [16] Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.Hormones (Athens). 2018 Dec;17(4):581-588. doi: 10.1007/s42000-018-0079-4. Epub 2018 Nov 20.
• [17] 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.
• [18] Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.Clin Endocrinol (Oxf). 2015 Jun;82(6):876-84. doi: 10.1111/cen.12706. Epub 2015 Feb 6.
• [19] 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.
• [20] ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency.Eur J Endocrinol. 2010 Jun;162(6):1021-5. doi: 10.1530/EJE-10-0077. Epub 2010 Mar 15.
• [21] Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes.J Clin Endocrinol Metab. 2013 Apr;98(4):E779-84. doi: 10.1210/jc.2012-3982. Epub 2013 Mar 8.
• [22] 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.