Details of Disease

General Information of Disease (ID: DISCC73U)

• Disease Name: Acromegaly
• Synonyms: somatotroph adenoma; pituitary giant; Growth hormone excess
• Disease Class: 5A60-5A61: Pituitary gland disorder
• Definition: Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.
• Disease Hierarchy:
  DISCNV73: Hyperpituitarism
  DISCC73U: Acromegaly
• ICD Code:
  ICD-11: ICD-11: 5A60.0
  ICD-10: ICD-10: E22.0
  ICD-9: ICD-9: 253
  Expand ICD-11: '5A60.0
  Expand ICD-10: 'E22.0
  Expand ICD-9: 253
• Disease Identifiers:
  MONDO ID: MONDO_0019933
  MESH ID: D000172
  UMLS CUI: C0001206
  MedGen ID: 1304
  Orphanet ID: 963
  SNOMED CT ID: 74107003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Bromocriptine	DMVE3TK	Approved	Small molecular drug	[1]
Dopamine	DMPGUCF	Approved	Small molecular drug	[2]
Lanreotide acetate	DMG6ZU4	Approved	Small molecular drug	[3]
Lisuride	DMCME17	Approved	Small molecular drug	[4]
Octreotide	DMHIDCJ	Approved	Small molecular drug	[5]
Pegvisomant	DMDEZI3	Approved	NA	[6]

This Disease is Treated as An Indication in 7 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
RG3806	DMPKX7A	Preregistration	Small molecular drug	[7]
Paltusotine	DM97IN2	Phase 3	Small molecule	[8]
BIM23A760	DM6EIZG	Phase 2	Small molecular drug	[9]
Edotreotide	DMQ08AJ	Phase 2	NA	[10]
IONIS-GHR-LRx	DMQ9711	Phase 2	NA	[11]
Somatoprim	DMTVS3A	Phase 2	Small molecular drug	[12]
ATL1103	DMR93S5	Phase 1	Antisense drug	[13]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
BIM-23268	DMIZ59O	Discontinued in Phase 2	Small molecular drug	[14]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
BVT-A	DMDSX58	Preclinical	NA	[15]

This Disease is Treated as An Indication in 3 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
L-054852	DMXB7G5	Investigative	Small molecular drug	[3]
Mutated growth hormone	DMAY50R	Investigative	NA	[3]
SOMATOSTATIN	DMIOFQE	Investigative	NA	[16]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SSTR2	TTZ6T9E	Limited	Altered Expression	[17]
ARRB1	TTMVD4A	Strong	Altered Expression	[18]
CA1	TTHQPL7	Strong	Biomarker	[19]
CYP11B2	TT9MNE2	Strong	Genetic Variation	[20]
FGF21	TTQ916P	Strong	Altered Expression	[21]
GHRHR	TTG4R8V	Strong	Genetic Variation	[22]
GIPR	TTYMKBE	Strong	Biomarker	[23]
GPR101	TTUKZVG	Strong	Genetic Variation	[24]
GPRC5D	TTHRAPJ	Strong	Biomarker	[25]
IGFBP3	TTZHNQA	Strong	Genetic Variation	[26]
RORC	TTGV6LY	Strong	Biomarker	[27]
SSTR1	TTIND6G	Strong	Biomarker	[28]
SSTR5	TT2BC4G	Strong	Altered Expression	[17]
TRHR	TT4J8MF	Strong	Altered Expression	[29]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Biomarker	[30]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GHRH	OT94U6MO	Limited	Biomarker	[31]
SMS	OT8JYKNH	Limited	Biomarker	[32]
DGCR2	OTEGL17Z	Strong	Biomarker	[33]
ESRP1	OTNCS4SL	Strong	Biomarker	[34]
GNAI2	OTTLGRGH	Strong	Genetic Variation	[22]
GPRC5C	OT45AJT3	Strong	Biomarker	[25]
IGSF1	OT3XD6U2	Strong	Biomarker	[35]
MEN1	OTN6U6V0	Strong	Genetic Variation	[36]
NPDC1	OT788NC8	Strong	Biomarker	[19]
PLAGL1	OTZAO900	Strong	Altered Expression	[37]
POU1F1	OTXT8A5C	Strong	Biomarker	[30]
PRKACB	OT6RMDCE	Strong	Genetic Variation	[38]
PTPN3	OTSLZBVY	Strong	Biomarker	[39]
PTPN4	OT6SXU5Y	Strong	Biomarker	[39]
RAB18	OTNMAQLS	Strong	Altered Expression	[40]
SRL	OT7IEBWZ	Strong	Biomarker	[41]
TRIM21	OTA4UJCF	Strong	Biomarker	[42]
AIP	OTDJ3OSV	Definitive	Altered Expression	[43]
PTPRF	OTH5KF2D	Definitive	Biomarker	[44]

References

• [1] Bromocriptine FDA Label
• [2] Dopamine FDA Label
• [3] Treatment strategies for acromegaly. Expert Opin Emerg Drugs. 2005 Nov;10(4):875-90.
• [4] [Treatment of hyperprolactinemia and acromegaly with lisuride]. Harefuah. 1989 Jun 15;116(12):634-7.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2055).
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7485).
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032322)
• [8] ClinicalTrials.gov (NCT04837040) A Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Paltusotine in Subjects With Acromegaly Treated With Long-acting Somatostatin Receptor Ligands (PATHFNDR-1). U.S.National Institutes of Health.
• [9] BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotide. J Endocrinol Invest. 2005;28(11 Suppl International):21-7.
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5638).
• [11] ClinicalTrials.gov (NCT04522180) An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients With Acromegaly. U.S.National Institutes of Health.
• [12] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8487).
• [13] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
• [14] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2083).
• [15] Emerging drugs for acromegaly. Expert Opin Emerg Drugs. 2008 Jun;13(2):273-93.
• [16] A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.
• [17] Pasireotide Responsiveness in Acromegaly Is Mainly Driven by Somatostatin Receptor Subtype 2 Expression.J Clin Endocrinol Metab. 2019 Mar 1;104(3):915-924. doi: 10.1210/jc.2018-01524.
• [18] Treatment of acromegaly in the era of personalized and predictive medicine.Clin Endocrinol (Oxf). 2015 Jul;83(1):3-14. doi: 10.1111/cen.12731. Epub 2015 Mar 5.
• [19] The efficacy of medical treatment in patients with acromegaly in clinical practice.Endocr J. 2018 Jan 30;65(1):33-41. doi: 10.1507/endocrj.EJ17-0125. Epub 2017 Sep 20.
• [20] CYP11B2 -344T/C gene polymorphism and blood pressure in patients with acromegaly.J Clin Endocrinol Metab. 2006 Dec;91(12):5008-12. doi: 10.1210/jc.2006-0049. Epub 2006 Sep 26.
• [21] Acromegaly is associated with high fibroblast growth factor-21 levels.J Endocrinol Invest. 2019 Jan;42(1):53-60. doi: 10.1007/s40618-018-0885-1. Epub 2018 May 12.
• [22] Study of the multiple endocrine neoplasia type 1, growth hormone-releasing hormone receptor, Gs alpha, and Gi2 alpha genes in isolated familial acromegaly.J Clin Endocrinol Metab. 2001 Feb;86(2):542-4. doi: 10.1210/jcem.86.2.7218.
• [23] The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas.Eur J Endocrinol. 2017 May;176(5):543-553. doi: 10.1530/EJE-16-0831. Epub 2017 Feb 8.
• [24] Mutations in GPR101 as a potential cause of X-linked acrogigantism and acromegaly.Prog Mol Biol Transl Sci. 2019;161:47-67. doi: 10.1016/bs.pmbts.2018.10.003. Epub 2018 Nov 23.
• [25] An orphan G-protein-coupled receptor causes human gigantism and/or acromegaly: Molecular biology and clinical correlations.Best Pract Res Clin Endocrinol Metab. 2018 Apr;32(2):125-140. doi: 10.1016/j.beem.2018.02.004. Epub 2018 Mar 17.
• [26] Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene.BMC Med Genet. 2018 Oct 5;19(1):182. doi: 10.1186/s12881-018-0698-2.
• [27] Attenuated RORC expression in the presence of EMT progression in somatotroph adenomas following treatment with somatostatin analogs is associated with poor clinical recovery.PLoS One. 2013 Jun 25;8(6):e66927. doi: 10.1371/journal.pone.0066927. Print 2013.
• [28] Molecular determinants of the response to medical treatment of growth hormone secreting pituitary neuroendocrine tumors.Minerva Endocrinol. 2019 Jun;44(2):109-128. doi: 10.23736/S0391-1977.19.02970-5. Epub 2019 Jan 16.
• [29] Pituitary adenomas of patients with acromegaly express thyrotropin-releasing hormone receptor messenger RNA: cloning and functional expression of the human thyrotropin-releasing hormone receptor gene.Biochem Biophys Res Commun. 1993 Sep 15;195(2):737-45. doi: 10.1006/bbrc.1993.2107.
• [30] Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly.EBioMedicine. 2019 May;43:537-552. doi: 10.1016/j.ebiom.2019.04.007. Epub 2019 Apr 8.
• [31] Primary pituitary diffuse large B-cell lymphoma with somatotroph hyperplasia and acromegaly: case report.J Neurosurg. 2017 May;126(5):1725-1730. doi: 10.3171/2016.5.JNS16828. Epub 2016 Aug 12.
• [32] CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience.J Neurooncol. 2018 Jun;138(2):291-298. doi: 10.1007/s11060-018-2793-9. Epub 2018 Feb 10.
• [33] Screening for comorbid conditions in patients enrolled in the SODA registry: a 2-year observational analysis.Endocrine. 2018 Jul;61(1):105-117. doi: 10.1007/s12020-018-1615-3. Epub 2018 May 16.
• [34] Epithelial splicing regulator protein 1 and alternative splicing in somatotroph adenomas.Endocrinology. 2013 Sep;154(9):3331-43. doi: 10.1210/en.2013-1051. Epub 2013 Jul 3.
• [35] Is IGSF1 involved in human pituitary tumor formation?.Endocr Relat Cancer. 2015 Feb;22(1):47-54. doi: 10.1530/ERC-14-0465. Epub 2014 Dec 19.
• [36] Three Novel MEN1 Variants in AIP-Negative Familial Isolated Pituitary Adenoma Patients.Pathobiology. 2019;86(2-3):128-134. doi: 10.1159/000495252. Epub 2019 Jan 10.
• [37] Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas.Eur J Endocrinol. 2013 Sep 12;169(4):391-400. doi: 10.1530/EJE-13-0134. Print 2013 Oct.
• [38] Sequence analysis of the catalytic subunit of PKA in somatotroph adenomas.Eur J Endocrinol. 2014 Dec;171(6):705-10. doi: 10.1530/EJE-14-0545. Epub 2014 Sep 15.
• [39] Gene Expression Signature in Adipose Tissue of Acromegaly Patients.PLoS One. 2015 Jun 18;10(6):e0129359. doi: 10.1371/journal.pone.0129359. eCollection 2015.
• [40] Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion.J Clin Endocrinol Metab. 2008 Jun;93(6):2269-76. doi: 10.1210/jc.2007-1893. Epub 2008 Mar 18.
• [41] Somatostatin receptor ligands and resistance to treatment in pituitary adenomas.J Mol Endocrinol. 2014 Jun;52(3):R223-40. doi: 10.1530/JME-14-0011. Epub 2014 Mar 19.
• [42] Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.Expert Rev Pharmacoecon Outcomes Res. 2020 Feb;20(1):105-114. doi: 10.1080/14737167.2019.1610396. Epub 2019 May 6.
• [43] Circulating aryl hydrocarbon receptor-interacting protein (AIP) is independent of GH secretion.Endocr Connect. 2019 Apr;8(4):326-337. doi: 10.1530/EC-19-0082.
• [44] Effects of Pegvisomant and Pasireotide LAR on Vertebral Fractures in Acromegaly Resistant to First-generation SRLs.J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz054. doi: 10.1210/clinem/dgz054.