Acromegaly

Summary

Acromegaly (MONDO:0019933) is a disease with 2 cohort genes and 185 clinical trials. Top therapeutic interventions include octreotide, pegvisomant, and pasireotide.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 92
• Clinical trials: 185

Clinical features

Epidemiology

Prevalence records

21 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.47	Worldwide	Validated
Point prevalence	1-9 / 100 000		Worldwide	Validated
Annual incidence	1-9 / 1 000 000	0.19	Belgium	Validated
Annual incidence	1-9 / 1 000 000	0.4	Ireland	Validated
Annual incidence	1-9 / 1 000 000	0.34	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.39	Korea, Republic of	Validated
Annual incidence	1-9 / 1 000 000	0.77	Iceland	Validated
Annual incidence	1-9 / 100 000	1.1	United States	Validated
Annual incidence	1-9 / 1 000 000	0.31	Malta	Validated
Annual incidence	1-9 / 1 000 000	0.35	Sweden	Validated
Annual incidence	1-9 / 1 000 000	0.38	Denmark	Validated
Point prevalence	1-9 / 100 000	3.6	Spain	Validated
Point prevalence	1-9 / 100 000	9.7	Italy	Validated
Point prevalence	1-9 / 100 000	8.6	United Kingdom	Validated
Point prevalence	1-5 / 10 000	12	Belgium	Validated
Point prevalence	1-9 / 100 000	6.3	Ireland	Validated
Point prevalence	1-9 / 100 000	2.79	Korea, Republic of	Validated
Point prevalence	1-5 / 10 000	13.4	Iceland	Validated
Point prevalence	1-9 / 100 000	7.8	United States	Validated
Point prevalence	1-9 / 100 000	8.5	Denmark	Validated

Signs & symptoms

Clinical features (HPO)

92 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001869	Deep plantar creases	Very frequent (80-99%)
HP:0002758	Osteoarthritis	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0003859	Cortical diaphyseal thickening of the upper limbs	Very frequent (80-99%)
HP:0004099	Macrodactyly	Very frequent (80-99%)
HP:0006191	Deep palmar crease	Very frequent (80-99%)
HP:0000158	Macroglossia	Very frequent (80-99%)
HP:0000276	Long face	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000293	Full cheeks	Very frequent (80-99%)
HP:0000303	Mandibular prognathia	Very frequent (80-99%)
HP:0000337	Broad forehead	Very frequent (80-99%)
HP:0000400	Macrotia	Very frequent (80-99%)
HP:0000445	Wide nose	Very frequent (80-99%)
HP:0000818	Abnormality of the endocrine system	Very frequent (80-99%)
HP:0000830	Anterior hypopituitarism	Very frequent (80-99%)
HP:0000845	Elevated circulating growth hormone concentration	Very frequent (80-99%)
HP:0000975	Hyperhidrosis	Very frequent (80-99%)
HP:0001051	Seborrheic dermatitis	Very frequent (80-99%)
HP:0001072	Thickened skin	Very frequent (80-99%)
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001182	Tapered finger	Very frequent (80-99%)
HP:0001386	Joint swelling	Very frequent (80-99%)
HP:0001769	Broad foot	Very frequent (80-99%)
HP:0011760	Pituitary growth hormone cell adenoma	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0033794	Acral overgrowth	Very frequent (80-99%)
HP:0011334	Facial shape deformation	Frequent (30-79%)
HP:0012185	Constrictive median neuropathy	Frequent (30-79%)
HP:0012471	Thick vermilion border	Frequent (30-79%)
HP:0012802	Broad jaw	Frequent (30-79%)
HP:0025406	Asthenia	Frequent (30-79%)
HP:0025693	Pituitary macroadenoma	Frequent (30-79%)
HP:0030269	Increased circulating insulin-like growth factor 1 concentration	Frequent (30-79%)
HP:0100540	Palpebral edema	Frequent (30-79%)
HP:0100607	Dysmenorrhea	Frequent (30-79%)
HP:0000044	Hypogonadotropic hypogonadism	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000336	Prominent supraorbital ridges	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0000687	Widely spaced teeth	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0000819	Diabetes mellitus	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0000855	Insulin resistance	Frequent (30-79%)
HP:0000870	Increased circulating prolactin concentration	Frequent (30-79%)
HP:0001609	Hoarse voice	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acromegaly
Mondo ID	MONDO:0019933
EFO	EFO:1001485
MeSH	D000172
Orphanet	963
DOID	DOID:2449
NCIT	C84533
SNOMED CT	74107003
UMLS	C0001206
MedGen	1304
GARD	0005725
MedDRA	10000599
NORD	723
Is cancer (heuristic)	no

Also known as: Growth hormone excess · pituitary giant · somatotroph adenoma

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › pituitary gland disorder › anterior pituitary gland disorder › hyperpituitarism › acromegaly

Related subtypes (3): hyperprolactinemia, pituitary gigantism, ACTH-dependent Cushing syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AIP	Supportive	Unknown	acromegaly	6
GPR101	Supportive	Unknown	acromegaly	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GPR101	Orphanet:963	Acromegaly
AIP	Orphanet:2965	Prolactinoma
AIP	Orphanet:314777	Familial isolated pituitary adenoma
AIP	Orphanet:314786	Silent pituitary adenoma
AIP	Orphanet:314790	Null pituitary adenoma
AIP	Orphanet:963	Acromegaly
AIP	Orphanet:99725	Pituitary gigantism

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GPR101	HGNC:14963	ENSG00000165370	Q96P66	Probable G-protein coupled receptor 101	gencc
AIP	HGNC:358	ENSG00000110711	O00170	AH receptor-interacting protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPR101	Probable G-protein coupled receptor 101	Orphan receptor.
AIP	AH receptor-interacting protein	May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPR101	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
AIP	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
hypothalamus	1
nucleus accumbens	1
granulocyte	1
popliteal artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPR101	23	tissue_specific	marker	nucleus accumbens, caudate nucleus, hypothalamus
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIP	1,268
GPR101	837

Intra-cohort edges

A	B	Sources
AIP	GPR101	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIP	O00170	5
GPR101	Q96P66	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Aryl hydrocarbon receptor signalling	1	1903.3×	0.005	AIP
Interleukin-12 family signaling	1	475.8×	0.008	AIP
Interleukin-12 signaling	1	407.9×	0.008	AIP
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.008	AIP
Phase I - Functionalization of compounds	1	219.6×	0.009	AIP
Biological oxidations	1	129.8×	0.013	AIP
Signaling by Interleukins	1	64.2×	0.022	AIP
Cytokine Signaling in Immune system	1	40.8×	0.031	AIP
Immune System	1	13.0×	0.086	AIP
Metabolism	1	11.6×	0.086	AIP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adenylate cyclase-activating adrenergic receptor signaling pathway	1	601.9×	0.008	GPR101
obsolete protein targeting to mitochondrion	1	290.6×	0.009	AIP
protein maturation	1	81.8×	0.017	AIP
xenobiotic metabolic process	1	74.6×	0.017	AIP
positive regulation of MAPK cascade	1	40.3×	0.025	GPR101

Therapeutics

Drugs indicated for this disease

1 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Pegvisomant	Approved (phase 4)
Lanreotide	Phase 3 (in late-stage trials)
Octreotide	Phase 3 (in late-stage trials)
Paltusotine	Phase 3 (in late-stage trials)
Pasireotide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Sodium Chloride.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AIP	1	2
GPR101	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	AIP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AIP	10	Binding:10
GPR101	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	AIP

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	AIP
C	Druggable family + PDB, no drug	1	GPR101
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GPR101	2	AIP

Clinical trials & evidence

Clinical trials

Clinical trials: 185.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	99
PHASE3	28
PHASE4	25
PHASE2	22
PHASE1	9
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00068029	PHASE4	COMPLETED	Pegvisomant And Sandostatin LAR Combination Study
NCT00068042	PHASE4	COMPLETED	A Study To Compare The Efficacy And Safety Of Pegvisomant To That Of Sandostatin Lar Depot In Patients With Acromegaly
NCT00145405	PHASE4	COMPLETED	Comparable Effects of Lanreotide Autogel and Octreotide LAR on GH, IGF-I Levels and Patient Satisfaction
NCT00149188	PHASE4	COMPLETED	Somatuline Autogel: Acromegaly Self/Partner Injection Study
NCT00151437	PHASE4	COMPLETED	Canadian Pegvisomant Compassionate Study In Acromegalic Patients
NCT00171886	PHASE4	COMPLETED	Octreotide Efficacy and Safety in First-line Acromegalic Patients
NCT00216398	PHASE4	COMPLETED	Lanreotide Autogel in Patients With Acromegaly Previously Treated With Octreotide LAR
NCT00242541	PHASE4	TERMINATED	Study Assessing the Efficacy and Safety of Octreotide Acetate in Patients With Acromegaly, With Micro or Macroadenomas
NCT00376064	PHASE4	COMPLETED	Efficacy of Octreotide Acetate and Cabergoline in Patients With Acromegaly
NCT00461149	PHASE4	COMPLETED	Dose Escalation of Octreotide-LAR as First-Line Therapy in Resistant Acromegaly
NCT00521300	PHASE4	COMPLETED	Preoperative Octreotide Treatment of Acromegaly
NCT00552071	PHASE4	COMPLETED	Ultrasound Guided Octreotide LAR Injection in Acromegaly
NCT00552851	PHASE4	UNKNOWN	Changes of Left Ventricular Mass and Cardiac Function in Patients With Active Acromegaly During Treatment With the Growth Hormone Receptor Antagonist Pegvisomant
NCT00595140	PHASE4	COMPLETED	Acute Application of Pegvisomant and Octreotide in Acromegaly
NCT00627796	PHASE4	COMPLETED	Lanreotide Autogel-120 mg as First-Line Treatment of Acromegaly
NCT00642720	PHASE4	COMPLETED	Change in Quality of Life After Addition of Weekly 40 mg Pegvisomant/Placebo in Controlled Acromegalic Patients
NCT00701363	PHASE4	COMPLETED	Study to Assess the Efficacy of an Extended Injection Interval Schedule of Lanreotide Autogel in Acromegalic Subjects
NCT01278342	PHASE4	COMPLETED	Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients
NCT01424241	PHASE4	COMPLETED	Effects of Sandostatin LAR® in Acromegaly
NCT01618513	PHASE4	COMPLETED	Treatment of Acromegaly With Somatostatin Analogs: GH vs. IGF-I as Primary Biochemical Target
NCT01794793	PHASE4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01861717	PHASE4	TERMINATED	A Pilot Study of Pre- and Post-operative Use of Somatuline Depot.
NCT02060383	PHASE4	COMPLETED	Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing’s Disease or Acromegaly
NCT02427295	PHASE4	UNKNOWN	Hormonal Outcomes in Acromegalic Patients With Treated Surgery With or Without Long Acting Somatostatin Analogues
NCT02668172	PHASE4	UNKNOWN	Pasireotide LAR and Pegvisomant Study in Acromegaly
NCT04837040	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly
NCT05192382	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2)
NCT06930625	PHASE3	RECRUITING	A Study to Assess the Efficacy and Safety of Debio 4126 in Participants With Acromegaly Previously Treated With Somatostatin Analogs
NCT00128232	PHASE3	COMPLETED	Safety and Efficacy of Octreotide Long Acting Release (LAR) in Treatment Naïve Acromegalic Patients
NCT00143416	PHASE3	COMPLETED	Long Term Study With B2036-PEG
NCT00210457	PHASE3	COMPLETED	Efficacy and Safety of Lanreotide Autogel (60, 90 or 120 mg) in Acromegalic Patients
NCT00225979	PHASE3	COMPLETED	Safety and Efficacy of Long-acting Repeatable Octreotide Acetate for Injectable Suspension vs. Surgery in Treatment-naïve Patients With Acromegaly
NCT00234572	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of Varying Doses of Lanreotide Autogel in Patients With Acromegaly
NCT00372697	PHASE3	COMPLETED	Efficacy/Safety of Octreotide Acetate in Patients With Uncontrolled Acromegaly
NCT00383708	PHASE3	COMPLETED	Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
NCT00444873	PHASE3	COMPLETED	Effect of 120mg Somatuline Autogel at Different Dose Intervals (28, 42 or 56 Days) in Patients With Acromegaly
NCT00447499	PHASE3	COMPLETED	Assessment of the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel
NCT00499993	PHASE3	COMPLETED	Efficacy and Tolerability of Lanreotide (Autogel 120 mg) in Patients With Acromegaly
NCT00600886	PHASE3	COMPLETED	Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly
NCT00616551	PHASE3	COMPLETED	Efficacy and Safety of C2L-OCT-01 PR in Acromegalic Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OCTREOTIDE	4	42
PEGVISOMANT	4	17
PASIREOTIDE	4	7
LANREOTIDE	4	5
CABERGOLINE	4	3
CLOMIPHENE	4	2
FLUPHENAZINE DECANOATE	4	1
INSULIN HUMAN	4	1
LIRAGLUTIDE	4	1
SITAGLIPTIN	4	1
PALTUSOTINE	3	5
ASPARTAME	3	1
ENCLOMIPHENE CITRATE	3	1
SOMATOSTATIN	3	1
THYROID	3	1
VELDOREOTIDE	2	2
CIMDERLIRSEN SODIUM	2	1
GADOLINIUM	2	1
CHEMBL3350037	0	16
CHEMBL4593105	0	3
CHEMBL5192470	0	3
CHEMBL3321996	0	1
CHEMBL3185489	0	1
CHEMBL439305	0	1
CHEMBL4524066	0	1
CHEMBL4645029	0	1
CHEMBL4785366	0	1
CHEMBL5219405	0	1
CHEMBL5275397	0	1
CHEMBL5287934	0	1