Prolactin-producing pituitary gland adenoma

Summary

Prolactin-producing pituitary gland adenoma (MONDO:0010911) is a cancer with 1 cohort gene and 22 clinical trials. Top therapeutic interventions include cabergoline, dopamine, and ropinirole.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 50
• Clinical trials: 22

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	50.7	Europe	Validated
Annual incidence	1-9 / 100 000	2.05	Malta	Validated
Point prevalence	1-5 / 10 000	44.4	United Kingdom	Validated
Point prevalence	6-9 / 10 000	62	Belgium	Validated
Point prevalence	1-5 / 10 000	45.7	Switzerland	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000026	Male hypogonadism	Very frequent (80-99%)
HP:0000044	Hypogonadotropic hypogonadism	Very frequent (80-99%)
HP:0000134	Female hypogonadism	Very frequent (80-99%)
HP:0000135	Hypogonadism	Very frequent (80-99%)
HP:0000140	Abnormality of the menstrual cycle	Very frequent (80-99%)
HP:0000141	Amenorrhea	Very frequent (80-99%)
HP:0000802	Impotence	Very frequent (80-99%)
HP:0000858	Irregular menstruation	Very frequent (80-99%)
HP:0000868	Decreased fertility in females	Very frequent (80-99%)
HP:0012041	Decreased fertility in males	Very frequent (80-99%)
HP:0012503	Abnormality of the pituitary gland	Very frequent (80-99%)
HP:0030018	Decreased female libido	Very frequent (80-99%)
HP:0100639	Erectile dysfunction	Very frequent (80-99%)
HP:0100829	Galactorrhea	Very frequent (80-99%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000771	Gynecomastia	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002615	Hypotension	Frequent (30-79%)
HP:0002920	Decreased circulating ACTH level	Frequent (30-79%)
HP:0003388	Easy fatigability	Frequent (30-79%)
HP:0008240	Secondary growth hormone deficiency	Frequent (30-79%)
HP:0008245	Pituitary hypothyroidism	Frequent (30-79%)
HP:0011362	Abnormal hair quantity	Frequent (30-79%)
HP:0011734	Central adrenal insufficiency	Frequent (30-79%)
HP:0011735	Adrenocorticotropin deficient adrenal insufficiency	Frequent (30-79%)
HP:0011748	Adrenocorticotropic hormone deficiency	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0030016	Dyspareunia	Frequent (30-79%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000651	Diplopia	Occasional (5-29%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0000830	Anterior hypopituitarism	Occasional (5-29%)
HP:0000845	Elevated circulating growth hormone concentration	Occasional (5-29%)
HP:0001117	Sudden loss of visual acuity	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0006897	Abducens palsy	Occasional (5-29%)
HP:0007011	Fourth cranial nerve palsy	Occasional (5-29%)
HP:0007942	Internal ophthalmoplegia	Occasional (5-29%)
HP:0012246	Oculomotor nerve palsy	Occasional (5-29%)
HP:0012377	Hemianopia	Occasional (5-29%)
HP:0030517	Heteronymous hemianopia	Occasional (5-29%)
HP:0030521	Bitemporal hemianopia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	prolactin-producing pituitary gland adenoma
Mondo ID	MONDO:0010911
EFO	EFO:1000496
MeSH	D015175
OMIM	600634
Orphanet	2965
DOID	DOID:5394
NCIT	C3342
SNOMED CT	134209002
UMLS	C0033375
MedGen	10936
GARD	0004508
MedDRA	10036832
Is cancer (heuristic)	yes

Also known as: Forbes-Albright syndrome (formerly) · lactotrope adenoma · lactotroph adenoma · lactotroph cell adenoma · pituitary gland prolactinoma · pituitary lactotrophic adenoma · pituitary prolactinoma · PRL producing pituitary gland adenoma · PRL-secreting pituitary adenoma · PRLoma · prolactin producing adenoma of pituitary · prolactin producing adenoma of pituitary gland · prolactin producing adenoma of the pituitary · prolactin producing adenoma of the pituitary gland · prolactin producing pituitary adenoma · prolactin producing pituitary gland adenoma · prolactin secreting adenoma · prolactin secreting adenoma of pituitary · prolactin secreting adenoma of pituitary gland · prolactin secreting adenoma of the pituitary (+10 more)

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › pituitary tumor › prolactin producing pituitary tumor › prolactin-producing pituitary gland adenoma

Related subtypes (1): prolactin-producing pituitary gland carcinoma

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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
374076	NM_004525.3(LRP2):c.13753C>T (p.Arg4585Ter)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP2	Orphanet:2143	Donnai-Barrow syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRP2	HGNC:6694	ENSG00000081479	P98164	Low-density lipoprotein receptor-related protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP2	Low-density lipoprotein receptor-related protein 2	Multiligand endocytic receptor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP2	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
adult organism	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP2	169	broad	marker	adult organism, adult mammalian kidney, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP2	2,501

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP2	P98164	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 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
Transport of RCbl within the body	1	1427.5×	0.008	LRP2
Vitamin D (calciferol) metabolism	1	878.5×	0.008	LRP2
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	634.4×	0.008	LRP2
Metabolism of fat-soluble vitamins	1	380.7×	0.011	LRP2
Visual phototransduction	1	259.6×	0.011	LRP2
Retinoid metabolism and transport	1	248.3×	0.011	LRP2
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.013	LRP2
Metabolism of steroids	1	137.6×	0.015	LRP2
Metabolism of vitamins and cofactors	1	116.5×	0.015	LRP2
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.015	LRP2
Sensory Perception	1	95.2×	0.015	LRP2
Clathrin-mediated endocytosis	1	85.2×	0.016	LRP2
Membrane Trafficking	1	37.1×	0.033	LRP2
Vesicle-mediated transport	1	34.8×	0.033	LRP2
Metabolism of lipids	1	31.6×	0.034	LRP2
Metabolism	1	11.6×	0.086	LRP2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
diol metabolic process	1	16852.0×	0.002	LRP2
positive regulation of oligodendrocyte progenitor proliferation	1	8426.0×	0.002	LRP2
folate import across plasma membrane	1	4213.0×	0.002	LRP2
positive regulation of lysosomal protein catabolic process	1	3370.4×	0.002	LRP2
pulmonary artery morphogenesis	1	2808.7×	0.002	LRP2
ventricular compact myocardium morphogenesis	1	2407.4×	0.002	LRP2
response to leptin	1	2407.4×	0.002	LRP2
cobalamin transport	1	1872.4×	0.002	LRP2
metal ion transport	1	1872.4×	0.002	LRP2
coronary artery morphogenesis	1	1872.4×	0.002	LRP2
neuron projection arborization	1	1872.4×	0.002	LRP2
transcytosis	1	1685.2×	0.002	LRP2
secondary heart field specification	1	1532.0×	0.002	LRP2
vitamin D metabolic process	1	1532.0×	0.002	LRP2
vagina development	1	1532.0×	0.002	LRP2
amyloid-beta clearance	1	936.2×	0.002	LRP2
cranial skeletal system development	1	936.2×	0.002	LRP2
outflow tract septum morphogenesis	1	648.1×	0.003	LRP2
positive regulation of neurogenesis	1	581.1×	0.003	LRP2
aorta development	1	561.7×	0.003	LRP2
retinoid metabolic process	1	495.6×	0.003	LRP2
ventricular septum development	1	495.6×	0.003	LRP2
forebrain development	1	351.1×	0.005	LRP2
cellular response to growth factor stimulus	1	318.0×	0.005	LRP2
negative regulation of BMP signaling pathway	1	290.6×	0.005	LRP2
receptor-mediated endocytosis	1	221.7×	0.007	LRP2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	LRP2
neural tube closure	1	187.2×	0.007	LRP2
transport across blood-brain barrier	1	179.3×	0.007	LRP2
male gonad development	1	156.0×	0.008	LRP2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
LRP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
LRP2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LRP2

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)
LRP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE4	2
PHASE2	2
PHASE2/PHASE3	1
PHASE3	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07045935	PHASE4	RECRUITING	Metabolic Outcomes in Patients With Prolactinomas Under Dopamine Agonist Treatment
NCT04107480	PHASE4	UNKNOWN	PRolaCT - Three Prolactinoma RCTs
NCT07463235	PHASE3	RECRUITING	Safety and Potency of a High Cabergoline Dosage in Microprolactinomas
NCT01620138	PHASE2/PHASE3	COMPLETED	Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas
NCT00697814	PHASE2	COMPLETED	Clomiphene in Males With Prolactinomas and Persistent Hypogonadism
NCT00939523	PHASE2	COMPLETED	Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy
NCT03038308	PHASE1/PHASE2	COMPLETED	Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole
NCT01088763	PHASE1	TERMINATED	Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia
NCT00001595	Not specified	RECRUITING	An Investigation of Pituitary Tumors and Related Hypothalmic Disorders
NCT06936813	Not specified	ACTIVE_NOT_RECRUITING	The PROMISE Survey
NCT07268183	Not specified	RECRUITING	How Estrogen Fluctuations Before Diagnosis Affect the Size Prolactin-secreting Tumors
NCT00460616	Not specified	COMPLETED	Cardiac Valve Complications in Prolactinomas Treated With Cabergoline
NCT00481299	Not specified	COMPLETED	Insulin Resistance in Women With Prolactinoma
NCT01504399	Not specified	COMPLETED	Rhinological Outcomes in Endonasal Pituitary Surgery
NCT01775332	Not specified	UNKNOWN	Interdisciplinary Pituitary Disorders Centre of Excellence: Assessment of Patient Education Tools
NCT03353025	Not specified	UNKNOWN	Study on Therapy of Non-invasive Prolactinoma
NCT03400865	Not specified	UNKNOWN	Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas
NCT03457389	Not specified	UNKNOWN	Comparison of Treatment Outcome of Cabergoline According to Target Prolactin Levels in Patients With Prolactinoma
NCT03474601	Not specified	UNKNOWN	Seoul National University Pituitary Disease Cohort Study
NCT03717454	Not specified	UNKNOWN	Dopamine D2 Receptors(D2R) Imaging in Prolactinomas
NCT04106531	Not specified	TERMINATED	Validation of a Quality of Life Metric Prolac-10
NCT05236829	Not specified	COMPLETED	Exercise Capacity and Physical Activity Level in Prolactinoma Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABERGOLINE	4	4
DOPAMINE	4	3
ROPINIROLE	4	3
CLOMIPHENE	4	2
PASIREOTIDE	4	1
ENCLOMIPHENE CITRATE	3	1
CHEMBL4593105	0	4
CHEMBL5192470	0	4