Adrenal gland hyperfunction

Summary

Adrenal gland hyperfunction (MONDO:0006640) is a disease with 5 GWAS associations across 5 studies and 4 clinical trials. Top therapeutic interventions include osilodrostat. A subtype of adrenal cortex disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 5
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	adrenal gland hyperfunction
Mondo ID	MONDO:0006640
EFO	EFO:1000797
MeSH	D000308
DOID	DOID:3947
SNOMED CT	275437005
UMLS	C0001622
MedGen	7899
Is cancer (heuristic)	no

Also known as: adrenal gland hyperfunction · hyperadrenalism · hyperadrenocorticism · hypercorticism · hypercortisolemia · hyperfunction, adrenal gland · hyperfunction, adrenocortical

Data availability: 5 GWAS associations (5 studies) · 1 HPO phenotype.

Disease family

This is a subtype of adrenal cortex disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › adrenal cortex disorder › adrenal gland hyperfunction

Related subtypes (2): adrenocortical insufficiency, adrenal cortex neoplasm

Subtypes (1): hyperaldosteronism

Genetics & variants

GWAS landscape

5 GWAS associations across 5 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6563624	2e-17	B3GLCT - RXFP2	T	0.31
rs574711622	1e-13	KLF12	C	3.66
chr13:32136829	2e-13		A	0.37
rs547043053	9e-12	RN7SKP191 - SLC44A1	T	2.95
rs78513618	2e-07	PNPT1 - EFEMP1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475694	Verma A	2024	946	449,815	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477342	Verma A	2024	746	120,851	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479901	Verma A	2024	746	120,851	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651964	Liu TY	2025	357	224,577	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90435727	Zhou W	2018	182	405,386	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	4

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	1

Functional consequences

Consequence	Count
intergenic_variant	1
intron_variant	1
unknown	1
non_coding_transcript_exon_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6563624	13	31619754	T>A,C,G	0.457	intergenic_variant	B3GLCT - RXFP2	2e-17	Tier 4: intronic/intergenic
rs574711622	13	73818208	C>T	0	intron_variant	KLF12	1e-13	Tier 4: intronic/intergenic
chr13:32136829				0.486			2e-13	Tier 4: intronic/intergenic
rs547043053	9	105199097	T>A,C	0.001	non_coding_transcript_exon_variant	RN7SKP191 - SLC44A1	9e-12	Tier 4: intronic/intergenic
rs78513618	2	55843147	A>G		regulatory_region_variant	PNPT1 - EFEMP1	2e-07	Tier 3: regulatory

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Dexamethasone	Approved (phase 4)
Levoketoconazole	Approved (phase 4)
Relacorilant	Phase 3 (in late-stage trials)

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07247162	PHASE4	NOT_YET_RECRUITING	Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing’s Syndrome
NCT00001180	Not specified	COMPLETED	Dose Response Relationship for Single Doses of Corticotropin Releasing Hormone (CRH) in Normal Volunteers and in Patients With Adrenal Insufficiency
NCT00001969	Not specified	COMPLETED	Heart Disease Risk Factors in Major Depression
NCT03607474	Not specified	COMPLETED	Patient and Partner Perception After Remission of Cushing’s Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OSILODROSTAT	4	1