Adrenocortical insufficiency
diseaseOn this page
Also known as adrenal cortical hypofunctionadrenal cortical insufficiencyadrenal gland insufficiencyadrenal insufficiencyhypoadrenalismhypocortisolemiahypocortisolism
Summary
Adrenocortical insufficiency (MONDO:0000004) is a disease with 1 GWAS associations across 2 studies and 102 clinical trials. Top therapeutic interventions include hydrocortisone, cosyntropin, and prasterone. 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: 1
- Clinical trials: 102
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | adrenocortical insufficiency |
| Mondo ID | MONDO:0000004 |
| EFO | EFO:0009491 |
| MeSH | D000309 |
| DOID | DOID:10493 |
| ICD-11 | 733056203 |
| NCIT | C26691 |
| SNOMED CT | 386584007 |
| UMLS | C0405580 |
| MedGen | 589758 |
| Is cancer (heuristic) | no |
Also known as: adrenal cortical hypofunction · adrenal cortical insufficiency · adrenal gland insufficiency · adrenal insufficiency · adrenocortical insufficiency · hypoadrenalism · hypocortisolemia · hypocortisolism
Data availability: 1 GWAS association (2 studies).
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 › adrenocortical insufficiency
Related subtypes (2): adrenal gland hyperfunction, adrenal cortex neoplasm
Subtypes (2): primary adrenal insufficiency, secondary adrenal insufficiency
Genetics & variants
GWAS landscape
1 GWAS associations across 2 studies. Top hits map to 0 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| chr11:3849907 | 2e-07 | ? |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90651939 | Liu TY | 2025 | 660 | 244,885 | Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population. |
| GCST90043644 | Jiang L | 2021 | 226 | 456,122 | A generalized linear mixed model association tool for biobank-scale data. |
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 | 0 |
| Tier 4: intronic/intergenic | 1 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 0 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 1 |
Functional consequences
| Consequence | Count |
|---|---|
| unknown | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| chr11:3849907 | 2e-07 | Tier 4: intronic/intergenic |
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
1 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Hydrocortisone | Approved (phase 4) |
| Prasterone | Phase 3 (in late-stage trials) |
| Prednisolone | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Prednisone.
Clinical trials & evidence
Clinical trials
Clinical trials: 102.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 69 |
| PHASE4 | 14 |
| PHASE3 | 7 |
| PHASE1 | 6 |
| PHASE2 | 3 |
| EARLY_PHASE1 | 2 |
| PHASE2/PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05193396 | PHASE4 | RECRUITING | Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment |
| NCT05435781 | PHASE4 | RECRUITING | Effect of Supplemental Hydrocortisone During Stress in Prednisolone-induced Adrenal Insufficiency |
| NCT06435481 | PHASE4 | NOT_YET_RECRUITING | Tolerability and Acceptance of Two Oral Hydrocortisone Compounding Formulation for Pediatrics |
| NCT00368381 | PHASE4 | WITHDRAWN | Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis |
| NCT00773058 | PHASE4 | UNKNOWN | Effect of Treatment With Stress-Doses Glucocorticoid in Patients With Acute Respiratory Distress Syndrome (ARDS) |
| NCT00851942 | PHASE4 | COMPLETED | Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test |
| NCT01045876 | PHASE4 | WITHDRAWN | The Effect of Dexamethasone on Cortisol Levels in Patients Undergoing Thyroid Surgery |
| NCT01546922 | PHASE4 | COMPLETED | Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT) |
| NCT01652495 | PHASE4 | COMPLETED | Evaluation of Efficacy and Hypothalamus-pituitary-adrenal Axis Suppression Due to Corticosteroids Intrabursal Injection |
| NCT02282150 | PHASE4 | UNKNOWN | Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism |
| NCT03282487 | PHASE4 | UNKNOWN | Optimising Steroid Replacement in Patients With Adrenal Insufficiency |
| NCT03752190 | PHASE4 | WITHDRAWN | Comparison of Intramuscular and Intravenous ACTH Stimulation Test in Normal Volunteers |
| NCT05457296 | PHASE4 | COMPLETED | Salivary Cortisol Measurement in Corticotrope Deficiency Substitution With Hydrocortisone. |
| NCT05806723 | PHASE4 | COMPLETED | Effects of High Intensity Statin Therapy on Steroid Hormones and Vitamin D in Type 2 Diabetic Men |
| NCT00575341 | PHASE3 | COMPLETED | Dehydroepiandrosterone Substitution in Adolescent and Young Women With Central Adrenal Insufficiency |
| NCT00915343 | PHASE2/PHASE3 | COMPLETED | Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency |
| NCT01093261 | PHASE3 | COMPLETED | Corticosteroid Therapy for Glucocorticoid Insufficiency Related to Traumatic Brain Injury |
| NCT02720952 | PHASE3 | COMPLETED | Treatment of Adrenal Insufficiency in Children |
| NCT02733367 | PHASE3 | COMPLETED | Extension Study for Patients Entered Into Study Infacort 003 |
| NCT03368066 | PHASE3 | COMPLETED | Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients? |
| NCT03936517 | PHASE3 | UNKNOWN | Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) |
| NCT06260462 | PHASE3 | COMPLETED | Effects of Steroid Replacement Therapy on Metabolic, Cardiovascular and Bone Outcomes in Adrenal Insufficiency |
| NCT01735617 | PHASE2 | COMPLETED | Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH |
| NCT01859312 | PHASE2 | COMPLETED | Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia |
| NCT02689960 | PHASE2 | COMPLETED | Vaginal Prednisone Administration for Prevention of Adrenal Crisis |
| NCT01960530 | PHASE1 | COMPLETED | An Investigational Study of Hydrocortisone |
| NCT03019614 | PHASE1 | COMPLETED | An Open Label Study in Healthy Volunteers to Compare Chronocort® to Hydrocortisone |
| NCT03051893 | PHASE1 | COMPLETED | A Two-part, Study to Compare the Pharmacokinetics and Dose Proportionality of up to 6 Chronocort Formulations |
| NCT03178214 | PHASE1 | COMPLETED | Bioavailability of Infacort When Administered Onto Food Compared to Direct Oral Administration |
| NCT03311932 | PHASE1 | COMPLETED | A Study of Infacort® Versus Cortef® in Healthy Adult Male and Female Subjects |
| NCT03343327 | PHASE1 | COMPLETED | A Study of Chronocort® Versus Cortef ® in Healthy Adult Male Subjects |
| NCT03709381 | EARLY_PHASE1 | COMPLETED | Effect of Adrenocorticotropic Hormone on Vascular Endothelial Growth Factor Release in Children Study |
| NCT05639127 | EARLY_PHASE1 | UNKNOWN | The Treatment of Adrenal Crisis With Inhaled Prednisolone |
| NCT02769975 | Not specified | RECRUITING | Evaluation of Children With Endocrine and Metabolic-Related Conditions |
| NCT04278404 | Not specified | RECRUITING | Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) |
| NCT04519580 | Not specified | ACTIVE_NOT_RECRUITING | Improved Diagnostics and Monitoring of Polymyalgia Rheumatica |
| NCT05149638 | Not specified | RECRUITING | Updated Diagnostic Cortisol Values for Adrenal Insufficiency |
| NCT05716607 | Not specified | NOT_YET_RECRUITING | Treatment Study in Patients Treated With Both Insulin & Hydrocortisone |
| NCT06430528 | Not specified | RECRUITING | A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement |
| NCT06637722 | Not specified | ACTIVE_NOT_RECRUITING | Self-management in Patients With Adrenal Insufficiency. |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| HYDROCORTISONE | 4 | 15 |
| COSYNTROPIN | 4 | 6 |
| PRASTERONE | 4 | 2 |
| BETAMETHASONE | 4 | 1 |
| DEXAMETHASONE | 4 | 1 |
| FLUDROCORTISONE ACETATE | 4 | 1 |
| MEGESTROL ACETATE | 4 | 1 |
| METHYLPREDNISOLONE ACETATE | 4 | 1 |
| OSILODROSTAT | 4 | 1 |
| SUXAMETHONIUM | 4 | 1 |
| TRIAMCINOLONE ACETONIDE | 4 | 1 |
| BLOOD, WHOLE | 3 | 1 |
| ESTROGEN | 3 | 1 |
| FLUDROCORTISONE | 2 | 1 |
| CHEMBL31399 | 0 | 2 |
| CHEMBL1200844 | 0 | 1 |
| CHEMBL4740452 | 0 | 1 |
| CHEMBL4567541 | 0 | 1 |