| domain | core finding | quantitative data/clinical threshold | suggested ontology terms |
|---|---|---|---|
| Disease identity | Adrenocortical adenoma (ACA) is a benign neoplasm of the adrenal cortex; in practice, many ACAs are detected as adrenal incidentalomas on imaging done for unrelated reasons. Distinguish disease-level entity (ACA) from imaging presentation (adrenal incidentaloma). (pqac-00000006, pqac-00000009, pqac-00000010) | Adrenal incidentaloma prevalence in imaging studies: 1–5%; older guideline summary: average 2% overall, rising to 4% in middle age and 10% in elderly. (pqac-00000009, pqac-00000010) | MONDO: adrenocortical adenoma [suggested, ID not source-validated]; MeSH: Adrenocortical Adenoma [suggested]; UBERON: adrenal gland [suggested: UBERON:0002369]; NCIT: Adrenal Cortex Adenoma [suggested] |
| Functional subtypes | Functional ACAs include cortisol-producing adenoma (CPA; overt Cushing syndrome or mild autonomous cortisol secretion/MACS), aldosterone-producing adenoma (APA), and more rarely mixed steroid-secreting tumors; many lesions are nonfunctioning. (pqac-00000006, pqac-00000009, pqac-00000010) | Japanese survey proportions among incidentalomas: 75% benign, 25% functional; 10.5% cortisol-producing, 5.1% aldosterone-producing, 8.5% pheochromocytoma. Older guideline summary: ~80% nonfunctional benign adenomas; ~12% cortisol-secreting, 2.5% aldosterone-secreting, 7% pheochromocytoma, 8% carcinoma. (pqac-00000009, pqac-00000010) | HPO: Hypercortisolism [suggested: HP:0001578]; Hyperaldosteronism [suggested: HP:0000848]; Hypertension [suggested: HP:0000822]; Hypokalemia [suggested: HP:0002900] |
| Cortisol genetics | CPA/MACS are strongly linked to cAMP/PKA pathway activation. PRKACA hotspot mutations are major drivers of cortisol-producing adenomas; GNAS is enriched in subclinical/MACS phenotypes; CTNNB1 also contributes in a subset. (pqac-00000001, pqac-00000003) | PRKACA mutations reported in 35–66% of CPA cases; GNAS mutations reported as most frequent in subclinical Cushing’s (~70% in the cited review summary); CTNNB1 accounts for ~23% of total CPA in the cited review summary. (pqac-00000003) | HGNC/genes [all suggested]: PRKACA, GNAS, CTNNB1; GO: cAMP-dependent protein kinase activity [suggested]; GO: Wnt signaling pathway [suggested]; CL: adrenal cortex cell [suggested] |
| Aldosterone genetics | APA is driven by mutually exclusive somatic mutations in ion channel/pump genes causing membrane depolarization, calcium influx/signaling, aldosterone excess, and tumor growth in zona glomerulosa-lineage cells. Recurrently implicated genes include KCNJ5, CACNA1D, ATP1A1, ATP2B3, CACNA1H, and CLCN2; CTNNB1 activation occurs in a minority but β-catenin activation is broader. (pqac-00000000, pqac-00000002, pqac-00000004) | KCNJ5 mutations account for ~40% of APAs and are especially associated with younger female patients; CTNNB1 mutations occur in ~5% of APAs, while β-catenin activation is present in the majority. Somatic CLCN2 variants were identified in 2/115 APAs (1.74%) in cited primary data referenced by the review set. (pqac-00000002, pqac-00000004) | HGNC/genes [all suggested]: KCNJ5, CACNA1D, ATP1A1, ATP2B3, CACNA1H, CLCN2, CTNNB1; GO: calcium ion transport [suggested]; GO: aldosterone biosynthetic process [suggested]; CL: zona glomerulosa cell [suggested] |
| Imaging | A homogeneous adrenal mass with low attenuation on non-contrast CT is strongly suggestive of benign adenoma. Indeterminate lesions require additional imaging rather than size-only management. (pqac-00000008, pqac-00000009) | Benign criterion: homogeneous mass with ≤10 Hounsfield units (HU) on unenhanced CT, with no further follow-up required regardless of size per 2023 ESE update summary. Indeterminate: 11–20 HU; growth concerning on follow-up if >20% and at least ≥5 mm increase in maximum diameter. (pqac-00000008) | RadLex/non-ontology note: unenhanced adrenal CT [suggested]; UBERON: adrenal gland [suggested: UBERON:0002369]; NCIT: Computed Tomography of Abdomen [suggested] |
| Hormonal tests | Standard hormonal work-up aims to detect cortisol autonomy, primary aldosteronism, and pheochromocytoma when clinically indicated. (pqac-00000008, pqac-00000009, pqac-00000010) | 1-mg overnight dexamethasone suppression: post-DST cortisol >50 nmol/L (>1.8 μg/dL) supports MACS; screening performance in one review summary: sensitivity 98.6%, specificity 90.6%. Plasma aldosterone-to-renin ratio: sensitivity 97%, specificity 80% for primary aldosteronism. Fractionated plasma-free metanephrines: sensitivity 95.7%, specificity 97.3% for pheochromocytoma. (pqac-00000008, pqac-00000009) | LOINC-related tests [all suggested]: serum cortisol after dexamethasone; aldosterone/renin ratio; plasma free metanephrines; HPO: Elevated serum cortisol [suggested], Elevated aldosterone level [suggested] |
| Treatment | Management depends on function and malignancy risk. Benign hormone-secreting tumors are typically treated with adrenalectomy; benign-appearing nonfunctioning lesions may be observed. Multidisciplinary review and experienced/high-volume surgeons are recommended. (pqac-00000008, pqac-00000009) | Minimally invasive adrenalectomy preferred for benign hormone-secreting tumors and suspicious masses ≤6 cm without invasion; recommended surgeon volume ≥12 adrenalectomies/year; perioperative glucocorticoid coverage advised for MACS patients undergoing surgery. (pqac-00000008) | NCIT [all suggested]: Adrenalectomy, Laparoscopic Adrenalectomy, Glucocorticoid Replacement Therapy, Active Surveillance |
| Prognosis | ACA prognosis is generally favorable because lesions are benign, but morbidity depends on hormonal excess and cardiovascular/metabolic complications rather than local tumor behavior. Functional disease requires correct diagnosis and perioperative management to avoid adrenal insufficiency or cardiovascular events. (pqac-00000009) | No disease-specific ACA survival statistic was established in gathered evidence; prognostic concern is driven by cortisol or aldosterone excess comorbidities and by radiologic suspicion for non-adenoma pathology. (pqac-00000008, pqac-00000009) | HPO: Cardiovascular abnormality [suggested], Adrenal insufficiency [suggested: HP:0000846]; NCIT: Cardiovascular Complication [suggested] |


*Table: This table condenses the key disease-knowledge elements for adrenocortical adenoma, including subtype-defining biology, current diagnostic thresholds, and management points. Ontology entries are explicitly marked as suggested when they were not source-validated in the gathered evidence.*