Endocrine

Adrenal incidentaloma: workup algorithm

Clinical Overview and When to Suspect Adrenal Incidentaloma

— Is it functional (hormonally active)?

— Is it malignant (primary adrenocortical carcinoma or metastasis)?

— CT or MRI of abdomen/chest done for trauma, abdominal pain, cancer staging, or nephrolithiasis reveals an adrenal nodule.

— Patient often asymptomatic; symptoms, if present, are subtle (mild hypertension, weight gain, glucose intolerance, hypokalemia).

— Known extra-adrenal malignancy (lung, breast, melanoma, renal, colon, lymphoma): ~50% of new adrenal masses are metastases.

— No cancer history: ~80% are benign nonfunctioning adenomas; pheochromocytoma 5%, cortisol-secreting adenoma 5–10%, aldosteronoma 1%, adrenocortical carcinoma (ACC) <5%, myelolipoma/cyst <5%.

— Confirm it is truly incidental (not imaging done to evaluate hypertension, hirsutism, or Cushingoid features — those are not incidentalomas and warrant directed workup).

— Document size, laterality, attenuation (Hounsfield units on noncontrast CT), homogeneity, margins, and growth on prior imaging if available.

Definition: An adrenal mass ≥1 cm discovered on imaging performed for a reason unrelated to adrenal disease. Prevalence rises with age — ~3% at age 50, up to 10% by age 70.

Two core questions drive every workup:

When to suspect/identify:

Epidemiologic priors that shift pretest probability:

Initial framework on discovery:

Step 3 management: Every adrenal incidentaloma gets two parallel evaluations on day one — a biochemical workup (overnight 1-mg dexamethasone suppression test, plasma metanephrines, and aldosterone/renin if hypertensive or hypokalemic) and a dedicated adrenal-protocol CT (noncontrast HU plus washout) to assess malignant potential.

Board pearl: A mass found during evaluation of resistant hypertension is not an incidentaloma — it is a targeted finding, and aldosterone/renin testing becomes mandatory regardless of size.

Presentation Patterns and Key History

— Cortisol excess (subclinical/mild autonomous): central weight gain, easy bruising, proximal muscle weakness, new-onset diabetes, osteoporosis/fragility fracture, hypertension, mood changes. Frank Cushingoid features are uncommon.

— Catecholamine excess (pheochromocytoma): episodic headache, palpitations, diaphoresis, anxiety, paroxysmal hypertension, orthostatic symptoms, panic-attack mimics. Up to 10% normotensive.

— Aldosterone excess: resistant hypertension (≥3 agents), spontaneous or thiazide-induced hypokalemia, muscle cramps, polyuria.

— Androgen/estrogen excess (suggests ACC): rapid-onset hirsutism, virilization, oligomenorrhea, or gynecomastia.

— Prior or current cancer (lung, breast, melanoma, renal, GI, lymphoma).

— Constitutional symptoms — weight loss, night sweats, flank/back pain.

— Family history: MEN2 (pheo + medullary thyroid CA), MEN1, von Hippel-Lindau, NF1, hereditary paraganglioma syndromes (SDHx mutations), Li-Fraumeni (ACC risk).

— Exogenous glucocorticoids (including inhaled, topical, intra-articular) → suppress HPA axis, invalidate cortisol testing.

— Tricyclics, SNRIs, levodopa, decongestants, labetalol → false-positive metanephrines.

— OCPs → ↑ CBG and total cortisol; ACEi/ARB, spironolactone, eplerenone, β-blockers → distort aldosterone/renin ratio.

Most common scenario: Asymptomatic patient, mass found on CT for unrelated reason (e.g., diverticulitis workup, trauma pan-scan, lung cancer staging).

Targeted history — screen for subclinical hormone excess:

Malignancy risk history:

Medication history that confounds workup:

Key distinction: A patient with episodic hypertension and a 4-cm adrenal mass should have plasma fractionated metanephrines drawn before any biopsy or contrast study — biopsying or stressing an undiagnosed pheo can precipitate fatal hypertensive crisis.

Step 3 management: Always reconcile the medication list and pause interfering drugs (when safe) before biochemical testing; document a 24-hour symptom diary for paroxysmal complaints.

Physical Exam Findings (and Hemodynamic Assessment)

— Most patients with incidentalomas appear well; overt physical findings argue against the term "incidental."

— Look for subtle Cushingoid stigmata: supraclavicular and dorsocervical fat pads, facial plethora, thin skin (≤2 mm on dorsum of hand), wide (>1 cm) violaceous striae, proximal muscle wasting on chair-rise test.

— BP in both arms, supine and standing — orthostatic hypotension with supine hypertension is classic for pheochromocytoma due to volume contraction.

— Resistant hypertension or hypertension in a young, nonobese patient → aldosteronoma or pheo.

— Tachycardia, tremor, pallor during a paroxysm support pheo.

— Café-au-lait macules, axillary freckling, neurofibromas → NF1 (pheo risk).

— Mucosal neuromas, marfanoid habitus → MEN2B.

— Hirsutism (Ferriman–Gallwey ≥8), temporal balding, clitoromegaly, deepened voice → virilizing ACC.

— Gynecomastia in a man with an adrenal mass → feminizing ACC (rare but high-yield).

— Hypertensive retinopathy or LV heave suggests chronic hormone-driven HTN.

— Murmurs, displaced PMI in long-standing aldosteronism (LVH out of proportion to BP).

— Palpable flank/abdominal mass is rare and concerning for large ACC, metastasis, or myelolipoma.

— Bruit over flank may suggest renal artery involvement.

— Proximal weakness on hip flexion (Cushing) vs. periodic flaccid paralysis from hypokalemia (aldosteronoma).

General appearance:

Vital signs:

Skin and adnexal exam:

Cardiopulmonary:

Abdomen:

Neurologic and musculoskeletal:

CCS pearl: Order orthostatics, BP in both arms, BMI, waist circumference, and skin photograph documentation at the index visit — these "free" data points reframe a "nonfunctioning" mass as biochemically suspicious and justify deeper testing.

Board pearl: Sustained hypertension + spontaneous hypokalemia in a patient not on diuretics is primary aldosteronism until proven otherwise — even with a small adrenal nodule.

Diagnostic Workup — Initial Labs and Imaging

— 1-mg overnight dexamethasone suppression test (DST): Take 1 mg dex at 11 PM, measure 8 AM serum cortisol.

· Cortisol ≤1.8 µg/dL → suppression normal (excludes autonomous cortisol secretion).

· 1.9–5.0 µg/dL → "possible autonomous cortisol secretion" (MACS).

· >5.0 µg/dL → "autonomous cortisol secretion," confirm with ACTH, 24-h urine free cortisol, late-night salivary cortisol.

— Plasma free metanephrines or 24-h urine fractionated metanephrines — sensitivity >95% for pheochromocytoma. Plasma sample drawn supine after 30 min rest reduces false positives.

— Aldosterone-to-renin ratio (ARR) — only if hypertensive or hypokalemic. ARR >20–30 with aldosterone >15 ng/dL is screen-positive.

— DHEA-S, total/free testosterone, 17-OH progesterone, estradiol (in men/postmenopausal women) — only if imaging suggests ACC or virilizing/feminizing features.

— Noncontrast HU ≤10 → lipid-rich adenoma (>70% specific).

— Absolute washout ≥60% or relative washout ≥40% at 15 min → lipid-poor adenoma.

— Size <4 cm + benign imaging features → low malignancy risk.

— Size >4 cm, heterogeneity, irregular margins, calcifications, necrosis, HU >20 → suspicious.

Biochemical screen — performed in ALL incidentalomas (Endocrine Society / European guidelines):

Dedicated adrenal-protocol CT (noncontrast + contrast + 15-min delayed):

Basic labs: CMP (potassium, glucose, bicarb), CBC, fasting glucose/HbA1c (cortisol/pheo screening adjuncts).

Board pearl: A noncontrast HU ≤10 essentially rules out pheochromocytoma and ACC — both are lipid-poor and read >20 HU. But you still must do biochemical testing because functional adenomas can have benign imaging.

Step 3 management: Do biochemistry before considering biopsy or contrasted imaging — never biopsy an adrenal mass until pheochromocytoma is excluded.

Diagnostic Workup — Advanced or Confirmatory Studies

— Repeat 1-mg DST or perform 2-day low-dose DST (0.5 mg q6h × 8 doses).

— Measure ACTH (suppressed <10 pg/mL → adrenal-dependent), 24-h urine free cortisol, late-night salivary cortisol (loss of diurnal rhythm).

— DHEA-S often low in cortisol-secreting adenoma.

— Elevated plasma metanephrines >3× upper limit → highly specific, proceed to imaging localization.

— Borderline values: repeat after stopping interfering drugs (TCAs, labetalol, acetaminophen for some assays); clonidine suppression test if persistent ambiguity.

— 123I-MIBG scintigraphy or 68Ga-DOTATATE PET for extra-adrenal paraganglioma, metastatic, or hereditary disease.

— Genetic testing (RET, VHL, NF1, SDHx) in patients <45, bilateral, extra-adrenal, or with family history.

— Screen-positive ARR → confirm with oral sodium loading + 24-h urine aldosterone (>12 µg/24h), saline infusion test (aldosterone >10 ng/dL after 2 L saline), or fludrocortisone suppression.

— If confirmed and surgery is desired in patients >35 with unilateral lesion → adrenal vein sampling (AVS) to lateralize (essential — imaging misclassifies up to 30%).

— MRI with chemical shift — signal dropout on out-of-phase confirms adenoma.

— FDG-PET/CT — SUV adrenal-to-liver ratio >1.5 favors malignancy.

— Image-guided biopsy — reserved for known extra-adrenal malignancy when result changes management AND pheochromocytoma is excluded biochemically; never first-line for suspected ACC (risk of tract seeding).

Confirming autonomous cortisol secretion (when 1-mg DST abnormal):

Confirming pheochromocytoma:

Confirming primary aldosteronism:

Indeterminate or suspicious imaging:

Key distinction: AVS, not CT, determines surgical candidacy in primary aldosteronism — a "nodule on CT" may be a nonfunctioning adenoma while the contralateral gland is the true hypersecretor.

Board pearl: Order abdominal MRI without gadolinium in pregnancy or renal dysfunction when adrenal characterization is needed.

Risk Stratification and First-Line Management Logic

— Nonfunctioning + benign imaging (HU ≤10, <4 cm, homogeneous): Observation. No further imaging needed if classic adenoma features; biochemistry repeat not routinely required if initial workup negative (updated 2023 ESE guideline).

— Functioning (any hormone excess): Treat the syndrome — typically surgical referral.

— Indeterminate imaging (HU >10, no washout data, 1–4 cm): Adrenal-protocol CT or chemical-shift MRI to characterize; reimage at 6–12 months.

— Suspicious imaging (>4 cm, HU >20, irregular, growth ≥20%/≥5 mm in 6–12 months): Surgical resection regardless of biochemistry.

— <4 cm: ~2% ACC risk.

— 4–6 cm: ~6% ACC risk.

— >6 cm: ~25% ACC risk → adrenalectomy.

— Associated with hypertension, T2DM, osteoporosis, CV mortality.

— Treat the comorbidities aggressively; consider adrenalectomy if young patient with multiple cortisol-related comorbidities worsening despite therapy.

— Consider metastases, congenital adrenal hyperplasia, bilateral macronodular hyperplasia, infiltrative disease (TB, histoplasmosis, lymphoma, hemorrhage).

— Check 8 AM cortisol + ACTH stim test to evaluate for adrenal insufficiency before any adrenalectomy.

Decision branches after initial workup converge on four phenotypes:

Size thresholds:

Mild autonomous cortisol secretion (MACS):

Bilateral masses:

Step 3 management: Document a clear written plan at the discovery visit: (1) which biochemical tests ordered, (2) timing of repeat imaging (if any), (3) surgical referral threshold, (4) primary care role in tracking cardiometabolic risk factors. This transition-of-care plan is heavily tested.

Board pearl: Growth threshold prompting resection is ≥20% AND ≥5 mm in linear dimension over 6–12 months — both criteria together, not either alone.

Pharmacotherapy — Preoperative and Medical Management

— Phenoxybenzamine (nonselective irreversible α-blocker) 10 mg BID, titrate to target SBP <130 mmHg seated and SBP >90 mmHg standing. Alternative: doxazosin (selective α1, fewer reflex tachycardia/postop hypotension issues).

— Liberal salt and fluid intake in last 3 days preop to restore volume.

— Add β-blocker (propranolol, atenolol) ONLY after adequate α-blockade — typically days 3–5. β-blockade first causes unopposed α-vasoconstriction and hypertensive crisis.

— Calcium channel blocker (amlodipine, nicardipine) as adjunct for residual HTN.

— Metyrosine (tyrosine hydroxylase inhibitor) in select high-catecholamine cases.

— Surgical candidate (lateralized on AVS) → adrenalectomy.

— Bilateral disease or nonsurgical → spironolactone (start 12.5–25 mg, titrate to 100 mg) or eplerenone (more selective, less gynecomastia).

— Monitor K+ and creatinine at 1, 2, 4 weeks.

— Definitive: unilateral adrenalectomy.

— Bridge or nonsurgical: ketoconazole, metyrapone, osilodrostat, mitotane.

— Perioperative stress-dose glucocorticoids required because contralateral adrenal is suppressed; taper hydrocortisone over 6–12 months postop with morning cortisol monitoring.

Pheochromocytoma — preoperative blockade (10–14 days):

Primary aldosteronism:

Cortisol-secreting adenoma (overt Cushing):

MACS: No specific cortisol-lowering drug; aggressive control of HTN (ACEi/ARB), T2DM (metformin, SGLT2i), dyslipidemia (statin), and osteoporosis (calcium/vit D, bisphosphonate if T-score warrants).

CCS pearl: When admitting a pheo patient for adrenalectomy, order: α-blocker, IV fluids, type & crossmatch, glucose monitoring (postop hypoglycemia from rebound insulin), and ICU bed for first 24 h.

Board pearl: Never start a β-blocker before α-blocker in pheochromocytoma — classic distractor.

Procedures — Adrenalectomy, AVS, and Biopsy

— All pheochromocytomas (cortical-sparing in bilateral or hereditary disease to preserve glucocorticoid function).

— Aldosteronomas after AVS lateralization.

— Cortisol-secreting adenomas.

— Nonfunctioning masses >4–6 cm with suspicious features.

— Tumors <6 cm without local invasion.

— Suspected ACC (en bloc resection, avoid capsular rupture; tumor spillage worsens prognosis).

— Tumor >6 cm with local invasion or IVC thrombus.

— Need for lymphadenectomy in malignancy.

— Indication: confirmed primary aldosteronism in patient who is a surgical candidate (generally <35 with clear unilateral adenoma may skip AVS).

— Technique: simultaneous bilateral adrenal vein cortisol and aldosterone with cosyntropin stimulation; selectivity index (adrenal vein cortisol / IVC cortisol) >5 with ACTH stim, lateralization index >4.

— Operator-dependent; refer to high-volume centers.

— Rare and specific: known extra-adrenal malignancy where adrenal biopsy alters staging/treatment AND pheochromocytoma biochemically excluded.

— Contraindicated for suspected ACC — tract seeding, nondiagnostic in lipid-rich cases.

— Pheo: arterial line, central access, vasopressors (norepinephrine, phenylephrine) and antihypertensives (nitroprusside, nicardipine, esmolol) on standby for intraop swings; post-clamp hypotension common.

— Cortisol-secreting: stress-dose hydrocortisone 100 mg IV at induction, then 50 mg q8h tapered.

— Aldosteronoma: monitor potassium (can spike postop) and discontinue spironolactone day of surgery.

Laparoscopic adrenalectomy — standard of care for:

Open adrenalectomy — preferred when:

Adrenal vein sampling (AVS):

Image-guided percutaneous biopsy:

Perioperative considerations:

CCS pearl: Postop day 1 after pheo resection — check fingerstick glucose q4h (hypoglycemia from rebound hyperinsulinemia is high-yield) and trend plasma metanephrines at 2–6 weeks to confirm biochemical cure.

Board pearl: Tumor spillage during ACC resection upstages disease and worsens 5-yr survival from ~60% to <20%.

Special Populations — Elderly and Renal/Hepatic Impairment

— Incidentalomas more common; baseline prevalence ~10%.

— Threshold for surgery higher — weigh perioperative risk (ACC scoring, frailty index, ASA class) against indolent natural history of small benign masses.

— MACS is highly relevant: even mild cortisol autonomy in older adults associates with osteoporotic fracture, T2DM, and CV mortality. Aggressively manage comorbidities.

— Pheo can present atypically — isolated orthostatic hypotension or unexplained heart failure (catecholamine cardiomyopathy) rather than paroxysmal HTN.

— Avoid iodinated contrast in eGFR <30 unless essential; use noncontrast CT + chemical-shift MRI.

— Gadolinium contraindicated in eGFR <30 (NSF risk) — use non-contrast MRI sequences.

— 24-h urine metanephrines may be unreliable in advanced CKD; use plasma fractionated metanephrines (still valid but cutoffs adjusted).

— Spironolactone/eplerenone — start low, monitor K+ closely; contraindicated if eGFR <30 or K+ >5.0.

— Metformin held around contrast administration if eGFR <30 or AKI risk.

— Ketoconazole and mitotane hepatotoxic — monitor LFTs; ketoconazole black-box warning.

— Phenoxybenzamine and doxazosin generally hepatically metabolized — dose-titrate by BP response.

— Elderly on SSRIs, MAOIs, methyldopa, sympathomimetics — common false-positive metanephrine triggers.

— Reconcile medications and consider 2-week washout when safe before retesting.

Elderly (>65):

Renal impairment:

Hepatic impairment:

Polypharmacy considerations:

Step 3 management: In a frail 82-year-old with a 2.5-cm lipid-rich (HU 4) nonfunctioning adenoma, the answer is reassurance and no further imaging — guidelines no longer recommend serial CT for clearly benign small masses, sparing radiation and cost.

Board pearl: Atypical pheo in the elderly = unexplained orthostasis + new dilated cardiomyopathy + impaired glucose tolerance — order plasma metanephrines.

Special Populations — Pregnancy, Pediatrics, and Hereditary Syndromes

— Adrenal incidentaloma in pregnancy is rare but high-stakes — undiagnosed pheochromocytoma carries maternal/fetal mortality up to 50%.

— Imaging of choice: MRI without gadolinium (T2 hyperintense "light bulb" pheo classic).

— Biochemistry: plasma metanephrines preferred (urine collection harder in pregnancy).

— Pheo management: phenoxybenzamine is preferred α-blocker (long clinical track record); add labetalol after α-block; delivery by C-section or controlled vaginal delivery at experienced center.

— Avoid dexamethasone for DST (crosses placenta); use late-night salivary cortisol if cortisol screen needed — though physiologic hypercortisolism of pregnancy limits interpretation.

— Primary aldosteronism: spironolactone teratogenic (antiandrogenic) — use eplerenone or amlodipine; consider adrenalectomy in 2nd trimester for refractory cases.

— Adrenal masses in children are not incidental — high rate of malignancy (neuroblastoma in infants, ACC in older children).

— Always pursue full workup including genetic testing (Li-Fraumeni TP53, Beckwith-Wiedemann).

— Adrenal mass in a child = oncology referral.

— MEN2A/2B (RET): medullary thyroid CA + pheo + (2A: hyperparathyroidism; 2B: mucosal neuromas, marfanoid).

— VHL: pheo (often bilateral) + retinal/CNS hemangioblastomas + RCC + pancreatic NET.

— NF1: café-au-lait, neurofibromas, ~5% develop pheo.

— Hereditary paraganglioma (SDHB/C/D): SDHB has high malignancy rate, head/neck and abdominal paragangliomas.

— Carney complex, Li-Fraumeni, Lynch: ACC risk.

Pregnancy:

Pediatrics:

Hereditary syndromes to recognize:

Step 3 management: Refer any patient <45 with pheo, bilateral pheo, paraganglioma, or family history for germline genetic testing and counseling — affects screening of first-degree relatives.

Board pearl: Pregnant patient + paroxysmal HTN + T2 bright adrenal mass on MRI = pheochromocytoma → α-block first, then β-block, then plan delivery.

Complications and Adverse Outcomes

— Pheochromocytoma: hypertensive crisis, stroke, MI, catecholamine cardiomyopathy (takotsubo-like), arrhythmia, multi-organ failure during surgery/trauma/contrast/anesthesia.

— Cortisol excess (overt or MACS): T2DM, hypertension, central obesity, osteoporosis with vertebral fractures, immunosuppression/infections, VTE, depression/psychosis, increased all-cause and CV mortality.

— Primary aldosteronism: independent CV risk amplifier — higher LVH, atrial fibrillation, stroke, MI, CKD than BP-matched essential HTN; hypokalemia → arrhythmia, rhabdomyolysis.

— ACC: local invasion, IVC tumor thrombus, lung/liver/bone metastases; 5-year survival 30–60% even after resection.

— Intraoperative hypertensive crisis or hypotensive collapse during pheo resection.

— Postop adrenal insufficiency after unilateral adrenalectomy for cortisol-secreting adenoma — can last 6–18 months; risk of adrenal crisis if steroid taper too rapid.

— Spironolactone: gynecomastia, hyperkalemia, AKI.

— Mitotane: GI toxicity, neurologic toxicity, adrenal insufficiency, hyperlipidemia.

— Ketoconazole: hepatotoxicity, QT prolongation, gynecomastia.

— Biopsy of unrecognized pheo → catastrophic hypertensive crisis.

— Contrast administration in unblocked pheo → catecholamine surge.

— Radiation exposure from unnecessary serial CT in clearly benign mass — guidelines now de-emphasize repeat imaging for HU ≤10 lesions.

— Overdiagnosis cascade: incidental finding → anxiety, repeat imaging, biopsies, unnecessary surgery.

— Spontaneous or anticoagulation-related; bilateral hemorrhage → Waterhouse-Friderichsen → acute adrenal insufficiency.

From the tumor itself (untreated functional disease):

Procedural and pharmacologic complications:

Workup-related harms (high-yield Step 3 safety):

Adrenal hemorrhage:

Board pearl: Any patient undergoing surgery or contrast with an unworked-up adrenal mass — pause and screen for pheo first.

Step 3 management: After unilateral adrenalectomy for Cushing, taper hydrocortisone slowly with morning cortisol/ACTH stim testing at 3, 6, 12 months; counsel patient on stress-dose steroids and MedicAlert bracelet.

When to Escalate Care — ICU, Consult, and Inpatient Triage

— Any positive biochemistry.

— Mass >4 cm or indeterminate imaging.

— Bilateral disease.

— Suspected hereditary syndrome.

— Pediatric or pregnant patient.

— Confirmed pheochromocytoma (after α-blockade).

— Confirmed aldosteronoma with lateralization on AVS.

— Cortisol-secreting adenoma with significant comorbidities.

— Mass >4 cm or growth/suspicious features.

— Suspected ACC → multidisciplinary tumor board.

— Hypertensive crisis with new-onset adrenal mass — admit, ICU, IV phentolamine or nicardipine, never pure β-blocker.

— Adrenal crisis in patient with bilateral adrenal hemorrhage/mass — IV hydrocortisone 100 mg, fluids, glucose, ICU.

— Symptomatic severe hypokalemia (K+ <2.5) from aldosteronism.

— Catecholamine cardiomyopathy with heart failure.

— Pheochromocytoma multisystem crisis (encephalopathy, MOSF, severe BP swings).

— Post-adrenalectomy for pheo (first 24 h).

— Adrenal crisis with hemodynamic instability.

Endocrinology referral — virtually all incidentalomas warrant at least one consultation when:

Surgical (endocrine surgery/urology) referral:

Oncology referral: ACC, adrenal metastasis with treatment implications, hereditary cancer syndromes.

Genetics referral: All pheo/paraganglioma; ACC <45; bilateral or multifocal disease; suggestive family history.

Inpatient admission triggers:

ICU criteria:

CCS pearl: A hospitalized patient with incidentally discovered adrenal mass during admission for unrelated illness — document the finding, initiate outpatient endocrinology referral, place biochemistry orders if feasible while inpatient (overnight DST, plasma metanephrines), and ensure explicit handoff to primary care with timeline for follow-up within 2–4 weeks. Failure of transition-of-care follow-up on incidentalomas is a documented patient-safety gap.

Board pearl: Always check 8 AM cortisol before any adrenalectomy involving suspected cortisol excess to anticipate need for stress-dose steroids.

Key Differentials — Same-Category (Adrenal) Lesions

— Lipid-rich, HU ≤10 noncontrast, homogeneous, well-circumscribed, <4 cm, stable on follow-up.

— May be nonfunctioning (most) or autonomously cortisol-secreting (MACS, overt Cushing), aldosterone-secreting, rarely androgen-secreting.

— Arises from chromaffin cells of medulla.

— Imaging: HU >20 noncontrast, T2 hyperintense ("light bulb") on MRI, avid enhancement, cystic/hemorrhagic areas.

— "Rule of 10s" outdated — up to 25% have germline mutations.

— Usually >4 cm at diagnosis, heterogeneous, irregular margins, calcifications, necrosis, local invasion.

— Often hyperfunctional (Cushing ± virilization in women).

— Elevated DHEA-S characteristic; 17-OH progesterone, 11-deoxycortisol elevated (steroidogenic precursors).

— Benign, contains macroscopic fat (HU −30 to −100) — pathognomonic on CT.

— Asymptomatic unless very large; resect if >6 cm or symptomatic (hemorrhage risk).

Benign cortical adenoma (~80% of incidentalomas):

Pheochromocytoma (~5%):

Adrenocortical carcinoma (<5%):

Myelolipoma (~5%):

Adrenal cyst: Simple, fluid-attenuating, thin walls — benign.

Adrenal hemorrhage: Hyperdense (HU 50–90) acutely, evolves; consider anticoagulation, trauma, antiphospholipid syndrome, sepsis (Waterhouse-Friderichsen).

Bilateral macronodular adrenal hyperplasia / primary pigmented nodular adrenal disease: Bilateral nodules with cortisol excess; Carney complex association.

Ganglioneuroma: Rare benign neural tumor, well-circumscribed, low attenuation.

Key distinction: Myelolipoma's macroscopic fat is on CT, not the "out-of-phase signal dropout" of a lipid-rich adenoma on chemical-shift MRI — these are different fat signals (macroscopic vs intracellular).

Board pearl: "Adrenal mass with macroscopic fat density (HU −30 to −100)" = myelolipoma, full stop. No further workup beyond size monitoring.

Key Differentials — Other-Category Causes of Adrenal Mass

— Most common cause of adrenal mass in patient with known malignancy.

— Primaries (in order): lung, breast, melanoma, renal, colon, lymphoma.

— Often bilateral; HU >20, no washout, FDG-avid.

— Adrenal insufficiency develops when >90% of bilateral cortex destroyed.

— Primary adrenal lymphoma rare; secondary involvement in DLBCL more common.

— Often bilateral, homogeneous, may compress adjacent structures.

— Biopsy diagnostic (after pheo excluded).

— Tuberculosis — historically leading cause of Addison disease worldwide; bilateral enlargement → atrophy with calcifications.

— Histoplasmosis — endemic Midwest US (Ohio/Mississippi River valleys), immunocompromised.

— Cryptococcus, blastomycosis — HIV/AIDS patients.

— CMV adrenalitis in AIDS.

— Trauma, anticoagulation, sepsis (meningococcemia → Waterhouse-Friderichsen), antiphospholipid syndrome, HIT.

— Bilateral → acute primary adrenal insufficiency.

— Nonclassic 21-hydroxylase deficiency can present with bilateral adrenal hyperplasia/nodules in adulthood; elevated 17-OH progesterone.

— Splenic lobulation, gastric diverticulum, pancreatic tail mass, renal upper-pole mass, retroperitoneal node — mimic adrenal lesion on initial imaging; dedicated adrenal protocol clarifies.

Metastatic disease:

Lymphoma:

Infectious adrenalitis:

Adrenal hemorrhage:

Congenital adrenal hyperplasia (CAH):

Pseudoadrenal masses:

Step 3 management: In a patient with prior melanoma and new bilateral adrenal masses — order 8 AM cortisol + ACTH stim test to screen for adrenal insufficiency before steroid stress (chemo, surgery, sepsis); also pursue tissue diagnosis after excluding pheo.

Key distinction: Bilateral adrenal enlargement + hyperpigmentation + hyponatremia/hyperkalemia + endemic exposure = TB/histoplasmosis-induced primary adrenal insufficiency, not nonfunctioning bilateral adenomas.

Long-Term Plan, Secondary Prevention, and Surveillance

— Per 2023 European/AACE updates: no repeat imaging or repeat biochemistry if initial workup unequivocal — represents major shift from older annual-imaging recommendations.

— Older guidelines (still tested): repeat imaging at 6–12 months and biochemistry annually × 4 years.

— Repeat dedicated adrenal CT or MRI at 6–12 months; resect if growth ≥20% AND ≥5 mm.

— No surveillance imaging once stable; lifelong screening and treatment of cardiometabolic comorbidities — HTN, T2DM, dyslipidemia, osteoporosis (DXA every 2 years).

— Annual reassessment of cortisol axis and comorbidities.

— Glucocorticoid replacement (hydrocortisone 10–20 mg/day in divided doses) tapered over months with morning cortisol monitoring.

— Stress-dose steroid teaching, MedicAlert bracelet, injectable hydrocortisone (Solu-Cortef) at home.

— Plasma/urine metanephrines at 2–6 weeks postop, then annually for at least 10 years (5% recurrence; lifelong if hereditary).

— Genetic testing-driven surveillance for paraganglioma/MTC.

— Discontinue spironolactone day of surgery; monitor K+ (can transiently rise).

— BP often improves but ~50% still need antihypertensives; reassess at 3 months.

— Adjuvant mitotane considered for high-risk disease; surveillance CT chest/abdomen + hormone markers every 3 months × 2 years, then less frequent.

Nonfunctioning, benign-appearing adenoma (HU ≤10, <4 cm):

Indeterminate imaging:

MACS:

Post-adrenalectomy for cortisol-secreting tumor:

Post-adrenalectomy for pheo:

Post-adrenalectomy for aldosteronoma:

ACC postresection:

Step 3 management: Coordinate primary care + endocrinology shared care — PCP tracks BP, glucose, lipids, DXA; endocrinology handles hormonal reassessment and surgical decisions. Document care plan in shared record.

Board pearl: Mild autonomous cortisol secretion patients still benefit from osteoporosis screening even with normal BMI — cortisol-driven bone loss is dose-independent.

Follow-Up, Monitoring, and Counseling

— Nonfunctioning benign (HU ≤10, <4 cm): no further imaging; reassure.

— Nonfunctioning indeterminate (HU 10–20, no washout): dedicated CT or chem-shift MRI at 6–12 months.

— MACS: annual clinical reassessment of HTN, DM, osteoporosis, weight; DXA every 2 years; no routine imaging.

— Postop pheo: metanephrines at 2–6 weeks, then annually × 10 years minimum (lifelong if hereditary).

— Postop aldosteronoma: BP, K+, creatinine at 1, 3, 6, 12 months.

— Postop Cushing: taper steroids with morning cortisol/ACTH stim at 3, 6, 12 months.

— ACC: CT every 3 months × 2 yrs, then every 6 months × 3 yrs, then annually.

— Explain "incidentaloma" — most are harmless; framing prevents over-investigation anxiety.

— Smoking cessation, alcohol moderation, weight management, exercise — leverages every cardiometabolic risk.

— Calcium 1000–1200 mg/day, vitamin D 800–1000 IU/day for MACS bone health.

— MedicAlert bracelet and emergency steroids for adrenal-insufficient patients.

— Family screening if hereditary syndrome — first-degree relatives.

— Cushing patients: physical therapy for proximal weakness; psychiatric follow-up for mood disturbance (resolves over 6–12 months postop).

— Pheo patients: gradual return to exercise as BP normalizes; reassurance about postural symptoms.

— Spironolactone and eplerenone affordability; consider generic spironolactone first, with switch to eplerenone for gynecomastia.

— Coordinate AVS at regional center; arrange transportation, time off work.

Cadence summary table — memorize for Step 3:

Patient counseling:

Rehab/lifestyle:

Adherence and access:

CCS pearl: At every visit, the order set for an established adrenal incidentaloma patient includes BP, weight, BMP (K+, Cr, glucose), HbA1c if MACS, and annual hormonal reassessment until 4 years of stability — then de-escalate per updated guidelines.

Board pearl: Persistently elevated metanephrines postop = residual or metastatic pheochromocytoma → MIBG or DOTATATE PET.

Ethical, Legal, and Patient Safety Considerations

— Ethical and legal duty to inform the patient of any incidentaloma noted on imaging, regardless of the reason for the study.

— Radiologist's report must be communicated; ordering clinician documents discussion and plan. Failure to communicate is a leading malpractice claim ("missed incidentaloma").

— Pheochromocytoma surgery: discuss intraoperative BP crisis, postop hypoglycemia, need for ICU.

— Cortisol-secreting tumor resection: discuss lifelong potential steroid dependence and adrenal crisis risk.

— Genetic testing: counsel on implications for family members, insurance discrimination (GINA protects health insurance/employment but not life/disability), and reproductive decisions.

— Adrenal incidentaloma discovered on ED/inpatient imaging often "falls through the cracks" — Joint Commission-flagged issue.

— Best practice: structured handoff including (1) explicit problem-list entry, (2) referral to PCP and endocrinology, (3) follow-up appointment booked before discharge, (4) patient education sheet, (5) closed-loop confirmation.

— Many institutions implement automated "incidentaloma tracking" registries.

— Performing IV contrast or surgery on unrecognized pheochromocytoma → preventable hypertensive crisis (sentinel event).

— Adrenal crisis post-Cushing surgery due to inadequate steroid coverage or patient education → preventable death.

— Overuse of repeat CT for clearly benign masses → radiation and cost; align with 2023 guidelines.

— Anesthesia events and unanticipated intraoperative deaths require institutional reporting.

— Genetic testing requires written informed consent per state and federal regs.

— Access to AVS and adrenal-protocol imaging varies — ensure referral to high-volume centers when feasible; address transportation, language, insurance barriers.

Incidental finding disclosure:

Informed consent edge cases:

Transition-of-care safety:

Avoidable harms:

Mandatory reporting and legal:

Health equity:

Step 3 management: When discovering an incidentaloma on a study ordered by another clinician, the ordering and reading physicians share responsibility; the primary care physician assumes coordination once notified — explicitly document the loop closure.

Board pearl: Failure to recognize and pre-block a pheo before contrast or surgery is a never event and a tested patient-safety scenario.

High-Yield Associations and Rapid-Fire Clinical Facts

— Noncontrast HU ≤10 → adenoma.

— Absolute washout ≥60% or relative ≥40% → adenoma.

— T2 "light bulb" bright → pheochromocytoma.

— Macroscopic fat (HU −30 to −100) → myelolipoma.

— >4 cm, heterogeneous, calcified, irregular → ACC until proven otherwise.

— Bilateral + cancer history → metastases.

— 1-mg DST cortisol ≤1.8 µg/dL = normal suppression.

— Plasma metanephrines >3× ULN = highly specific for pheo.

— ARR >20–30 with aldo >15 = screen-positive primary aldosteronism.

— Suppressed ACTH + autonomous cortisol = adrenal source.

— DHEA-S high in ACC; low in benign cortisol-secreting adenoma.

— MEN2 (RET): pheo + MTC ± hyperparathyroidism.

— VHL: bilateral pheo + RCC + hemangioblastoma.

— NF1: café-au-lait + pheo.

— SDHB: malignant paraganglioma.

— Li-Fraumeni (TP53): ACC + sarcoma + breast.

— Carney complex: PPNAD, atrial myxoma, skin pigmentation.

— TCAs, labetalol, MAOIs, levodopa, sympathomimetics → false-positive metanephrines.

— OCPs → ↑ CBG, total cortisol.

— Spironolactone, ACEi/ARB, β-blockers → distort ARR.

— Exogenous steroids (any route) → invalidate DST.

— α-block before β-block in pheo.

— Spironolactone/eplerenone for non-surgical aldosteronism.

— Stress-dose steroids perioperatively for Cushing resection.

— Mitotane adjuvant for high-risk ACC.

— Size thresholds: 4 cm (resect if other features), 6 cm (resect almost always).

— Growth: ≥20% AND ≥5 mm prompts resection.

— AVS lateralization index >4 with cosyntropin stim.

Imaging triggers — memorize:

Biochemistry must-knows:

Syndromes/genetics:

Drugs that confound:

Treatment essentials:

Numbers to memorize:

Board pearl: "Adrenal mass + hypokalemia + resistant HTN" = aldosteronoma. "Adrenal mass + episodic HTN + headache + diaphoresis" = pheo. "Adrenal mass + central obesity + striae + diabetes" = cortisol-secreting adenoma.

Board Question Stem Patterns

— "58-year-old has CT for kidney stone; 2.5-cm left adrenal mass, HU 6, homogeneous. Next step?" → 1-mg DST + plasma metanephrines (+ ARR if hypertensive). No biopsy. No further imaging if biochemistry negative.

— "Patient with newly discovered 4-cm adrenal mass scheduled for cholecystectomy develops severe HTN on induction." → Unrecognized pheochromocytoma. Answer: phentolamine IV, cancel surgery, full biochemical workup.

— "Patient with pheo diagnosis started on metoprolol; develops severe HTN, pulmonary edema." → Unopposed α stimulation. Answer: add phenoxybenzamine and stop pure β-blockade.

— "45-year-old with HTN on 3 drugs, K+ 3.0, no diuretics. Next step?" → ARR. Then confirmatory saline suppression. Then AVS before surgery.

— "62-year-old woman with rapid-onset hirsutism, hypertension; CT shows 8-cm heterogeneous right adrenal mass with calcifications." → Open adrenalectomy, avoid biopsy (tract seeding), tumor board, mitotane consideration.

— "Lung cancer patient with new 3-cm right adrenal mass." → Biochemistry first (rule out pheo) → PET-CT → biopsy to confirm metastasis if it changes staging.

— "Anticoagulated patient with abdominal pain, hypotension, hyponatremia, hyperkalemia." → Bilateral adrenal hemorrhage → IV hydrocortisone, fluids, imaging.

— "Pregnant patient, paroxysmal HTN, T2 bright adrenal mass on MRI." → Phenoxybenzamine, then labetalol, plan controlled C-section.

— "Cortisol 3.0 after 1-mg DST, mild HTN, T2DM, osteoporosis." → Treat comorbidities aggressively; consider adrenalectomy if young and worsening.

— "Patient discharged from ED, CT noted 'incidental adrenal nodule.' What ensures follow-up?" → Communicate finding to patient and PCP, document referral, close the loop.

Stem 1 — Classic incidentaloma:

Stem 2 — Pre-anesthesia trap:

Stem 3 — β-blocker error:

Stem 4 — Aldosteronism:

Stem 5 — ACC:

Stem 6 — Metastasis:

Stem 7 — Bilateral masses + hypotension:

Stem 8 — Pregnancy:

Stem 9 — MACS comorbidities:

Stem 10 — Transition-of-care safety:

Board pearl: When in doubt — biochemistry first, contrast/biopsy never before pheo is excluded.

One-Line Recap

Every adrenal incidentaloma requires two parallel determinations — functionality (1-mg dexamethasone suppression test + plasma metanephrines, plus aldosterone/renin if hypertensive or hypokalemic) and malignant potential (size, noncontrast HU, washout, growth) — with surgery reserved for any functional tumor, suspicious imaging (>4 cm, HU >20, ≥20%/≥5 mm growth), or confirmed ACC, while clearly benign nonfunctioning lipid-rich adenomas no longer require routine repeat imaging.

— 1-mg overnight DST (≤1.8 µg/dL normal).

— Plasma fractionated or 24-h urine metanephrines.

— ARR only if hypertensive or hypokalemic.

— Adrenal-protocol CT: noncontrast HU, washout at 15 min.

— Any functional tumor (with appropriate medical prep — α-block before β-block in pheo).

— Mass >4 cm OR HU >20 OR growth ≥20% AND ≥5 mm.

— Suspected ACC → open en bloc resection, never biopsy first.

— Never biopsy or stress an adrenal mass before excluding pheochromocytoma.

— Stress-dose steroids perioperatively for cortisol-secreting tumor.

— Genetic testing if <45, bilateral, paraganglioma, or family history.

— Closed-loop communication between ED/radiology/PCP/endocrinology.

— Document plan, schedule follow-up before discharge, track in registry.

Board pearl: Biochemistry before biopsy, α before β, AVS before adrenalectomy in aldosteronism, and stress-dose steroids before extubation in any Cushing resection — these four "before" rules cover most Step 3 traps in adrenal incidentaloma management.

Workup essentials:

Surgical triggers:

Safety nonnegotiables:

Transition of care: