Perioperative & Surgical Care

Adrenalectomy: indications and perioperative management

Clinical Overview and When to Suspect Adrenalectomy

— Pheochromocytoma/paraganglioma (functional catecholamine-secreting tumor) — virtually always resected after α-blockade

— Aldosterone-producing adenoma (Conn syndrome) with confirmed lateralization on adrenal vein sampling

— Cortisol-secreting adenoma causing ACTH-independent Cushing syndrome

— Adrenocortical carcinoma (ACC) — suspected when mass >4 cm, irregular, heterogeneous, or with high unenhanced HU

— Adrenal metastasis in oligometastatic disease (lung, RCC, melanoma) with controlled primary

— Nonfunctioning incidentaloma if >4 cm, growing >0.8 cm/yr, or radiographically suspicious

— Resistant hypertension + hypokalemia → primary aldosteronism workup

— Episodic HTN, headache, palpitations, diaphoresis → pheochromocytoma

— Central obesity, striae, proximal weakness, easy bruising → Cushing

— Virilization or feminization → consider ACC

— Incidental mass on CT done for other reasons (very common entry point)

— Laparoscopic transabdominal or posterior retroperitoneoscopic — preferred for benign lesions <6 cm

— Open adrenalectomy — for ACC, masses >6–8 cm, local invasion, or IVC thrombus

Board pearl: Never biopsy an adrenal mass until pheochromocytoma has been biochemically excluded — biopsy can precipitate fatal hypertensive crisis. Biochemical workup (metanephrines, aldosterone/renin, dexamethasone suppression) precedes any tissue sampling or surgical planning in every adrenal incidentaloma case on Step 3.

Adrenalectomy is removal of one or both adrenal glands, performed for hormonally active tumors, suspected or confirmed malignancy, or symptomatic/large adrenal masses. Step 3 emphasizes patient selection, perioperative hormonal control, and longitudinal follow-up more than operative technique.

Core indications:

When to suspect a surgical adrenal lesion:

Approaches:

Presentation Patterns and Key History

— Ask about family history: MEN2A/2B (medullary thyroid Ca, hyperparathyroidism), VHL (hemangioblastomas, RCC), NF1 (café-au-lait, neurofibromas), SDHB/SDHD mutations

— Sustained vs paroxysmal HTN; orthostasis between spells is classic

— Often normokalemic — do not require low K+ to screen

— Symptoms: muscle weakness, polyuria, fatigue, headache

— Ask explicitly about exogenous steroids (inhaled, topical, joint injections, megestrol) — most common cause overall

Key distinction: β-blocker started before α-blockade in pheochromocytoma causes unopposed α-vasoconstriction → hypertensive crisis. Always confirm α-blockade for ≥10–14 days before adding β-blocker for reflex tachycardia. This is a recurring Step 3 stem trap.

Pheochromocytoma triad: episodic headache, palpitations, diaphoresis — present in ~90% of symptomatic cases. Paroxysms triggered by exertion, anesthesia induction, micturition (bladder paragangliomas), tyramine foods, or β-blocker monotherapy.

Primary aldosteronism: screen any patient with HTN + spontaneous or diuretic-induced hypokalemia, resistant HTN (≥3 drugs), HTN <30, HTN + adrenal incidentaloma, HTN + sleep apnea, or HTN + family hx early stroke.

Cushing syndrome: weight gain, moon facies, dorsocervical fat pad, abdominal striae >1 cm wide and purple, proximal myopathy, glucose intolerance, osteoporosis, mood lability, recurrent infections.

Adrenocortical carcinoma: rapid-onset mixed hormonal syndrome (Cushing + virilization in women), abdominal pain, palpable mass, weight loss.

Incidentaloma history: review prior imaging for stability, prior malignancy history (metastasis suspicion), and medication list.

Physical Exam Findings and Hemodynamic Assessment

— Paroxysmal severe HTN (SBP often >200), tachycardia, pallor (vasoconstriction, not flushing), tremor, diaphoresis

— Orthostatic hypotension between spells — clue to volume contraction from chronic α-stimulation

— Retinal exam: hypertensive retinopathy

— Skin: café-au-lait (NF1), mucosal neuromas (MEN2B), marfanoid habitus

— Sustained HTN, often without end-organ damage proportional to BP

— Usually no edema (aldosterone escape phenomenon)

— Proximal weakness if profoundly hypokalemic

— Centripetal obesity, supraclavicular/dorsocervical fat pads, facial plethora, thin skin, ecchymoses, wide violaceous striae, proximal muscle wasting (rise from chair test)

— Hyperpigmentation suggests ACTH-dependent etiology (not adrenal primary)

— Palpable flank/abdominal mass, signs of mixed hormone excess, virilization (hirsutism, clitoromegaly, deepened voice) or feminization (gynecomastia)

— Baseline BP/HR trends, orthostatics

— Volume status — patients with pheochromocytoma are chronically volume-contracted; document mucous membranes, JVP, capillary refill

— ECG for LVH, strain, ischemia, prolonged QT

— Echocardiogram if longstanding HTN, catecholamine cardiomyopathy suspected, or planned major resection

— Glucose (catecholamine-induced insulin resistance), electrolytes (K+, Mg2+, HCO3-)

Step 3 management: Adequate preoperative α-blockade is judged clinically by target BP <130/80 seated, ≥90/60 standing, HR 60–80 seated, 70–90 standing, and mild nasal stuffiness/orthostasis — these endpoints, not a fixed drug dose, guide readiness for OR.

Pheochromocytoma:

Primary aldosteronism:

Cushing syndrome:

Adrenocortical carcinoma:

Preoperative hemodynamic assessment:

Diagnostic Workup — Initial Labs and Imaging

— Pheochromocytoma: plasma free metanephrines (highest sensitivity ~99%) OR 24-hr urinary fractionated metanephrines. Avoid TCAs, labetalol, acetaminophen, levodopa before test — false positives common.

— Primary aldosteronism: morning aldosterone-to-renin ratio (ARR). ARR >20 with aldosterone >15 ng/dL is suggestive. Discontinue MR antagonists (spironolactone, eplerenone) and amiloride 4–6 weeks before; ACEi/ARB/diuretics can usually be continued but verify per Endocrine Society.

— Cushing syndrome: any of — overnight 1-mg dexamethasone suppression test (cortisol >1.8 µg/dL = positive), late-night salivary cortisol ×2, or 24-hr urine free cortisol ×2. If positive → measure ACTH to distinguish adrenal (low/suppressed) vs pituitary/ectopic (normal/high).

— Sex steroids/precursors (DHEA-S, testosterone, 17-OH-progesterone) if virilization, feminization, or suspected ACC

— Unenhanced HU ≤10 → lipid-rich adenoma (benign)

— Absolute washout >60% or relative washout >40% at 15 min → benign adenoma

— High unenhanced HU + poor washout, heterogeneity, irregular margins, necrosis, calcification → suspicious for ACC or pheochromocytoma

— Size >4 cm raises ACC risk; >6 cm has ~25% ACC risk

— MRI with chemical shift: signal drop on out-of-phase = adenoma; pheochromocytomas often T2 bright ("light bulb")

Board pearl: FDG-PET is useful when ACC or metastasis is suspected. MIBG scintigraphy or Ga-68 DOTATATE PET localizes extra-adrenal or metastatic paragangliomas — order when biochemistry is positive but cross-sectional imaging is unrevealing.

Every adrenal incidentaloma gets a biochemical and radiographic workup:

Biochemical screening — functional status:

Imaging characterization — CT adrenal protocol (unenhanced + delayed):

Diagnostic Workup — Advanced and Confirmatory Studies

— Oral salt loading with 24-hr urine aldosterone >12 µg/24h confirms

— Saline infusion test, fludrocortisone suppression, or captopril challenge are alternatives

— Cosyntropin-stimulated protocol most common; selectivity index ≥5 confirms adequate cannulation; lateralization index ≥4 indicates unilateral disease

— Patients <35 yr with unilateral CT adenoma and classic biochemistry may proceed to surgery without AVS

— CT or MRI abdomen/pelvis locates >95%

— 123I-MIBG or Ga-68 DOTATATE for metastatic, multifocal, or extra-adrenal disease

— Genetic testing offered to ALL patients (≥40% carry germline mutation): RET, VHL, NF1, SDHx, MAX, TMEM127

— Calcitonin and PTH if MEN2 suspected

— Low ACTH (<5 pg/mL) → adrenal CT/MRI

— Normal/high ACTH → pituitary MRI ± high-dose dexamethasone suppression and inferior petrosal sinus sampling (IPSS) to distinguish pituitary from ectopic ACTH

— CRH stimulation test as adjunct

— Full hormonal panel (cortisol, aldosterone, metanephrines, DHEA-S, testosterone/estradiol, 17-OHP)

— Chest/abdomen/pelvis CT for staging; FDG-PET for metastases

— Avoid percutaneous biopsy (seeding risk, often nondiagnostic, only useful if metastasis suspected and pheo excluded)

Step 3 management: AVS is operator-dependent — refer to a high-volume center. Skipping AVS in PA >35 yr is a common board "wrong move."

Primary aldosteronism — confirmatory testing (required before AVS unless spontaneous hypokalemia + suppressed renin + aldosterone >20):

Adrenal vein sampling (AVS): the gold standard to lateralize aldosterone hypersecretion before unilateral adrenalectomy. Required in nearly all patients >35 yr with confirmed PA considering surgery, because CT can miss small adenomas and falsely identify nonfunctional nodules.

Pheochromocytoma — after positive biochemistry:

Cushing syndrome — source localization after ACTH measurement:

Adrenocortical carcinoma:

Risk Stratification and First-Line Management Logic

— All biochemically proven tumors → surgical resection after medical preparation

— Bilateral disease (often hereditary) → cortical-sparing adrenalectomy when feasible to preserve steroidogenesis and avoid lifelong replacement

— Metastatic → multimodal: surgery, MIBG therapy, sunitinib, chemotherapy

— Unilateral on AVS → laparoscopic adrenalectomy (curative HTN in ~50%, biochemical cure ~95%)

— Bilateral hyperplasia → medical management with spironolactone (or eplerenone if gynecomastia/sexual side effects)

— Open en-bloc resection at experienced center (laparoscopy generally avoided due to capsular rupture/seeding)

— Adjuvant mitotane for high-risk (large, high Ki-67, positive margins, stage III)

— Adjuvant radiation for positive margins; chemotherapy (EDP-M) for advanced disease

— Any functional tumor

— Size >4 cm with suspicious imaging features

— Growth >0.8 cm/year or to >4 cm

— Imaging features concerning for malignancy regardless of size

Board pearl: A nonfunctional, benign-appearing (<10 HU, smooth, <4 cm) incidentaloma needs no surgery and no repeat imaging per 2023 European Society of Endocrinology updated guidance — a major change from older "repeat at 6/12/24 months" answers. Confirm with hormonal workup at baseline only.

Decision tree by lesion type:

Pheochromocytoma/paraganglioma:

Primary aldosteronism:

Cushing syndrome from adrenal adenoma: unilateral laparoscopic adrenalectomy is first-line; expect postoperative adrenal insufficiency from contralateral suppression — plan stress-dose and taper.

Adrenocortical carcinoma:

Adrenal incidentaloma — surgical thresholds:

Adrenal metastasis: consider adrenalectomy if isolated, primary controlled, disease-free interval >6 months, good performance status.

Pharmacotherapy — Preoperative Medical Optimization

— Phenoxybenzamine (non-selective, irreversible) 10 mg BID, titrate up by 10–20 mg every 2–3 days to target BP and orthostasis; typical doses 1 mg/kg/day. Long half-life can cause post-op hypotension.

— Alternative: doxazosin (selective α1, reversible) 2–8 mg daily — less reflex tachycardia, faster postop recovery, increasingly preferred

— Duration: minimum 10–14 days preop

— High-sodium diet (>5 g/day) + generous fluid intake during last 3–5 days to re-expand contracted intravascular volume and prevent post-resection hypotension

— β-blocker (propranolol, atenolol, metoprolol) only after α-blockade established, to control reflex tachycardia or catecholamine-induced arrhythmia. Labetalol is NOT adequate as initial blockade — its α:β ratio is too β-heavy (1:7 IV).

— Metyrosine (α-methyl-tyrosine, inhibits tyrosine hydroxylase) added for refractory cases, very large tumors, or malignant pheo

— Calcium channel blockers (nicardipine, amlodipine) as adjuncts

— Spironolactone 25–100 mg daily or eplerenone to normalize K+ and BP; hold MR antagonists 4–6 weeks before AVS, then resume bridging to surgery

— Replete potassium; correct metabolic alkalosis

— If severe hypercortisolism → ketoconazole, metyrapone, osilodrostat, or mifepristone to lower cortisol, control glucose/BP, reduce infection and thromboembolism risk

— VTE prophylaxis — Cushing is a hypercoagulable state

Step 3 management: Document at preop visit — α-blockade duration, orthostatic vitals (mild orthostasis is the goal), nasal stuffiness, K+ normalized, glucose controlled, VTE prophylaxis ordered, and stress-dose steroid plan in chart. These appear on CCS as time-sensitive orders.

Pheochromocytoma — α-blockade first, ALWAYS:

Primary aldosteronism preop:

Cushing syndrome preop:

Operative Approach and Intraoperative Management

— Benign functional adenomas (Conn, cortisol-secreting, most pheochromocytomas)

— Tumors <6 cm without invasion

— Approaches: transabdominal lateral, posterior retroperitoneoscopic (faster recovery, prone position, ideal for bilateral)

— Suspected/confirmed ACC (preserves capsule, allows en-bloc resection)

— Tumors >6–8 cm, local invasion, IVC tumor thrombus

— Large or invasive paragangliomas

— Arterial line, large-bore IV access, often CVC

— Avoid drugs that release histamine or catecholamines: morphine, atracurium, succinylcholine, ephedrine, metoclopramide, glucagon — all can trigger crisis

— Tumor manipulation → catecholamine surge: treat with IV nicardipine, nitroprusside, phentolamine, esmolol, or magnesium

— After venous ligation → catecholamine withdrawal + residual α-blockade → profound hypotension: treat with fluids, vasopressin, norepinephrine

— Watch for hypoglycemia post-resection (loss of catecholamine-driven insulin suppression)

— Give stress-dose hydrocortisone (100 mg IV at induction, then 50 mg q8h) — contralateral gland is suppressed

— Continue tapered replacement until HPA axis recovers (months)

— Monitor K+ — risk of hyperkalemia postop from suppressed contralateral zona glomerulosa

— Hold spironolactone postoperatively

CCS pearl: On intraop hypotension after pheo resection, fluids + vasopressin/norepinephrine beats escalating pressors blindly; on hypertensive surge during dissection, phentolamine or nicardipine bolus — avoid pure β-blocker alone.

Laparoscopic adrenalectomy is standard for:

Open adrenalectomy for:

Intraoperative anesthetic priorities — pheochromocytoma:

Cushing/cortisol-secreting adenoma:

Aldosteronoma:

Bilateral adrenalectomy (e.g., refractory Cushing, bilateral pheo): lifelong glucocorticoid + mineralocorticoid (fludrocortisone) replacement required; counsel on Nelson syndrome risk after bilateral adrenalectomy for Cushing disease.

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline cardiovascular risk; obtain preop ECG, echocardiogram if functional capacity <4 METs or new symptoms, and risk-stratify with RCRI or NSQIP MICA calculator

— Polypharmacy increases interaction risk with α-blockers and antihypertensives — reconcile carefully

— Orthostatic hypotension from α-blockade is more pronounced and more dangerous (fall risk); titrate slower, target less aggressive orthostasis

— Frailty assessment (gait speed, grip strength) predicts postoperative morbidity better than age alone

— Delirium prevention: minimize benzodiazepines, anticholinergics, opioids; early mobilization, sleep hygiene, reorientation

— Metanephrine assays unaffected, but plasma metanephrines may be mildly elevated in CKD — interpret with caution

— Avoid gadolinium (NSF risk) at eGFR <30; use noncontrast MRI or unenhanced CT with washout protocol

— Adjust antihypertensives: prefer dihydropyridine CCB and α-blockers; ACEi/ARB cautiously with K+ monitoring

— Spironolactone/eplerenone: avoid if eGFR <30 or K+ >5.0

— Mitotane after ACC resection — no major renal adjustment but monitor lipids, liver

— Ketoconazole, metyrapone, mitotane, osilodrostat all hepatically metabolized — baseline LFTs, monitor closely; ketoconazole contraindicated with significant hepatic dysfunction (boxed warning)

— Coagulopathy increases bleeding risk — correct INR, optimize albumin and nutrition

— Phenoxybenzamine has reduced clearance — start lower dose

— Catecholamine cardiomyopathy (Takotsubo-like) from pheo can reverse after resection — preop echo + cardiology co-management

— Optimize EF before elective surgery if possible

Board pearl: In elderly patients with adrenal incidentaloma <4 cm, nonfunctional, and benign features, surveillance is appropriate — the operative risk often exceeds the malignant potential. Shared decision-making is the right Step 3 answer.

Elderly patients:

Renal impairment:

Hepatic impairment:

Cardiac dysfunction:

Special Populations — Pregnancy and Pediatrics

— Rare but highly lethal if undiagnosed (maternal mortality up to 50%); masquerades as preeclampsia but lacks proteinuria and has paroxysmal pattern

— Diagnosis: plasma or 24-hr urine metanephrines (safe); imaging with MRI without gadolinium

— Management:

— α-blockade with phenoxybenzamine or doxazosin — both used in pregnancy; phenoxybenzamine crosses placenta and may cause neonatal hypotension/respiratory depression — coordinate with neonatology

— β-blocker (labetalol acceptable in pregnancy, only after α-blockade)

— Timing of surgery:

— Diagnosed <24 weeks → laparoscopic adrenalectomy in second trimester after medical preparation

— Diagnosed ≥24 weeks → medical management to term, planned cesarean with concurrent or subsequent adrenalectomy

— Avoid vaginal delivery (uterine contractions trigger catecholamine release)

— Rare; adrenal adenoma is more common cause in pregnancy than pituitary

— High fetal loss, preterm birth, gestational diabetes/HTN

— Adrenalectomy in 2nd trimester preferred; metyrapone if medical control needed

— Higher proportion are malignant (ACC, neuroblastoma) and hereditary

— Pheochromocytomas in children: often bilateral, extra-adrenal, hereditary (VHL, SDHB, NF1) → genetic testing mandatory, consider cortical-sparing surgery

— Neuroblastoma in <5 yr: urinary HVA/VMA, MIBG scan, staging-based multimodal therapy

Step 3 management: Any pregnant patient with paroxysmal HTN, headache, and palpitations — especially before 20 weeks or without proteinuria — order plasma metanephrines before assuming preeclampsia. Missing pheochromocytoma in pregnancy is a sentinel safety event.

Pheochromocytoma in pregnancy:

Cushing in pregnancy:

Primary aldosteronism in pregnancy: spironolactone contraindicated (antiandrogen, feminization of male fetus); use eplerenone or amiloride; adrenalectomy in 2nd trimester for unilateral disease.

Pediatric adrenal tumors:

Complications and Adverse Outcomes

— Hypertensive crisis during tumor manipulation (pheo) — stroke, MI, arrhythmia

— Hemorrhage from adrenal vein, IVC, renal vessels, splenic injury (left adrenalectomy)

— Pneumothorax (posterior approach), diaphragmatic injury

— Conversion to open ~5%

— Hypotension after pheo resection (catecholamine withdrawal + residual α-blockade): fluids, norepinephrine, vasopressin

— Hypoglycemia within 24 h after pheo resection (rebound insulin release) — monitor q1–2h x 24h

— Acute adrenal insufficiency after unilateral resection for cortisol-secreting adenoma or bilateral adrenalectomy: hypotension, hyponatremia, hypoglycemia, hyperkalemia, nausea — treat with hydrocortisone 100 mg IV immediately

— Hyperkalemia after aldosteronoma resection (suppressed contralateral zona glomerulosa) — usually transient

— VTE — Cushing patients especially; continue prophylaxis

— Persistent hypertension after PA surgery: ~50% require ongoing antihypertensives, more likely with age >50, duration >6 yr, ≥2 prior meds, family history

— Recurrence of pheochromocytoma: 15% over 10 yr (higher in hereditary, paraganglioma, large tumors) — lifelong biochemical surveillance

— Nelson syndrome after bilateral adrenalectomy for Cushing disease: pituitary corticotroph adenoma growth, hyperpigmentation, mass effect

— Adrenal crisis triggered by illness/surgery/missed steroid dose in patients on replacement

— Incisional hernia, chronic pain, wound infection

— Local recurrence, peritoneal carcinomatosis (worse with capsular rupture or laparoscopic approach in unsuspected ACC)

— Mitotane toxicity: GI, neurologic, adrenal insufficiency, gynecomastia, hyperlipidemia, hepatotoxicity

Board pearl: Any postop adrenalectomy patient who is hypotensive, hyponatremic, and hyperkalemic on POD 1–3 — give IV hydrocortisone first, then investigate. Empiric stress-dose steroids in suspected adrenal crisis save lives; the cosyntropin test can wait.

Intraoperative:

Immediate postoperative:

Subacute/late:

ACC-specific:

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

— All pheochromocytoma resections for ≥24 h (hemodynamic lability, hypoglycemia monitoring, arterial line)

— Large ACC resections with significant blood loss or IVC reconstruction

— Bilateral adrenalectomy

— Catecholamine cardiomyopathy or preop EF <40%

— Endocrinology — biochemical confirmation, preop preparation, postop replacement plan

— Cardiology — if catecholamine cardiomyopathy, severe HTN, or significant cardiac history

— Anesthesiology — high-risk preop evaluation, especially pheo

— Genetics — all pheo/paraganglioma, young Cushing/PA, ACC

— Medical oncology + radiation oncology — ACC and adrenal metastasis

— High-risk OB — pregnancy

— SBP <90 unresponsive to 2 L crystalloid → vasopressors, urgent steroid bolus

— New arrhythmia, chest pain, troponin rise → cardiology

— Persistent abdominal pain, dropping Hgb → CT, return to OR

— Altered mental status with hyponatremia or hypoglycemia → adrenal crisis workup, ICU

— Refractory hyperglycemia in Cushing patient → insulin drip, endocrine input

CCS pearl: On a CCS pheochromocytoma case, after resection — transfer to ICU, arterial line, q1h glucose × 24h, stress-dose hydrocortisone if cortisol-secreting, continuous telemetry. Forgetting glucose monitoring loses points.

Mandatory ICU admission post-adrenalectomy:

Stepdown/floor acceptable: uncomplicated laparoscopic adrenalectomy for aldosteronoma or small cortisol adenoma — early ambulation, advance diet POD 1, discharge POD 1–2.

Multidisciplinary consults preop:

Escalation triggers postoperatively:

Transfer to high-volume center for: suspected ACC, large pheochromocytoma, hereditary syndromes requiring cortical-sparing surgery, AVS, IPSS, complex reoperative adrenal surgery. Volume-outcome relationship for adrenal surgery is well documented (>20 cases/year associated with lower morbidity).

Key Differentials — Same-Category (Adrenal) Causes

— Adenoma: unilateral, ACTH suppressed, treated by unilateral adrenalectomy

— Bilateral macronodular: both glands, may require bilateral adrenalectomy or mifepristone/osilodrostat

— PPNAD: small pigmented nodules, often syndromic; bilateral adrenalectomy curative

— APA → surgical cure with unilateral adrenalectomy after AVS lateralization

— IHA → medical (spironolactone/eplerenone); surgery does not help

— Glucocorticoid-remediable aldosteronism (FH-I): autosomal dominant, early-onset HTN/stroke, treated with low-dose dexamethasone, not surgery

— Pheo: adrenal medulla; paraganglioma: extra-adrenal sympathetic chain (organ of Zuckerkandl, bladder, mediastinum) or parasympathetic (head/neck, often nonsecretory)

— Paragangliomas: higher malignancy risk, especially SDHB-mutated

— ACC: >4 cm, heterogeneous, high HU, irregular margins, often hyperfunctional with mixed steroid excess, weight loss, rapid progression

— Adenoma: homogeneous, lipid-rich, <4 cm, washout >60%

Key distinction: CT washout is the workhorse for benign adenoma. A mass with <10 HU unenhanced is virtually always a benign adenoma — even if 4–6 cm, can sometimes be observed if nonfunctional, though most are still resected by convention.

Functional adrenal masses to distinguish before surgery:

Cortisol-secreting adenoma vs bilateral macronodular hyperplasia vs PPNAD (Carney complex):

Aldosterone-producing adenoma (APA) vs idiopathic bilateral hyperplasia (IHA):

Pheochromocytoma vs paraganglioma:

Adrenocortical carcinoma vs large adenoma:

Adrenal myelolipoma: benign, fat-containing on CT, surgery only if symptomatic or >6 cm with hemorrhage risk

Adrenal cyst, hematoma, ganglioneuroma, neuroblastoma (pediatric): characterize by imaging and clinical context.

Key Differentials — Other-Category Causes

— Nonadherence (most common), white-coat HTN, suboptimal regimen, high salt intake, NSAIDs, OCPs, decongestants, licorice, stimulants

— Renovascular disease (fibromuscular dysplasia in young women, atherosclerotic in elderly) — abdominal bruit, asymmetric kidneys, ACEi-induced AKI

— Obstructive sleep apnea — coexists in >40% of resistant HTN

— Cushing syndrome, hyperthyroidism, hyperparathyroidism

— Coarctation of aorta in young patients — BP differential, rib notching

— Panic disorder, hyperventilation

— Cocaine, amphetamines, MDMA, decongestants

— MAOI + tyramine ("cheese reaction")

— Clonidine or β-blocker withdrawal

— Baroreflex failure, autonomic epilepsy, mast cell disorders/carcinoid

— Renovascular HTN with intermittent flow

— Exogenous glucocorticoids (most common — always ask)

— Chronic alcoholism, severe depression, poorly controlled diabetes, obesity (pseudo-Cushing) — overlapping biochemistry, distinguished by dexamethasone-CRH test, late-night salivary cortisol, clinical context

— Diuretics, vomiting, Liddle syndrome (low aldosterone, low renin), apparent mineralocorticoid excess (licorice, AME), CAH (11-β or 17-α hydroxylase deficiency), Cushing with high cortisol overwhelming 11β-HSD2, renovascular HTN with secondary hyperaldosteronism (high renin)

Board pearl: Always check renin along with aldosterone — low renin points to primary aldosteronism or other low-renin states (Liddle, AME, CAH, Cushing); high renin with high aldosterone suggests renovascular or diuretic-related secondary hyperaldosteronism, not surgical disease.

Causes of resistant hypertension to consider before assuming PA:

Causes of episodic HTN mimicking pheo ("pseudopheochromocytoma"):

Causes of Cushingoid appearance without endogenous Cushing:

Causes of hypokalemia + HTN besides PA:

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Discontinue α- and β-blockers gradually; antihypertensives often unnecessary if cured

— Lifelong annual biochemical surveillance: plasma or 24-hr urine metanephrines — recurrence and metachronous tumors common in hereditary disease

— Genetic counseling and family screening if mutation identified

— Patient ID/medical alert noting prior pheochromocytoma (avoid triggering drugs in future anesthetics)

— Stop spironolactone/eplerenone

— Monitor K+ — may need transient supplementation withdrawal and watch for hyperkalemia for weeks

— Continue or wean antihypertensives based on BP response; many patients still need 1–2 agents

— Annual BP, K+, renin/aldosterone if hypertension persists

— Hydrocortisone replacement (typically 15–25 mg/day divided, with larger morning dose) — required until HPA axis recovers, often 6–18 months

— Stress dosing instructions: triple oral dose for fever/illness; IM hydrocortisone 100 mg emergency kit; medical alert bracelet

— Periodic morning cortisol or cosyntropin test to assess recovery before weaning

— Address persistent comorbidities: osteoporosis (DEXA, bisphosphonate if indicated), diabetes, dyslipidemia, mood disorder, VTE prophylaxis continuation if bedbound

— Lifelong glucocorticoid + fludrocortisone 0.05–0.2 mg daily

— If for Cushing disease: monitor for Nelson syndrome with annual ACTH and pituitary MRI

— Adjuvant mitotane (target levels 14–20 mg/L), with glucocorticoid replacement (mitotane induces CYP3A4 and accelerates cortisol metabolism — double-dose hydrocortisone)

— Imaging every 3 months × 2 years, then every 6 months

Step 3 management: Every patient discharged on glucocorticoid replacement leaves with: written sick-day rules, IM hydrocortisone emergency kit + training, medical alert ID, and clear endocrinology follow-up within 2–4 weeks.

Discharge medications by indication:

Pheochromocytoma post-resection:

Aldosteronoma post-resection:

Cortisol-secreting adenoma post-resection:

Bilateral adrenalectomy:

ACC:

Follow-Up, Monitoring Parameters, and Counseling

— Plasma/urine metanephrines at 2–6 weeks post-op to confirm biochemical cure

— Then annually for life (recurrence rate 15% at 10 yr, higher in hereditary/SDHB/paraganglioma/large tumors)

— Imaging only if biochemistry abnormal or hereditary syndrome warrants periodic scanning

— Genetic testing for all; cascade testing for family

— Stop K+ supplements and MR antagonists day of surgery

— Check K+ and creatinine within 1 week, then periodically

— BP daily at home, follow up at 4–6 weeks; expect gradual improvement over 3–6 months

— Reassess ARR at 3 months if hypertension persists

— Morning cortisol (before AM hydrocortisone dose) every 3–6 months to assess HPA recovery

— Cosyntropin stimulation when morning cortisol >10 µg/dL — pass = wean replacement

— Monitor weight, glucose, lipids, BP, bone density, mood — expect gradual reversal of features over 6–12 months but full normalization may take 2 years; striae and osteoporosis often persist

— CT chest/abdomen/pelvis every 3 months × 2 yr, then every 6 months × 3 yr

— Hormonal markers (whichever were elevated preop) at same intervals

— Mitotane levels every 4 weeks until therapeutic, then every 3 months

— Activity: no heavy lifting >10 lb for 4–6 weeks (laparoscopic) or 6–8 weeks (open)

— Return to work: 2 weeks laparoscopic, 4–6 weeks open

— Wound care, signs of infection, when to call

— Mental health support post-Cushing (depression and anxiety common)

— Smoking cessation, BP/glucose home monitoring, diet/weight management

Board pearl: Persistent HTN after PA surgery occurs in ~50%. Counsel preoperatively that surgery cures hypokalemia and excess aldosterone but may not cure hypertension — manages expectations and prevents perceived "treatment failure."

Pheochromocytoma — surveillance schedule:

Primary aldosteronism — post-op:

Cushing syndrome — recovery monitoring:

ACC — oncologic surveillance:

Counseling and rehabilitation:

Ethical, Legal, and Patient Safety Considerations

— Risks beyond standard surgical risks: hypertensive crisis intraop, adrenal insufficiency requiring lifelong steroid replacement (especially bilateral, Cushing), recurrence, infertility/sexual dysfunction implications of hormonal changes, conversion to open

— In suspected ACC: discuss need for open approach and rationale; document

— Shared decision-making for incidentalomas in elderly/frail patients where surveillance may be safer than surgery — document goals, life expectancy, comorbidity discussion

— Genetic implications for hereditary pheochromocytoma/paraganglioma — explain that genetic testing affects family members and may have insurance/employment ramifications (GINA protects health insurance and employment but not life/disability/long-term care insurance in the US)

— Steroid replacement post-adrenalectomy is the leading preventable cause of post-discharge adrenal crisis. Confirm at discharge: prescription filled, patient/family demonstrates IM hydrocortisone injection, written sick-day plan in hand, follow-up scheduled. Medication reconciliation across handoffs is critical.

— Medical alert identification for all patients on chronic glucocorticoids

— Avoid premature discontinuation of α-blockade in pheo patients before tumor removal — document indication if changes made

— Hereditary pheochromocytoma/paraganglioma: encourage but cannot mandate family disclosure; offer to facilitate communication with relatives via genetic counselors

— Avoid unnecessary repeat imaging on benign-appearing nonfunctional incidentalomas (Choosing Wisely / 2023 ESE guidance) — overdiagnosis and overtreatment risks

— Adrenal surgery outcomes correlate with volume; ethically obligated to refer ACC and complex cases to high-volume centers

Step 3 management: A patient on hydrocortisone replacement scheduled for any future surgery, illness, or procedure needs stress-dose steroid protocol communicated to every new provider. Failure to communicate is a sentinel event — use structured handoff (SBAR, EHR alerts) and patient-held medical alert documentation.

Informed consent — adrenalectomy-specific elements:

Patient safety — high-risk transitions:

Mandatory reporting / public health:

Resource stewardship:

Surgeon volume and referral ethics:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: Pheochromocytoma stem with hypertensive crisis on induction → IV phentolamine (or nicardipine), volume, then esmolol for reflex tachycardia. Never push pure β-blocker first.

Phenoxybenzamine = irreversible, non-selective α-blocker; long half-life → postop hypotension risk

β-blocker before α-blocker in pheo = hypertensive crisis

Plasma free metanephrines = most sensitive screening test for pheo (99%)

CT washout >60% absolute / >40% relative = benign adenoma

Unenhanced HU ≤10 = lipid-rich adenoma

>4 cm + suspicious features or >6 cm = surgical resection regardless of function

ARR >20 + aldosterone >15 = screen positive for PA

AVS required before unilateral adrenalectomy for PA in patients >35 yr

MEN2A = medullary thyroid Ca + pheo + primary hyperparathyroidism (RET)

MEN2B = medullary thyroid Ca + pheo + mucosal neuromas + marfanoid (RET)

VHL = pheo + RCC + hemangioblastoma + pancreatic NET

NF1 = café-au-lait + neurofibromas + pheo (5%)

SDHB mutation = highest malignant transformation risk for paraganglioma

10% rule for pheo (legacy): 10% bilateral, 10% extra-adrenal, 10% malignant, 10% pediatric, 10% familial — outdated; now up to 40% hereditary

Cushing screening: overnight 1-mg dex (cortisol >1.8 µg/dL), late-night salivary cortisol, 24-hr UFC — confirm with two positive tests

ACTH distinguishes Cushing disease (pituitary) from adrenal Cushing (low ACTH)

Inferior petrosal sinus sampling distinguishes pituitary vs ectopic ACTH

Mitotane = adjuvant for ACC; induces CYP3A4 → must double hydrocortisone replacement

Hypoglycemia after pheo resection = monitor q1–2h × 24 h

Bilateral adrenalectomy for Cushing disease → Nelson syndrome risk

Spironolactone in pregnancy = contraindicated (antiandrogenic); use eplerenone

Adrenal incidentaloma without function and benign imaging = no repeat imaging needed (2023 ESE)

Catecholamine cardiomyopathy can reverse after pheo resection

Board Question Stem Patterns

Key distinction: "Next step" in adrenal stems usually means biochemical workup first, then imaging, then localization (AVS or MIBG/DOTATATE), then medical preparation, then surgery — skipping steps is the wrong answer.

Stem 1 — Pheochromocytoma preop: Young patient with episodic headaches, palpitations, diaphoresis, BP 180/110. Plasma metanephrines elevated, CT shows 4-cm adrenal mass. Best next step? → Start α-blockade (phenoxybenzamine or doxazosin) for 10–14 days with high-salt diet, then add β-blocker if tachycardic, then surgery. Distractor: "immediate adrenalectomy" or "start atenolol now."

Stem 2 — β-blocker trap: Patient with newly diagnosed pheochromocytoma started on metoprolol and develops worsening HTN, chest pain. Cause? → Unopposed α-vasoconstriction. Treatment: phentolamine IV, add α-blocker, then resume β-blocker only after adequate α-blockade.

Stem 3 — Primary aldosteronism workup: 45-year-old with resistant HTN on 3 drugs, K+ 3.0. Next step? → Plasma aldosterone-renin ratio (not adrenal CT first). After positive screen → confirmation test → adrenal CT → AVS → unilateral adrenalectomy if lateralized.

Stem 4 — Adrenal incidentaloma: 6-cm heterogeneous adrenal mass with HU 35, irregular margins, washout 30% found on trauma CT. Hormonal workup negative. Next step? → Adrenalectomy (size + suspicious imaging features → ACC concern); open approach if ACC suspected.

Stem 5 — Postop hypotension after pheo: Patient hypotensive immediately after tumor venous ligation. Cause and management? → Catecholamine withdrawal + residual α-blockade; fluids, vasopressin or norepinephrine, monitor for hypoglycemia.

Stem 6 — Postop adrenal insufficiency: POD 1 after unilateral adrenalectomy for cortisol-secreting adenoma, patient is hypotensive, nauseated, Na 128, K 5.5. Next step? → IV hydrocortisone 100 mg immediately, fluids; do not wait for testing.

Stem 7 — Pregnancy: 22-week pregnant patient with paroxysmal HTN and headaches, no proteinuria. Next step? → Plasma metanephrines, not preeclampsia workup alone.

Stem 8 — Hereditary syndrome: Bilateral pheochromocytoma in a young patient with retinal hemangioblastoma. Diagnosis? → VHL. Surgical approach? → Cortical-sparing adrenalectomy to preserve steroidogenesis.

Stem 9 — Persistent HTN post-PA surgery: 60-yr-old, 10-yr HTN history, post unilateral adrenalectomy still on 2 antihypertensives at 6 months. Explanation? → Long-standing HTN with vascular remodeling; counsel — biochemical cure ≠ HTN cure.

One-Line Recap

Adrenalectomy is indicated for hormonally functional tumors (pheochromocytoma, lateralized aldosteronoma, cortisol-secreting adenoma), suspected adrenocortical carcinoma, oligometastatic disease, and adrenal masses >4 cm with suspicious features — with success hinging on rigorous biochemical confirmation, lesion-specific preoperative medical preparation, and structured postoperative hormone replacement and surveillance.

Board pearl: The two most common Step 3 traps in this topic are giving β-blocker first in pheo and skipping AVS before unilateral adrenalectomy for aldosteronism — recognizing both earns the points and prevents real-world harm.

Pheochromocytoma: α-blockade ≥10–14 days + high-salt diet → β-blocker if needed → resection → ICU with glucose monitoring → lifelong annual metanephrines + genetic testing.

Primary aldosteronism: ARR screen → confirm → CT → AVS in patients >35 yr → unilateral adrenalectomy only if lateralized; bilateral hyperplasia is medical (spironolactone/eplerenone).

Cushing from adrenal adenoma: low ACTH confirms adrenal source → unilateral adrenalectomy → stress-dose then taper hydrocortisone with emergency IM kit, sick-day rules, and HPA recovery testing over 6–18 months.

Adrenocortical carcinoma and large suspicious incidentalomas: open en-bloc resection at high-volume center, adjuvant mitotane (with doubled glucocorticoid replacement), close oncologic surveillance every 3 months.

Universal Step 3 safety nets: never biopsy an adrenal mass before excluding pheo; never start β-blocker before α-blocker; always give empiric IV hydrocortisone for suspected postoperative adrenal crisis before chasing labs; communicate steroid dependence at every care transition with medical alert ID and emergency injection training.