Adrenal Cortex (Cortisol, Aldosterone) And Medulla (Catecholamines)

Foundations and mechanisms

Adrenal cortical architecture, steroidogenesis and regulation

The adrenal cortex comprises three functional zones: zona glomerulosa producing mineralocorticoids, zona fasciculata producing glucocorticoids, and zona reticularis producing adrenal androgens. Steroid hormones are synthesised from cholesterol; the acute rate-limiting step is cholesterol transport into mitochondria by steroidogenic acute regulatory protein (StAR). This is clinically relevant because enzymatic blocks produce predictable steroid excess/deficiency patterns and because steroid synthesis is not stored: secretion depends on synthesis rate.

Zone	Principal product	Key enzymes	Dominant control	Core physiological role
Zona glomerulosa	Aldosterone	CYP11A1, 3β-HSD, CYP21A2, CYP11B2 aldosterone synthase	Angiotensin II, extracellular K+; ACTH minor/acute	Na+ retention, K+/H+ excretion, ECF volume
Zona fasciculata	Cortisol	CYP17A1, CYP21A2, CYP11B1	CRH–ACTH axis; circadian rhythm; stress	Permissive vascular tone, metabolism, anti-inflammatory effects
Zona reticularis	DHEA, androstenedione	CYP17A1 17,20-lyase	ACTH	Androgen precursor production

Cortisol secretion is pulsatile and circadian, peaking at approximately 0600–0800 h and nadiring around midnight. Normal production is about 5–10 mg/m²/day, roughly 10–20 mg hydrocortisone/day. Plasma cortisol is approximately 90% bound to corticosteroid-binding globulin and albumin; only free cortisol is biologically active. The plasma half-life is 60–90 minutes, but genomic effects persist for many hours. ACTH secretion is inhibited by cortisol via negative feedback at pituitary and hypothalamic levels.

Cortisol: receptor biology and physiological effects

Cortisol acts via intracellular glucocorticoid receptors that translocate to the nucleus and regulate gene transcription. Non-genomic effects also occur, particularly at high concentrations. Cortisol is permissive for catecholamine responsiveness: it upregulates α₁-adrenoceptors, maintains vascular smooth muscle reactivity, supports myocardial contractility, and contributes to normal free water clearance. Deficiency therefore causes vasodilatory shock, hyponatraemia and hypoglycaemia; excess causes hypertension, insulin resistance, myopathy, immune suppression and poor wound healing.

Steroid	Glucocorticoid potency	Mineralocorticoid potency	Approximate equivalent anti-inflammatory dose	Biological duration
Hydrocortisone	1	1	20 mg	8–12 h
Prednisolone	4	0.8	5 mg	12–36 h
Methylprednisolone	5	Minimal	4 mg	12–36 h
Dexamethasone	25–30	Negligible	0.75 mg	36–54 h

Clinically significant hypothalamic–pituitary–adrenal suppression is likely after prednisolone ≥5 mg/day for >4 weeks, although risk depends on dose, timing, route and potency. Short Synacthen testing commonly uses 250 micrograms tetracosactide IV/IM; many laboratories regard peak cortisol >430–500 nmol/L at 30 or 60 minutes as adequate, but assay-specific thresholds are essential.

Aldosterone and mineralocorticoid physiology

Aldosterone binds cytosolic mineralocorticoid receptors in principal cells of the cortical collecting duct, increasing transcription of epithelial sodium channels (ENaC) and basolateral Na⁺/K⁺-ATPase. The result is electrogenic Na⁺ reabsorption with K⁺ secretion; α-intercalated cells increase H⁺ secretion. Aldosterone excess therefore produces hypertension, hypokalaemia and metabolic alkalosis; deficiency produces hypovolaemia, hyperkalaemia and non-anion gap metabolic acidosis.

The glomerulosa is regulated predominantly by the renin–angiotensin–aldosterone system and plasma potassium. A fall in renal perfusion pressure, reduced macula densa NaCl delivery or β₁-sympathetic stimulation increases renin release. Angiotensin II constricts efferent arterioles and stimulates aldosterone synthesis. Plasma K⁺ is a direct and powerful stimulus: small increases above approximately 4.5–5.0 mmol/L augment aldosterone secretion. ACTH produces only a transient aldosterone rise.

Adrenal medulla: catecholamine synthesis, storage and metabolism

The adrenal medulla is a modified sympathetic ganglion. Preganglionic sympathetic fibres release acetylcholine onto nicotinic receptors on chromaffin cells. Catecholamine synthesis proceeds from tyrosine to DOPA via tyrosine hydroxylase rate limitation, then dopamine, noradrenaline and adrenaline. Cortisol-rich cortical venous drainage induces phenylethanolamine-N-methyltransferase, converting noradrenaline to adrenaline; hence the adrenal medulla secretes predominantly adrenaline, about 80%, with noradrenaline about 20%.

Catecholamines are stored in chromaffin granules with ATP and chromogranins, released by calcium-dependent exocytosis, and act through G-protein-coupled adrenoceptors. Their plasma half-life is short, approximately 1–3 minutes, due to neuronal uptake, extraneuronal uptake and metabolism by monoamine oxidase and catechol-O-methyltransferase to metanephrines and vanillylmandelic acid.

Receptor	G protein	Second messenger	Major effects relevant to anaesthesia
α1	Gq	IP3/DAG, ↑Ca2+	Arteriolar and venous constriction, ↑SVR, mydriasis
α2	Gi	↓cAMP	Presynaptic inhibition of noradrenaline, sedation, analgesia, bradycardia
β1	Gs	↑cAMP	↑Heart rate, contractility, conduction; renin release
β2	Gs	↑cAMP	Bronchodilation, skeletal muscle vasodilation, intracellular K+ shift
β3	Gs	↑cAMP	Lipolysis, thermogenesis

Core pathological classifications

Adrenal disorders are classified by hormone excess or deficiency and by primary adrenal versus secondary/tertiary hypothalamic–pituitary disease. Primary adrenal insufficiency causes low cortisol with high ACTH and usually aldosterone deficiency; secondary disease causes low ACTH with preserved aldosterone because RAAS remains intact. Cortisol excess is classified as ACTH-dependent, usually pituitary Cushing disease or ectopic ACTH, or ACTH-independent adrenal disease. Mineralocorticoid excess may be renin-suppressed primary hyperaldosteronism or renin-driven secondary hyperaldosteronism. Phaeochromocytoma and paraganglioma produce episodic or sustained catecholamine excess, with diagnosis based on plasma free or urinary fractionated metanephrines rather than catecholamines because metanephrine production is continuous within tumour cells.

Clinical assessment and investigations

Clinical presentation and diagnostic framing

Adrenal disease is examined clinically as syndromes of hormone excess or deficiency, with particular anaesthetic relevance because occult disease may present as refractory hypotension, hypertensive crisis, dysrhythmia, hypokalaemia, hyperglycaemia or unexplained lactic acidosis. Assessment should define the axis involved: glucocorticoid, mineralocorticoid or catecholamine, and distinguish primary adrenal pathology from secondary pituitary/hypothalamic or drug-related causes.

Syndrome	Typical clinical clues	Key differentials	High-yield perioperative concern
Adrenal insufficiency	Fatigue, weight loss, postural hypotension, salt craving; hyperpigmentation in primary disease; hyponatraemia, hyperkalaemia, hypoglycaemia	Sepsis, hypovolaemia, SIADH, hypopituitarism, chronic opioid or glucocorticoid exposure, etomidate-induced steroidogenesis inhibition	Vasopressor-resistant shock; need for stress-dose hydrocortisone
Cushing syndrome	Proximal myopathy, easy bruising, wide purple striae, osteoporosis, diabetes, hypertension, infection, mood disturbance	Exogenous glucocorticoids, alcohol-related pseudo-Cushing, severe depression, obesity, PCOS	Difficult airway, VTE risk, poor wound healing, hyperglycaemia
Primary aldosteronism	Resistant hypertension, hypokalaemia, metabolic alkalosis, muscle weakness; may be normokalaemic	Renal artery stenosis, diuretics, liquorice/carbenoxolone, Liddle syndrome, Cushing syndrome	Arrhythmia risk; correction of K+ and intravascular volume
Phaeochromocytoma/paraganglioma	Paroxysmal headache, sweating, palpitations, tremor, pallor, panic-like episodes; sustained or labile hypertension	Thyrotoxicosis, carcinoid, panic disorder, cocaine/amphetamine use, MAOI interaction, withdrawal states	Induction/intubation or tumour manipulation causing hypertensive crisis

Investigation of cortisol deficiency and excess

For suspected adrenal crisis, treatment must not await confirmatory testing: draw cortisol and ACTH if possible, then give hydrocortisone 100 mg IV immediately, followed by 50 mg IV 6-hourly or 200 mg/24 h infusion with isotonic crystalloid. Random cortisol interpretation is context-dependent; in severe acute illness a cortisol <400–500 nmol/L is concerning, but dynamic testing is preferred outside emergencies.

Test	Protocol	Interpretation and thresholds	Comments
09:00 serum cortisol + ACTH	Sample at circadian peak	Cortisol <100–140 nmol/L strongly suggests insufficiency; >400–500 nmol/L usually excludes it. ACTH high = primary; low/inappropriately normal = secondary/tertiary.	Cortisol-binding globulin changes in pregnancy, oestrogen therapy, liver disease and critical illness alter total cortisol.
Short Synacthen test	Tetracosactide 250 micrograms IV/IM; cortisol at 0 and 30 minutes, often 60 minutes	Peak cortisol generally >430–550 nmol/L excludes adrenal insufficiency; assay-specific cut-offs are mandatory.	May be falsely normal early after pituitary insult before adrenal atrophy develops.
Low-dose dexamethasone suppression	Dexamethasone 1 mg orally at 23:00; cortisol at 08:00	Cortisol <50 nmol/L suppresses normally; failure suggests Cushing syndrome.	Dexamethasone half-life 36–54 h; enzyme inducers such as phenytoin, carbamazepine and rifampicin cause false positives.
Late-night salivary cortisol	Two samples around 23:00	Loss of circadian nadir supports Cushing syndrome; typical cut-off assay-dependent, approximately >4 nmol/L.	Useful screening test; avoid shift work, acute stress and oral steroid contamination.
24 h urinary free cortisol	Two complete collections	>3 times upper limit of normal is highly suggestive.	False low in renal impairment; false high in high fluid intake or pseudo-Cushing states.

After biochemical confirmation of hypercortisolism, ACTH directs localisation: suppressed ACTH suggests adrenal adenoma/carcinoma; normal/high ACTH requires pituitary MRI and, when discordant, inferior petrosal sinus sampling. Adrenal incidentalomas require hormonal screening for autonomous cortisol secretion, phaeochromocytoma and, if hypertensive or hypokalaemic, primary aldosteronism; non-contrast CT attenuation <10 Hounsfield units supports lipid-rich benign adenoma.

Investigation of mineralocorticoid excess

The Endocrine Society recommends screening for primary aldosteronism in resistant hypertension, hypertension with spontaneous or diuretic-induced hypokalaemia, adrenal incidentaloma, sleep apnoea, early-onset hypertension/stroke, or affected first-degree relatives. The screening test is the aldosterone-to-renin ratio (ARR), interpreted with the absolute aldosterone concentration.

• Typical positive screen: plasma aldosterone concentration >10–15 ng/dL (>280–420 pmol/L) with suppressed renin and ARR >20–30 ng/dL per ng/mL/h, or local SI-unit equivalent.
• Preparation: correct hypokalaemia, liberalise salt intake, and consider drug effects. Mineralocorticoid antagonists require withdrawal for approximately 4–6 weeks if safe; ACE inhibitors, ARBs and diuretics raise renin and may cause false negatives; beta-blockers suppress renin and may cause false positives.
• Confirmatory tests: saline infusion test, oral salt loading, fludrocortisone suppression, or captopril challenge. Failure of aldosterone suppression after 2 L 0.9% saline over 4 h, with post-infusion aldosterone >10 ng/dL, supports autonomous secretion.

Subtype classification is by adrenal CT and, in most surgical candidates, adrenal venous sampling because non-functioning nodules are common with age. Unilateral aldosterone-producing adenoma is treated by adrenalectomy; bilateral hyperplasia by spironolactone or eplerenone.

Investigation of catecholamine excess

Biochemical testing precedes imaging. Plasma free metanephrines have sensitivity approximately 96–99% and specificity 85–89%; 24 h urinary fractionated metanephrines have slightly lower sensitivity but better specificity in some series. Samples should be taken after 20–30 minutes supine rest using an indwelling cannula; stress, acute illness, obstructive sleep apnoea, tricyclics, SNRIs, sympathomimetics, levodopa and cocaine may elevate results.

• Diagnostic threshold: plasma or urinary metanephrines >3 times the upper reference limit are highly suggestive and usually proceed to imaging.
• Borderline elevation: repeat optimised sampling; consider clonidine suppression for normetanephrine-dominant cases. Failure of normetanephrine to suppress by >40% or into the reference range after clonidine 300 micrograms orally supports autonomous secretion.
• Imaging: CT or MRI adrenal/abdomen-pelvis after biochemical diagnosis; MRI preferred in pregnancy, children and hereditary paraganglioma syndromes. Functional imaging includes ¹²³I-MIBG, ¹⁸F-FDG PET, or somatostatin receptor PET depending on genotype and metastatic risk.

Risk stratification should elicit MEN2, von Hippel-Lindau, NF1 and succinate dehydrogenase mutations, bilateral disease, extra-adrenal tumours and malignant potential. Preoperative biochemical certainty is critical because unrecognised phaeochromocytoma may cause catastrophic catecholamine-mediated vasoconstriction, myocardial injury, pulmonary oedema and arrhythmia during anaesthesia.

Management, pharmacology and procedures

Acute adrenal insufficiency and perioperative steroid replacement

Adrenal crisis is a time-critical diagnosis in the shocked perioperative or critical care patient, particularly after chronic glucocorticoid exposure, pituitary disease, bilateral adrenal disease, sepsis, trauma or etomidate administration. Treatment should not await biochemical confirmation: take cortisol/ACTH if feasible, then administer hydrocortisone.

Clinical context	Recommended regimen	Physiological rationale
Adrenal crisis	Hydrocortisone 100 mg IV immediately, then 200 mg/24 h IV infusion or 50 mg IV 6-hourly; 0.9% saline 1 L rapidly, repeated according to haemodynamics; add 5–10% dextrose if hypoglycaemic	Hydrocortisone provides glucocorticoid and, at high dose, sufficient mineralocorticoid activity; restores vascular α1-adrenergic responsiveness and gluconeogenesis
Major surgery in steroid-dependent patient	Hydrocortisone 100 mg IV at induction, then 200 mg/24 h for 24 h; taper to double usual oral dose for 24–48 h when stable	Major surgical stress normally produces cortisol secretion approximately 75–150 mg/day
Minor/moderate surgery	Continue usual steroids; hydrocortisone 25–50 mg IV at induction may be used for moderate stress, followed by prompt oral dosing	Avoids both under-replacement and unnecessary hyperglycaemia, infection and impaired wound healing

Chronic replacement in primary adrenal insufficiency is typically hydrocortisone 15–25 mg/day orally in 2–3 divided doses, or prednisolone 3–5 mg/day. Mineralocorticoid replacement is fludrocortisone 50–200 micrograms/day, titrated to postural symptoms, blood pressure, sodium, potassium and plasma renin. Patients require “sick-day rules”, steroid emergency card/bracelet and access to hydrocortisone 100 mg IM. Excess replacement causes hypertension, diabetes, osteoporosis and adrenal suppression; under-replacement causes weight loss, hyperpigmentation, hyponatraemia, hyperkalaemia and crisis.

Glucocorticoid excess and steroid pharmacology

Cushing syndrome management is directed at the source: trans-sphenoidal surgery for pituitary ACTH adenoma, adrenalectomy for adrenal tumours, and ectopic ACTH tumour treatment where possible. Perioperatively, severe hypercortisolism increases infection, venous thromboembolism, proximal myopathy, hypokalaemic alkalosis and difficult blood pressure/glucose control; thromboprophylaxis is essential.

Drug	Mechanism	Typical use/dose	Important adverse effects
Metyrapone	11β-hydroxylase inhibition	250 mg tds, titrate rapidly to 1–6 g/day	Hypertension, hypokalaemia, hirsutism from androgen/11-deoxycorticosterone accumulation
Ketoconazole	Inhibits CYP steroidogenesis enzymes	200 mg bd, titrate to 400 mg tds	Hepatotoxicity, QT prolongation, CYP3A4 interactions
Etomidate	Potent 11β-hydroxylase inhibition	ICU control: 0.03–0.1 mg/kg/h infusion	Adrenal suppression after even a single induction dose; avoid in sepsis when alternatives exist
Mifepristone	Glucocorticoid receptor antagonist	300–1200 mg/day	Hypokalaemia, endometrial thickening; cortisol cannot monitor efficacy

Primary hyperaldosteronism

Primary aldosteronism should be suspected in resistant hypertension, spontaneous or diuretic-induced hypokalaemia, adrenal incidentaloma or early-onset cerebrovascular disease. Screening uses the aldosterone-renin ratio; many centres regard ARR >20–30 with plasma aldosterone concentration >10–15 ng/dL as positive, but interpretation depends on assay, posture, potassium and antihypertensive drugs. Confirmatory testing includes saline infusion, oral salt loading or captopril challenge. Adrenal CT defines anatomy, but adrenal venous sampling is the reference procedure for lateralisation unless a young patient has a classical unilateral adenoma.

Unilateral aldosterone-producing adenoma is treated by laparoscopic adrenalectomy; bilateral hyperplasia is treated medically. Spironolactone 12.5–25 mg/day titrated to 100–400 mg/day antagonises mineralocorticoid receptors but causes gynaecomastia and menstrual disturbance through androgen/progesterone receptor effects. Eplerenone 25–50 mg bd is more selective but shorter acting and less potent. Aim for normokalaemia, blood pressure control and unsuppressed renin; persistent renin suppression suggests inadequate blockade and ongoing cardiovascular risk.

Catecholamine excess: phaeochromocytoma and paraganglioma

Phaeochromocytoma management is a classic anaesthetic examination topic because induction, intubation, pneumoperitoneum and tumour handling can produce extreme catecholamine surges. Diagnosis is by plasma free metanephrines or urinary fractionated metanephrines; plasma testing has sensitivity approximately 96–99% but lower specificity, requiring correct supine sampling and avoidance of interfering drugs.

Preoperative preparation for elective resection requires α-blockade before β-blockade. Phenoxybenzamine, an irreversible non-selective α-antagonist, is started at 10 mg bd and increased every 2–3 days to 20–40 mg bd or more. Selective α₁-blockade with doxazosin 1–2 mg/day titrated to 8–16 mg/day causes less postoperative hypotension. Targets include seated BP <130/80 mmHg, standing systolic BP >90 mmHg, mild orthostasis, controlled arrhythmia and expanded intravascular volume with high-salt intake. β-blockers, typically propranolol 10–40 mg tds or atenolol 25–50 mg/day, are added only after adequate α-blockade for tachyarrhythmias; premature β-blockade risks unopposed α-mediated hypertensive crisis.

Intraoperative crises are treated with short-acting titratable vasodilators: sodium nitroprusside 0.5–10 micrograms/kg/min, phentolamine 1–5 mg IV boluses, glyceryl trinitrate 0.5–10 micrograms/kg/min or magnesium sulphate 30–60 mg/kg loading then 1–2 g/h. Esmolol 50–200 micrograms/kg/min is useful after α-control for tachycardia. After adrenal vein ligation, abrupt catecholamine withdrawal and residual α-blockade cause hypotension requiring volume, noradrenaline or vasopressin; hypoglycaemia may occur because insulin secretion rebounds after removal of α₂-mediated inhibition. Long-term follow-up includes annual metanephrines for at least 10 years, lifelong surveillance in hereditary disease, large tumours or paraganglioma, and genetic testing consideration for RET, VHL, NF1 and SDHx mutations.

Exam controversies and advanced synthesis

Peri-operative glucocorticoid supplementation: physiology versus evidence

The traditional “stress-dose steroid” regimen is frequently overused. Normal cortisol secretion is approximately 5–10 mg/m²/day, equivalent to 15–25 mg hydrocortisone/day, but rises to around 75–150 mg/day after major surgery, trauma or sepsis. The key viva distinction is between hypothalamic–pituitary–adrenal suppression and primary adrenal failure: the former may retain mineralocorticoid function because aldosterone is predominantly regulated by angiotensin II and potassium.

Clinical situation	Suggested peri-operative approach	Exam pitfall
Chronic prednisolone <5 mg/day	No additional steroid usually required	Do not equate any steroid exposure with clinically significant HPA suppression
Prednisolone ≥5 mg/day for >4 weeks, or Cushingoid features	Continue usual dose; supplement according to surgical stress	Morning cortisol may be misleading if exogenous steroid interferes with assay
Known primary adrenal insufficiency	Hydrocortisone 100 mg IV at induction, then 50 mg IV 6-hourly or infusion 200 mg/24 h for major surgery	Requires volume, sodium and sometimes mineralocorticoid replacement once enteral therapy resumes
Minor procedure under local/regional anaesthesia	Usually continue normal dose only; consider 25 mg IV hydrocortisone if unable to take orally	Overtreatment causes hyperglycaemia, infection risk, impaired wound healing and delirium

A pragmatic endocrine threshold is that a 09:00 cortisol >350–500 nmol/L makes significant adrenal insufficiency unlikely, whereas <100 nmol/L is strongly suggestive; intermediate values require dynamic testing. The standard short Synacthen test uses 250 micrograms tetracosactide IV/IM, with cortisol at 0 and 30 minutes; a stimulated cortisol exceeding roughly 430–500 nmol/L is usually adequate, but cut-offs vary with assay. In critical illness, total cortisol is confounded by low albumin and corticosteroid-binding globulin; free cortisol may be biologically more relevant but is rarely available clinically.

Corticosteroids in septic shock: why the answer changed

For FRCA candidates, septic shock steroids are a classic example of pathophysiological plausibility modified by trial design. Steroids restore vascular adrenergic responsiveness by increasing α₁-receptor expression, inhibiting inducible nitric oxide synthase, reducing capillary leak and suppressing excessive inflammatory transcription. However, mortality benefit has been inconsistent.

Trial/guideline	Intervention	Main message
Annane et al., 2002	Hydrocortisone 50 mg IV 6-hourly plus fludrocortisone 50 micrograms enterally daily for 7 days	Mortality benefit reported in vasopressor-dependent septic shock, especially ACTH non-responders
CORTICUS, 2008	Hydrocortisone 50 mg IV 6-hourly	Faster shock reversal, no mortality benefit; more hyperglycaemia and infection
ADRENAL, 2018	Hydrocortisone 200 mg/day infusion	No 90-day mortality reduction; earlier shock resolution and ventilation liberation
APROCCHSS, 2018	Hydrocortisone plus fludrocortisone	Reduced 90-day mortality in severe septic shock
Surviving Sepsis Campaign 2021	Hydrocortisone 200 mg/day when ongoing vasopressor requirement persists	Weak recommendation; use after adequate fluids and vasopressors, not for sepsis without shock

The viva trap is to quote “relative adrenal insufficiency” as if diagnostic ACTH testing guides therapy. Current practice generally does not require Synacthen testing before hydrocortisone in vasopressor-refractory septic shock; the decision is clinical, based on persistent shock despite fluids and vasopressors. Hydrocortisone is preferred because it has both glucocorticoid and some mineralocorticoid activity; dexamethasone lacks mineralocorticoid effect and is not the usual septic shock agent.

Aldosterone: resistant hypertension, hypokalaemia and peri-operative relevance

Primary aldosteronism is no longer considered rare: it may account for 5–10% of hypertension and up to 20% of resistant hypertension. Screening uses the aldosterone–renin ratio, but interpretation requires attention to posture, sodium intake, potassium correction and drug effects. Spironolactone, eplerenone, amiloride and diuretics can invalidate testing; β-blockers suppress renin and may produce false positives. Hypokalaemia suppresses aldosterone and can produce false negatives. Exam-relevant physiology: aldosterone increases epithelial sodium channel activity and basolateral Na⁺/K⁺-ATPase in the cortical collecting duct, causing sodium retention, potassium wasting and hydrogen ion secretion; severe disease therefore produces hypertension, hypokalaemic metabolic alkalosis and peri-operative arrhythmia risk.

Phaeochromocytoma and catecholamine synthesis: integration for anaesthesia

Phaeochromocytoma management tests understanding of receptor physiology and drug sequencing. Catecholamines have short plasma half-lives, typically 1–3 minutes, due to neuronal reuptake, catechol-O-methyltransferase and monoamine oxidase metabolism, yet tumours cause sustained or paroxysmal haemodynamic instability. Pre-operative preparation aims to restore intravascular volume and prevent catecholamine-triggered crises. Phenoxybenzamine is irreversible, non-selective α-blockade, commonly started at 10 mg twice daily and titrated over 10–14 days; doxazosin is selective α₁-blockade, often 1–2 mg daily titrated upward. β-blockade is introduced only after adequate α-blockade, because unopposed α-mediated vasoconstriction may precipitate hypertensive crisis.

• Induction/intubation: avoid sympathetic surges; use deep anaesthesia, opioids, magnesium, remifentanil or short-acting vasodilators as appropriate.
• Tumour manipulation: hypertension may require phentolamine, sodium nitroprusside, nitroglycerin, magnesium sulphate or nicardipine; tachyarrhythmias may require esmolol after α-control.
• Post-ligation: profound hypotension reflects sudden catecholamine withdrawal, residual α-blockade, vasodilatation and hypovolaemia; treat with volume, noradrenaline or vasopressin.
• Post-operative hypoglycaemia: catecholamine excess suppresses insulin; after resection, insulin rebound may occur, so glucose monitoring is essential.

The advanced synthesis is that adrenal physiology is compartmental: cortisol is ACTH-driven and stress-adaptive; aldosterone is renin–angiotensin–potassium driven and volume-protective; catecholamines are neurally triggered, fast and receptor-specific. In examinations, errors usually arise from conflating these control systems, using obsolete blanket steroid cover, diagnosing adrenal failure from a single random cortisol in critical illness, or giving β-blockade before α-blockade in catecholamine excess.