Adrenal Surgery: Phaeochromocytoma, Conn's Syndrome, Cushing's Syndrome & Adrenalectomy

Definition / Overview

The adrenal glands sit at the superior pole of each kidney within Gerota's fascia. Each gland has a cortex (derived from mesoderm) and a medulla (derived from neural crest cells). They are functionally and anatomically distinct:

• Cortex, secretes glucocorticoids (zona fasciculata), mineralocorticoids (zona glomerulosa), and sex steroids (zona reticularis); all are cholesterol derivatives
• Medulla, secretes catecholamines (epinephrine ≈ 80%, norepinephrine, dopamine) from chromaffin cells; amino acid tyrosine is the precursor

Surgical disease arises from autonomous hormone hypersecretion or from mass lesions. The four conditions dominating surgical practice are phaeochromocytoma, Conn's syndrome, Cushing's syndrome, and non-functioning adrenal incidentaloma.

Phaeochromocytoma

Pathophysiology

Phaeochromocytoma is a catecholamine-secreting tumour arising from chromaffin cells of the adrenal medulla (or, when extra-adrenal, termed a paraganglioma). Autonomous release of epinephrine and norepinephrine drives $\alpha_1$-mediated vasoconstriction, $\beta_1$-mediated tachycardia and inotropy, and metabolic effects (hyperglycaemia, lipolysis). Episodic release causes the characteristic "crises." Up to 25% are hereditary (MEN2A/2B, VHL, NF1, SDHx mutations); the rule of 10s is a useful aide-mémoire:

Clinical Features

• Classic triad: episodic headache, diaphoresis, palpitations
• Hypertensive crises (sustained or paroxysmal), pallor, anxiety
• Hyperglycaemia, weight loss
• Cardiomyopathy (catecholamine-induced)

Investigation

Perioperative Management, Critical Detail

Inadequate preoperative preparation is the leading cause of perioperative mortality. A structured approach is mandatory:

1. $\alpha$-blockade first, phenoxybenzamine (non-selective, irreversible; start 7-14 days preoperatively) or selective $\alpha_1$-blockers (prazosin, doxazosin). Target: seated BP $<130/80\,\text{mmHg}$, nasal stuffiness confirming blockade.
2. $\beta$-blockade second, only after adequate $\alpha$-blockade established (unopposed $\alpha$ stimulation if $\beta$ given first causes severe vasoconstriction and hypertensive crisis). Propranolol or atenolol for tachycardia control.
3. Volume loading, liberal salt and fluid intake to counter the contracted intravascular volume caused by chronic vasoconstriction; prevents precipitous post-resection hypotension.
4. Intraoperative: invasive arterial monitoring mandatory; SNP or phentolamine IV infusion for hypertensive surges on tumour handling; avoid histamine-releasing drugs (morphine, atracurium, mivacurium) and dopamine agonists.
5. Post-resection: expect hypotension, treated with IV fluids and vasopressors; blood glucose monitoring (rebound hypoglycaemia from insulin surge).

Conn's Syndrome (Primary Hyperaldosteronism)

Pathophysiology

Autonomous aldosterone hypersecretion from the zona glomerulosa, most commonly a unilateral adrenal adenoma (aldosteronoma), less commonly bilateral adrenal hyperplasia. Excess aldosterone drives sodium retention in the collecting duct (via ENaC upregulation) with obligate potassium and hydrogen ion loss, producing:

$$\text{Hypertension} + \text{Hypokalaemia} + \text{Metabolic Alkalosis}$$

Elevated aldosterone suppresses renin, creating the hallmark low-renin hypertension. Over time, aldosterone causes direct cardiovascular fibrosis independent of blood pressure.

Clinical Features

• Hypertension, often resistant to multiple agents
• Hypokalaemia (may be absent in up to 40%): muscle weakness, cramps, polyuria, polydipsia
• Metabolic alkalosis
• Symptoms of hypokalaemia may be subtle; always screen in resistant hypertension

Investigation

Note: Aldosterone antagonists (spironolactone, eplerenone) must be withheld $\geq 4$ weeks before testing; $\beta$-blockers and ACE inhibitors also affect ARR.

Management

• Unilateral adenoma or unilateral hyperplasia: laparoscopic adrenalectomy
  • Preoperative preparation: aldosterone antagonist (spironolactone) + potassium supplementation to normalise $K^+$
  • Hypertension cured in ~50%; improved in ~90%
  • Fewer antihypertensives required postoperatively
• Bilateral hyperplasia: medical management with aldosterone antagonist preferred; surgery rarely indicated

Cushing's Syndrome

Pathophysiology

Glucocorticoid excess from any source produces a characteristic catabolic state. Classified by ACTH dependency:

Cortisol excess causes protein catabolism, impaired wound healing, immunosuppression, hyperglycaemia (peripheral insulin resistance), mineralocorticoid cross-reactivity (hypertension, hypokalaemia), and direct central adiposity.

Clinical Features

• Central obesity, moon facies, buffalo hump, supraclavicular fat pads
• Proximal myopathy, easy bruising, wide purple striae
• Osteoporosis, pathological fractures
• Hypertension, hyperglycaemia/diabetes
• Immunosuppression → opportunistic infections
• Amenorrhoea, hirsutism, acne
• Psychiatric disturbance (depression, psychosis)

Diagnosis, Stepwise Algorithm

1. Confirm hypercortisolism (any one of three):

   • 24-hour urinary free cortisol (elevated)
   • Late-night salivary cortisol (loss of normal diurnal nadir)
   • Overnight 1 mg dexamethasone suppression test (failure to suppress morning cortisol to $<50\,\text{nmol/L}$)

2. Determine ACTH dependency:

   • Plasma ACTH: suppressed → ACTH-independent (adrenal source); elevated → ACTH-dependent

3. Localise the source:

   • ACTH-dependent: MRI pituitary; high-dose dexamethasone suppression test; bilateral inferior petrosal sinus sampling (BIPSS) if equivocal, petrosal:peripheral ACTH ratio $>2$ (basal) or $>3$ (post-CRH) confirms pituitary source
   • ACTH-independent: CT adrenals to identify adenoma vs carcinoma vs hyperplasia
   • Ectopic ACTH: CT chest/abdomen/pelvis; Ga-DOTATATE PET for occult sources

Management by Cause

Medical temporisation (while awaiting surgery or if inoperable):

• Metyrapone, blocks 11$\beta$-hydroxylase ($\downarrow$ cortisol synthesis)
• Ketoconazole, inhibits multiple steroidogenic enzymes
• Mifepristone, glucocorticoid receptor antagonist (does not lower cortisol levels; useful in type 2 DM/glucose intolerance)
• Pasireotide, somatostatin analogue; reduces ACTH from some pituitary tumours

Perioperative Steroid Management, Critical

All patients undergoing adrenalectomy for Cushing's syndrome have a suppressed contralateral gland (or, after bilateral adrenalectomy, no adrenal tissue). Failure to provide cover causes Addisonian crisis.

• Intraoperative: hydrocortisone 100 mg IV at induction
• Postoperative taper: hydrocortisone $12\,\text{mg/m}^2/\text{day}$ equivalent; taper over weeks to months guided by morning cortisol and ACTH stimulation testing
• Replacement may be required for up to 2 years after unilateral adrenalectomy for Cushing's
• After bilateral adrenalectomy: permanent glucocorticoid and mineralocorticoid replacement (fludrocortisone)

Nelson's Syndrome

Following bilateral adrenalectomy for Cushing's disease, the pre-existing pituitary tumour loses cortisol feedback inhibition and may enlarge aggressively:

• Rising plasma ACTH, hyperpigmentation (MSH cross-reactivity), visual field defects, headache, extraocular palsies
• Affects approximately 30% of patients after bilateral adrenalectomy for Cushing's disease
• Management: transsphenoidal resection; external beam radiotherapy for residual/invasive disease; stereotactic radiosurgery pre-adrenalectomy may reduce incidence

Adrenalectomy, Operative Principles

Indications Summary

Surgical Approaches

Laparoscopic transabdominal lateral flank (most common):

• Patient in lateral decubitus; 3-4 ports
• Right side: mobilise liver, identify IVC; right adrenal vein is short (1-2 cm), drains directly into IVC, clip early
• Left side: mobilise spleen/splenic flexure of colon; left adrenal vein drains into left renal vein (longer, more forgiving)
• Advantages: direct visualisation, larger working space, familiar anatomy

Laparoscopic retroperitoneoscopic posterior:

• Direct retroperitoneal access; avoids peritoneal cavity
• Ideal for small lesions, bilateral surgery (single position), previous abdominal surgery
• Adrenal vein identification can be more challenging but feasible

Open anterior (subcostal or midline):

• Reserved for large/malignant tumours, en bloc resection, or when adjacent organ involvement suspected

Key Anatomical Relationships

• Right adrenal: posterior to IVC; superior to right renal hilum; inferior to liver; adrenal vein → IVC directly
• Left adrenal: medial to upper pole left kidney; posterior to pancreatic tail and splenic vessels; adrenal vein → left renal vein
• Arterial supply: superior adrenal (inferior phrenic), middle adrenal (aorta), inferior adrenal (renal artery), multiple small vessels; venous drainage is single on each side
• The adrenal lies within Gerota's fascia; the gland itself is invested in periglandular fat distinct from perirenal fat

Intraoperative Hazards

• Uncontrolled bleeding from IVC (right adrenal vein) or left renal vein injury
• Injury to adjacent viscera: liver, spleen, pancreatic tail, stomach
• Pneumothorax from retroperitoneal gas tracking
• Haemodynamic instability during phaeochromocytoma manipulation

Complications & Special Considerations

Postoperative Adrenal Insufficiency

• After unilateral adrenalectomy for Cushing's: contralateral suppression; hydrocortisone taper required
• After bilateral adrenalectomy: permanent replacement; patient education on sick-day rules; medic-alert bracelet; parenteral hydrocortisone supply for emergencies
• Signs of Addisonian crisis: haemodynamic instability, fever, abdominal pain, hyponatraemia, hyperkalaemia, hypoglycaemia
• Treatment: hydrocortisone 100 mg IV stat, then 50-100 mg 6-hourly; IV fluid resuscitation

Post-resection Hypotension (Phaeochromocytoma)

• Expected; due to sudden catecholamine withdrawal from a volume-depleted patient
• Managed with IV crystalloid ± vasopressors (noradrenaline); avoids exogenous catecholamines where possible

Post-resection Hypoglycaemia (Phaeochromocytoma)

• Rebound insulin release as catecholamine inhibition of insulin secretion is removed
• Monitor blood glucose closely for 24-48 hours postoperatively

Subclinical Cushing's Syndrome

• Biochemical hypercortisolism without classic clinical features; associated with adrenal incidentalomas
• Risk of progression to overt Cushing's and cardiovascular comorbidity
• Adrenalectomy reasonable in young patients, those with hypertension, diabetes, obesity, or osteopenia; steroid taper still required postoperatively

Perioperative Summary Table

High-Yield GSSE Viva Points

• Always $\alpha$-block before $\beta$-block in phaeochromocytoma, giving $\beta$-blocker first leaves $\alpha$-receptors unopposed, causing hypertensive crisis
• The right adrenal vein is short and drains directly to the IVC, the most dangerous structure in right adrenalectomy
• ARR is the screening test for primary hyperaldosteronism; adrenal vein sampling lateralises disease and determines surgical candidacy
• BIPSS is the gold standard for distinguishing pituitary vs ectopic ACTH: petrosal:peripheral ratio $>2$ basal or $>3$ post-CRH confirms pituitary source
• Nelson's syndrome complicates ~30% of bilateral adrenalectomies for Cushing's disease, monitor ACTH and pituitary MRI
• Open adrenalectomy is the standard for lesions $\geq 6\,\text{cm}$ or those with malignant radiological features (Hounsfield units $>10$, heterogeneity, necrosis)
• All patients undergoing adrenalectomy for Cushing's need perioperative hydrocortisone cover, the contralateral gland is suppressed regardless of whether surgery is unilateral or bilateral

Sources

• RACS position statements & curriculum (Royal Australasian College of Surgeons)
• Therapeutic Guidelines (eTG)