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 (adrenaline ≈ 80%, noradrenaline, 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 adrenaline and noradrenaline 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 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 (present in only ~9-37%; normokalaemia is the commonest presentation): 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 ≥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 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 ≥6 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