Special Surgery 1. Diseases of the Adrenal Glands, Surgical Consequences

I. Anatomy and General Surgical Logic

Anatomy Reminder

Paired retroperitoneal endocrine glands on upper pole of kidneys
Right adrenal → Pyramidal, close to IVC and liver
Left adrenal → Semilunar, close to stomach, pancreas tail, spleen and left kidney
Blood supply → Superior, middle and inferior suprarenal arteries
Venous drainage is surgically important

Right adrenal vein → Short vein directly to IVC → High bleeding risk
Left adrenal vein → Left renal vein, often with inferior phrenic vein

Hormones

Adrenal cortex

Zona glomerulosa → Aldosterone
Zona fasciculata → Cortisol
Zona reticularis → Androgens

Adrenal medulla → Catecholamines: epinephrine, norepinephrine

Why Adrenal Disease Matters Surgically

Mass can be functional → Hormone excess causes perioperative risk
Mass can be malignant → Need oncological adrenalectomy
Mass can be incidentaloma → Must exclude hormone secretion and carcinoma
Wrong preparation can be fatal

Pheochromocytoma without alpha-blockade → Hypertensive crisis
Cortisol-producing tumor after removal → Acute adrenal insufficiency
Conn syndrome without potassium correction → Arrhythmia risk

II. Functional Adrenal Diseases

Cushing Syndrome

Cushing syndrome: Chronic glucocorticoid/cortisol excess
Cushing disease: Pituitary ACTH-producing adenoma causing Cushing syndrome

Etiology

ACTH-independent → Low ACTH due to negative feedback

Adrenal cortisol-producing adenoma
Adrenocortical carcinoma
Bilateral adrenal hyperplasia/macronodular disease
Iatrogenic glucocorticoid therapy → Most common overall cause

ACTH-dependent → High/inappropriately normal ACTH

Pituitary adenoma → Cushing disease
Ectopic ACTH production → Small cell lung cancer, bronchial carcinoid, neuroendocrine tumor

Clinical Features

Central obesity, moon face, buffalo hump
Thin skin, easy bruising, skin atrophy, livid/violaceous striae, acne, hirsutism
Proximal muscle weakness
Hyperglycemia → Type 2 diabetes / impaired glucose tolerance
Hypertension; cortisol can stimulate mineralocorticoid receptors → Na retention, hypokalemia in severe cases
Increased infection risk, poor wound healing
Peptic ulcer/gastritis, fatty liver, pancreatitis risk
Irregular menstruation, infertility, decreased libido
Osteoporosis, pathological fractures
Glaucoma, cataract
Psychiatric symptoms → Depression, anxiety, memory loss, insomnia, psychosis
Hyperpigmentation if ACTH is high

Diagnosis

Screen for cortisol excess

24 h urinary free cortisol
Late-night salivary/plasma cortisol
1 mg overnight low-dose dexamethasone suppression test

Low-dose dexamethasone test

Cortisol suppression → Cushing syndrome unlikely
No cortisol suppression → Cushing syndrome possible

ACTH level

Low ACTH → Adrenal source
High/inappropriately normal ACTH → Pituitary or ectopic ACTH source

High-dose dexamethasone / endocrine localization tests

Cortisol suppression > 50% → Pituitary adenoma more likely
No/poor suppression → Ectopic ACTH more likely

Imaging after biochemical proof

Adrenal CT/MRI → Adrenal adenoma/carcinoma/hyperplasia
Pituitary MRI → Cushing disease
Chest/abdomen imaging → Ectopic ACTH source

Treatment

Principle → Remove/control source of cortisol excess
Pituitary adenoma → Transsphenoidal resection; bilateral adrenalectomy only if refractory/failed selected cases
Ectopic ACTH → Remove tumor if possible; medical cortisol blockade if not controlled
Primary adrenal adenoma → Laparoscopic adrenalectomy if benign-appearing and localized
Adrenocortical carcinoma → Open oncological adrenalectomy if resectable
Perioperative glucocorticoid replacement is needed after adrenal cortisol-producing tumor removal

Conn Syndrome / Primary Hyperaldosteronism

Primary hyperaldosteronism: Autonomous aldosterone overproduction from adrenal gland
Aldosterone excess → Na/water retention + K/H loss → Hypertension + hypokalemia + metabolic alkalosis

Etiology

Aldosterone-producing adrenal adenoma
Bilateral idiopathic adrenal hyperplasia
Familial hyperaldosteronism
Aldosterone-producing adrenocortical carcinoma → Rare

Clinical Features

Hypertension → Often resistant or early onset
Hypokalemia → Muscle weakness, cramps, paresthesia, constipation
Arrhythmia, QT prolongation
Metabolic alkalosis
Polyuria/polydipsia possible from hypokalemia-induced nephropathy

Diagnosis

Screening → Aldosterone-renin ratio (ARR)

High aldosterone + suppressed renin → Primary aldosteronism likely
Correct hypokalemia before interpretation because low K can suppress aldosterone

Confirmatory testing if needed → Saline infusion, oral salt loading, captopril challenge or fludrocortisone suppression
Localization/subtyping

Adrenal CT/MRI → Detect adenoma/carcinoma/hyperplasia
Adrenal venous sampling (AVS) → Aldosterone/cortisol from both adrenal veins and IVC
AVS distinguishes unilateral adenoma from bilateral hyperplasia before surgery in most surgical candidates

Treatment

Unilateral lateralized aldosterone-producing adenoma → Unilateral adrenalectomy
Preoperative spironolactone/eplerenone → Control BP and correct hypokalemia
Bilateral idiopathic adrenal hyperplasia → Medical treatment with mineralocorticoid receptor antagonist
MRA examples → Spironolactone, eplerenone

Pheochromocytoma

Rare tumor of adrenal medulla derived from chromaffin cells
Produces catecholamines, usually norepinephrine ± epinephrine
Extra-adrenal equivalent = Paraganglioma
Can be sporadic or hereditary → MEN2, VHL, NF1, SDHx mutations

Clinical Features

Classic triad → Headache + sweating + palpitations/tachycardia
Episodic or sustained severe hypertension
Anxiety, tremor, pallor, weight loss, hyperglycemia
High-risk consequences → Malignant arrhythmia, heart failure, angina, MI, stroke, aortic dissection
Triggers → Anesthesia, surgery, palpation of tumor, biopsy, contrast, certain drugs

Diagnosis

Biochemistry first → Plasma free metanephrines or 24 h urinary fractionated metanephrines
Vanillylmandelic acid (VMA) can be elevated but is less sensitive than metanephrines
Chromogranin A may be elevated; adjunct only
Localization → Adrenal CT or MRI
Functional imaging → MIBG scintigraphy, PET/CT in selected metastatic, extra-adrenal or hereditary cases
Do not biopsy an adrenal mass until pheochromocytoma is excluded

Treatment

Preoperative preparation

Alpha-blockade first → Phenoxybenzamine or selective alpha-1 blocker: doxazosin/prazosin/terazosin/urapidil depending on practice
Duration commonly 7-14 days, adjusted to BP/orthostasis
Volume expansion/high-salt intake if appropriate → Prevent postoperative hypotension
Beta-blocker only after adequate alpha-blockade if tachycardia persists
Never give beta-blocker first → Unopposed alpha stimulation → Hypertensive crisis

Adrenalectomy

Laparoscopic adrenalectomy for suitable localized benign-appearing tumors
No-touch technique, minimal tumor manipulation
Early adrenal vein ligation often used to reduce catecholamine surge
Intraoperative arterial BP monitoring and rapid vasoactive drugs are essential

Postoperative care

Monitor hypotension, hypoglycemia, arrhythmia
Follow metanephrines for persistent/recurrent disease

III. Adrenal Tumors and Incidentaloma

Adrenocortical Carcinoma

Rare, aggressive malignant tumor of adrenal cortex
Can be functional or non-functional
Functional symptoms

Hypercortisolism
Hyperaldosteronism rarely
Androgen/estrogen excess → Virilization/feminization

Suspicious signs → Large size, irregular margins, heterogeneous necrosis/hemorrhage, invasion, rapid growth, high HU/poor washout on CT
Diagnosis → Hormonal workup + adrenal protocol CT/MRI + staging CT chest/abdomen/pelvis
Treatment → Complete en bloc R0 resection if possible
Open adrenalectomy preferred when carcinoma suspected or local invasion present
Adjuvant/advanced treatment → Mitotane ± chemotherapy depending on stage/risk
Debulking only in selected advanced functional/symptomatic disease; R0 resection is the main curative aim

Adrenal Incidentaloma

Adrenal incidentaloma: Incidentally found adrenal mass, usually ≥ 1 cm, discovered during imaging for unrelated reason
Key questions

Is it hormonally active?
Is it malignant/suspicious?
Does it need surgery or follow-up?

Workup

Hormonal screening

1 mg overnight dexamethasone suppression test → Autonomous cortisol secretion
Plasma free or urinary fractionated metanephrines → Pheochromocytoma, especially if imaging not clearly benign
Aldosterone-renin ratio → If hypertension and/or hypokalemia

Imaging assessment

Non-contrast CT HU ≤ 10 and homogeneous → Lipid-rich benign adenoma likely
Size, growth, heterogeneity, irregular border, necrosis, invasion and washout pattern guide malignancy risk

Surgical Indications

Functioning tumor with clinically relevant hormone excess
Pheochromocytoma
Suspicious imaging features or likely adrenocortical carcinoma
Large indeterminate mass, commonly > 4 cm depending on imaging phenotype and center policy
Significant growth during follow-up

Small, homogeneous, clearly benign non-functioning adenoma → Usually observation, not surgery

Adrenal Metastases

Common primary tumors → Lung, breast, kidney, melanoma, GI cancers
Usually non-functional
Can be bilateral → Consider adrenal insufficiency if extensive bilateral destruction
Biopsy only if result changes management and pheochromocytoma is excluded
Surgery → Selected isolated metastasis, long disease-free interval, controlled primary tumor or symptomatic mass

IV. Adrenalectomy and Perioperative Consequences

Indications for Adrenalectomy

Functional adrenal masses → Cortisol, aldosterone, catecholamine or androgen excess
Suspicion of malignancy / adrenocortical carcinoma
Selected adrenal incidentaloma
Selected isolated adrenal metastasis
Large/symptomatic adrenal cyst, hemorrhage or mass effect in selected cases

Approaches

Approach	Typical use	Key points
Laparoscopic transabdominal	Most benign small/moderate adrenal tumors	Good working space; familiar anatomy; preferred for many benign lesions
Posterior retroperitoneoscopic	Small benign tumors, bilateral adrenalectomy, obese patients in experienced centers	Direct retroperitoneal access; avoids peritoneal cavity; prone/jackknife position
Open transabdominal/thoracoabdominal	Large tumor, suspected carcinoma, invasion, difficult reoperation	Allows en bloc resection and vascular control; incisions include subcostal, chevron or midline

Operative Principles

Identify and control adrenal vein early, especially in pheochromocytoma
Gentle handling/no-touch technique for pheochromocytoma and carcinoma suspicion
Avoid capsule rupture in suspected adrenocortical carcinoma
Know adjacent structures

Right → Liver, IVC, right kidney, diaphragm
Left → Spleen, pancreas tail, stomach, colon splenic flexure, left kidney

Complications and Surgical Consequences

Bleeding → Adrenal vein/IVC/renal vein/splenic vessels
Injury to adjacent organs → Liver, spleen, pancreas, kidney, colon, diaphragm
Pneumothorax/pleural injury, especially high retroperitoneal dissection
Infection, wound complication, conversion from laparoscopy to open surgery
Adrenal crisis / adrenal insufficiency

Risk after bilateral adrenalectomy
Risk after unilateral removal of cortisol-producing tumor because contralateral adrenal is suppressed
Symptoms → Hypotension, shock, hyponatremia, hyperkalemia, hypoglycemia, fever, weakness
Treatment/prevention → Perioperative hydrocortisone, taper, long-term replacement if needed

After bilateral adrenalectomy → Lifelong glucocorticoid + mineralocorticoid replacement
After pheochromocytoma removal → Hypotension and hypoglycemia monitoring
After Conn adenoma removal → Monitor potassium, BP, aldosterone/renin response; reduce antihypertensives as appropriate

Exam focus: For adrenal masses always ask: functional or non-functional, benign or malignant, unilateral or bilateral. Know Cushing syndrome, Conn syndrome, pheochromocytoma, adrenocortical carcinoma, incidentaloma and metastasis. Surgical safety points: alpha-block pheochromocytoma before beta-blocker, correct hypokalemia in Conn syndrome, give steroid coverage after cortisol-producing tumor/bilateral adrenalectomy, and use open en bloc surgery if carcinoma is suspected.