Educational disclaimer. This article is intended for clinician education and historical context. It is not a substitute for current society guidelines or individualized clinical judgement. Patients with suspected adrenal disease should be evaluated and managed by an experienced endocrinology and endocrine-surgery team.
Introduction
Adrenal surgery has been transformed since the 1980s by improved biochemical diagnosis, modern cross-sectional and functional imaging, and — most consequentially — the introduction of laparoscopic adrenalectomy in 1992 (Gagner, Lacroix, and Bolté 1992). When performed at experienced centres, adrenalectomy is now safe and often curative, with most operations completed via a minimally invasive approach (Yip et al. 2022). A historical case of Cushing’s syndrome with adrenal hyperplasia is presented first, followed by a discussion of current indications, perioperative care, and surgical approaches.
Case report
D.D., a thirty-two year-old woman, complained of weakness in the proximal muscles of her limbs, weight gain, and increased facial and truncal hair growth. She was hypertensive and a year prior to presentation was treated for pulmonary embolism. On physical examination she was found to be Cushingoid with centripetal obesity, moon face, buffalo hump, abdominal apron, striae, acne and hypertrichosis. Power in her proximal limb muscles was Grade IV/V. Hemoglobin concentration was 13 g/dL and white blood cell count 10 × 10⁹/L. Serum urea, electrolytes and creatinine were normal.
| Test | Time | Result | Normal | Unit |
|---|---|---|---|---|
| Glucose | fasting | 9.3 | mmol/L | |
| post-breakfast | 16.2 | mmol/L | ||
| Urinary | 17 ketogenic steroids | 17 | 20–51 | μmol/24 hrs |
| 17 ketosteroids | 30 | 10–51 | μmol/24 hrs | |
| Cortisol | a.m. | 880 | 175–700 | μmol/L |
| p.m. | 730 | 88–350 | μmol/L | |
| ACTH | a.m. | 110 | 0–54 | pg/mL |
| p.m. | 96 | pg/mL |
After low-dose dexamethasone suppression:
| Test | Time | Result | Unit |
|---|---|---|---|
| cortisol | a.m. | 533 | μmol/L |
| p.m. | 645 | μmol/L |
After high-dose dexamethasone suppression:
| Test | Time | Result | Unit |
|---|---|---|---|
| cortisol | a.m. | 690 | μmol/L |
| p.m. | 655 | μmol/L | |
| ACTH | 67 | pg/mL |
Thyroid function tests, intravenous urogram, skull, chest and abdominal radiographs were normal. Abdominal ultrasonography showed enlarged adrenal glands. Computed tomography of the pituitary fossa showed no abnormality. Serum ACTH was elevated and the high-dose dexamethasone suppression test failed to suppress cortisol. The patient was assessed as having Cushing’s syndrome with occult ectopic ACTH production, and bilateral adrenalectomy was offered to ameliorate the Cushing’s syndrome.
Hypertension was controlled with methyldopa and propranolol and diabetes with glibenclamide. After prophylactic heparin and antibiotics, bilateral adrenalectomy was performed through a Chevron abdominal incision with perioperative hydrocortisone cover. Oral cortisone acetate was commenced four days after surgery. The only complication was a wound infection. She was discharged 21 days after surgery for follow-up at the endocrine clinic on cortisone acetate, with hypertension controlled by propranolol and diabetes by metformin and chlorpropamide.
The adrenal glands weighed 11.1 g and on histology showed hyperplasia, particularly of the zona fasciculata, often arranged in a nodular fashion. The zona reticularis was thickened in places; the zona glomerulosa was markedly attenuated.
Current Cushing’s screening uses two of three first-line tests — the 1 mg overnight dexamethasone suppression test, late-night salivary cortisol, or 24-hour urinary free cortisol — rather than 17-ketogenic and 17-ketosteroid measurements (Nieman et al. 2008). Plasma ACTH then distinguishes ACTH-dependent from ACTH-independent disease, directing pituitary MRI ± inferior petrosal sinus sampling in the former, or adrenal CT/MRI in the latter (Nieman et al. 2015). Bilateral adrenalectomy for ACTH-dependent disease refractory to source control is now performed laparoscopically, with operative morbidity around 10% and mortality near 3%, and requires lifelong glucocorticoid and mineralocorticoid replacement plus surveillance for Nelson’s syndrome (Yip et al. 2022; Reincke et al. 2023).
Discussion
1. Indications for adrenalectomy
Current indications for adrenalectomy, distilled from the AAES 2022 guideline and the ESE-ENSAT 2023 adrenal incidentaloma guideline, are:
- Functioning adrenal tumours: cortisol-producing adenoma (overt Cushing’s syndrome), aldosterone-producing adenoma, and pheochromocytoma.
- Mild autonomous cortisol secretion (MACS) with relevant cortisol-attributable comorbidities (e.g., hypertension, type 2 diabetes, vertebral fractures), discussed individually with the patient.
- Known or suspected adrenocortical carcinoma (ACC).
- Bilateral adrenalectomy for ACTH-dependent hypercortisolism refractory to source control, and for bilateral macronodular adrenal hyperplasia.
- Isolated adrenal metastasis amenable to resection.
- Bilateral pheochromocytoma (cortical-sparing adrenalectomy when technically feasible) (Yip et al. 2022).
The historical 6 cm “incidentaloma” cutoff has been superseded. Current guidelines recommend resection of adrenal masses ≥ 4 cm that are heterogeneous or have unenhanced CT attenuation > 20 Hounsfield units (HU). For 4–6 cm masses the prevalence of ACC is approximately 5%; for masses > 6 cm it rises to roughly 35% (Yip et al. 2022; Fassnacht et al. 2023).
The ESE-ENSAT 2023 incidentaloma algorithm replaces the older “six-monthly CT” surveillance with a single follow-up scan. A noncontrast CT showing a homogeneous mass with HU ≤ 10 is sufficient to exclude malignancy regardless of size, and no further imaging is required. Indeterminate masses receive one repeat noncontrast CT or MRI at 6–12 months; surgical resection is suggested if the lesion grows by more than 20% in maximum diameter and at least 5 mm. Every newly detected adrenal mass ≥ 1 cm undergoes biochemical evaluation: 1 mg overnight dexamethasone suppression test in all patients; plasma free or 24-hour urinary fractionated metanephrines if imaging is not typical of a benign adenoma (e.g., unenhanced HU > 10); and an aldosterone–renin ratio in patients with hypertension or unexplained hypokalemia (Fassnacht et al. 2023).
2. Preoperative preparation
General principles. All patients with adrenal cortical disorders receive perioperative antibiotic and venous thromboembolism prophylaxis, and hypertension and diabetes are optimised before surgery (Yip et al. 2022).
Glucocorticoid replacement. After unilateral adrenalectomy for overt Cushing’s syndrome, adrenal insufficiency is expected in nearly 100% of patients, so empirical postoperative glucocorticoid replacement is recommended. After unilateral adrenalectomy for MACS, adrenal insufficiency develops in approximately 60% of patients; a postoperative day-1 morning cortisol or cosyntropin (ACTH) stimulation test directs the need for replacement. All patients undergoing bilateral adrenalectomy require lifelong glucocorticoid and mineralocorticoid replacement and structured education on sick-day stress dosing and adrenal-crisis prevention (Yip et al. 2022; Bornstein et al. 2016).
The steroid replacement regimens are shown below for historical reference; contemporary practice tapers from a perioperative hydrocortisone bolus to maintenance hydrocortisone (typically 15–25 mg/day in divided doses) and fludrocortisone 0.05–0.2 mg/day after bilateral adrenalectomy, individualised to the patient.
Table II: Historical steroid replacement regimen to cover bilateral adrenalectomy for conditions other than Cushing’s syndrome (Hughes and Lynn 1989).
| Day 0 and postoperatively | Dosage |
|---|---|
| hydrocortisone | 100 mg IV with premed |
| then Q6h until swallowing | |
| First oral day | |
| hydrocortisone | 20 mg qds |
| 2nd and 3rd oral days | |
| hydrocortisone | 20 mg tds |
| 4th to 7th oral days | |
| hydrocortisone | 20 mg bd |
| Oral long-term replacement | |
| hydrocortisone | 10 mg tds |
| fludrocortisone | 0.1 mg daily |
Table III: Historical steroid regimen to cover adrenal surgery to relieve Cushing’s syndrome (Hughes and Lynn 1989).
| Day 0 | Dosage |
|---|---|
| hydrocortisone | infusion commenced with premed |
| first 6 hrs at 30 mg/hr | |
| next 18 hrs at 10 mg/hr | |
| Day 1 | |
| hydrocortisone | IV 200 mg/24 hrs |
| Day 2 | |
| hydrocortisone | IV 100 mg/24 hrs |
| hydrocortisone | tabs 20 mg Q6h |
| Day 3 | |
| hydrocortisone | tabs 25 mg Q6h |
| fludrocortisone | tabs 0.1 mg daily |
| Day 4 to 7 | |
| hydrocortisone | tabs 20 mg Q6h |
| fludrocortisone | tabs 0.1 mg daily |
| Day 8 to 10 | |
| hydrocortisone | tabs 20 mg Q8h |
| fludrocortisone | tabs 0.1 mg daily |
| Day 11 to 14 | |
| hydrocortisone | tabs 10 mg Q6h |
| fludrocortisone | tabs 0.1 mg daily |
| Day 15+ | |
| hydrocortisone | tabs 10 mg Q8h |
| fludrocortisone | tabs 0.1 mg daily |
Primary aldosteronism. Patients are managed with a mineralocorticoid-receptor antagonist (spironolactone, or eplerenone for tolerability) titrated to restore normokalemia and to control blood pressure. Before unilateral adrenalectomy, adrenal venous sampling (AVS) is the reference standard for lateralization in patients older than 35 years; AVS may be deferred in patients ≤ 35 with biochemically confirmed primary aldosteronism and a clear unilateral adenoma on cross-sectional imaging with a normal contralateral gland (Funder et al. 2016; Yip et al. 2022). After unilateral adrenalectomy, glucocorticoid replacement is not routinely needed; transient mineralocorticoid insufficiency is managed with intravenous saline and, if needed, short-course fludrocortisone.
Pheochromocytoma. Preoperative α-adrenergic blockade is started at least 7 days before surgery; either a nonselective agent (phenoxybenzamine) or a selective α₁-blocker (doxazosin) is acceptable, with similar overall morbidity and mortality. Phenoxybenzamine may give superior intraoperative blood-pressure control at the cost of more postoperative hypotension; doxazosin is more readily available in many regions. A high-sodium diet and oral or intravenous volume loading are added in the days before surgery to expand the contracted plasma volume. β-blockade (e.g., propranolol, metoprolol) is added only after adequate α-blockade for reflex tachycardia or arrhythmia. Germline genetic testing and counselling are recommended for all patients with pheochromocytoma or paraganglioma, since approximately 30–40% carry an identifiable germline mutation (Lenders et al. 2014; Yip et al. 2022). Intraoperative arterial and central venous monitoring remains standard, with sodium nitroprusside, phentolamine, or nicardipine for hypertensive crises and intravascular volume expansion (with vasopressors if refractory) after tumor devascularisation.
3. Surgical approaches: from open access to minimally invasive adrenalectomy
Since the first laparoscopic adrenalectomy in 1992 (Gagner et al. 1992), minimally invasive adrenalectomy (MIA) has become the standard of care for the great majority of adrenal lesions. The AAES 2022 guideline recommends MIA over open adrenalectomy whenever patient and tumor characteristics allow, citing improved perioperative outcomes — less pain, shorter hospital stay, and faster recovery — with comparable oncologic results for benign disease (Yip et al. 2022). Two minimally invasive approaches are well established, and both are supported by guidelines:
- Laparoscopic transabdominal (lateral) adrenalectomy, with the patient in lateral decubitus; the workhorse approach in most centres.
- Posterior retroperitoneoscopic adrenalectomy (PRA), performed with the patient prone in the jackknife position through three small incisions; favoured for patients with prior abdominal surgery or bilateral tumours, with low conversion rates and short length of stay in high-volume series (Walz et al. 2006).
Robotic adrenalectomy is now widely used as an alternative to laparoscopic technique, particularly for obese patients, large lesions, or anatomically challenging cases, with low complication rates and comparable or shorter hospital stays in recent series (Aliyev et al. 2024).
Open adrenalectomy is reserved for known or suspected adrenocortical carcinoma and for locally invasive tumours, where an en bloc R0 resection with an intact capsule is critical to oncologic outcome (Yip et al. 2022; Fassnacht et al. 2018). Open access — through anterior subcostal/midline, lateral flank, or thoracoabdominal incisions — also remains in the surgical armamentarium for very large or anatomically complex tumours when an oncologically sound minimally invasive resection is not feasible.
4. Disease-specific surgical management
Primary aldosteronism. Laparoscopic unilateral adrenalectomy is recommended for unilateral disease confirmed on AVS. Adrenalectomy reduces the long-term risks of atrial fibrillation, chronic kidney disease, stroke, and all-cause mortality compared with medical therapy; fewer than 20% of patients require the same or higher antihypertensive doses postoperatively (Yip et al. 2022; Funder et al. 2016).
Cushing’s syndrome. Laparoscopic unilateral adrenalectomy is recommended for unilateral cortisol-producing adenomas and for MACS in patients with relevant comorbidities. For bilateral macronodular adrenal hyperplasia, unilateral laparoscopic adrenalectomy targeting the larger gland often achieves biochemical remission while avoiding lifelong adrenal insufficiency, although recurrence rates of 13–68% at four years have been reported. Bilateral laparoscopic adrenalectomy is suggested for moderate-to-severe ACTH-dependent hypercortisolism refractory to source control (incurable pituitary disease or metastatic/occult ectopic ACTH source), with operative morbidity around 10% and mortality near 3%; long-term surveillance for Nelson’s syndrome is mandatory (Yip et al. 2022; Reincke et al. 2023; Nieman et al. 2015).
Pheochromocytoma. Most non-syndromic unilateral pheochromocytomas up to roughly 6 cm are resected via laparoscopic transabdominal or posterior retroperitoneoscopic approaches. Approximately 10–17% of pheochromocytomas and paragangliomas demonstrate malignant (metastatic) behaviour, with substantially higher rates among SDHB-mutation carriers. Cortical-sparing adrenalectomy is recommended for bilateral pheochromocytomas (typically associated with multiple endocrine neoplasia type 2 or von Hippel–Lindau disease) when technically feasible, in order to preserve adrenocortical function and avoid lifelong steroid replacement; steroid dependency and recurrence rates are each in the 9–30% range (Lenders et al. 2014; Yip et al. 2022). Early ligation of the adrenal vein remains a standard technical principle to limit catecholamine release during tumor manipulation.
Adrenocortical carcinoma. ACC is a rare and aggressive tumor for which surgery is the cornerstone of potentially curative therapy. Management at high-volume multidisciplinary centres is recommended. Open en bloc resection with an intact capsule and microscopically negative (R0) margins is the goal; minimally invasive resection is acceptable only at expert high-volume centres for select tumours without local invasion. Neoadjuvant systemic therapy is recommended for advanced ACC when up-front R0 resection is not feasible. Adjuvant mitotane is recommended for patients at high risk of recurrence; cytotoxic chemotherapy (EDP–mitotane) is used for advanced or progressive disease. Approximately 22–35% of patients have distant metastases at diagnosis (Fassnacht et al. 2018; Yip et al. 2022).
5. Operative technical considerations
Important technical principles, regardless of the access route:
- Pleural injury — managed with intraoperative re-expansion and suction during closure; a postoperative chest radiograph is obtained when the pleura has been entered.
- Right adrenalectomy — the short right adrenal vein drains directly into the posterolateral inferior vena cava; meticulous dissection and early control are required to avoid major haemorrhage. Lumbar arteries arising from the abdominal aorta near the diaphragm can be obscured and a source of bleeding if injured.
- Left adrenalectomy — pancreatic and splenic injury is the main risk. Iatrogenic splenectomy rates as high as 18% were reported in an old open series (Russell et al. 1982); modern minimally invasive series report markedly lower rates. The left adrenal can be exposed safely by incising the transverse mesocolon, dividing the inferior mesenteric vein, and elevating the pancreatic tail by blunt dissection.
- Pheochromocytoma — early ligation and division of the adrenal vein limits intraoperative catecholamine release; intraoperative hypertension is managed with short-acting agents (sodium nitroprusside, phentolamine, or nicardipine) and post-resection hypotension with volume expansion and vasopressors if required.
6. Conclusion
Adrenalectomy is now a highly effective, low-morbidity operation when performed at experienced centres. Most operations for benign functioning tumours, MACS with relevant comorbidities, indeterminate masses ≥ 4 cm with suspicious features, and unilateral primary aldosteronism are performed via a minimally invasive approach — laparoscopic transabdominal, posterior retroperitoneoscopic, or robotic. Open adrenalectomy is reserved for known or suspected adrenocortical carcinoma and locally invasive disease, where en bloc R0 resection at a high-volume multidisciplinary centre offers the best chance of cure. Preoperative preparation has matured into disease-specific protocols — overnight dexamethasone suppression and stratified workup for cortisol disorders, plasma or urinary metanephrines and α-blockade for pheochromocytoma (with genetic counselling), and adrenal venous sampling for primary aldosteronism — and perioperative steroid management is now guided by the type and severity of cortisol excess and by postoperative dynamic testing (Yip et al. 2022; Fassnacht et al. 2023; Fassnacht et al. 2018).
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