Adrenal Gland Tumors And Their Managment

Presented ByDr.Faisal Zia

Post Graduate Resident Leady Reading Hospital Peshawar

Outline• Anatomy of Adrenal Glands• Short Review Of Physiology• Classification Of Tumors Of Adrenal Glands• Symptoms/Signs• Diagnosis• Management Strategies

Anatomy of Adrenal Glands

Vascular Supply Of Adrenal Gland

-The Arterial supply of each adrenal gland may arise from three main sources: superior adrenal arteries (branches from the inferior phrenic arteries), middle adrenal arteries (direct visceral branches from the aorta) and inferior adrenal arteries (branches from the ipsilateral renal artery.

The short right adrenal vein drains directly into the vena cava. On the left, the adrenal vein is long compared with the right and is joined by the inferior phrenic vein prior to draining into the left renal vein.

• Functionally Adrenal Glands Has two Parts1. Adrenal Cortex2. Adrenal Medulla

Adrenal Cortex is Characterized by Zonal Configuration i.ea. Zona Glumerulosa ---- Aldosterone ( Na+, k+ Homeostasis)b. Zona Fasiculata ------ Cortisol ( Stress Hormone)c. Zona Reticularis ----- Dehydroepiandrosterone (Androgen

precursor)

Adrenal Medulla The Medulla secretes Epinephrine (80%), Norepinephrine(19%), and Dopamine (1%).

A. Classification Of Adrenal Tumors1. Adrenal Cortical Tumors2. Adrenal Medullay Tumours

1. AdrenoCortical Tumorsa. Benign b. Malignant

Adenoma/Nodular hyperplasia Adrenocortical Carcinoma2. Medullay tumours

Benign MalignantGanglioNeuroma, Pheochromocytoma Neuroblastoma

Other Tumours are :• Myelolipoma• Adrenal Mets

AdrenoCortical AdenomaAdenomas are the most common neoplasms arising from the adrenal

glandThe incidence of adenomas rises with age.Adrenal adenomas are by definition benign and the vast majority are

metabolically silent (Non-Functional i-e Non-hormone producing) But Some May produce Hormone producing Signs and Symtoms depend Upon Zone Involved.

May be Unilateral Or Bilateral

Clinical featuresDepend upon Type of Adenoma i.e1. Small Size, Non Hormone producing are usually Asymptomatic, Incidently diagnosed

In CT/MRI Done for Some Other reason where they r Called Incidentaloma.2. Large Size, Non functioning Tumours Frequently Present with Abdominal Discomfort

or Back Pain, however with increasing use of Abdominal imaging they are detected early now

3. Hormone Producing Adenomas will produce Signs/Symtoms of The Hormones Produced. I-e

Cushing Syndrome If hypersecretion of Cortisol OccursConn’s Syndrome If hypersecretion of Aldosteron occurs

• Cushing Syndrome

Weight Gain/Central Obesity Diabetes Hirsutism Hypertension Skin changes (Striae, Facial Plethora, ecchymosis, acne) Muscle weakness Menstrual irregulariety/Impotence Depression/Mania Osteoporosis Hypokalemia

• Conn’s Syndrome

Headache Hypertension Muscle Weakness Cramps Intermittent Paralysis Polyuria Polydipsia Nocturia

Diagnosis• Complete History• Clinical Examination• Biochemical evaluation

• Morning and Midnight Plasma Cortisol Measurement• Dexamethasone Suppression Test• 24 hr Urinary Cortisol measurement• Serum Potassium, Plasma aldosterone and Plasma Renin Activity• Serum Dehydroepiandrosterone or 17 B-hydroxyestradiol (Virilising or feminizing tumour).

• Abdominal Imaging• CT Scan :

• Is the Initial procedure and will localize Adenoma in approx 90% of Patients• MRI Scan• Equally effective in distinguishing adrenocortical adenoma from Carcinoma

• Adrenal vein Catheterization• If no adenoma is visualized, adrenal vein sampling for aldosterone and cortisol will correctly differentiate

adenoma from hyperplasia in virtually all cases.• Similarly Samples From Both the Adrenal Vein And Determing Aldosterone to Cortisol Ratio ACR will differentiate

between unilateral and bilateral disease

Treatment• Any Non-Functioning Adrenal Tumour Greater tha 4cm in diameter

and smaller tumours that increase in size over time should Undergo Surgical resection.• Non-Functioning Tumours Smaller than 4cm should be followed up

after 6, 12 and 24 months by Imaging and Hormonal evaluation.• Options for Functioning Tumors• Medical Management

• Dietary Sodium Restriction• Spironolactone ------ Conn’s syndrome• Metyrapone or KetoConazole ------ reduce Steroid Synthesis ------- Cushing syndrome

• Surgical Management• Unilateral Adenoma ----- Unilateral Adrenalectomy• Bilateral Disease ------------ Bilateral Adrenalectomy

• Pre-Op Management • Conn’s and Cushing Related Disease (Hypertension, Diabetes) and Biochemical

Abnormalities should be corrected.• Patients with Cushing’s Syndrome are at an increased risk of Hospital Acquired

Infection and thromboembolic and myocardial Complications. Therefore, Prophylactic anticoagulation and the use of prophylactic antibiotics are essential.

• Post-Op Management• Supplementary Cortisol should be give after surgery. In total 15 mg h-1 is required

parentally for the first 12 hr followed by a daily dose of 100 mg for 3 days which is gradually reduced thereafter.

• After Unilateral adrenalectomy, the contralateral suppressed Gland need Up2 1 year to recover adequate function.

Adrenocortical Carcinoma• A rare malignancy with an incidence of 0.5 to 2 per million but generally

poor prognosis.• Peaks in children in the first decade of life and adults in the fourth to

fifth decades of life.• Slight female predominance.• The majority of ACCs are unilateral.

Clinical features• Approx 60% present with evidence of Steroid hormone excess i-e

Cushing Syndrome. Else any Hormone Excess can be the Presentation.• Patients with Non-Functioning tumours frequently complain of

Abdominal discomfort or Back pain caused by Large tumours

Diagnosis• Complete History• Clinical Examination• Biochemical evaluation

• Morning and Midnight Plasma Cortisol Measurement• Dexamethasone Suppression Test• 24 hr Urinary Cortisol measurement• Serum Potassium, Plasma aldosterone and Plasma Renin Activity• Serum Dehydroepiandrosterone or 17 B-hydroxyestradiol (Virilising or feminizing tumour).

• Abdominal Imaging• CT Scan• MRI Scan • MRI Angiography ---- TO exclude tumour thrombus in the vena Cava which must be

excluded before Adrenalectomy.• As Distant Metastasis Is frequently Present So a CT scan of the Lung is recommended

Equally effective in distinguishing adrenocortical adenoma from Carcinoma

Staging Of Adrenocortical Ca• The World Health Organization Classification of 2004 is based on the

McFarlane classification and defines Four Stages:I. Stage = Tumour < 5cmII. Stage = Tumour >5 cmIII. Stage = Locally invasive tumoursIV. Stage = Tumour with distant metasis

Managment• Complete Tumour Resection (R0) is associated with favourable

Outcome and should be attempted Whenever Possible.• En bloc resection with removal of locally involved organs is often

required and incase of tumour thrombus in the vena cava the assistance of a cardiac surgeon is sometimes needed.• Tumour debulking plays a role in functioning tumours to control

hormone excess.• Laproscopic adrenalectomy is Associated with a high incidence of

local recurrence and cannot be recommended.

• Adjuvent Chemotherapy• Patient should be treated Postoperatively with Mitotane alone or in

combination with Etoposide, Doxorubicin or Cisplatin in 30% and 50% of cases respectively.

• Adjuvent Radiotherapy• May reduce the rate of local recurrence.

• Follow Up• After surgery, Restaging every 3 months is required as the risk of tumour

relapse is high.

• Prognosis• Depends On the stage of Disease and Complete Removal of the tumour.• Patients with stage I or II disease have a 5-year survival rate of 25% whereas

patient with stage III and stage IV disease have 5-year survival rate of 6% and 0% respectively.

Phaeochromocytoma (Adrenal Paraganglioma)• Catecholamine-producing tumor derived from the sympathetic and parasympathetic nervous

system, usually located in the adrenal gland.• May also produce Calcitonin, ACTH, VIP, PTHrP• Prevalence in Hypertensive patients is 0.1 – 0.6% with over all prevalence of 0.05% In autopsy

series.• Sporadic Phaechromocytoma occur after the fourth decade whereas patients with hereditary

form are diagnosed early.• Also known as the 10% Tumour i-e

• 10% are inherited• 10% Extraadrenal• 10% Malignant• 10% Bilateral• 10% Occur in Children

• Hereditary Phaechoromocytoma are Usually Associated with Syndromes like• Multiple Endocrine Neoplasia Type 2

• Medullay thyroid Carcina• Primary Hyperparathyroi• Phaechromoctoma

• Familial paraganglioma Syndrome• Von Hippel-Lindau Syndrome• Neurofibromatosis Type I

Clinical features• Can be continuous or Intermittent.• Headache• Palpitation• Sweating• Hypertension ( Paroxysmal or continuous)• Pallor• Weight loss• Nausea• Hyperglycemia• Psychological effects• Paroxysms may be precipitated by physical training, induction of Anesthesia

and Drugs like TCA, Metochlopramide, Opiates or Contrast media

Diagnosis• Complete History• Clinical Examination• Biochemical evaluation

• Determination of Adrenaline, Noradrenaline, Metanephrine and normetanephrine levels in a 24-hr Urine Collection. Level exceeding Normal range by 2- 40 times will be found in affected patients.

• Determination of Plasma free Metanephrine and Normetanephine Levels has a high sensitivity

• Biochemical tests Should be performed at least twice

• Imaging• For Localization of Tomour and/Or Metastases MRI is preferred because Contrast Media

used for CT scans can provoke Paroxysms.• 123I-MIBG (meta-Iodobenzyl guanidine) single- photon emission computerized

tomography SPECT will identify about 90% of primary Tumours. And is essential for the detection of Multiple Extra-Adrenal Tumours and Metastases.

Management• Laparoscopic resection.• If tumour Larger than 8—10cm or radiological signs of malignancy are detected, then an Open

Approach Should be Considered

• PreOperative Care• Once Diagnosed, An alpha adrenergic Blocker (Phenoxybenzamine) is used to block

Catecholamine excess and its consequences during Surgery.• A dose of 20 mg of Phenoxybenzamine initially, should be increased daily by 10mg until a

daily dose of 100—160 mg is achieved and the patient reports symptomatic postural Hypotension.

• Additional Beta-Blockade is required if tachycardia or arrhythmias develops, and this should not be introduced until the patient is alpha Blocked.

• PerOperative Care• In Some patients, a dramatic changes in heart rate and Blood pressure may occur and require

sudden administration of Pressor or Vasodilator agents. A central Venous Catheter and invasive arterial monitoring are essential.

• Special attention is required when the adrenal vein is ligated as a sudden Drop in Blood Pressure may Occur.

• Rarely, Infusion of large volume of Fluid or even administration of Adrenaline can be necessary.

• Post Operative Care• Patient should be Observed for 24 hr in the ICU as Hypovolemia and hypoglycemia may

Occur.

• Follow Up• Biochemical cure should be confirmed by an assessment of catecholamine 2-3 weaks

Postoperatively.• Lifelong Yearly Biochemical tests should be performed to identify recurrent, metastatic

or metachronous phaeochromocytoma.

Malignant phaechromocytoma• App 10% of Phaechromocytoma are malignant• Rate is higher in Extra-adrenal tumours (Paraganliomas).• Diagnosis of Malignancy Implies Mets to Lymph Node, bone and liver.• About 8% apparently benign tumour subsequently develop metastasis.

• Treatment• Surgical excision Is only chance of Cure.• Even in patient with metastatic disease, tumour debulking can be considered to

reduce the tumour burden and to control the catecholamine excess.• Symtomatic treatment can be obtained with alpha-blockers.• Mitotane should be started as Adjuvent Or Pallistive treatment.• Treatment with 131I-MIBG or combination chemotherapy has resulted In a partial

response in 30% and an improvement of symtoms in 80% of patients.• The natural History is highly Variable with a 5 year survival rate of < 50%.

• A Malignant tumour Derived from Sympathetic nervous system in the Adrenal Medulla (38%) or from any site along the sympathetic chain in the paravertebral sites of the abdomen (30%), chest (20) and rarely, the neck or Pelvis.

• Predominantly Newborn Infants and Young Children (<5 years of age) are affected• Metastatic disease is present in 70% of patients.

• Clinical Features• Symtoms are caused by tumour growth or bone metastases.• Patients present with a mass in the abdomen, neck or chest, proptosis, bone pain, painless

bluish skin metastases, weakness or paralysis.• The catecholamine exces is asymptomatic and an excess ACTH or VIP may Occur.

NeuroBlastOMA

• Diagnosis• Biochemical Evaluation

• Urinary excretion (24 hr Urine) of VMA, Homovanillic acid, Dopamine and Noradrenaline, an increased levels are present in about 80% of patients.

• Accurate staging requires CT/MRI of the Chest and Abdomen, a bone scan, bone marrow aspiration and core Bioipsies as well as an MIBG scan.

• Treatment• Prognosis and Treatment plan can be predicted by the tumour stage and the age at diagnosis. • Patients are classified as low, intermediate or high risk.• Low Risk

• Patients are treated by surgery alone ( the Addition of 6—12 weeks of chemotherapy is optional.• 3 year survival rate of 90%.

• Intermediate Risk• Patients are treated by surgery with Adjuvent Multi-agent chemotherapy i.e carboplatin,

cyclophosphamide, etoposide, doxorubicin.• 3 year survival rate of 70--90%.

• High risk• Patient receive High dose Multi-agent chemotherapy followed by surgical resection in responding tumours

and myeloablative stem cell rescue.• 3 year survival rate of 30%.

Ganglioneuroma• Benign adrenal Neoplasm of neural crest tissue i.e adrenal medulla,

paravertebral sympathetic plexus.• Found in all age groups More Common Before 60 year of age.• Most often they are identified incidentally by CT or MRI Performed for other

indications.• Treatment is by Surgical excision, Laparoscopic when adrenalectomy is indicated.

Myelolipoma• Myelolipoma is a rare lesion of the adrenal gland that contains hematopoietic

elements and mature adipose tissues.• Surgery is indicated only for extremely large or symptomatic lesions.

SURGERY OF THE ADRENAL GLAND• Laparoscopic or Retroperitoneoscopic Adrenalectomy had become the Gold Standard

in the resection of Adrenal Tumours, except for tumours with signs of malignancy.• The more popular approach is the laparoscopic Transperitoneal approach, which

offers a better view of the adrenal region and may be easier to learn.• Advantage of the retroperitoneoscopic approach is the minimal dissection required

by this extra-abdominal procedure.• In case of small, bilateral tmours or in patients with hereditary tumour syndromes a

subtotal resection is warranted.• The mortality rate ranges from 0 to 2% in specialized centres.• An Open Approach should be considered if radiological signs, distant metastases,

large tumours (>8-10cm) or a distinct hormonal pattern suggest malignancy. The surgical access in such cases should be thoracoabdominal.

• Laparoscopic Adrenalectomy• Knowledge of the anatomy of the adrenal region is essential as anatomical landmarks guide the surgeon

during operation. If these landmarks are respected, injury to the vena cava or renal vein, the pancreatic tail or the spleen can be avoided.

• Carefull haemostasis is essential as small amount of blood can impair the surgeon’s view. • To prevent spillage, direct grasping of the adrenal tissue/tumour has to be avoided.

• Laparascopic Transperitoneal Approach• Althought this Approach is possible with the patient Supine, it is usually better to place the patient in

lateral decubitus Position, Head up and the table broken to open the renal angle, so that gravity acts as a natural retractor.

• Right Adrenalectomy• Three or four right subcostal ports are commonly used.• The right triangular ligament is divided and the liver retracted medially to expose the kidney and IVC. A

vertical incision medial to the upper pole of the kidney exposes the Gland.• The Dissection continues at the level of the periadrenal fat using careful coagulation and is finished by

complete or subtotal removal of he adrenal gland.• Left Adrenalectomy

• With the patient positioned On his or her right side, three left subcostal ports usually suffice. • The splenic flexure is mobilized and the lienorenal ligament divided. The spleen then displaces forward

under gravity to expose the kidney and adrenal gland.• The resection is completed by the transection of the adrenal gland at the level of the periadrenal fat.

• Retroperitoneoscopic adrenalectomy• The patient is positioned in the lateral decubitus or the prone jack-knife position as for

the open retroperitoneal approach.• The first port is placed under direct vision into the retroperitoneum and a

retroperitoneal space is created by balloon insufflation. Completeness of adrenal gland excision can be a particular problem with the posterior retroperitoneal approach.

• Recurrent cushing’s syndrome has been reported in upto 20% of cases.

• Open Adrenalectomy• Through a thoracoabdominal approach, it is almost exclusively performed when a

malignant adrenal tumour is suspected.• A transverse Upper abdominal incision is satisfactory; alternatively, it can be a curved

incision, convex upwards. A subcostal incision is suitable for a unilateral adrenalectomy.• On the right Side the Hepatic Flexure of the colon is Mobilised and the right liver lobe is

cranially retracted to achieve an optimal exposure of the inferior vena cava and the adrenal gland.

• On the left side the adrenal gland can be exposed after mobilization of the splenic flexure of the colon, through the transverse mesocolon or through the gastrocolic ligament.

• The remaining dissection is the same as in laparoscopic adrenalectomy.• A resection of regional lymph nodes Is recommended in malignant adrenal tumours and

should include resection of the tissue between the renal pedicle and the diaphragm• Open Loin And Posterior Approach

• Any of the loin Approaches for renal surgery can be used. The lateral decubitus position is used for a loin incision and the prone jack-knife position for the posterior lumbotomy incision.

• Posterior inicisions have an advantage if both adrenal glands must be explored, as the patient does not need to be turned.