Most adrenal masses in children will be functional and evaluation should include evaluation for hypersecretion of cortisol, sex hormones, aldosterone, and catecholamines.
Differentiating between a benign or malignant adrenal cortical tumor preoperatively is difficult.
MRI or CT is useful to localize adrenal lesions. For cortical lesions a radiolabelled iodo-cholesterol (NP-59 scan may be required; for medullary lesions a MIBG scan may be necessary). If these imaging techniques fail to localize the lesion, adrenal venous sampling should be considered.
Patients with pheochromocytoma require premedication with phenoxybenzamine preoperatively.
The adrenal gland arises from the mesoderm and neural crest cells. During the fifth gestational week mesodermal cells migrate into the mesenchyme forming thick buds of fetal cortical cells. This is followed by a second migration of mesoderm that envelops the fetal cortical cells and will become adult cortical cells. Shortly after birth the fetal cortical cells degenerate and the adult cortical cells proliferate. The cortex then forms 3 layers (listed from deep to superficial): zona reticularis, zona fasciculate, and zona glomerulosa. The adrenal medulla arises from neural crest cells migrating to the initial fetal cortical mass. There is a close relationship between primordial adrenal cells and the genital ridge which can lead to ectopic adrenal tissue (cortical or medullary) along the course of gonadal descent.
Both adrenal glands are situated in the retroperitoneum within the Gerota fascia superior to the kidneys reflecting the early nomenclature for these glands as suprarenal glands (see Fig. 86-13A). The arterial supply to both glands is primarily through multiple small branches from the posterior inferior phrenic arteries. Branches of the sympathetic chain and the celiac plexus course along the adrenal vessels to innervate the medulla. Despite similar arterial blood supply, venous drainage and the anatomic relationships to adjacent organs is very different between the right and left adrenal glands. These differences must be understood by the surgeon undertaking adrenalectomy.
Anatomy of the adrenal glands: A. The adrenal glands are superior to the kidneys bilaterally and derive their arterial supply from branches of the inferior phrenic artery. B. AXIAL view of the right adrenal gland and its anatomic relationships to the liver, IVC, and diaphragm.
The right adrenal gland sits atop the right kidney, behind the right lobe of the liver, and is in contact with the posterior diaphragm (see Fig. 86-13B). The venous drainage is directly into the inferior vena cava (IVC) via the right adrenal vein (see Fig. 86-14A). The left adrenal gland is situated superior to the left kidney, posterior to the pancreas and the splenic vessels (see Fig. 86-15). It is also in contact with the posterior diaphragm. Venous drainage of the left adrenal gland is via the left adrenal vein which drains directly into the left renal vein (see Fig. 86-14B).
A. The right adrenal vein drains into the inferior vena cava. B. The left adrenal vein drains into the left renal vein.
The left adrenal gland and its anatomic relationship to the pancreas and spleen.
The adrenal cortex synthesizes and secretes the corticosteroids which are inclusive of mineralocorticoids, glucocorticoids, and sex hormones all of which are derived from cholesterol (see Fig. 86-16). The outermost layer of the cortex is the zona glomerulosa which produces the mineralocorticoid, aldosterone. Secretion of aldosterone is tightly regulated by extracellular potassium levels and angiotensin II through the rennin–angiotensin system which is activated by decreased renal blood flow. Aldosterone maintains fluid and electrolyte balances via increased renal resorption of sodium, increased renal resorption of water, and increased renal excretion of potassium.
Hormone synthesis from cholesterol in the adrenal cortex.
The middle layer of the adrenal cortex is the zona fasciculate which primarily produces the glucocorticoids, primarily cortisol, in response to stimulation from adrenocorticotropic hormone (ACTH) which is released from the anterior pituitary gland. ACTH release is in turn controlled by corticotrophin-releasing hormone (CRH) from the hypothalamus which is either enhanced or suppressed by blood cortisol levels as part of a negative feedback loop.
The innermost layer of the adrenal cortex is the zona reticularis which produces the sex hormones, primarily the androgens dihydroepiandrosterone (DHEA) androstenedione. These prescursors are converted to testosterone and estrogen in the testes and ovaries.
The adrenal medulla synthesizes and secretes epinephrine and norepinephrine (see Fig. 86-17). In humans, epinephrine is the primary catecholamine secreted from the adrenal glands—nearly 80% epinephrine and 20% norepinephrine. Acetylcholine release from preganglionic sympathetic fibers stimulates catecholamine release in response to stress.
Catecholamine synthesis in the adrenal medulla.
Primary malignancies of the adrenal gland in children are extremely rare. When an adrenal mass is present, a thorough endocrine work-up should be pursued to detect a hyperfunctioning lesion and its location in preparation for resection. Lesions of the cortex may secrete androgen, cortisol, or aldosterone. Lesions of the medulla secrete catecholamines, and this should always be evaluated during the work-up of any adrenal mass because these patients require special preoperative management to avoid a hypertensive crisis during resection.
Hyperfunction may be due to solitary or multiple adenomas, cortical carcinoma, or gland hyperplasia. When solitary neoplasms are present, surgical resection is indicated. Distinguishing malignant from benign adrenal disease preoperatively is difficult. Size and radiographic characteristics are unreliable in the pediatric patient. Therefore, resected tissue is often required for histopathologic examination. In the setting of adrenal gland hyperplasia bilateral adrenalectomy may be necessary to alleviate symptoms of hormone excess if medical therapy is not tolerated.
In contrast to adults, more than 95% of primary adrenal cortical lesions in children are functional. These patients typically present with signs and symptoms of virilization due to overproduction of androgens but can also present with cushingoid features due to cortisol excess. Hypersecretion can be due to an adrenal adenoma (or adenomas) or adrenal cortical carcinoma (ACC). ACC tend to be advanced at the time of diagnosis and even with resection recurrence rates are reported to be as high as 40% with a 5-year survival of 34%. Complete resection is the best chance for cure, whereas complete excision for adenomas portends an excellent prognosis.
Distinguishing between benign adenoma and ACC preoperatively is difficult. Urinary 17-ketosteroids are usually elevated, especially in the setting of a malignancy. The presence of distant metastases or local invasion is certainly suggestive of malignancy. If the patients presents with the Cushing syndrome then plasma cortisol levels will be elevated as well. In the setting of adrenal-dependent hypercortisolism, a high-dose dexamethasone suppression test will fail to suppress cortisol secretion. Imaging, with either MRI or CT, should be undertaken to localize the lesion in preparation for resection. In rare cases, hypercortisolism can be due ectopic ACTH secretion. In this instance of hypercortisolism, plasma cortisol levels are not suppressed during a high-dose dexamethasone suppression test. Treatment of the source of ectopic ACTH should be sought. Bilateral adrenalectomy, may need to be considered if a source cannot be found.
Hyperaldosteronism, or Conn Syndrome, is rare in the pediatric patient. In children, this is most commonly associated with hyperplasia as opposed to an adenoma. However, in the setting of an adenoma or, very rarely, a carcinoma, resection is indicated. Imaging with either MRI or CT should be pursued to localize a lesion. If one cannot be identified with these modalities then a radiolabelled iodo-cholesterol (NP-59) or adrenal venous sampling can be utilized.
Adrenal Medullary Lesions
Pheochromocytomas are functional tumors of the adrenal medulla. These neoplasms are predominately sporadic but may arise in familial kindreds or as part of the MEN IIA or IIB syndromes. The mean age of onset is 11 years and, unlike adults who have paroxysmal hypertension, pediatric patients have sustained hypertension with vision changes, headaches, nausea, and weight loss. The work-up should include a 24-hour urinary excretion of fractionated catecholamines (dopamine, norepinephrine, and epinephrine) as well as metanephrine, normetanephrine, vanillymandelic acid, and homovanillic acid. Including fractionated catecholamines helps the clinician distinguish pheochromocytoma and paraganglioma from neuroblastoma.
Imaging should include either CT or MRI. A 131I metaiodobenzylguanidine (MIBG) scan can also be useful to localize small (<1 cm) or extra-adrenal lesions. Up to 10% of pheochromocytomas will be familial or associated with MEN IIA or IIB and in this circumstance there is a 25% incidence of bilateral lesions. Once localized, resection should be undertaken as complete excision is the most effective treatment.
Prior to resection, patients with a pheochromocytoma should be premedicated with phenoxybenzamine to achieve adequate alpha-blockade for 7 to 10 days preoperatively. If rebound tachycardia develops then a beta-blocker should be added. The night prior to resection patients should be preadmitted for intravenous volume repletion as their long-standing vasoconstriction has led to volume depletion and places them at risk for hypotension after removal of the neoplasm.
Up to 47% of pheochromocytomas in children are malignant. However, with complete resection, 5-year survival is as high as 90% despite a 47% incidence of malignant pheochromocytomas. Sporadic tumors and tumors >6 cm carry a higher risk of malignancy. For patients with unresectable metastatic disease, MIBG combined with chemotherapy can palliate symptoms. Repeat urinary catecholamines should be checked one week after resection to ensure a cure.
Other Adrenal Masses (Table 86-7)
Table 86-7Differential Diagnosis for an Adrenal Mass Categorized as Functional and Nonfunctional |Favorite Table|Download (.pdf) Table 86-7 Differential Diagnosis for an Adrenal Mass Categorized as Functional and Nonfunctional
|Functional ||Nonfunctional |
|Adrenal adenoma ||Neuroblastoma |
|Adrenal cortical carcinoma ||Adrenal cyst |
|Pheochromocytoma ||Hemangioma |
|Metastatic disease ||Leiomyoma/leiomyosarcoma |
| ||Lymphoma |
| ||Melanoma |
| ||Metastatic disease |
| ||Myelolipoma |
Myelolipoma is a benign adrenal mass that is rarely encountered in the pediatric population. This neoplasm is made up of adipose tissue and bone marrow. These are most commonly incidental findings and are asymptomatic. Indications to resect these neoplasms include a large, symptomatic mass or inability to distinguish it from a malignancy. Adrenal hemorrhage presenting as an adrenal mass in the infant is not uncommon. This most commonly occurs in the right adrenal gland due to trauma during labor or coagulopathy. Expectant management is usually indicated although life-threatening hemorrhage may necessitate surgical control. Once the hematoma resolves calcification or cyst formation may result in an abnormal-appearing adrenal gland. If the hematoma is seeded hematogenously an abscess may develop. Metastatic lesions to the adrenal gland can also occur.
The approaches to adrenalectomy are highly variable and include open approaches that consist of: anterior, posterior, trans-peritoneal, retroperitoneal, and even thoracoabdominal exposures. Since the original description by Gagner in 1992, laparoscopic adrenalectomy is being utilized more frequently and provides a less invasive approach that hastens recovery. Most adrenalectomies can be performed laparoscopically, however, local extension or invasion, concern for malignancy particularly with lymph node involvement, large neoplasms, major vascular invasion, or extensive adhesions from prior abdominal procedures are relative contraindications to a minimally invasive approach. Furthermore, the anatomy of the right versus the left adrenal gland is different and can change the degree of difficulty of adrenalectomy. The surgeon should tailor his or her approach based on the patient, the tumor characteristics, and the tumor location.
Laparoscopic Right Adrenalectomy
Laparoscopic adrenalectomy is performed under general endotracheal anesthesia with the patient in a lateral decubitus position. For a right adrenalectomy the left lateral decubitus position is used, a bean bag helps maintain the positioning and flexion is used on the operating room table to open the space between the iliac crest and the costal margin. All pressure points should be carefully padded and straps should be used to secure the patient. An orogastric tube should be placed to decompress the stomach and an indwelling urinary catheter is placed to monitor urine output.
The surgeon is positioned behind the patient and the assistant is situated in front of the patient. The monitors are placed at the patient's head. The first trocar is a 5-mm camera port made half-way between the anterior iliac spine and the umbilicus. We favor an open cut-down although some surgeons prefer use of the Veress needle. A 5-mm 45° angled scope is used to explore the abdomen. Additional ports are then placed including a 10-mm working port just lateral to the initial port (which will be used for specimen retrieval); cephalad to the camera port in the mid-axillary line an additional 5-mm trocar is placed for liver retraction; the final port site is a 5-mm working port placed in the posterior axillary line (see Fig. 86-18). It is important to keep the port sites close to the costal margin so that the iliac crest does not prohibit manipulation of the laparoscopic instruments.
Port placement for laparoscopic right adrenalectomy with the patient in the lateral decubitus position.
Initially the right colon may need to be mobilized to facilitate placement of the lateral most trocar. The right colon is then reflected medially and the triangular ligament of the right hepatic lobe is divided with the Harmonic scalpel. Once the right lobe of the liver has been mobilized the liver retractor is used to reflect it medially exposing the right adrenal gland. The Harmonic scalpel is then used to dissect the adrenal gland. Oftentimes it is easier to mobilize the adrenal gland's lateral, superior, and inferior attachments to allow lateral retraction. In doing this the arterial supply is usually taken and the lateral retraction exposes the right adrenal vein which drains directly into the inferior vena cava (IVC). Care must be taken to gently retract the gland to avoid avulsing the adrenal vein from the IVC which leads to brisk bleeding and requires conversion to an open procedure. A 5-mm clip applier is used to ligate the adrenal vein. After division of the adrenal vein, care should still be taken in retracting the gland laterally as there may be accessory veins from the IVC that require ligation. The remainder of the dissection is then completed with the Harmonic scalpel and the specimen is removed in an EndoCatch bag through the 10-mm port site. The surgical site is then re-explored to ensure hemostasis. The skin of all 5-mm trocar sites is then closed with absorbable suture; the 10-mm trocar site fascia is closed with absorbable suture prior to skin closure.
Laparoscopic adrenalectomy can be performed with the patient supine; however, retraction of the abdominal viscera medially can make this approach more cumbersome. We find that the supine approach is more suitable for bilateral disease to avoid repositioning of the patient (see below). An endoscopic retroperitoneal or posterior approach has also been described. With the patient in the prone jackknife position a balloon dissector is placed through a 10-mm trocar placed into the retroperitoneal space just lateral to the 12th rib and is insufflated to create a working space. Three additional 5-mm ports are then placed: the first one just lateral to the 11th rib, another more lateral between the 9th and 10th ribs, and the third just below the 12th rib. This approach may be useful for bilateral disease as it avoids repositioning of the patient as well as avoiding complications related to trans-peritoneal access, yet the working space is tight and can make the operation more difficult especially for larger masses.
Open Right Adrenalectomy—Anterior Approach
An open approach to the right adrenal gland is occasionally required to perform an adrenalectomy and can include an anterior trans-peritoneal approach, a retroperitoneal approach, flank approach, a posterior approach, or even a thoracoabdominal approach. When using an open technique, we prefer a transabdominal approach. This allows a thorough abdominal exploration and, because an en bloc resection may be required when performing an open adrenalectomy, the anterior, trans-peritoneal approach makes en bloc resection technically much easier than a retroperitoneal or posterior approach. We reserve a thoracoabdominal approach for very large tumors with major vascular involvement where access to the suprahepatic inferior vena cava may be necessary.
Under general endotracheal anesthesia the patient is placed supine with a roll under the right flank. An indwelling urinary catheter is placed to monitor urine output and an orogastric or nasogastric tube is used decompress the gastrointestinal tract. An anterior approach to the right adrenal gland can include a bilateral subcostal incision, a right subcostal incision, or a midline incision. We prefer a right subcostal incision. Upon entry into the abdomen, exploration is conducted. Similar to the laparoscopic approach, the triangular ligament of the right liver is divided to allow the liver to be retracted medially. The right colon is also reflect medially (which may require taking down the hepatic flexure in the case of larger tumors) to expose the duodenum which is then Kocherized to expose the right adrenal gland and IVC.
If the mass is large or there is a high suspicion for malignancy, the dissection is typically started on the medial portion to ensure that there is a plane between the neoplasm and the IVC. If a plane cannot be created, the surgeon must determine if the extent of invasion precludes resection. If an IVC resection is required and distal control of the IVC cannot be achieved below the liver then extension of the incision to the chest may be necessary to allow access to the suprahepatic IVC. If a free plane is present between the adrenal gland and the IVC, the right adrenal vein and any accessory branches can readily be identified and ligated. The remainder of the dissection is then carried medial to lateral to complete the adrenalectomy. Hemostasis is then ensured and the subcostal incision is closed in layers with absorbable suture including the posterior fascia, the anterior fascia, and skin.
Open Right Adrenalectomy—Posterior Approach
For patients who have had extensive abdominal procedures who are not laparoscopic candidates and in whom an anterior approach would be difficult due to adhesions, a posterior approach is an option. However, a posterior approach should not be utilized for large tumors with local invasion. The posterior approach requires prone positioning of the patient under general endotracheal anesthesia. A Hugh–Young paraspinous incision is made to the right side of the midline from the 12th rib in a hockey-stick fashion carrying the curve towards the iliac crest (see Fig. 86-19). This approach requires removal of a portion of the 12th rib (and sometimes excision of the 11th rib) as well as division of the latissimus dorsi muscle to facilitate exposure. The pleura is then encountered and must be dissected away from the diaphragm. Care should be taken to not violate the pleura during this mobilization. After opening the diaphragm, the Gerota fascia is then divided to expose the right kidney and adrenal gland. The adrenal gland is then dissected free ligating the adrenal vein and arteries as described above. If the pleura had been violated, at the conclusion of the case the incision should be closed over a red rubber catheter placed into the pleural space and hooked to suction which is then removed quickly with the patient in Valsalva. The incision is closed in layers and a post-operative chest radiograph should routinely be obtained.
Incision for posterior approach to right adrenalectomy.
Laparoscopic Left Adrenalectomy
For a laparoscopic left adrenalectomy the patient is placed in the right lateral decubitus position under general endotracheal anesthesia. As previously mentioned, an orogastric tube is placed along with an indwelling urinary catheter. The surgeon operates form the patient's back, the assistant is at the patient's front, and the monitors are positioned towards the patient's head. With appropriate padding, straps, and flexion of the bed an initial 5-mm camera port is placed half-way between the anterior iliac spine and the umbilicus. We prefer an open technique versus the Veress needle for this initial trocar. The port sites are similar as for a laparoscopic right adrenalectomy; however, the medial most 5-mm port may not be necessary unless the spleen and pancreas need to be retracted medially for exposure. Rotating the patient face down will allow gravity to pull the spleen and pancreas medially—therefore it is critical to ensure the patient is adequately strapped to the table. A 10-mm working port is placed just lateral to the camera port, and a 5-mm working port is placed lateral to this in the posterior axillary line (see Fig. 86-20). Again, placement of the fourth trocar for retraction is at the surgeon's discretion.
Port placement for laparoscopic left adrenalectomy with the patient in the lateral decubitus position.
The abdomen is initially explored and then a Harmonic scalpel is used to mobilize the left colon medially. This maneuver may be necessary to create room for the lateral most trocar. Contrary to the right side, on the left side the left adrenal vein can be identified early on at the inferior-medial aspect of the adrenal gland which is ideal in the setting of a pheochromocytoma. Once the adrenal vein has been ligated, the remainder of the gland can be mobilized using the Harmonic scalpel including ligation of the arterial supply. The specimen is then removed via an EndoCatch bag and the incisions are closed as previously described. During dissection of the adrenal gland care must be taken to avoid injury to the pancreas. If a pancreatic injury occurs, a surgical drain should be left.
Open Left Adrenalectomy—Anterior Approach
As mentioned previously, an open approach may be necessary for large tumors with local invasion, vascular involvement, suspicious lymph nodes, or adhesive disease where laparoscopy may not be feasible. Open approaches include an anterior trans-peritoneal approach, a retroperitoneal approach (through an anterior or flank incision), or a posterior approach. As for right adrenalectomies, when using an open technique for a left adrenalectomy, we prefer a transabdominal approach for the same reasons.
The patient is placed supine and under general endotracheal anesthesia a roll is positioned under the left side. An indwelling urinary catheter is placed and the gastrointestinal tract is decompressed with either an orogastric or nasogastric tube. Multiple incisions can be used including a bilateral subcostal, a left subcostal, or midline incision. We prefer a left subcostal incision. Upon entry to the abdomen manual exploration is undertaken. The splenic flexure is taken down and along with the spleen and tail of the pancreas is reflected medially. If an en bloc resection involving the spleen and/or pancreas is required, the gastrocolic ligament will need to be divided to allow access into the lesser sac for mobilization of these organs.
Reflection of the splenic flexure, pancreatic tail, and spleen will expose the Gerota fascia and the left kidney and adrenal gland (see Fig. 86-15). The retroperitoneal fat may make it difficult to readily identify the adrenal gland. The lateral and medial attachments should then be taken down with particular care at the inferomedial border of the adrenal gland where the left adrenal vein drains into the left renal vein (see Fig. 86-14B). Once identified this should be ligated. The left inferior phrenic vein drains into the left adrenal vein and may need to be divided as well. For hyperfunctioning neoplasms, particularly pheochromocytomas, the adrenal vein should be ligated first to avoid ongoing catecholamine release. While mobilizing the medial and lateral portions of the left adrenal gland the surgeon will encounter the arterial branches which should be ligated as well. At this point the posterior and superior attachments can be divided completing the adrenalectomy. After hemostasis has been ensured closure of the subcostal incision with absorbable suture should include 3 layers: the posterior fascia, the anterior fascia, and the skin.
Open Left Adrenalectomy—Posterior Approach
For patients who have had extensive abdominal procedures who are not laparoscopic candidates and in whom an anterior approach would be difficult due to adhesions, a posterior approach is an option (exclusive of large tumors and/or local invasion). For a left adrenalectomy the posterior approach is performed in similar fashion as described above for the right adrenalectomy except that the incision will be to the left side of the midline. As for right adrenalectomies, a retroperitoneal approach either anterior or through a flank incision is rarely needed. We feel that the exposure is better through a trans-peritoneal approach for larger tumors with local invasion. Lesions that would be easily excised through a retroperitoneal approach are best approached laparoscopically.
Patients with bilateral disease (most commonly bilateral adrenal hyperplasia) may require a bilateral adrenalectomy. We still favor a minimally invasive approach in this subset of patients. A lateral approach can be used, however, this requires that the patient be repositioned. As mentioned above, the posterior minimally invasive approach allows for a bilateral adrenalectomy to be performed without repositioning the patient, however, most surgeons are not familiar with this approach.
One alternative is to use a laparoscopic anterior approach with the patient in the supine position. A 10-mm camera port is placed in an open fashion at the umbilicus. A 5-mm port for retraction is placed sub xiphoid and 2 additional 5-mm working ports are placed subcostally (one at the anterior axillary line and the other at the mid-clavicular line) on the right and left hand side. The procedure is performed in a similar fashion to the lateral approach; however, further mobilization and retraction of the colon, liver, spleen, and pancreas are required to obtain adequate visualization of the operative field. It is helpful to have the patient securely strapped to the operating table to allow for right and left “air planing” of the bed to facilitate exposure. An additional 5-mm working port in the upper midline can also be useful to help retract the viscera medially.
If a minimally invasive approach cannot be offered, then an open approach should be utilized. Bilateral adrenalectomy can be performed through an anterior approach using either a bilateral subcostal incision or a midline celiotomy. A posterior approach for bilateral disease has also been advocated to avoid the potential complications from a trans-peritoneal approach although this requires 2 separate incisions.
Hemorrhage is the most worrisome complication of adrenalectomy, particularly for right adrenalectomies where the dissection occurs along the IVC. The anterior approaches (either laparoscopic or open) lend themselves to the pitfalls of accessing the peritoneal cavity including adhesion formation, iatrogenic injuries to the viscera, and post-operative ileus. Most patients undergoing laparoscopic adrenalectomy have minimal pain and can be dismissed the following day. Patients having an open procedure require a longer hospitalization of 3 to 5 days for recovery. Patients having bilateral adrenalectomies must have appropriate hormone replacement to avoid an adrenal crisis.