Barbra S. Miller
Presentation
A 45-year-old female is seen in her primary care physician’s office with complaints of muscle cramps, fatigue, headaches, polyuria, polydipsia, and nocturia. She has a 10-year history of hypertension requiring four medications to achieve adequate blood pressure control. She also has long-standing hypokalemia, thought to be due to her diuretic, which is being treated with 60 mEq daily of supplemental oral potassium. She denies symptoms of chest pain, shortness of breath, or abdominal pain. She has had no episodes of flushing, tachycardia, tremors, or anxiety. Her vital signs are normal other than a blood pressure of 150/90. Her physical examination is unremarkable other than mild peripheral edema
Differential Diagnosis
Difficult-to-control hypertension should prompt investigation of secondary causes for hypertension. These include renal artery stenosis, hyperaldosteronism, hyperthyroidism, intrinsic renal dysfunction, hypercortisolism, pheochromocytoma, sleep apnea, medications, and other supplements.
Workup
A thorough history and physical examination should be completed, including specific questions related to symptomatology and family history of cardiac disorders, sudden death, or genetic syndromes leading to hypertension. Laboratory studies to evaluate secondary causes of hypertension include a complete metabolic profile, serum aldosterone and renin levels, and fractionated plasma metanephrines. Certain antihypertensives may confound laboratory results. Antihypertensives such as spironolactone, eplere-none, angiotensin-converting enzyme inhibitors, and diuretics affect renin-aldosterone regulation and should be discontinued for 4 to 6 weeks in advance of testing if possible. Alpha blockers may be substituted. Antidepressants and beta blockers may affect plasma metanephrine levels, which should be considered when ruling out pheochromocytoma. Misdiagnosis of a pheochromocytoma and inadequate preoperative alpha blockade can lead to intraoperative complications and death. Diagnosis of primary hyperaldosteronism is confirmed with an elevated aldosterone level, suppressed renin level, and an aldosterone:renin ratio >20:1. Additional testing should be pursued when initial testing is equivocal. Recognizing the inability to suppress aldosterone secretion after sodium loading or administration of captopril can be helpful in this setting.
If evidence of primary hyperaldosteronism is identified, biochemical evaluation should be followed by radiologic evaluation of the adrenal glands. Imaging should not be obtained first without biochemical confirmation of the diagnosis, as many inconsequential “incidentalomas” are discovered on imaging studies. The adrenal glands are best evaluated by adrenal protocol computed tomography (CT). Thin cuts through the adrenal glands show small abnormalities and allow for assessment of tumor/nodule characteristics if present. Concern for an aldosterone-producing adrenocortical carcinoma, which is extremely rare, can usually be ruled out based on size criteria and calculation of Hounsfield units (HU) of the tumor/nodule and washout characteristics. Magnetic resonance images or NP-59 scans are alternative imaging modalities that may be requested.
Selective venous sampling of the bilateral adrenal veins should be obtained in all patients to confirm imaging findings (Figure 1). Venous sampling allows differentiation of unilateral from bilateral excess aldosterone production from the adrenal glands regardless of imaging findings, as CT and MRI findings tend not to correlate well with venous sampling results. Criteria suggesting unilateral excess aldosterone production are shown in Table 1.
FIGURE 1 • A: Contrast injection of right adrenal vein to confirm catheter placement prior to selective venous sampling. B: Catheters placed in bilateral adrenal veins.
TABLE 1. Criteria Used to Confirm Unilateral Excess Aldosterone Secretion After Bilateral Adrenal Vein Sampling
A, Aldosterone; C, Cortisol; A/C, aldosterone to cortisol ratio; IVC, inferior vena cava
Diagnosis and Treatment
Primary hyperaldosteronism is most commonly due to an aldosterone-producing adenoma or adrenal hyperplasia leading to difficult-to-control hypertension, volume excess, and hypokalemia (40% to 50%). Patients who develop hypertension at a young age or those requiring more than three antihypertensive medications for blood pressure control should be investigated for secondary causes of hypertension. Those patients found to have primary hyperaldosteronism due to unilateral excess aldosterone production are offered surgery for cure, while those found to have bilateral production of excess aldosterone are managed medically with aldosterone receptor antagonists, as the risks of iatrogenically induced Addison’s disease after bilateral adrenalectomy (despite steroid replacement) outweigh the risks of continued medical management. Selective venous sampling of the adrenal veins is imperative, especially for those with bilateral normal-or abnormal-appearing adrenal glands but also for those with a single adrenal nodule, as cases are described in which a nonfunctioning incidentaloma is noted on imaging studies with excess production coming from the opposite normal-appearing adrenal gland. Selective venous sampling results should dictate which adrenal gland is removed rather than imaging results.
Laparoscopic resection of the affected adrenal gland has become the gold standard if malignancy is not suspected. Laparoscopic resection of primary adrenocortical malignancies has been shown to be associated with shorter time to local recurrence and a greater chance of margin-positive resections. Aldosterone-secreting adenomas seen on imaging studies are generally quite small with a median size <2 cm (Figure 2). Larger aldosterone-secreting adenomas are rare, and concern for an aldosterone-secreting adrenocortical malignancy (even more rare) is raised in those nodules >3 to 3.5 cm having other concerning imaging characteristics (HU, washout characteristics, in-phase/out-of-phase changes). This size criterion for concern for malignancy is smaller than the 4- to 6-cm criteria normally used for assessment of other adrenal nodules.
FIGURE 2 • Typical, small, benign-appearing aldosteronesecreting adenoma in the left adrenal gland.
Surgical Approach
The lateral transperitoneal approach to the adrenal gland is the most commonly employed when performing a laparoscopic adrenalectomy. Other approaches include anterior, lateral retroperitoneal, and posterior retroperitoneal. Open approaches (both anterior and posterior) may be used, but the laparoscopic approach has been shown to be associated with less pain, less morbidity, and shorter hospital stays.
Prior to operation, careful review of adrenal imaging should be undertaken to assess the position and course of the relevant vasculature including the adrenal veins, renal arteries and veins. On the left side, the surgeon should note the proximity of the splenic flexure of the colon, spleen, tail of the pancreas, and the splenic artery and vein. Patients with primary hyperaldosteronism should be prepared for surgery by correcting volume, metabolic abnormalities, and hypertension. Aldosterone receptor antagonists, such as spironolactone or eplerenone, are most useful and help correct hypertension and hypokalemia and reduce the need for other antihypertensive medications.
Left lateral transperitoneal laparoscopic adrenalectomy requires placement of the patient in the right lateral decubitus position (Table 2). Padding of pressure points is extremely important. The bed is extended to widen the space between the pelvis and the rib cage. The left arm is extended to the right side. The abdomen is accessed by an open Hasson technique at the junction of the lateral edge of the rectus muscle and the oblique musculature. Once the abdomen is insufflated and examined using a 30-degree laparoscope, at least two other ports are placed in a triangulated position. Using scissors, cautery, or ultrasonic instruments, attachments of the splenic flexure of the colon and the spleen are released and the spleen is rotated medially. The retroperitoneum is incised between the superior-medial aspect of the kidney and the inferior lateral aspect of the adrenal gland. Using cautery, ultrasonic shears and blunt dissection, the adrenal gland is mobilized from the retroperitoneal fat. At the superomedial aspect of the gland, the surgeon may encounter a branch from a phrenic vessel and should carefully ligate and divide this. Dissection at the inferior aspect should proceed cautiously to ensure no damage to the renal vessels. The adrenal vein will be found medially near a seven o’clock position draining into the renal vein. The adrenal vein should be ligated with clips and divided. The adrenal gland should be removed using an endo-bag and inspected to ensure complete removal of the gland prior to being sent to pathology.
TABLE 2. Key Technical Steps and Potential Pitfalls of Lateral Transperitoneal Laparoscopic Adrenalectomy
Right lateral transperitoneal laparoscopic adrenalectomy proceeds in a fashion similar to the left side. A fourth port is usually required to retract the right lobe of the liver using a paddle retractor after mobilizing the triangular and coronary ligaments. The right adrenal vein drains directly into the vena cava. Meticulous dissection along the vena cava is required to prevent massive bleeding.
Special Intraoperative Considerations
It may be difficult to identify the adrenal gland in obese patients with large quantities of retroperitoneal fat. The adrenal gland has a golden-rod yellow color that is darker than the surrounding fat. Laparoscopic ultrasound can be extremely helpful in these situations as well and can help identify the adrenal veins and renal vessels. On the left side, lobulations of pancreatic tissue may appear similar to adrenal tissue and be mistakenly removed although the pancreas is usually lighter in color than the adrenal gland. The supposed adrenal gland should be carefully inspected after removal to ensure the characteristic cortical and medullary tissue is identified upon incision of the gland. If at any time malignancy is suspected, convert to an open procedure.
Postoperative Management
Patients generally do not require postoperative ICU management. Antihypertensive medications are held after surgery. Essential hypertension may necessitate reinstitution of some medications. Factors including age of onset of hypertension, length of time with hypertension, and number of medications required to control the blood pressure preoperatively allow for prediction of resolution of hypertension and hypokalemia after surgery. Hypertension due to hyperaldosteronism will resolve if patients have been evaluated appropriately (venous sampling used to differentiate between unilateral and bilateral excess aldosterone secretion) in the preoperative setting. Hypokalemia and need for potassium supplementation resolve within 24 hours and patients may become hyperkalemic for a short time. Autodiuresis of excess volume from hyperaldosteronism usually also occurs in the postoperative period. Most patients may be discharged on the first or second postoperative day.
Case Conclusion
The patient is found to have an aldosterone:renin ratio of 38. Computed tomography reveals a 1.4-cm lesion in the left adrenal gland. Selective venous sampling confirms unilateral excess aldosterone secretion with a dominant left A:C to nondominant right A:C ratio of 7. A left laparoscopic adrenalectomy is performed. Postoperatively, the patient’s hypokalemia resolves; however, the blood pressure remains slightly elevated in the postoperative setting and she is reinstituted on beta-blocker therapy for the perioperative period. At the postoperative visit, her blood pressure is 124/68, potassium is 4.0 mEq/L, aldosterone is 8, and renin is 1.4.
TAKE HOME POINTS
· Secondary causes for hypertension should be sought in young patients or those with difficult to control blood pressure requiring more than three antihypertensive medications.
· Hypokalemia may not be present in all patients (40% to 50%).
· Diagnosis is by biochemical means, requiring an elevated aldosterone level and aldosterone:renin >20:1.
· Selective venous sampling of the adrenal veins is imperative to differentiate between unilateral and bilateral excess aldosterone secretion. Those with evidence of unilateral excess secretion should be offered surgery.
· Resection by a laparoscopic approach is the gold standard except in the case of malignancy.
· Resolution of hypertension is variable but predictable depending on age, severity of hypertension, and the degree to which essential hypertension contributes to the process.
SUGGESTED READINGS
McKenzie TJ, Lillegard JB, Young WF Jr, et al. Aldosteronomas—state of the art. Surg Clin North Am. 2009;89(5):1241–1253.
Nwariaku F, Miller B, Auchus R, et al. Primary hyperaldosteronism: effect of adrenal vein sampling on surgical outcome. Arch Surg. 2006;141(5):497–502;discussion 502–503.
White ML, Gauger PG, Doherty GM, et al. The role of radiologic studies in the evaluation and management of primary hyperaldosteronism. Surgery. 2008;144(6):926–933.
Zarnegar R, Young WF Jr, Lee J, et al. The aldosteronoma resolution score: predicting complete resolution of hypertension after adrenalectomy for aldosteronoma. Ann Surg. 2008;247(3).